Nuedexta

Agents for Amyotrophic Lateral Sclerosis (ALS)
MS Agents

Oral Administration Oral Solid Formulations

May be administered without regard to meals.

Severe

lupus-like symptoms / Delayed / Incidence not known
seizures / Delayed / Incidence not known
hearing loss / Delayed / Incidence not known
night blindness / Delayed / Incidence not known
optic neuritis / Delayed / Incidence not known
visual impairment / Early / Incidence not known

Moderate

peripheral edema / Delayed / 5.0-5.0
thrombocytopenia / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
QT prolongation / Rapid / Incidence not known
ataxia / Delayed / Incidence not known
depression / Delayed / Incidence not known
psychosis / Early / Incidence not known
confusion / Early / Incidence not known
blurred vision / Early / Incidence not known
photophobia / Early / Incidence not known
delirium / Early / Incidence not known
keratopathy / Delayed / Incidence not known
scotomata / Delayed / Incidence not known

Mild

diarrhea / Early / 13.0-13.0
dizziness / Early / 10.0-10.0
vomiting / Early / 5.0-5.0
cough / Delayed / 5.0-5.0
asthenia / Delayed / 5.0-5.0
infection / Delayed / 4.0-4.0
influenza / Delayed / 4.0-4.0
flatulence / Early / 3.0-3.0
abdominal pain / Early / 0-2.0
muscle cramps / Delayed / 0-2.0
restlessness / Early / Incidence not known
drowsiness / Early / Incidence not known
nausea / Early / Incidence not known
diplopia / Early / Incidence not known
tinnitus / Delayed / Incidence not known
headache / Early / Incidence not known
vertigo / Early / Incidence not known
photosensitivity / Delayed / Incidence not known
mydriasis / Early / Incidence not known
skin discoloration / Delayed / Incidence not known

Nuedexta

Rx

Oral combination of dextromethorphan and low-dose quinidine.
Used for pseudobulbar affect (PBA); quinidine, a 2D6 inhibitor, increases the bioavailability of dextromethorphan, the active entity.
Due to the potential for quinidine to cause QT prolongation, contraindications apply to patients with certain cardiac conditions or those receiving medications that both prolong the QT interval and are CYP2D6 substrates (e.g., pimozide).

For the treatment of pseudobulbar affect (PBA). Oral dosage Adults

1 capsule (20 mg dextromethorphan with 10 mg quinidine per capsule) PO once daily for 7 days. Then, titrate to 1 capsule PO every 12 hours. Limited numbers of geriatric patients were studied in clinical trials; use caution during dose titration in the elderly. Periodically reassess the need for continued treatment. Efficacy for FDA-approval was demonstrated in controlled trials of patients with underlying amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS); compared to placebo, dextromethorphan; quinidine significantly decreased laughing and crying episodes. The drug combination has also been studied in a smaller number of patients with PBA coexistent with other underlying neurological conditions.

Hepatic Impairment

Dosage adjustments are not required in mild to moderate hepatic impairment. Dextromethorphan; quinidine has not been studied in patients with severe hepatic impairment.

Renal Impairment

Dosage adjustments are not required in mild to moderate renal impairment. Dextromethorphan; quinidine has not been studied in patients with severe renal impairment.

Abarelix: (Contraindicated) Since abarelix can cause QT prolongation, abarelix should be used cautiously, if at all, with other drugs that are associated with QT prolongation, such as Class IA antiarrhythmics.
Abiraterone: (Moderate) Abiraterone inhbits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. If dextromethorphan- related side effects occur, a dose reduction or discontinuation of dextromethorphan may be necessary. In an in vivo drug-drug interaction trial, the Cmax and AUC of the CYP2D6 substrate dextromethorphan were increased 2.8- and 2.9-fold, respectively when dextromethorphan 30 mg was given with abiraterone acetate 1,000 mg daily along with prednisone 5 mg twice daily. The AUC for dextrorphan, the active metabolite of dextromethorphan, increased approximately 1.3 fold.
Acebutolol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like acebutololl. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block and heart failure. Reduce the beta-blocker dosage if necessary.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Caution is recommended when administering quinidine with medications extensively metabolized by CYP2D6 such as diphenhydramine because quinidine inhibits CYP2D6 and may increase concentrations of drugs metabolized by this enzyme.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with quinidine may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of quinidine could decrease dihydrocodeine plasma concentrations and increase dihydromorphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If quinidine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Quinidine is a strong inhibitor of CYP2D6.
Acetaminophen; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Concomitant use of codeine with quinidine may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of quinidine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If quinidine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Quinidine is a strong inhibitor of CYP2D6.
Acetaminophen; Diphenhydramine: (Moderate) Caution is recommended when administering quinidine with medications extensively metabolized by CYP2D6 such as diphenhydramine because quinidine inhibits CYP2D6 and may increase concentrations of drugs metabolized by this enzyme.
Acetaminophen; Hydrocodone: (Moderate) Concomitant use of hydrocodone with quinidine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of quinidine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If quinidine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Quinidine is a strong inhibitor of CYP2D6.
Acetazolamide: (Major) Acetazolamide can decrease excretion of quinidine because carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized drug available for renal tubular reabsorption. The effects of quinidine can be prolonged or enhanced.
Adagrasib: (Major) Avoid concomitant use of adagrasib and quinidine due to the potential for increased quinidine exposure and additive risk for QT/QTc prolongation and torsade de pointes (TdP). If use is necessary, monitor for quinidine-related adverse effects and consider taking additional steps to minimize the risk for QT prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Quinidine is a CYP3A substrate, adagrasib is a strong CYP3A inhibitor, and both medications have been associated with QT interval prolongation.
Adefovir: (Moderate) Adefovir is eliminated renally by a combination of glomerular filtration and active tubular secretion; coadministration of adefovir dipivoxil with drugs that reduce renal function or compete for active tubular secretion, such as quinidine, may decrease adefovir elimination by competing for common renal tubular transport systems, therefore increasing serum concentrations of either adefovir and/or these coadministered drugs.
Afatinib: (Moderate) If the concomitant use of quinidine and afatinib is necessary, monitor for afatinib-related adverse reactions. If the original dose of afatinib is not tolerated, consider reducing the daily dose of afatinib by 10 mg; resume the previous dose of afatinib as tolerated after discontinuation of quinidine. The manufacturer of afatinib recommends permanent discontinuation of therapy for severe or intolerant adverse drug reactions at a dose of 20 mg per day, but does not address a minimum dose otherwise. Afatinib is a P-glycoprotein (P-gp) substrate and quinidine is a P-gp inhibitor; coadministration may increase plasma concentrations of afatinib. Administration with another P-gp inhibitor, given 1 hour before a single dose of afatinib, increased afatinib exposure by 48%; there was no change in afatinib exposure when the P-gp inhibitor was administered at the same time as afatinib or 6 hours later. In healthy subjects, the relative bioavailability for AUC and Cmax of afatinib was 119% and 104%, respectively, when coadministered with the same P-gp inhibitor, and 111% and 105% when the inhibitor was administered 6 hours after afatinib.
Aldesleukin, IL-2: (Moderate) Quinidine causes a dose-dependent QT prolongation and is metabolized via CYP3A4. Concurrent use of quinidine with CYP3A4 inhibitors such as aldesleukin, IL-2 may result in elevated quinidine plasma concentrations with the potential for enhanced QT-prolonging effects.
Alfentanil: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering alfentanil with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Alfuzosin: (Major) Alfuzosin should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Based on electrophysiology studies performed by the manufacturer, alfuzosin has a slight effect to prolong the QT interval. The QT prolongation appeared less with alfuzosin 10 mg than with 40 mg. The manufacturer warns that the QT effect of alfuzosin should be considered prior to administering the drug to patients taking other medications known to prolong the QT interval.
Alkalinizing Agents: (Major) Urinary alkalinization increases the renal tubular reabsorption of quinidine, resulting in higher quinidine serum concentrations which may lead to toxicity. Avoid citric acid; potassium citrate; sodium citrate administration to any patient receiving treatment with quinidine.
Alvimopan: (Moderate) Alvimopan is a substrate of P-glycoprotein (P-gp). Although the concomitant use of mild to moderate inhibitors of P-gp did not influence the pharmacokinetics of alvimopan, the concomitant use of strong P-gp inhibitors, such as quinidine, has not been studied. Coadministration of quinidine and alvimopan may result in elevated concentrations of alvimopan. If these drugs are coadministered, patients should be monitored for increased toxicity as well as increased therapeutic effect of alvimopan.
Amantadine: (Minor) Concomitant administration of quinidine with amantadine has been shown to decrease the renal clearance of amantadine. An in vivo study demonstrated that quinidine, a known organic cation transporter inhibitor, reduced amantadine clearance by approximately 33% in humans. The proposed mechanism is inhibition of the renal tubular secretion of amantadine, but the mechanism appears to be independent of OCT2 or other known renal drug transporters. The clinical significance is not known. Monitor for possible side effects of amantadine, including dizziness, confusion, nausea/vomiting, xerostomia, and anticholinergic effects.
Amiloride: (Contraindicated) Seven of ten patients with inducible ventricular tachycardia developed adverse reactions including sustained ventricular tachycardia and other somatic complaints during concomitant amiloride and quinidine administration. The therapeutic antiarrhythmic actions of quinidine were antagonized by amiloride. In addition, quinidine exerts either direct or indirect (alpha-adrenergic blockade) peripheral vasodilatory effects, which can decrease blood pressure. Hypotension is more severe with parenteral quinidine. Until more data are available, this drug combination should be avoided whenever possible.
Amiloride; Hydrochlorothiazide, HCTZ: (Contraindicated) Seven of ten patients with inducible ventricular tachycardia developed adverse reactions including sustained ventricular tachycardia and other somatic complaints during concomitant amiloride and quinidine administration. The therapeutic antiarrhythmic actions of quinidine were antagonized by amiloride. In addition, quinidine exerts either direct or indirect (alpha-adrenergic blockade) peripheral vasodilatory effects, which can decrease blood pressure. Hypotension is more severe with parenteral quinidine. Until more data are available, this drug combination should be avoided whenever possible.
Amiodarone: (Major) Amiodarone coadministration increases quinidine concentrations by about 33% after 2 days, by decreasing its renal clearance or by inhibiting its hepatic metabolism. Quinidine may also be displaced from tissue and protein binding sites. Prolongation of the QT interval is well documented with quinidine, and the addition of amiodarone may increase this effect, placing the patient at an increased risk for the development of torsade de pointes. Careful clinical observation of the patient as well as close monitoring of the ECG and serum quinidine concentrations are essential with adjustment of the quinidine dosing regimen performed as necessary to avoid enhanced toxicity or pharmacodynamic effects. An empiric reduction of the quinidine dose by 33-50% is suggested within 2 days following initiation of amiodarone therapy, with consideration given to immediately discontinuing of quinidine once amiodarone therapy is begun. Combination antiarrhythmic therapy is reserved for patients with refractory life-threatening arrhythmias. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
Amisulpride: (Major) Monitor ECGs for QT prolongation when amisulpride is administered with quinidine. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Amisulpride causes dose- and concentration- dependent QT prolongation.
Amitriptyline: (Contraindicated) Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions. Quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Tricyclic antidepressants are associated with a possible risk of QT prolongation, particularly at high dosages or in overdose, and are substrates for CYP2D6.
Amlodipine: (Moderate) Monitor for increased quinidine adverse reactions if coadministered with amlodipine. Taking these drugs together may increase quinidine plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; quinidine is a substrate of CYP3A4 with a narrow therapeutic index. In addition, quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Amlodipine; Atorvastatin: (Moderate) Monitor for increased quinidine adverse reactions if coadministered with amlodipine. Taking these drugs together may increase quinidine plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; quinidine is a substrate of CYP3A4 with a narrow therapeutic index. In addition, quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Amlodipine; Benazepril: (Moderate) Monitor for increased quinidine adverse reactions if coadministered with amlodipine. Taking these drugs together may increase quinidine plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; quinidine is a substrate of CYP3A4 with a narrow therapeutic index. In addition, quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Amlodipine; Celecoxib: (Moderate) Monitor for increased quinidine adverse reactions if coadministered with amlodipine. Taking these drugs together may increase quinidine plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; quinidine is a substrate of CYP3A4 with a narrow therapeutic index. In addition, quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Amlodipine; Olmesartan: (Moderate) Monitor for increased quinidine adverse reactions if coadministered with amlodipine. Taking these drugs together may increase quinidine plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; quinidine is a substrate of CYP3A4 with a narrow therapeutic index. In addition, quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Amlodipine; Valsartan: (Moderate) Monitor for increased quinidine adverse reactions if coadministered with amlodipine. Taking these drugs together may increase quinidine plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; quinidine is a substrate of CYP3A4 with a narrow therapeutic index. In addition, quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for increased quinidine adverse reactions if coadministered with amlodipine. Taking these drugs together may increase quinidine plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; quinidine is a substrate of CYP3A4 with a narrow therapeutic index. In addition, quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Amobarbital: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
Amoxapine: (Major) Because most cyclic antidepressants are partially metabolized by CYP2D6, caution is advisable during co-administration of amoxapine and potent CYP2D6 inhibitors such as quinidine. Elevated plasma concentrations of amoxapine may result in more pronounced anticholinergic effects and the risk of seizures may be increased. Anti-arrhythmics that are less potent inhibitors of CYP2D6, such as propafenone, may similarly interact with amoxapine. CYP2D6 substrates including flecainide may compete with amoxapine for the same metabolic pathway.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP). Quinidine (including dextromethorphan; quinidine) and disopyramide are also associated with QT prolongation and TdP. There have been post-marketing reports of TdP occurring with the coadministration of clarithromycin and quinidine or disopyramide. If used concomitantly, monitor ECGs for QT prolongation and consider monitoring serum concentrations of quinidine or disopyramide.
Amphetamines: (Moderate) Warn patients that the risk of amphetamine toxicity may be increased during concurrent use of quinidine, a strong CYP2D6 inhibitor. Amphetamines are partially metabolized by CYP2D6 and have serotonergic properties; inhibition of amphetamine metabolism may increase the risk of serotonin syndrome or other toxicity. If serotonin syndrome occurs, both the amphetamine and CYP2D6 inhibitor should be discontinued and appropriate medical treatment should be implemented.
Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported during post-marketing use of anagrelide. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with anagrelide include quinidine.
Angiotensin II receptor antagonists: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Angiotensin-converting enzyme inhibitors: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Antacids: (Major) Alkalinizing agents such as antacids can increase renal tubular reabsorption of quinidine by alkalinizing the urine; higher quinidine serum concentrations and quinidine toxicity are possible.
Apalutamide: (Moderate) Closely monitor quinidine concentrations if apalutamide is added to existing quinidine therapy. No special precautions appear necessary if apalutamide is started several weeks before quinidine, but quinidine doses may require adjustment if apalutamide is added or discontinued during quinidine therapy. Quinidine is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the half-life and corresponding AUC of quinidine by 50% to 60%.
Apomorphine: (Major) Use apomorphine and quinidine together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Quinidine administration is associated with QT prolongation and torsades de pointes.
Aprepitant, Fosaprepitant: (Major) Use caution if quinidine and aprepitant, fosaprepitant are used concurrently and monitor for an increase in quinidine-related adverse effects, including QT prolongation and torsade de pointes (TdP), for several days after administration of a multi-day aprepitant regimen. Quinidine is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of quinidine. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
Aripiprazole: (Contraindicated) Avoid use of aripiprazole with quinidine unless the benefit outweighs the risk. Quinidine is generally contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6, such as aripiprazole, as the effects on the QT interval may be increased. Manufacturer recommendations for this combination have varied. Do not use the combination product of dextromethorphan; quinidine with aripiprazole. The manufacturers of aripiprazole products do not contraindicate use of quinidine, but recommend dosage adjustments of aripiprazole when used with potent CYP2D6 inhibitors, such as quinidine. For example, the oral aripiprazole dose should be reduced by 50%. Injectable forms of aripiprazole require dose adjustment when the potent CYP2D6 inhibitor will be used for more than 14 days. See the manufacturer prescribing information for detailed recommendations. Both aripiprazole and quinidine are associated with QT prolongation. Increased aripiprazole exposure is likely when a potent CYP2D6 inhibitor like quinidine is used concurrently. In one evaluation, concurrent use of quinidine and oral aripiprazole resulted in an increase in the AUC of aripiprazole of 112% and a decrease in the AUC of its active metabolite by 35%.
Arsenic Trioxide: (Major) If possible, quinidine should be discontinued prior to initiating arsenic trioxide therapy. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported.
Artemether; Lumefantrine: (Moderate) Use of dextromethorphan with lumefantrine may result in increased dextromethorphan exposure. Lumefantrine inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Articaine; Epinephrine: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
Asenapine: (Major) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Asenapine has been associated with QT prolongation. According to the manufacturer of asenapine, the drug should be avoided in combination with other agents also known to have this effect.
Aspirin, ASA; Butalbital; Caffeine: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Concomitant use of codeine with quinidine may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of quinidine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If quinidine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Quinidine is a strong inhibitor of CYP2D6.
Atazanavir: (Major) Caution is advised when administering quinidine with atazanavir. If atazanavir is boosted with ritonavir, concurrent use of quinidine is contraindicated. Use of all 3 drugs together may significantly increase quinidine concentrations and increase the risk for QT prolongation and serious or life-threatening cardiac arrhythmias. Atazanavir and ritonavir are CYP3A4 inhibitors; quinidine is metabolized by this enzyme.
Atazanavir; Cobicistat: (Major) Caution is advised when administering quinidine with atazanavir. If atazanavir is boosted with ritonavir, concurrent use of quinidine is contraindicated. Use of all 3 drugs together may significantly increase quinidine concentrations and increase the risk for QT prolongation and serious or life-threatening cardiac arrhythmias. Atazanavir and ritonavir are CYP3A4 inhibitors; quinidine is metabolized by this enzyme. (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of quinidine with cobicistat. Quinidine is a substrate for CYP3A4 and P-glycoprotein (P-gp) and an inhibitor of CYP2D6 and P-gp; cobicistat is a substrate and inhibitor of both these enzymes and an inhibitor of P-gp. Concurrent use may result in elevated plasma concentration of both drugs. (Moderate) Use of dextromethorphan with cobicistat may result in increased dextromethorphan exposure. Cobicistat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Atenolol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like atenolol. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block and heart failure. Reduce the beta-blocker dosage if necessary.
Atenolol; Chlorthalidone: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like atenolol. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block and heart failure. Reduce the beta-blocker dosage if necessary.
Atomoxetine: (Major) If possible, quinidine should be avoided in patients receiving atomoxetine. Coadministration of quinidine with atomoxetine may result in additive QT prolongation and increased exposure to atomoxetine. When administered as quinidine; dextromethorphan, coadministration with atomoxetine is contraindicated. Quinidine is a CYP2D6 inhibitor that is associated with QT prolongation and torsade de pointes (TdP). Atomoxetine is a CYP2D6 substrate. In children and adolescents up to 70 kg receiving quinidine, atomoxetine should be initiated at 0.5 mg/kg/day and only increased to the usual target dose of 1.2 mg/kg/day if symptoms fail to improve after 4 weeks and the initial dose is well tolerated. In children and adolescents over 70 kg and adults receiving quinidine, atomoxetine should be initiated at 40 mg/day and only increased to the usual target dose of 80 mg/day if symptoms fail to improve after 4 weeks and the initial dose is well tolerated. Coadministration of a strong CYP2D6 inhibitor and atomoxetine in extensive metabolizers of CYP2D6, increased atomoxetine steady-state plasma concentrations by approximately 6 to 8-fold. This increase is similar to exposures observed in poor metabolizers. Concurrent use of a strong CYP2D6 inhibitor with atomoxetine in poor metabolizers is not expected to increase atomoxetine exposure.
Atracurium: (Moderate) Concomitant use of neuromuscular blockers and quinidine may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Atropine: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
Atropine; Difenoxin: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
Azithromycin: (Major) Concomitant use of quinidine and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Barbiturates: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
Bedaquiline: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering bedaquiline with quinidine or quinidine-containing products, such as dextromethorphan; quinidine. Both drugs have been reported to prolong the QT interval. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Because of the potential risk and severity of serotonin syndrome, coadministration of dextromethorphan and IV methylene blue should be avoided if possible. Methylene blue has been demonstrated to be a potent monoamine oxidase inhibitor (MAOI) and may cause potentially fatal serotonin toxicity (serotonin syndrome) when combined with serotonin reuptake inhibitors (SRIs). Dextromethorphan increases central serotonin effects. If methylene blue is judged to be indicated, all SRIs, including dextromethorphan, must be ceased prior to treatment/procedure/surgery. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Major) Hyoscyamine may increase the absorption of quinidine by decreasing GI motility and thereby enhancing absorption with possible toxicity. Increased monitoring is advised in patients receiving a combination of these drugs.
Benztropine: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
Berotralstat: (Major) Reduce the berotralstat dose to 110 mg PO once daily in patients chronically taking quinidine. Concurrent use may increase berotralstat exposure and the risk of adverse effects. Additionally, monitor ECG and for quinidine-related adverse reactions as concurrent use may result in increased plasma concentrations of quinidine. Berotralstat is a P-gp substrate and moderate CYP3A4 inhibitor; quinidine is a CYP3A4 substrate and P-gp inhibitor. Coadministration with another P-gp inhibitor increased berotralstat exposure by 69%.
Betaxolol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like betaxolol. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block and heart failure, Reduce the beta-blocker dosage if necessary. Ophthalmic betaxolol is not as likely to interact; however, bradycardia and heart block have been reported, and additive effects on conduction may be considered.
Bethanechol: (Moderate) Drugs that possess antimuscarinic properties, such as quinidine, are pharmacologic opposites of bethanechol. These agents should not be used with bethanechol except when the specific intent is to counteract excessive actions of one or the other.
Betrixaban: (Major) Avoid betrixaban use in patients with severe renal impairment receiving quinidine. Reduce betrixaban dosage to 80 mg PO once followed by 40 mg PO once daily in all other patients receiving quinidine. Bleeding risk may be increased; monitor patients closely for signs and symptoms of bleeding. Betrixaban is a substrate of P-gp; quinidine inhibits P-gp.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and quinidine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and quinidine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bisoprolol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like pindolol. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block and heart failure, Reduce the beta-blocker dosage if necessary.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like pindolol. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block and heart failure, Reduce the beta-blocker dosage if necessary.
Blinatumomab: (Moderate) No drug interaction studies have been performed with blinatumomab. The drug may cause a transient release of cytokines leading to an inhibition of CYP450 enzymes. The interaction risk with CYP450 substrates is likely the highest during the first 9 days of the first cycle and the first 2 days of the second cycle. Monitor patients receiving concurrent CYP450 substrates that have a narrow therapeutic index (NTI) such as quinidine. The dose of the concomitant drug may need to be adjusted.
Brexpiprazole: (Major) Because brexpiprazole is primarily metabolized by CYP3A4 and CYP2D6, the manufacturer recommends that the brexpiprazole dose be reduced to one-half of the usual dose in patients receiving a strong CYP2D6 inhibitor and one-quarter (25%) of the usual dose in patients receiving a moderate to strong inhibitor of CYP3A4 in combination with a moderate to strong inhibitor of CYP2D6. Quinidine is a strong inhibitor of CYP2D6. If these agents are used in combination, the patient should be carefully monitored for brexpiprazole-related adverse reactions. It should be noted that no dosage adjustment is needed in patients taking a strong CYP2D6 inhibitor who are receiving brexpiprazole as adjunct treatment for major depressive disorder because CYP2D6 considerations are already factored into general dosing recommendations.
Brimonidine; Timolol: (Major) In general, patients receiving combined therapy with quinidine and beta-blockers should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block, and heart failure. Reduce the beta-blocker dosage if necessary. Quinidine may have additive effects on cardiovascular parameters when used together with beta-blockers, such as timolol. Decreased heart rate (bradycardia) has been reported during combination timolol and quinidine therapy. Additive hypotension is also possible. Additionally, quinidine is a known inhibitor of CYP2D6, and may impair the hepatic clearance of timolol (CYP2D6 substrate). Patients should be monitored for excess beta-blockade. Quinidine has been reported to potentiate timolol-induced bradycardia even after use of ophthalmic timolol.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
Bupivacaine; Epinephrine: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
Bupivacaine; Lidocaine: (Major) Avoid concurrent use of quinidine with other antiarrhythmics with Class I activities, such as lidocaine. Concurrent use may result in additive or antagonistic cardiac effects and additive toxicity.
Buprenorphine: (Major) Buprenorphine should be avoided in combination with Class IA antiarrhythmics. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. (Moderate) If concomitant use of buprenorphine and dextromethorphan is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Buprenorphine; Naloxone: (Major) Buprenorphine should be avoided in combination with Class IA antiarrhythmics. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. (Moderate) If concomitant use of buprenorphine and dextromethorphan is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Bupropion: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of bupropion is necessary. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and bupropion is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Bupropion; Naltrexone: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of bupropion is necessary. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and bupropion is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Butabarbital: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
Butalbital; Acetaminophen: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
Butalbital; Acetaminophen; Caffeine: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy. (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Concomitant use of codeine with quinidine may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of quinidine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If quinidine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Quinidine is a strong inhibitor of CYP2D6.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy. (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Concomitant use of codeine with quinidine may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of quinidine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If quinidine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Quinidine is a strong inhibitor of CYP2D6.
Cabotegravir; Rilpivirine: (Major) Rilpivirine should be used cautiously with Class IA antiarrhythmics (disopyramide, procainamide, quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval.
Cabozantinib: (Minor) Monitor for an increase in quinidine-related adverse reactions if coadministration with cabozantinib is necessary; a dose adjustment of quinidine may be necessary. Quinidine is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Calcium Carbonate: (Major) By increasing urinary pH, calcium carbonate can decrease the urinary excretion of quinidine.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Major) By increasing urinary pH, calcium carbonate can decrease the urinary excretion of quinidine.
Calcium Carbonate; Magnesium Hydroxide: (Major) By increasing urinary pH, calcium carbonate can decrease the urinary excretion of quinidine.
Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Major) By increasing urinary pH, calcium carbonate can decrease the urinary excretion of quinidine.
Calcium Carbonate; Simethicone: (Major) By increasing urinary pH, calcium carbonate can decrease the urinary excretion of quinidine.
Calcium; Vitamin D: (Major) By increasing urinary pH, calcium carbonate can decrease the urinary excretion of quinidine.
Capreomycin: (Moderate) Partial neuromuscular blockade has been reported with capreomycin after the administration of large intravenous doses or rapid intravenous infusion. Quinidine could potentiate the neuromuscular blocking effect of capreomycin by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects.
Carbamazepine: (Moderate) Carbamazepine is metabolized by the hepatic isoenzyme CYP3A4. Quinidine inhibits CYP3A4 and may decrease carbamazepine metabolism and increase carbamazepine plasma concentrations. Serum carbamazepine concentrations should be monitored closely if quinidine is added during carbamazepine therapy. It may be necessary to reduce the dose of carbamazepine in this situation.
Cardiac glycosides: (Major) Coadministration of quinidine and oral digoxin has resulted in a 100% increase in digoxin serum concentrations. When quinidine is coadministered with intravenous (IV) digoxin, the digoxin AUC is increased by 54 to 83%. Digoxin is a P-gp substrate and quinidine inhibits P-gp. The inhibition of P-gp in the intestinal cell wall may lead to increased oral absorption of digoxin. It also has been shown that quinidine inhibits the secretion of digoxin by P-gp transporters in the kidney leading to decreased renal tubular elimination of digoxin and increased serum concentrations. Measure serum digoxin concentrations before initiating quinidine. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 30 to 50% or by modifying the dosing frequency and continue monitoring.
Carteolol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like carteololl. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block, and heart failure, Reduce the beta-blocker dosage if necessary. Carteolol is not as likely to interact as it is a nonselective beta-adrenoceptor antagonist with intrinsic sympathomimetic activity (ISA); however, additive effects on conduction may be considered, even with ophthalmic use.
Carvedilol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with carvedilol, a beta-blocker. Altered concentrations of quinidine and/or carvedilol may occur during coadministration. Quinidine is a CYP2D6 inhibitor and P-glycoprotein (P-gp) inhibitor and substrate. Carvedilol is a P-gp inhibitor and substrate and a substrate of CYP2D6. Patients should be monitored for excess beta-blockade. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block, and heart failure. Reduce the beta-blocker dosage if necessary.
Celecoxib; Tramadol: (Moderate) As quinidine is a potent inhibitor of CYP2D6 and tramadol is partially metabolized by CYP2D6, concurrent therapy may decrease tramadol metabolism. This interaction may result in decreased tramadol efficacy and/or increased tramadol-induced risks of serotonin syndrome or seizures. The analgesic activity of tramadol is due to the activity of both the parent drug and the O-desmethyltramadol metabolite (M1), and M1 formation is dependent on CYP2D6. Therefore, use of tramadol with a CYP2D6-inhibitor may alter tramadol efficacy. In addition, inhibition of CYP2D6 metabolism is expected to result in reduced metabolic clearance of tramadol. This in turn may increase the risk of tramadol-related adverse events including serotonin syndrome and seizures. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Central-acting adrenergic agents: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Ceritinib: (Major) Avoid coadministration of ceritinib with quinidine if possible due to the risk of QT prolongation; plasma concentrations of quinidine may also increase. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Quinidine is a CYP3A4 substrate that is associated with QT prolongation and torsade de pointes (TdP). Ceritinib is a strong CYP3A4 inhibitor that causes concentration-dependent QT prolongation.
Cevimeline: (Moderate) Cevimeline is metabolized by cytochrome P450 3A4 and CYP2D6. Concurrent administration of inhibitors of these enzymes, such as quinidine, may lead to increased cevimeline plasma concentrations.
Chlordiazepoxide; Amitriptyline: (Contraindicated) Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions. Quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Tricyclic antidepressants are associated with a possible risk of QT prolongation, particularly at high dosages or in overdose, and are substrates for CYP2D6.
Chlordiazepoxide; Clidinium: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics. Anticholinergic agents administered concurrently with quinidine may produce additive antivagal effects on AV nodal conduction.
Chloroquine: (Major) Avoid coadministration of chloroquine with quinidine due to the increased risk of QT prolongation or other drug toxicities. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. Quinidine administration is also associated with QT prolongation and TdP.
Chlorpheniramine; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Concomitant use of codeine with quinidine may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of quinidine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If quinidine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Quinidine is a strong inhibitor of CYP2D6.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with quinidine may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of quinidine could decrease dihydrocodeine plasma concentrations and increase dihydromorphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If quinidine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Quinidine is a strong inhibitor of CYP2D6.
Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with quinidine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of quinidine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If quinidine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Quinidine is a strong inhibitor of CYP2D6.
Chlorpromazine: (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include chlorpromazine.
Cimetidine: (Major) Quinidine concentrations should be monitored closely after cimetidine is added; choose an alternate acid-reducing therapy if possible. Quinidine is eliminated primarily by the CYP3A4 isoenzyme. Cimetidine can inhibit quinidine metabolism and produce quinidine toxicity.
Ciprofloxacin: (Major) Concomitant us

e of quinidine and ciprofloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Cisapride: (Contraindicated) QT prolongation and ventricular arrhythmias, including torsade de pointes (TdP) and death, have been reported with cisapride. Administration of Class IA antiarrhythmics (disopyramide, procainamide, and quinidine) is associated with QT prolongation and TdP. Because of the potential for TdP, concurrent use of Class IA antiarrhythmics and cisapride is contraindicated.
Cisatracurium: (Moderate) Concomitant use of neuromuscular blockers and quinidine may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Citalopram: (Major) Concomitant use of quinidine and citalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with citalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Citric Acid; Potassium Citrate; Sodium Citrate: (Major) Alkalinizing agents such as potassium citrate can increase renal tubular reabsorption of quinidine by alkalinizing the urine; higher quinidine serum concentrations and quinidine toxicity are possible.
Clarithromycin: (Major) Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP). Quinidine (including dextromethorphan; quinidine) and disopyramide are also associated with QT prolongation and TdP. There have been post-marketing reports of TdP occurring with the coadministration of clarithromycin and quinidine or disopyramide. If used concomitantly, monitor ECGs for QT prolongation and consider monitoring serum concentrations of quinidine or disopyramide.
Clobazam: (Moderate) Use of dextromethorphan with clobazam may result in increased dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Clobazam inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. A dosage reduction of dextromethorphan may be necessary for some patients. During one in vivo study, co-administration of dextromethorphan and clobazam resulted in increased AUC and Cmax of dextromethorphan by 90% and 59%, respectively.
Clofarabine: (Moderate) Concomitant use of clofarabine, a substrate of OCT1, and quinidine, an inhibitor of OCT1, may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g., hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 inhibitors.
Clofazimine: (Major) Concomitant use of clofazimine and quinidine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Clomipramine: (Contraindicated) Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions. Quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Tricyclic antidepressants are associated with a possible risk of QT prolongation, particularly at high dosages or in overdose, and are substrates for CYP2D6.
Clozapine: (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include clozapine.
Cobicistat: (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of quinidine with cobicistat. Quinidine is a substrate for CYP3A4 and P-glycoprotein (P-gp) and an inhibitor of CYP2D6 and P-gp; cobicistat is a substrate and inhibitor of both these enzymes and an inhibitor of P-gp. Concurrent use may result in elevated plasma concentration of both drugs. (Moderate) Use of dextromethorphan with cobicistat may result in increased dextromethorphan exposure. Cobicistat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Cobimetinib: (Minor) If concurrent use of cobimetinib and quinidine is necessary, use caution and monitor for a possible increase in cobimetinib-related adverse effects. Cobimetinib is a P-glycoprotein (P-gp) substrate, and quinidine is a P-gp inhibitor; coadministration may result in increased cobimetinib exposure. However, coadministration of cobimetinib with another P-gp inhibitor, vemurafenib (960 mg twice daily), did not result in clinically relevant pharmacokinetic drug interactions.
Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Concomitant use of codeine with quinidine may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of quinidine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If quinidine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Quinidine is a strong inhibitor of CYP2D6.
Codeine; Guaifenesin: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Concomitant use of codeine with quinidine may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of quinidine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If quinidine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Quinidine is a strong inhibitor of CYP2D6.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Concomitant use of codeine with quinidine may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of quinidine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If quinidine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Quinidine is a strong inhibitor of CYP2D6.
Codeine; Phenylephrine; Promethazine: (Contraindicated) Quinidine (including dextromethorphan; quinidine) administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6, such as promethazine, as the effects on the QT interval may be increased during concurrent use of these agents. (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Concomitant use of codeine with quinidine may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of quinidine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If quinidine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Quinidine is a strong inhibitor of CYP2D6.
Codeine; Promethazine: (Contraindicated) Quinidine (including dextromethorphan; quinidine) administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6, such as promethazine, as the effects on the QT interval may be increased during concurrent use of these agents. (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Concomitant use of codeine with quinidine may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of quinidine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If quinidine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Quinidine is a strong inhibitor of CYP2D6.
Colchicine: (Major) Avoid concomitant use of colchicine and quinidine due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and quinidine is a P-gp inhibitor.
Colesevelam: (Moderate) Colesevelam may decrease the bioavailability of antiarrhythmics if coadministered. To minimize potential for interactions, consider administering oral antiarrhythmics at least 1 hour before or at least 4 hours after colesevelam.
Colistin: (Moderate) Quinidine can potentiate the neuromuscular blocking effect of colistimethate sodium by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
Conivaptan: (Moderate) Monitor ECG and for quinidine-related adverse reactions if coadministration with conivaptan is necessary. Concomitant use may result in increased plasma concentrations of quinidine. Quinidine is a CYP3A substrate and conivaptan is a moderate CYP3A inhibitor.
Crizotinib: (Major) Avoid coadministration of crizotinib with quinidine due to the risk of QT prolongation; exposure to quinidine may also increase. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Quinidine administration is also associated with QT prolongation and torsade de pointes (TdP).
Dabigatran: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with quinidine, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like quinidine in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with quinidine, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. Coadministration of quinidine 200 mg every 2 hours up to a total dose of 1000 mg and dabigatran administered over 3 consecutive days, the last evening dose on Day 3 with or without quinidine pre-dosing, resulted in an increase in dabigatran AUC and Cmax of 53% and 56%, respectively. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Daclatasvir: (Major) Systemic exposure of quinidine, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of quinidine; monitor patients for potential adverse effects.
Dacomitinib: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of dacomitinib is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and dacomitinib is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Dalfopristin; Quinupristin: (Moderate) Coadministration of quinidine with dalfopristin; quinupristin may result in elevated quinidine plasma concentrations. If these drugs are used together, closely monitor for signs of quinidine-related adverse events. Quinidine is a substrate of CYP3A; dalfopristin; quinupristin is a weak CYP3A inhibitor.
Danazol: (Moderate) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of CYP3A4 substrates including quinidine.
Darifenacin: (Moderate) Clinicians should monitor patients for increased anticholinergic effects when CYP2D6 inhibitors, such as quinidine, are coadministered with darifenacin; the dosage of darifenacin should be adjusted, if necessary. (Minor) Use of dextromethorphan with darifenacin may result in increased dextromethorphan exposure. Darifenacin is a moderate inhibitor of CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Darunavir: (Major) Darunavir is an inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme should be expected with concurrent use. Coadministration of darunavir with quinidine should be done with extreme caution. Therapeutic monitoring of antiarrhythmic concentrations is recommended.
Darunavir; Cobicistat: (Major) Darunavir is an inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme should be expected with concurrent use. Coadministration of darunavir with quinidine should be done with extreme caution. Therapeutic monitoring of antiarrhythmic concentrations is recommended. (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of quinidine with cobicistat. Quinidine is a substrate for CYP3A4 and P-glycoprotein (P-gp) and an inhibitor of CYP2D6 and P-gp; cobicistat is a substrate and inhibitor of both these enzymes and an inhibitor of P-gp. Concurrent use may result in elevated plasma concentration of both drugs. (Moderate) Use of dextromethorphan with cobicistat may result in increased dextromethorphan exposure. Cobicistat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Darunavir is an inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme should be expected with concurrent use. Coadministration of darunavir with quinidine should be done with extreme caution. Therapeutic monitoring of antiarrhythmic concentrations is recommended. (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of quinidine with cobicistat. Quinidine is a substrate for CYP3A4 and P-glycoprotein (P-gp) and an inhibitor of CYP2D6 and P-gp; cobicistat is a substrate and inhibitor of both these enzymes and an inhibitor of P-gp. Concurrent use may result in elevated plasma concentration of both drugs. (Moderate) Use of dextromethorphan with cobicistat may result in increased dextromethorphan exposure. Cobicistat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Dasatinib: (Major) Monitor for evidence of QT prolongation and torsade de pointes (TdP) if coadministration of dasatinib and quinidine is necessary. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Quinidine administration is associated with QT prolongation and TdP.
Degarelix: (Major) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents such as class IA antiarrhythmics. Class IA antiarrhythmics (disopyramide, procainamide, and quinidine) are associated with QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy (i.e., degarelix) may also prolong the QT/QTc interval.
Delavirdine: (Major) Delavirdine is a potent inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as quinidine, should be expected with concurrent use. Increased quinidine concentrations may be associated with severe cardiovascular adverse reactions. Quinidine doses may require adjustment if delavirdine is added or discontinued during quinidine therapy. (Moderate) Use of dextromethorphan with delavirdine may result in increased dextromethorphan exposure. Delavirdine inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Desflurane: (Major) Halogenated anesthetics should be used cautiously with class IA antiarrhythmics (disopyramide, procainamide, quinidine). Halogenated anesthetics can prolong the QT interval and class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP).
Desipramine: (Contraindicated) Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions. Quinidine and dextromethorphan; quinidine are contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Tricyclic antidepressants are associated with a possible risk of QT prolongation, particularly at high dosages or in overdose, and are substrates for CYP2D6.
Desvenlafaxine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with desvenlafaxine. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. In addition, the manufacturer of desvenlafaxine recommends that the dose of CYP2D6 substrates, such as dextromethorphan, be reduced by up to 50% if used with desvenlafaxine 400 mg/day, a CYP2D6 inhibitor.
Deutetrabenazine: (Contraindicated) Quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range. Quinidine is a strong CYP2D6 inhibitor, and the metabolites of deutetrabenazine, alpha- and beta-HTBZ, are CYP2D6 substrates. The systemic exposure of alpha- and beta-HTBZ may be increased resulting in an increase in deutetrabenazine-related adverse reactions.
Dexmedetomidine: (Major) Concomitant use of dexmedetomidine and quinidine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Dextromethorphan; Bupropion: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of bupropion is necessary. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and bupropion is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Caution is recommended when administering quinidine with medications extensively metabolized by CYP2D6 such as diphenhydramine because quinidine inhibits CYP2D6 and may increase concentrations of drugs metabolized by this enzyme.
Diazoxide: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Dicyclomine: (Moderate) Additive anticholinergic effects may be seen when dicyclomine is used concomitantly with other drugs that possess anticholinergic properties, such as quinidine. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
Digoxin: (Major) Coadministration of quinidine and oral digoxin has resulted in a 100% increase in digoxin serum concentrations. When quinidine is coadministered with intravenous (IV) digoxin, the digoxin AUC is increased by 54 to 83%. Digoxin is a P-gp substrate and quinidine inhibits P-gp. The inhibition of P-gp in the intestinal cell wall may lead to increased oral absorption of digoxin. It also has been shown that quinidine inhibits the secretion of digoxin by P-gp transporters in the kidney leading to decreased renal tubular elimination of digoxin and increased serum concentrations. Measure serum digoxin concentrations before initiating quinidine. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 30 to 50% or by modifying the dosing frequency and continue monitoring.
Diltiazem: (Major) Diltiazem significantly decreases the clearance and increases the half-life of quinidine. Quinidine does not alter the kinetics of diltiazem. Concurrent use of diltiazem and quinidine in some patients may cause additive hypotension. Due to the potential for additive effects, caution and careful titration are warranted in patients receiving diltiazem concomitantly with other agents known to affect cardiac contractility and/or conduction. Medications that possess negative inotropic effects and/or slow AV conduction, such as quinidine, should be administered with caution to patients receiving concomitant therapy with diltiazem due to the risk of additive effects. Diltiazem may increase serum quinidine concentrations (AUC increases by 51%) by reducing the oral clearance of quinidine by 33%. During diltiazem coadministration, monitor quinidine serum concentrations and therapeutic response; adjust quinidine dosage if needed.
Diphenhydramine: (Moderate) Caution is recommended when administering quinidine with medications extensively metabolized by CYP2D6 such as diphenhydramine because quinidine inhibits CYP2D6 and may increase concentrations of drugs metabolized by this enzyme.
Diphenhydramine; Ibuprofen: (Moderate) Caution is recommended when administering quinidine with medications extensively metabolized by CYP2D6 such as diphenhydramine because quinidine inhibits CYP2D6 and may increase concentrations of drugs metabolized by this enzyme.
Diphenhydramine; Naproxen: (Moderate) Caution is recommended when administering quinidine with medications extensively metabolized by CYP2D6 such as diphenhydramine because quinidine inhibits CYP2D6 and may increase concentrations of drugs metabolized by this enzyme.
Diphenhydramine; Phenylephrine: (Moderate) Caution is recommended when administering quinidine with medications extensively metabolized by CYP2D6 such as diphenhydramine because quinidine inhibits CYP2D6 and may increase concentrations of drugs metabolized by this enzyme.
Diphenoxylate; Atropine: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
Disopyramide: (Major) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). The administration of artemether; lumefantrine is associated with prolongation of the QT interval. Although there are no studies examining the effects of artemether; lumefantrine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation and should be avoided.
Dofetilide: (Contraindicated) Coadministration of dofetilide and quinidine is contraindicated as concurrent use may increase the risk QT prolongation and torsades de pointes (TdP). Class I antiarrhythmic agents, such as quinidine, should be withheld for at least 3 half-lives prior to initiating dofetilide therapy. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Quinidine administration is associated with QT prolongation and TdP.
Dolasetron: (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include dolasetron.
Dolutegravir; Rilpivirine: (Major) Rilpivirine should be used cautiously with Class IA antiarrhythmics (disopyramide, procainamide, quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval.
Donepezil: (Contraindicated) Quinidine and combination products containing quinidine (e.g., dextromethorphan; quinidine) are contraindicated for use with medications that both prolong the QT interval and are CYP2D6 substrates, such as donepezil. Quinidine has QT prolonging actions and has been shown in vitro to inhibit the metabolism of donepezil by CYP2D6 inhibition; therefore, the effects on the QT interval may be increased during concurrent use of these agents. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy, and the drug is considered a drug with a known risk of TdP.
Donepezil; Memantine: (Contraindicated) Quinidine and combination products containing quinidine (e.g., dextromethorphan; quinidine) are contraindicated for use with medications that both prolong the QT interval and are CYP2D6 substrates, such as donepezil. Quinidine has QT prolonging actions and has been shown in vitro to inhibit the metabolism of donepezil by CYP2D6 inhibition; therefore, the effects on the QT interval may be increased during concurrent use of these agents. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy, and the drug is considered a drug with a known risk of TdP. (Major) Cationic drugs that are eliminated by renal tubular secretion, such as quinidine, may compete with memantine for common renal tubular transport systems, thus possibly decreasing the elimination of one of the drugs. Although theoretical, careful patient monitoring of response to memantine and/or quinidine is recommended to assess for needed dosage adjustments. In selected individuals, quinidine serum concentration monitoring may be appropriate. (Moderate) Dextromethorphan is a NMDA antagonist and may lead to additive adverse effects if combined with memantine, also an NMDA antagonist. It may be prudent to avoid coadministration of dextromethorphan with memantine. If coadministration cannot be avoided, monitor for increased adverse effects such as agitation, dizziness and other CNS events.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as quinidine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Dorzolamide; Timolol: (Major) In general, patients receiving combined therapy with quinidine and beta-blockers should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block, and heart failure. Reduce the beta-blocker dosage if necessary. Quinidine may have additive effects on cardiovascular parameters when used together with beta-blockers, such as timolol. Decreased heart rate (bradycardia) has been reported during combination timolol and quinidine therapy. Additive hypotension is also possible. Additionally, quinidine is a known inhibitor of CYP2D6, and may impair the hepatic clearance of timolol (CYP2D6 substrate). Patients should be monitored for excess beta-blockade. Quinidine has been reported to potentiate timolol-induced bradycardia even after use of ophthalmic timolol.
Doxazosin: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Doxepin: (Contraindicated) Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions. Quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Tricyclic antidepressants are associated with a possible risk of QT prolongation, particularly at high dosages or in overdose, and are substrates for CYP2D6.
Doxercalciferol: (Moderate) Cytochrome P450 enzyme inhibitors, such as quinidine, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
Doxorubicin Liposomal: (Major) Avoid coadministration of quinidine with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Quinidine is a potent CYP2D6 inhibitor and P-glycoprotein (P-gp) inhibitor; doxorubicin is a major substrate of CYP2D6 and P-gp. Concurrent use of CYP2D6 or P-gp inhibitors with doxorubicin has resulted in clinically significant interactions.
Doxorubicin: (Major) Avoid coadministration of quinidine with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Quinidine is a potent CYP2D6 inhibitor and P-glycoprotein (P-gp) inhibitor; doxorubicin is a major substrate of CYP2D6 and P-gp. Concurrent use of CYP2D6 or P-gp inhibitors with doxorubicin has resulted in clinically significant interactions.
Dronedarone: (Contraindicated) Concurrent use of dronedarone and quinidine is contraindicated. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. (Moderate) Use of dextromethorphan with dronedarone may result in increased dextromethorphan exposure. Dronedarone inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Droperidol: (Major) Class IA antiarrhythmics (disopyramide, procainamide, quinidine) are associated with QT prolongation and torsades de pointes (TdP). Droperidol should be administered with extreme caution to patients receiving other agents that may prolong the QT interval. Droperidol administration is associated with an established risk for QT prolongation and torsades de pointes (TdP). In December 2001, the FDA issued a black box warning regarding the use of droperidol and its association with QT prolongation and potential for cardiac arrhythmias based on post-marketing surveillance data. According to the revised 2001 labeling for droperidol, any drug known to have potential to prolong the QT interval should not be coadministered with droperidol.
Duloxetine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with duloxetine. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Monitor for increased duloxetine-related adverse effects if coadministered with quinidine. Concurrent use may result in increased duloxetine exposure resulting in excessive serotonin activity. Quinidine is a strong CYP2D6 inhibitor; duloxetine is a CYP2D6 substrate. Coadministration with another strong CYP2D6 inhibitor increased the duloxetine AUC by about 60%.
Dutasteride; Tamsulosin: (Moderate) Use caution when administering tamsulosin with a strong CYP2D6 inhibitor such as quinidine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure. If concomitant use in necessary, monitor patient closely for increased side effects.
Edoxaban: (Major) Reduce the dose of edoxaban to 30 mg/day PO in patients being treated for deep venous thrombosis (DVT) or pulmonary embolism and receiving concomitant therapy with quinidine. No dosage adjustment is required in patients with atrial fibrillation. Edoxaban is a P-glycoprotein (P-gp) substrate and quinidine is a P-gp inhibitor. Increased concentrations of edoxaban may occur during concomitant use of quinidine; monitor for increased adverse effects of edoxaban. Similar interactions may occur with dextromethorphan; quinidine.
Efavirenz: (Major) Coadministration of efavirenz and quinidine may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Quinidine administration is associated with QT prolongation and TdP. In addition, efavirenz induces CYP3A4 and may decrease serum concentrations of drugs metabolized by this enzyme, such as quinidine.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of efavirenz and quinidine may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Quinidine administration is associated with QT prolongation and TdP. In addition, efavirenz induces CYP3A4 and may decrease serum concentrations of drugs metabolized by this enzyme, such as quinidine. (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as quinidine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of efavirenz and quinidine may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Quinidine administration is associated with QT prolongation and TdP. In addition, efavirenz induces CYP3A4 and may decrease serum concentrations of drugs metabolized by this enzyme, such as quinidine. (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as quinidine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Elbasvir; Grazoprevir: (Moderate) Administering quinidine with elbasvir; grazoprevir may result in elevated quinidine plasma concentrations. Quinidine is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
Eliglustat: (Contraindicated) Coadministration of quinidine (including dextromethorphan; quinidine) and eliglustat is contraindicated. Quinidine is a P-glycoprotein (P-gp) substrate and strong CYP2D6 inhibitor associated with a well-established risk of QT prolongation and torsades de pointes (TdP); its use is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6. Eliglustat is a CYP2D6 substrate and P-gp inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Coadministration of quinidine and eliglustat may result in additive effects on the QT interval and, potentially, increased plasma concentrations of one or both drugs, further increasing the risk of serious adverse events (e.g., cardiac arrhythmias). (Moderate) Use of dextromethorphan with eliglustat may result in increased dextromethorphan exposure. Eliglustat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of quinidine with cobicistat. Quinidine is a substrate for CYP3A4 and P-glycoprotein (P-gp) and an inhibitor of CYP2D6 and P-gp; cobicistat is a substrate and inhibitor of both these enzymes and an inhibitor of P-gp. Concurrent use may result in elevated plasma concentration of both drugs. (Moderate) Use of dextromethorphan with cobicistat may result in increased dextromethorphan exposure. Cobicistat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of quinidine with cobicistat. Quinidine is a substrate for CYP3A4 and P-glycoprotein (P-gp) and an inhibitor of CYP2D6 and P-gp; cobicistat is a substrate and inhibitor of both these enzymes and an inhibitor of P-gp. Concurrent use may result in elevated plasma concentration of both drugs. (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as quinidine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions. (Moderate) Use of dextromethorphan with cobicistat may result in increased dextromethorphan exposure. Cobicistat inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Emapalumab: (Moderate) Monitor for decreased efficacy of quinidine and adjust the dose as needed during coadministration with emapalumab. Quinidine is a CYP3A4 substrate with a narrow therapeutic range. Emapalumab may normalize CYP450 activity, which may decrease the efficacy of drugs that are CYP450 substrates due to increased metabolism.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Rilpivirine should be used cautiously with Class IA antiarrhythmics (disopyramide, procainamide, quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Major) Rilpivirine should be used cautiously with Class IA antiarrhythmics (disopyramide, procainamide, quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval. (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as quinidine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as quinidine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Encorafenib: (Major) Avoid coadministration of encorafenib and quinidine due to the potential for additive QT prolongation. If concurrent use cannot be avoided, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib is associated with dose-dependent prolongation of the QT interval. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP).
Entecavir: (Major) Both entecavir and quinidine are secreted by active tubular secretion. In theory, coadministration of entecavir with quinidine may increase the serum concentrations of either drug due to competition for the drug elimination pathway. The manufacturer of entecavir recommends monitoring for adverse effects when these drugs are coadministered.
Entrectinib: (Major) Avoid coadministration of entrectinib with quinidine due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP).
Enzalutamide: (Moderate) Closely monitor quinidine concentrations if enzalutamide is added to existing quinidine therapy. No special precautions appear necessary if enzalutamide is started several weeks before quinidine, but quinidine doses may require adjustment if enzalutamide is added or discontinued during quinidine therapy. Quinidine is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the half-life and corresponding AUC of quinidine by 50% to 60%.
Ephedrine: (Moderate) Carefully monitor blood pressure in patients who have received both ephedrine and quinidine; quinidine antagonizes the pressor effect of ephedrine.
Ephedrine; Guaifenesin: (Moderate) Carefully monitor blood pressure in patients who have received both ephedrine and quinidine; quinidine antagonizes the pressor effect of ephedrine.
Epinephrine: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
Eplerenone: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Epoprostenol: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Eribulin: (Major) Eribulin has been associated with QT prolongation. Class IA antiarrhythmics (disopyramide, procainamide, quinidine) are associated with QT prolongation and torsades de pointes (TdP). If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
Erythromycin: (Major) Concomitant use of quinidine and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and may result in increased plasma concentrations of quinidine. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Quinidine is a CYP3A substrate, and erythromycin is a moderate CYP3A inhibitor.
Escitalopram: (Major) Concomitant use of quinidine and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with escitalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Esmolol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like esmolol. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block, and heart failure. Reduce the beta-blocker dosage if necessary.
Etravirine: (Major) Etravirine is an inducer of CYP3A4; quinidine concentrations may be decreased with coadministration. Coadminister these drugs with caution. It is recommended to monitor quinidine concentrations when possible.
Everolimus: (Moderate) Monitor everolimus whole blood trough concentrations as appropriate and watch for everolimus-related adverse reactions if coadministration with quinidine is necessary. The dose of everolimus may need to be reduced. Everolimus is a P-glycoprotein (P-gp) substrate and quinidine is a P-gp inhibitor. Coadministration with P-gp inhibitors may decrease the efflux of everolimus from intestinal cells and increase everolimus blood concentrations.
Fedratinib: (Moderate) Use of dextromethorphan with fedratinib may result in increased dextromethorphan exposure. Fedratinib is a moderate inhibitor of CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Felodipine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Fenfluramine: (Major) Do not exceed a maximum dose of fenfluramine 20 mg per day if coadministered with quinidine; for patients also receiving stiripentol plus clobazam, do not exceed a maximum dose of fenfluramine 17 mg per day. Concomitant use may increase fenfluramine plasma concentrations and the risk of adverse reactions. Fenfluramine is a CYP2D6 substrate and quinidine is a strong CYP2D6 inhibitor. Coadministration with another strong CYP2D6 inhibitor increased fenfluramine overall exposure by 81% and decreased norfenfluramine overall exposure by 13%. (Moderate) Use fenfluramine and dextromethorphan with caution due to an increased risk of serotonin syndrome. Monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Fenoldopam: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Fentanyl: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering fentanyl with dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Quinidine increases fentanyl serum concentrations by inhibiting intestinal P-glycoprotein (P-gp). Receipt of fentanyl 2.5 mcg/kg orally 1 hour after a single dose of immediate-release quinidine 600 mg led to a fentanyl mean area under the plasma concentration-time curve (AUC) of 2.34 +/- 0.63 ng x hour/mL as compared with 0.9 +/- 0.47 ng x hour/mL with placebo. Elevated fentanyl serum concentrations can result in an increase in the pharmacologic effects of fentanyl, such as CNS or respiratory depression.
Finasteride; Tadalafil: (Moderate) Tadalafil is metabolized predominantly by the hepatic isoenzyme CYP3A4. Inhibitors of CYP3A4, such as quinidine, may reduce tadalafil clearance. Increased systemic exposure to tadalafil may result in an increase in tadalafil-induced adverse effects, including hypotension.
Fingolimod: (Contraindicated) Concurrent use of fingolimod with class Ia antiarrhythmics such as disopyramide, quinidine, and procainamide is contraindicated. Fingolimod initiation results in decreased heart rate, and class IA antiarrhythmic drugs have been associated with cases of torsades de pointes in patients with bradycardia.
Flavoxate: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
Flecainide: (Contraindicated) Class IC antiarrhythmic agents, such as flecainide, have proarrhythmic properties, and may have additive electrophysiologic effects with other Class I agents such as quinidine. In addition, quinidine should be considered contraindicated with flecainide. Quinidine and flecainide are associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; therefore, the effects on the QT interval may be increased during concurrent use of quinidine with flecainide or propafenone.
Fluconazole: (Contraindicated) The concomitant administration of fluconazole and quinidine is contraindicated. Fluconazole has been associated with QT prolongation and is contraindicated for use with other drugs that both prolong the QT interval and are CYP3A4 substrates, such as quinidine. Coadministration of fluconazole with quinidine may result in elevated plasma concentrations of quinidine, causing an increased risk for adverse events, such as QT prolongation.
Fluoxetine: (Contraindicated) Concurrent use of either quinidine or dextromethorphan; quinidine and fluoxetine is considered a contraindication. Quinidine and dextromethorphan; quinidine are contraindicated for use in patients taking drugs that prolong the QT interval and are metabolized by CYP2D6. Fluoxetine is a primary substrate of CYP2D6, and is associated with a risk of QT prolongation and torsade de pointes (TdP). (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of fluoxetine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Additionally, monitor patients for signs and symptoms of serotonin syndrome. Concomitant use may increase dextromethorphan exposure and the risk for serotonin syndrome. Dextromethorphan is a CYP2D6 substrate and fluoxetine is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Fluphenazine: (Minor) Fluphenazine should be used cautiously with Class IA antiarrhythmics (disopyramide, procainamide, and quinidine). Fluphenazine, a phenothiazine, is associated with a possible risk for QT prolongation.
Fluvoxamine: (Major) There may be an increased risk for QT prolongation, torsade de pointes (TdP), or elevated plasma concentrations of either quinidine or fluvoxamine during coadministration. Quinidine administration is associated with QT prolongation and TdP. QT prolongation and TdP have been reported during postmarketing use of fluvoxamine. In addition, fluvoxamine is a moderate CYP3A4 inhibitor and the metabolism of CYP3A4 substrates such as quinidine may be reduced. In a small open-label study (n = 6), fluvoxamine 100 mg/day decreased the total oral clearance of quinidine by 29%. Conversely, quinidine is a CYP2D6 inhibitor and CYP2D6 is partially responsible for fluvoxamine metabolism, which may lead to elevated fluvoxamine concentrations. (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with fluvoxamine. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Fosamprenavir: (Moderate) Monitor ECG and for quinidine-related adverse reactions if coadministration with fosamprenavir is necessary. Concomitant use may result in increased plasma concentrations of quinidine. Quinidine is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as quinidine. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Quinidine administration is also associated with QT prolongation and TdP. If these drugs are administered together, obtain an electrocardio gram and electrolyte concentrations before and periodically during treatment.
Fostamatinib: (Moderate) Monitor for quinidine toxicities that may require quinidine dose reduction if given concurrently with fostamatinib. Concomitant use of fostamatinib with a CYP3A4 or P-gp substrate may increase the concentration of the CYP3A4 or P-gp substrate. Fostamatinib is a P-gp inhibitor, and the active metabolite of fostamatinib, R406, is a CYP3A4 inhibitor; quinidine is a CYP3A4 and P-gp substrate. Coadministration of fostamatinib with a sensitive CYP3A4 substrate increased the substrate AUC by 64% and Cmax by 113%. Coadministration of fostamatinib with another P-gp substrate increased the P-gp substrate AUC by 37% and Cmax by 70%.
Fostemsavir: (Major) Avoid coadministration of quinidine with fostemsavir as concomitant use may increase the risk of QT prolongation. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
Gefitinib: (Moderate) Monitor for an increase in gefitinib-related adverse reactions if coadministration with quinidine is necessary; the risk is increased in CYP2D6 poor metabolizers. Based on in vitro data, gefitinib is metabolized to O-desmethyl gefitinib by CYP2D6 and quinidine is strong CYP2D6 inhibitor. In healthy CYP2D6 poor metabolizers, the concentration of O-desmethyl gefitinib was not measurable and mean exposure to gefitinib was 2-fold higher compared to extensive metabolizers. The impact of CYP2D6 inhibitors on gefitinib pharmacokinetics has not been evaluated; however, the manufacturer recommends precautions based on exposure in patients with poor CYP2D6 metabolism.
Gemifloxacin: (Major) According to the manufacturer, gemifloxacin should be avoided in patients receiving Class IA antiarrhythmics (such as disopyramide, quinidine and procainamide). Gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5-10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
Gemtuzumab Ozogamicin: (Major) Use gemtuzumab ozogamicin and quinidine together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Quinidine administration is also associated with QT prolongation and TdP.
Gilteritinib: (Major) Use caution and monitor for additive QT prolongation if concurrent use of gilteritinib and quinidine is necessary. Gilteritinib has been associated with QT prolongation. Quinidine is associated with QT prolongation and torsade de pointes (TdP).
Ginger, Zingiber officinale: (Minor) In vitro studies have demonstrated the positive inotropic effects of ginger, Zingiber officinale. It is theoretically possible that ginger could affect the action of antiarrhythmics, however, no clinical data are available.
Givosiran: (Moderate) If possible, avoid concomitant use of dextromethorphan with givosiran due to the risk of increased dextromethorphan-related adverse reactions. If use is necessary, consider decreasing the dextromethorphan dose. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Dextromethorphan is a sensitive CYP2D6 substrate. Givosiran may moderately reduce hepatic CYP2D6 enzyme activity because of its pharmacological effects on the hepatic heme biosynthesis pathway.
Glasdegib: (Major) Avoid coadministration of glasdegib with quinidine due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP).
Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of glecaprevir and quinidine as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Glecaprevir and quinidine are both substrates and inhibitors of P-glycoprotein (P-gp). (Moderate) Caution is advised with the coadministration of pibrentasvir and quinidine as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Both pibrentasvir and quinidine are substrates and inhibitors of P-glycoprotein (P-gp).
Glycerol Phenylbutyrate: (Moderate) Concomitant use of glycerol phenylbutyrate and quinidine may result in decreased exposure of quinidine. Quinidine is a CYP3A substrate; glycerol phenylbutyrate is a weak inducer of CYP3A4. Monitor for decreased efficacy of quinidine during coadministration.
Glycopyrrolate: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
Glycopyrrolate; Formoterol: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
Goserelin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., goserelin) outweigh the potential risks of QT prolongation in patients receiving quinidine. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
Granisetron: (Major) Granisetron should be used cautiously and with close monitoring with Class IA antiarrhythmics (disopyramide, procainamide, and quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron in patients concurrently treated with drugs known to prolong the QT interval and/or are arrhythmogenic, may result in clinical consequences.
Grapefruit juice: (Major) Grapefruit juice contains an unknown compound that inhibits cytochrome P-450 3A4 isozymes in the gut wall. Coadministration of quinidine with grapefruit juice to healthy volunteers delayed quinidine absorption and inhibited the conversion of quinidine to the major metabolite. Although the clinical significance of the interaction is unknown, concomitant administration with grapefruit juice should be avoided. (Minor) Intake of grapefruit juice or seville orange juice increased dextromethorphan bioavailability in one study. Patients with increased concentrations of dextromethorphan may experience drowsiness or serotonergic side effects (dizziness, nervousness or restlessness, nausea, vomiting, stomach upset) not usually noted with prescribed or nonprescription product doses. Grapefruit juice and seville orange juice contain compounds that can inhibit P-glycoprotein in the intestinal wall, and dextromethorphan absorption may be affected by P-glycoprotein activity. Dextromethorphan is largely metabolized by CYP2D6, so this particular interaction with grapefruit juice may be more relevant in patients who are poor CYP2D6 metabolizers.
Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with quinidine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of quinidine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If quinidine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Quinidine is a strong inhibitor of CYP2D6.
Halogenated Anesthetics: (Major) Halogenated anesthetics should be used cautiously with class IA antiarrhythmics (disopyramide, procainamide, quinidine). Halogenated anesthetics can prolong the QT interval and class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP).
Haloperidol: (Contraindicated) Quinidine should be considered contraindicated with haloperidol. QT prolongation and torsade de pointes (TdP) have been observed during both haloperidol and quinidine treatment. Excessive doses (particularly in the overdose setting) of haloperidol may be associated with a higher risk of QT prolongation. According to the manufacturer of haloperidol, caution is advisable when prescribing the drug concurrently with medications known to prolong the QT interval; however, quinidine is contraindicated for use with drugs that are CYP2D6 substrates that prolong the QT interval. Pretreatment with quinidine caused peak haloperidol serum concentrations and haloperidol AUC to increase.
Histrelin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving quinidine. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
Homatropine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with quinidine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of quinidine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If quinidine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Quinidine is a strong inhibitor of CYP2D6. (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
Hydantoins: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Inducers of CYP3A4, such as fosphenytoin or phenytoin, may increase hepatic elimination of quinidine and decrease its serum concentrations. Quinidine concentrations should be monitored closely after the anticonvulsant is added to the treatment regimen. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
Hydralazine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Hydrocodone: (Moderate) Concomitant use of hydrocodone with quinidine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of quinidine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If quinidine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Quinidine is a strong inhibitor of CYP2D6.
Hydrocodone; Ibuprofen: (Moderate) Concomitant use of hydrocodone with quinidine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of quinidine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If quinidine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Quinidine is a strong inhibitor of CYP2D6.
Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with quinidine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of quinidine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If quinidine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Quinidine is a strong inhibitor of CYP2D6.
Hydroxychloroquine: (Major) Concomitant use of quinidine and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Hydroxyzine: (Major) Concomitant use of quinidine and hydroxyzine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Hyoscyamine: (Major) Hyoscyamine may increase the absorption of quinidine by decreasing GI motility and thereby enhancing absorption with possible toxicity. Increased monitoring is advised in patients receiving a combination of these drugs.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Because of the potential risk and severity of serotonin syndrome, coadministration of dextromethorphan and IV methylene blue should be avoided if possible. Methylene blue has been demonstrated to be a potent monoamine oxidase inhibitor (MAOI) and may cause potentially fatal serotonin toxicity (serotonin syndrome) when combined with serotonin reuptake inhibitors (SRIs). Dextromethorphan increases central serotonin effects. If methylene blue is judged to be indicated, all SRIs, including dextromethorphan, must be ceased prior to treatment/procedure/surgery. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Major) Hyoscyamine may increase the absorption of quinidine by decreasing GI motility and thereby enhancing absorption with possible toxicity. Increased monitoring is advised in patients receiving a combination of these drugs.
Ibutilide: (Contraindicated) Combined use of antiarrhythmic drugs can have additive, antagonistic, or synergistic electrophysiologic, pharmacodynamic, or toxic effects. Because of their potential to prolong refractoriness, Class IA antiarrhythmics (e.g., disopyramide, quinidine, and procainamide) and other Class III antiarrhythmics (e.g., amiodarone, dofetilide and sotalol) are not recommended for use concurrently or within 4 hours after an infusion of ibutilide. In general, combination therapy with Class III antiarrhythmics has been reported to increase the risk of proarrhythmias. The manufacturer reported that during clinical trials, Class IA or other Class III antiarrhythmics were not given for at least 5 half-lives prior to ibutilide infusion or 4 hours after ibutilide dosing. Before switching from ibutilide to dofetilide therapy, ibutilide should generally be withheld for at least three half-lives prior to initiating dofetilide.
Idelalisib: (Contraindicated) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with quinidine, a CYP3A substrate, as quinidine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Iloperidone: (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include iloperidone.
Imatinib: (Major) Imatinib, STI-571 is a potent inhibitor of cytochrome P450 3A4 and may inhibit quinidine metabolism leading to increased concentrations and risk of adverse reactions. (Moderate) Use of dextromethorphan with imatinib may result in increased dextromethorphan exposure. Imatinib inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Imipramine: (Contraindicated) Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions. Quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Tricyclic antidepressants are associated with a possible risk of QT prolongation, particularly at high dosages or in overdose, and are substrates for CYP2D6.
Indacaterol; Glycopyrrolate: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
Indinavir: (Moderate) Concurrent administration of indinavir and quinidine caused indinavir AUC to increase by about 10%. There were no effects on quinidine pharmacokinetics.
Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with quinidine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Quinidine administration is also associated with QT prolongation and TdP.
Isavuconazonium: (Moderate) Caution and therapeutic drug concentration monitoring, if available, are recommended during coadministration of quinidine with isavuconazonium. Quinidine is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Concurrent use may result in elevated quinidine plasma concentrations.
Isocarboxazid: (Contraindicated) Dextromethorphan products are contraindicated in patients taking a monoamine oxidase inhibitor (MAOI) or in patients who have taken an MAOI within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of an MAOI. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotonergic agents, a sufficient amount of time must be allowed for clearance of the serotonergic agent and its active metabolites.
Isoflurane: (Major) Halogenated anesthetics should be used cautiously with class IA antiarrhythmics (disopyramide, procainamide, quinidine). Halogenated anesthetics can prolong the QT interval and class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP).
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Inducers of CYP3A4 may increase hepatic elimination of quinidine. Rifampin is a potent inducer of this isoenzyme. Quinidine concentrations should be monitored closely after rifampin is added to the treatment regimen. No special precautions appear necessary if rifampin is begun several weeks before quinidine is added but quinidine doses may require adjustment if it is added or discontinued during quinidine therapy.
Isoniazid, INH; Rifampin: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Inducers of CYP3A4 may increase hepatic elimination of quinidine. Rifampin is a potent inducer of this isoenzyme. Quinidine concentrations should be monitored closely after rifampin is added to the treatment regimen. No special precautions appear necessary if rifampin is begun several weeks before quinidine is added but quinidine doses may require adjustment if it is added or discontinued during quinidine therapy.
Isradipine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Istradefylline: (Moderate) Monitor for quinidine-related adverse reactions if coadministration of istradefylline 40 mg daily is necessary. Quinidine is a CYP3A4 substrate; istradefylline administered as 40 mg daily is a weak CYP3A4 inhibitor. There was no effect on drug exposure when istradefylline 20 mg daily was coadministered with a sensitive CYP3A4 substrate.
Itraconazole: (Contraindicated) Quinidine is contraindicated for use during and for 2 weeks after itraconazole therapy. Serious cardiovascular events including EKG changes (i.e., QT prolongation) and cardiac arrhythmias, including ventricular arrhythmias and torsade de pointes, cardiac arrest, and/or sudden death have occurred when these drugs were administered together. Reports have documented cases in which substantial elevations in serum quinidine concentrations occurred after the addition of itraconazole. Quinidine is a CYP3A4 substrate; itraconazole is a strong CYP3A4 inhibitor. Transient or permanent hearing loss has also been reported in elderly patients receiving quinidine in combination with itraconazole.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with quinidine due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP).
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and quinidine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Labetalol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like labetalol. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block, and heart failure. Reduce the beta-blocker dosage if necessary.
Lacosamide: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as Class IA antiarrhythmics, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as quinidine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Lamotrigine: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as class IA antiarrhythmics. Concomitant use of class IA antiarrhythmics with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Lanreotide: (Major) Monitor ECGs for QT prolongation and watch for an increase in quinidine-related adverse reactions if coadministration with lanreotide is necessary. Quinidine is a CYP3A4 substrate with a narrow therapeutic range. Limited published data available indicate that somatostatin analogs may decrease the metabolic clearance of CYP3A4 substrates, which may be due to the suppression of growth hormone; it cannot be excluded that lanreotide has this effect.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP). Quinidine (including dextromethorphan; quinidine) and disopyramide are also associated with QT prolongation and TdP. There have been post-marketing reports of TdP occurring with the coadministration of clarithromycin and quinidine or disopyramide. If used concomitantly, monitor ECGs for QT prolongation and consider monitoring serum concentrations of quinidine or disopyramide.
Lapatinib: (Major) Monitor for an increase in treatment-related adverse reactions if coadministration of lapatinib with quinidine is necessary; also monitor ECGs for QT prolongation and monitor electrolytes. Correct any electrolyte abnormalities prior to treatment. Lapatinib is a P-glycoprotein (P-gp) substrate/inhibitor that has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have also been reported in postmarketing experience. Quinidine is also a P-gp substrate/inhibitor that is also associated with QT prolongation and TdP. Increased plasma concentrations of lapatinib are likely when administered with P-gp inhibitors.
Lasmiditan: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Ledipasvir; Sofosbuvir: (Moderate) Caution and close monitoring of adverse reactions is advised with concomitant administration of quinidine and ledipasvir; sofosbuvir. Both ledipasvir and quinidine are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp); sofosbuvir is a P-gp substrate. Taking these drugs together may increase plasma concentrations of all three drugs. According to the manufacturer, no dosage adjustments are required when ledipasvir; sofosbuvir is administered concurrently with P-gp inhibitors.
Lefamulin: (Major) Avoid coadministration of lefamulin with quinidine as concurrent use may increase the risk of QT prolongation; concurrent use may also increase exposure from lefamulin tablets which may increase the risk of adverse effects. If coadministration cannot be avoided, monitor ECG during treatment; additionally, monitor for lefamulin-related adverse effects if oral lefamulin is administered. Lefamulin is a CYP3A4 and P-gp substrate that has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Quinidine is a P-gp inhibitor that is associated with QT prolongation and torsade de pointes (TdP).
Lenacapavir: (Moderate) Monitor ECG and for quinidine-related adverse reactions if coadministration with lenacapavir is necessary. Concomitant use may result in increased plasma concentrations of quinidine. Quinidine is a CYP3A substrate and lenacapavir is a moderate CYP3A inhibitor.
Lenvatinib: (Major) Avoid coadministration of lenvatinib with quinidine due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Quinidine administration is also associated with QT prolongation as well as torsade de pointes (TdP).
Lesinurad: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of quinidine; monitor for potential reduction in efficacy. Quinidine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Lesinurad; Allopurinol: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of quinidine; monitor for potential reduction in efficacy. Quinidine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Letermovir: (Moderate) Closely monitor for quinidine-related adverse events including arrhythmias, if given with letermovir. In patients who are also receiving treatment with cyclosporine, the magnitude of this interaction may be amplified. A clinically relevant increase in the plasma concentration of quinidine, a CYP3A4 substrate, may occur during concurrent administration with letermovir, a moderate CYP3A4 inhibitor. The combined effect of letermovir and cyclosporine on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor.
Leuprolide: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving quinidine. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
Leuprolide; Norethindrone: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving quinidine. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
Levamlodipine: (Moderate) Monitor for increased quinidine adverse reactions if coadministered with amlodipine. Taking these drugs together may increase quinidine plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; quinidine is a substrate of CYP3A4 with a narrow therapeutic index. In addition, quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Levobunolol: (Moderate) The concomitant use of ophthalmic beta-blockers, like levobunolol, in patients receiving antiarrhythmics which slow AV conduction (quinidine) may result in additive negative dromotropic effects, especially in patients with pre-existing cardiac disease or left ventricular dysfunction. Since ophthalmic levobunolol may be systemically absorbed, there is potential for enhanced hypotensive effects when it is given with beta-blockers.
Levofloxacin: (Major) Levofloxacin should be avoided in combination with Class IA antiarrhythmics (disopyramide, procainamide, and quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Levofloxacin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Rare cases of TdP have been spontaneously reported during postmarketing surveillance in patients receiving levofloxacin. According to the manufacturer, levofloxacin should be avoided in patients taking drugs that can result in prolongation of the QT interval.
Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and quinidine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Levomilnacipran: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with levomilnacipran. Dextromethorphan has serotonergic activity. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Lidocaine: (Major) Avoid concurrent use of quinidine with other antiarrhythmics with Class I activities, such as lidocaine. Concurrent use may result in additive or antagonistic cardiac effects and additive toxicity.
Lidocaine; Epinephrine: (Major) Avoid concurrent use of quinidine with other antiarrhythmics with Class I activities, such as lidocaine. Concurrent use may result in additive or antagonistic cardiac effects and additive toxicity. (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
Lidocaine; Prilocaine: (Major) Avoid concurrent use of quinidine with other antiarrhythmics with Class I activities, such as lidocaine. Concurrent use may result in additive or antagonistic cardiac effects and additive toxicity.
Linezolid: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering linezolid with dextromethorphan. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor and has potential to interact with serotonergic agents. Dextromethorphan has serotonergic activity. However, the potential for interaction has been studied. Subjects were administered dextromethorphan (two 20-mg doses given 4 hours apart) with or without linezolid. No serotonin syndrome effects (confusion, delirium, restlessness, tremors, blushing, diaphoresis, hyperpyrexia) have been observed in normal subjects receiving linezolid and dextromethorphan.
Lithium: (Major) Concomitant use of quinidine and lithium increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Lofexidine: (Contraindicated) Concomitant use of lofexidine and quinidine is contraindicated due to the potential for additive QT prolongation and torsade de pointes (TdP). Lofexidine is a CYP2D6 substrate that prolongs the QT interval. In addition, there are postmarketing reports of TdP. Quinidine is a CYP2D6 inhibitor and is associated with QT prolongation and TdP.
Lonafarnib: (Moderate) Monitor ECG and for quinidine-related adverse reactions if coadministration with lonafarnib is necessary. Concomitant use may result in increased plasma concentrations of quinidine. Quinidine is a CYP3A4 substrate and lonafarnib is a strong CYP3A4 inhibitor.
Loop diuretics: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Loperamide: (Major) Concomitant use of loperamide and quinidine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Concomitant use may also increase loperamide exposure and the risk for other loperamide-related adverse effects; loperamide is a P-gp substrate and quinidine is a P-gp inhibitor. Coadministration with quinidine increased loperamide plasma concentrations by 2- to 3-fold.
Loperamide; Simethicone: (Major) Concomitant use of loperamide and quinidine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Concomitant use may also increase loperamide exposure and the risk for other loperamide-related adverse effects; loperamide is a P-gp substrate and quinidine is a P-gp inhibitor. Coadministration with quinidine increased loperamide plasma concentrations by 2- to 3-fold.
Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with quinidine due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Lopinavir is associated with QT prolongation. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). (Major) Coadministration of HIV treatment doses of ritonavir and quinidine is contraindicated due to the potential for serious or life-threatening reactions, such as cardiac arrhythmias. Cautious consideration may be given to administering quinidine with boosting doses of ritonavir. Ritonavir is an inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as quinidine, should be expected with concurrent use.
Lorcaserin: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with lorcaserin. Both medications have serotonergic activity. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. In addition, lorcaserin inhibits CYP2D6-mediated metabolism of dextromethorphan, increasing dextromethorphan Cmax by approximately 76% and AUC by approximately 2-fold. Increased dextromethorphan exposure may result in adverse effects consistent with the serotonin syndrome.
Lumacaftor; Ivacaftor: (Major) Lumacaftor; ivacaftor may alter the therapeutic effects of quinidine. Use these agents together with caution; monitor quinidine concentrations and adjust the dosage as needed to attain antiarrhythmic efficacy endpoints. Quinidine is a substrate of CYP3A and the P-glycoprotein (P-gp) efflux transporter. Lumacaftor is a strong CYP3A inducer; in vitro data also suggest lumacaftor; ivacaftor may induce and/or inhibit P-gp. Although induction of quinidine metabolism through the CYP3A pathway may lead to decreased drug efficacy, the net effect of lumacaftor; ivacaftor on P-gp transport is not clear. Monitor the patient for decreased antiarrhythmic efficacy or increased or prolonged therapeutic effects and adverse events.
Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as quinidine. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP).
Maprotiline: (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include maprotiline.
Maraviroc: (Moderate) Use caution and careful monitoring with the coadministration of maraviroc and quinidine as increased maraviroc concentrations may occur. Maraviroc is a substrate of P-glycoprotein (P-gp); quinidine is an inhibitor of P-gp. The effects of P-gp on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
Mavacamten: (Moderate) Expect additive negative inotropic effects during concomitant use of mavacamten and quinidine. If concomitant therapy with quinidine is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved.
Mecamylamine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Mefloquine: (Contraindicated) The use of mefloquine is contraindicated in patients receiving quinidine or quinidine containing drugs, including dextromethorphan; quinidine. Quinidine is a Class IA antiarrhythmic agent and is associated with a well-established risk of QT prolongation and torsade de pointes (TdP); using these drugs together could increase the risk of TdP.
Memantine: (Major) Cationic drugs that are eliminated by renal tubular secretion, such as quinidine, may compete with memantine for common renal tubular transport systems, thus possibly decreasing the elimination of one of the drugs. Although theoretical, careful patient monitoring of response to memantine and/or quinidine is recommended to assess for needed dosage adjustments. In selected individuals, quinidine serum concentration monitoring may be appropriate. (Moderate) Dextromethorphan is a NMDA antagonist and may lead to additive adverse effects if combined with memantine, also an NMDA antagonist. It may be prudent to avoid coadministration of dextromethorphan with memantine. If coadministration cannot be avoided, monitor for increased adverse effects such as agitation, dizziness and other CNS events.
Methadone: (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include methadone.
Methazolamide: (Major) Methazolamide can decrease the urinary excretion and enhance the clinical effects of quinidine. Carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized drug available for renal tubular reabsorption into the systemic circulation.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) Because of the potential risk and severity of serotonin syndrome, coadministration of dextromethorphan and IV methylene blue should be avoided if possible. Methylene blue has been demonstrated to be a potent monoamine oxidase inhibitor (MAOI) and may cause potentially fatal serotonin toxicity (serotonin syndrome) when combined with serotonin reuptake inhibitors (SRIs). Dextromethorphan increases central serotonin effects. If methylene blue is judged to be indicated, all SRIs, including dextromethorphan, must be ceased prior to treatment/procedure/surgery. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Major) Hyoscyamine may increase the absorption of quinidine by decreasing GI motility and thereby enhancing absorption with possible toxicity. Increased monitoring is advised in patients receiving a combination of these drugs.
Methohexital: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
Methscopolamine: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
Methylene Blue: (Major) Because of the potential risk and severity of serotonin syndrome, coadministration of dextromethorphan and IV methylene blue should be avoided if possible. Methylene blue has been demonstrated to be a potent monoamine oxidase inhibitor (MAOI) and may cause potentially fatal serotonin toxicity (serotonin syndrome) when combined with serotonin reuptake inhibitors (SRIs). Dextromethorphan increases central serotonin effects. If methylene blue is judged to be indicated, all SRIs, including dextromethorphan, must be ceased prior to treatment/procedure/surgery. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Metoclopramide: (Major) Dose reductions of oral metoclopramide are recommended when administered in combination with quinidine due to likely increased metoclopramide exposure and an increased risk of extrapyramidal adverse reactions. In patients with diabetic gastroparesis, avoid coadministration of metoclopramide with quinidine. If coadministration cannot be avoided, the recommended dose of metoclopramide is 5 mg PO four times daily times daily. In patients with gastroesophageal reflux, the recommended dose of metoclopramide is 5 mg PO four times daily or 10 mg PO three times daily when coadministered with quinidine. Metoclopramide is a substrate of CYP2D6 and quinidine is a strong CYP2D6 inhibitor. Coadministration with another strong CYP2D6 inhibitor increased the metoclopramide Cmax and AUC by 40% and 90%, respectively.
Metoprolol: (Major) Patients receiving combined therapy with quinidine and metoprolol should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block, and heart failure. Reduce the beta-blocker dosage if necessary. Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used with metoprolol. Quinidine is also a known inhibitor of CYP2D6 and metoprolol is a CYP2D6 substrate. In healthy subjects with CYP2D6 extensive metabolizer (normal metabolizer) phenotype, coadministration of quinidine 100 mg and immediate release metoprolol 200 mg tripled the concentration of S-metoprolol and doubled the metoprolol elimination half-life. This interaction may be more pronounced in poor CYP2D6 metabolizers. Patients should be monitored for excess beta-blockade.
Metoprolol; Hydrochlorothiazide, HCTZ: (Major) Patients receiving combined therapy with quinidine and metoprolol should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block, and heart failure. Reduce the beta-blocker dosage if necessary. Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used with metoprolol. Quinidine is also a known inhibitor of CYP2D6 and metoprolol is a CYP2D6 substrate. In healthy subjects with CYP2D6 extensive metabolizer (normal metabolizer) phenotype, coadministration of quinidine 100 mg and immediate release metoprolol 200 mg tripled the concentration of S-metoprolol and doubled the metoprolol elimination half-life. This interaction may be more pronounced in poor CYP2D6 metabolizers. Patients should be monitored for excess beta-blockade.
Metreleptin: (Moderate) Upon initiation or discontinuation of metreleptin in a patient receiving quinidine, drug concentration monitoring should be performed and the quinidine dosage adjusted as needed. Leptin is a cytokine and may have the potential to alter the formation of cytochrome P450 (CYP450) enzymes. The effect of metreleptin on CYP450 enzymes may be clinically relevant for CYP450 substrates with a narrow therapeutic index, such as quinidine.
Metronidazole: (Major) Concomitant use of metronidazole and quinidine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mexiletine: (Moderate) Quinidine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme. Caution is recommended when administering quinidine with other CYP2D6 substrates, such as mexiletine, that have a narrow therapeutic range or where large increases in serum concentrations may be associated with severe adverse reactions.
Midodrine: (Minor) Although the exact mechanism is uncertain, midodrine may be excreted by the same base-secreting pathway of the kidneys responsible for secretion of other basic drugs like quinidine. By this pathway, midodrine may potentially interact with quinidine; however, no drug interactions of this kind have been reported.
Midostaurin: (Major) The concomitant use of midostaurin and quinidine may lead to additive QT interval prolongation. If these drugs are used together, consider electrocardiogram monitoring. In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. Quinidine is a Class IA antiarrhythmic agent; it is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Quinidine should be discontinued if significant QT prolongation or TdP occur during therapy.
Mifepristone: (Contraindicated) Use of quinidine with mifepristone is contraindicated when mifepristone is used chronically for hormonal conditions, such as in the treatment of Cushing's syndrome. Mifepristone, a CYP3A4 inhibitor, is likely to increase quinidine concentrations and adverse effects, since quinidine is a CYP3A4 substrate with a narrow therapeutic index. Increased quinidine concentrations are likely to cause proarrythmia and ECG changes, as well as symptoms of cinchonism. Both quinidine and mifepristone have been associated with QT prolongation and a risk for torsade de pointes (TdP). Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
Milnacipran: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with milnacipran. Dextromethorphan has serotonergic activity. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Minoxidil: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Mirabegron: (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Mirtazapine: (Major) Concomitant use of quinidine and mirtazapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with mirtazapine. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Mitotane: (Major) Use caution if mitotane and quinidine are used concomitantly, and monitor for decreased efficacy of quinidine and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and quinidine is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of quinidine. Quinidine concentrations should be monitored closely after mitotane is added to the treatment regimen.
Mivacurium: (Moderate) Concomitant use of neuromuscular blockers and quinidine may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Mobocertinib: (Major) Concomitant use of mobocertinib and quinidine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Monoamine oxidase inhibitors: (Contraindicated) Dextromethorphan products are contraindicated in patients taking a monoamine oxidase inhibitor (MAOI) or in patients who have taken an MAOI within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of an MAOI. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotonergic agents, a sufficient amount of time must be allowed for clearance of the serotonergic agent and its active metabolites.
Morphine: (Moderate) Morphine is a substrate for P-glycoprotein (P-gp), and quinidine is a P-gp substrate and inhibitor. Coadministration may lead to increased systemic exposure of morphine and morphine-related side effects.
Morphine; Naltrexone: (Moderate) Morphine is a substrate for P-glycoprotein (P-gp), and quinidine is a P-gp substrate and inhibitor. Coadministration may lead to increased systemic exposure of morphine and morphine-related side effects.
Moxifloxacin: (Major) Moxifloxacin should be avoided in combination with Class IA antiarrhythmics (disopyramide, quinidine, and procainamide). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Prolongation of the QT interval has been reported with administration of moxifloxacin. Post-marketing surveillance has identified very rare cases of ventricular arrhythmias including torsade de pointes (TdP), usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded. According to the manufacturer, moxifloxacin should be avoided in patients taking drugs that can result in prolongation of the QT interval.
Nadolol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like nadolol. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block and heart failure, Reduce the beta-blocker dosage if necessary.
Nanoparticle Albumin-Bound Sirolimus: (Major) Avoid concomitant use of sirolimus and quinidine. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and quinidine is a P-gp inhibitor.
Nebivolol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with nebivolol, a beta-blocker. Quinidine is a known inhibitor of CYP2D6 and nebivolol is metabolized by CYP2D6. Quinidine could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition. Patients should be monitored for excess beta-blockade. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block, and heart failure. Reduce the beta-blocker dosage if necessary.
Nebivolol; Valsartan: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with nebivolol, a beta-blocker. Quinidine is a known inhibitor of CYP2D6 and nebivolol is metabolized by CYP2D6. Quinidine could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition. Patients should be monitored for excess beta-blockade. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block, and heart failure. Reduce the beta-blocker dosage if necessary.
Nefazodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with nefazodone. Both drugs have serotonergic activity. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Quinidine causes a dose-dependent QT prolongation and is metabolized via CYP3A4. Concurrent use of quinidine with moderate CYP3A4 inhibitors, such as nefazodone, may result in elevated quinidine plasma concentrations with the potential for enhanced QT-prolonging effects.
Nelfinavir: (Contraindicated) Coadministration of quinidine and nelfinavir is contraindicated. Nelfinavir inhibits the CYP3A4 metabolism of quinidine; concurrent use increases the potential for serious and/or life-threatening cardiac arrhythmias.
Neostigmine; Glycopyrrolate: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
Netupitant, Fosnetupitant; Palonosetron: (Moderate) Coadminister with caution. Palonosetron is metabolized by CYP2D6, and quinidine is an inhibitor of this isoenzyme. Coadministration may result in elevated plasma concentrations of palonosetron, causing ain increased risk for serotonin-related adverse events.
Neuromuscular blockers: (Moderate) Concomitant use of neuromuscular blockers and quinidine may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional do ses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Nicardipine: (Moderate) Quinidine concentrations decrease by 20 to 40% when nicardipine is added and rise after nicardipine is withdrawn. Although this appears to be an idiosyncratic reaction, quinidine doses may need to be adjusted when nicardipine is added or withdrawn. Careful monitoring of serum quinidine concentrations is prudent following the addition or discontinuation of nicardipine.
Nifedipine: (Moderate) Nifedipine has been reported to rarely decrease quinidine serum concentrations. Quinidine concentrations may decrease by 20% to 40% when nifedipine is added, and potentially increase after nifedipine is withdrawn. There have also been reports of no significant change in quinidine concentrations or effect. In addition, both drugs can cause hypotension, and these effects can be additive. Careful monitoring of serum quinidine concentrations is prudent following the addition or discontinuation of nifedipine, with dose adjustment as clinically warranted. Monitor heart rate, blood pressure, and cardiac response.
Nilotinib: (Major) Avoid coadministration of nilotinib with quinidine due to an increased risk for QT prolongation and torsade de pointes (TdP). Systemic exposure of quinidine may be increased resulting in an increase in quinidine-related adverse reactions. Nilotinib is a moderate CYP3A4 inhibitor. Sudden death and QT interval prolongation have occurred in patients who received nilotinib therapy. Quinidine is a CYP3A4 substrate that has also been associated with QT prolongation and torsade de pointes (TdP).
Niraparib; Abiraterone: (Moderate) Abiraterone inhbits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. If dextromethorphan- related side effects occur, a dose reduction or discontinuation of dextromethorphan may be necessary. In an in vivo drug-drug interaction trial, the Cmax and AUC of the CYP2D6 substrate dextromethorphan were increased 2.8- and 2.9-fold, respectively when dextromethorphan 30 mg was given with abiraterone acetate 1,000 mg daily along with prednisone 5 mg twice daily. The AUC for dextrorphan, the active metabolite of dextromethorphan, increased approximately 1.3 fold.
Nirmatrelvir; Ritonavir: (Contraindicated) Concomitant use of ritonavir-boosted nirmatrelvir and quinidine is contraindicated; consider an alternative COVID-19 therapy. Coadministration may increase quinidine exposure resulting in increased toxicity. Quinidine is a CYP3A substrate and nirmatrelvir is a CYP3A inhibitor. (Major) Coadministration of HIV treatment doses of ritonavir and quinidine is contraindicated due to the potential for serious or life-threatening reactions, such as cardiac arrhythmias. Cautious consideration may be given to administering quinidine with boosting doses of ritonavir. Ritonavir is an inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as quinidine, should be expected with concurrent use.
Nisoldipine: (Moderate) Quinidine may decrease the bioavailability of nisoldipine by 26% without affecting the peak concentration. Monitoring serum quinidine concentrations is prudent following the addition or discontinuation of nisoldipine.
Nitroglycerin: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as quinidine. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with quinidine.
Nitroprusside: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Nortriptyline: (Contraindicated) Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions. Quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Tricyclic antidepressants are associated with a possible risk of QT prolongation, particularly at high dosages or in overdose, and are substrates for CYP2D6.
Octreotide: (Moderate) Monitor ECG and for quinidine-related adverse reactions if coadministration with octreotide is necessary; monitor quinidine concentrations as clinically indicated. Concomitant use may result in increased plasma concentrations of quinidine.
Ofloxacin: (Major) Class IA antiarrhythmics (such as disopyramide, quinidine, and procainamide) should be used cautiously and with close monitoring with ofloxacin. Class IA antiarrhythmics (such as disopyramide, quinidine, and procainamide) are associated with QT prolongation and torsades de pointes (TdP). Some quinolones, including ofloxacin, have been associated with QT prolongation and infrequent cases of arrhythmia. Post-marketing surveillance for ofloxacin has identified very rare cases of torsades de pointes (TdP).
Olanzapine: (Major) Quinidine and dextromethorphan; quinidine cause dose-dependent QT prolongation. These drugs should be avoided in patients receiving drugs that may prolong the QT interval and are metabolized by CYP2D6, such as olanzapine. The manufacturer recommends an ECG in patients taking these drugs together.
Olanzapine; Fluoxetine: (Contraindicated) Concurrent use of either quinidine or dextromethorphan; quinidine and fluoxetine is considered a contraindication. Quinidine and dextromethorphan; quinidine are contraindicated for use in patients taking drugs that prolong the QT interval and are metabolized by CYP2D6. Fluoxetine is a primary substrate of CYP2D6, and is associated with a risk of QT prolongation and torsade de pointes (TdP). (Major) Quinidine and dextromethorphan; quinidine cause dose-dependent QT prolongation. These drugs should be avoided in patients receiving drugs that may prolong the QT interval and are metabolized by CYP2D6, such as olanzapine. The manufacturer recommends an ECG in patients taking these drugs together. (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of fluoxetine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Additionally, monitor patients for signs and symptoms of serotonin syndrome. Concomitant use may increase dextromethorphan exposure and the risk for serotonin syndrome. Dextromethorphan is a CYP2D6 substrate and fluoxetine is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Olanzapine; Samidorphan: (Major) Quinidine and dextromethorphan; quinidine cause dose-dependent QT prolongation. These drugs should be avoided in patients receiving drugs that may prolong the QT interval and are metabolized by CYP2D6, such as olanzapine. The manufacturer recommends an ECG in patients taking these drugs together.
Oliceridine: (Moderate) If concomitant use of oliceridine and dextromethorphan is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and quinidine is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and quinidine may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If quinidine is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and quinidine is a strong CYP2D6 inhibitor.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for increased quinidine adverse reactions if coadministered with amlodipine. Taking these drugs together may increase quinidine plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; quinidine is a substrate of CYP3A4 with a narrow therapeutic index. In addition, quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) Rifabutin is an inducer of the cytochrome P-450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of quinidine.
Ondansetron: (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include ondansetron.
Oritavancin: (Moderate) Administration of oritavancin, a weak inducer of CYP2D6 and CYP3A4, with dextromethorphan resulted in a 31% reduction in the ratio of dextromethorphan to dextrorphan concentrations in the urine. The efficacy of dextromethorphan may be reduced if these drugs are administered concurrently. (Moderate) Quinidine is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of quinidine may be reduced if these drugs are administered concurrently. Quinidine concentrations should be monitored closely after oritavancin is added to the treatment regimen. No special precautions appear necessary if oritavancin is begun several weeks before quinidine is added but quinidine doses may require adjustment if oritavancin is added or discontinued during quinidine therapy.
Osilodrostat: (Major) Use osilodrostat and quinidine together with caution and consider more frequent ECG monitoring due to the risk of additive QT prolongation. Osilodrostat is associated with dose-dependent QT prolongation. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP.
Osimertinib: (Major) Avoid coadministration of quinidine with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor for an increase in quinidine-related adverse reactions, periodically monitor ECGs for QT prolongation, and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Quinidine administration is associated with both QT prolongation and TdP. Additionally, quinidine is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor.
Oxaliplatin: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of quinidine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
Oxybutynin: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
Ozanimod: (Contraindicated) Coadministration of ozanimod with dextromethorphan is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of dextromethorphan. Consider if an alternative to dextromethorphan would be appropriate. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for serious and possibly fatal drug interactions with dextromethorphan, including serotonin syndrome. (Major) In general, do not initiate ozanimod in patients taking quinidine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Quinidine administration is associated with QT prolongation and TdP.
Pacritinib: (Major) Concomitant use of pacritinib and quinidine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Paliperidone: (Major) Coadministration of paliperidone and quinidine should be avoided if possible due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinidine, a CYP2D6 inhibitor, is associated with QT prolongation and torsades de pointes (TdP). According to the manufacturer of paliperidone, the drug should be avoided in combination with other agents also known to have this effect. Paliperidone has been associated with QT prolongation; TdP and ventricular fibrillation have been reported in the setting of overdose. While in vitro studies indicate that CYP2D6 is minimally involved in paliperidone metabolism, in vivo studies do not show decreased elimination by CYP2D6 and it contributes to only a small fraction of total body clearance of paliperidone. If coadministration is necessary and the patient has known risk factors for cardiac disease or arrhythmias, close monitoring is essential.
Palonosetron: (Moderate) Coadminister with caution. Palonosetron is metabolized by CYP2D6, and quinidine is an inhibitor of this isoenzyme. Coadministration may result in elevated plasma concentrations of palonosetron, causing ain increased risk for serotonin-related adverse events.
Pancuronium: (Moderate) Concomitant use of neuromuscular blockers and quinidine may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Panobinostat: (Contraindicated) Because of the potential for torsade de pointes, avoid the use of quinidine or dextromethorphan; quinidine with panobinostat. Panobinostat is a CYP2D6 inhibitor and quinidine is a CYP2D6 substrate. When a single 60-mg dose of dextromethorphan was administered after 3 doses of panobinostat (20 mg given on days 3, 5, and 8), the CYP2D6 substrate Cmax increased by 20% to 200% and the AUC value increased by 20% to 130% in 14 patients with advanced cancer; exposure was highly variable (coefficient of variance > 150%). (Major) Avoid coadministrating panobinostat with sensitive CYP2D6 substrates such as dextromethorphan due to increased dextromethorphan exposure. Consider alternatives to dextromethorphan if possible. If concomitant use cannot be avoided, closely monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Panobinostat inhibits CYP2D6. When a single 60-mg dose of dextromethorphan (DM) was administered after 3 doses of panobinostat (20 mg on days 3, 5, and 8), the DM Cmax increased by 20% to 200% and DM exposure (AUC) increased by 20% to 130% (interquartile ranges) vs. when DM was given alone; however, the change in exposure was highly variable among the patients studied.
Paroxetine: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with quinidine is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and quinidine is a strong CYP2D6 inhibitor. (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of paroxetine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Additionally, monitor patients for signs and symptoms of serotonin syndrome. Concomitant use may increase dextromethorphan exposure and the risk for serotonin syndrome. Dextromethorphan is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Concomitant use with paroxetine increased dextromethorphan overall exposure by 2.69-fold.
Pasireotide: (Major) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Cautious use of pasireotide and drugs that prolong the QT interval is needed, as coadministration may have additive effects on the prolongation of the QT interval.
Patiromer: (Moderate) Separate the administration of patiromer and quinidine by at least 3 hours if concomitant use is necessary. Simultaneous coadministration may reduce gastrointestinal absorption of quinidine and reduce its efficacy. Patiromer has been observed to bind some oral medications when given at the same time and separating administration by at least 3 hours has effectively mitigated this risk.
Pazopanib: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib and quinidine (including dextromethorphan; quinidine have been reported to prolong the QT interval. If pazopanib and quinidine must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4 and a substrate for P-glycoprotein (P-gp). Quinidine is a substrate for CYP3A4 and an inhibitor of P-gp. Concurrent administration of quinidine and pazopanib may result in increased pazopanib and/or quinidine concentrations. Use caution when concurrent administration is necessary. (Moderate) Use of dextromethorphan with pazopanib may result in increased dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Results from drug-drug interaction trials conducted in cancer patients suggest that pazopanib is a weak inhibitor of CYP2D6 and dextromethorphan is a CYP2D6 substrate. Coadministration of dextromethorphan and pazopanib resulted in an increase of 33% to 64% in the ratio of dextromethorphan to dextrorphan concentrations in the urine, indicating reduced CYP2D6 metabolism to the dextrorphan metabolite.
Peginterferon Alfa-2b: (Minor) Monitor for adverse effects associated with increased exposure to dextromethorphan if peginterferon alfa-2b is coadministered. Peginterferon alfa -2b is a CYP2D6 inhibitor, while dextromethorphan is a CYP2D6 substrate.
Pentamidine: (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include systemic pentamidine.
Pentobarbital: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
Perindopril; Amlodipine: (Moderate) Monitor for increased quinidine adverse reactions if coadministered with amlodipine. Taking these drugs together may increase quinidine plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; quinidine is a substrate of CYP3A4 with a narrow therapeutic index. In addition, quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Perphenazine: (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include perphenazine.
Perphenazine; Amitriptyline: (Contraindicated) Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions. Quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Tricyclic antidepressants are associated with a possible risk of QT prolongation, particularly at high dosages or in overdose, and are substrates for CYP2D6. (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include perphenazine.
Pexidartinib: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with quinidine. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
Phenelzine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking a monoamine oxidase inhibitor (MAOI) or in patients who have taken an MAOI within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of an MAOI. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotonergic agents, a sufficient amount of time must be allowed for clearance of the serotonergic agent and its active metabolites.
Phenobarbital: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Hyoscyamine may increase the absorption of quinidine by decreasing GI motility and thereby enhancing absorption with possible toxicity. Increased monitoring is advised in patients receiving a combination of these drugs. (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy. (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics. (Moderate) The reduction in GI motility produced by scopolamine may increase the absorption of some drugs, including quinidine, resulting in increased anticholinergic effects. Increased monitoring is advised in patients receiving this combination.
Phenoxybenzamine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Phentolamine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Pimavanserin: (Major) Pimavanserin may cause QT prolongation and should generally be avoided in patients receiving other medications known to prolong the QT interval, such as quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP).
Pimozide: (Contraindicated) Coadministration of pimozide and quinidine is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). Pimozide exposure may also be increased; elevated concentrations of pimozide can lead to QT prolongation, ventricular arrhythmias, and sudden death. Quinidine is a strong CYP2D6 inhibitor that has been associated with QT prolongation and rare cases of TdP. Pimozide is a CYP2D6 substrate that is associated with a well-established risk of QT prolongation and TdP. Coadministration of pimozide with another strong CYP2D6 inhibitor increased the pimozide AUC by 151%.
Pindolol: (Major) Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, like pindolol. In general, patients receiving combined therapy should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block and heart failure, Reduce the beta-blocker dosage if necessary.
Pitolisant: (Major) Avoid coadministration of pitolisant and quinidine as concurrent use may increase the risk of QT prolongation. When administered as quinidine; dextromethorphan, coadministration with pitolisant is contraindicated. If concurrent use is unavoidable, initiate pitolisant at 8.9 mg once daily in patients taking quinidine; increase pitolisant after 7 days to a maximum dosage of 17.8 mg once daily. If quinidine is initiated in a patient on a stable dose of pitolisant, reduce the pitolisant dose by half. Pitolisant is a CYP2D6 substrate that prolongs the QT interval; quinidine is a strong CYP2D6 inhibitor that has been associated with QT prolongation and torsade de pointes. Coadministration of strong CYP2D6 inhibitors increases pitolisant exposure by 2.2-fold.
Ponesimod: (Major) In general, do not initiate ponesimod in patients taking quinidine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Quinidine administration is associated with QT prolongation and TdP.
Posaconazole: (Contraindicated) The concurrent use of posaconazole and quinidine (or products containing quinidine such as dextromethorphan; quinidine) is contraindicated due to the risk of life threatening arrhythmias such as torsades de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of quinidine. Further, both posaconazole and quinidine are inhibitors and substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of either drug. This complex interaction may ultimately result in altered plasma concentrations of both posaconazole and quinidine. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as quinidine.
Potassium Bicarbonate: (Major) Alkalinizing agents such as potassium citrate can increase renal tubular reabsorption of quinidine by alkalinizing the urine; higher quinidine serum concentrations and quinidine toxicity are possible.
Potassium Chloride: (Major) Alkalinizing agents such as potassium citrate can increase renal tubular reabsorption of quinidine by alkalinizing the urine; higher quinidine serum concentrations and quinidine toxicity are possible.
Potassium Citrate: (Major) Alkalinizing agents such as potassium citrate can increase renal tubular reabsorption of quinidine by alkalinizing the urine; higher quinidine serum concentrations and quinidine toxicity are possible.
Potassium Citrate; Citric Acid: (Major) Alkalinizing agents such as potassium citrate can increase renal tubular reabsorption of quinidine by alkalinizing the urine; higher quinidine serum concentrations and quinidine toxicity are possible.
Pralsetinib: (Major) Avoid concomitant use of quinidine with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and quinidine is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Prazosin: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Pretomanid: (Major) Avoid coadministration of pretomanid with quinidine, especially in patients with impaired hepatic function, due to increased risk for hepatotoxicity. Monitor for evidence of hepatotoxicity if coadministration is necessary. If new or worsening hepatic dysfunction occurs, discontinue hepatotoxic medications.
Prilocaine; Epinephrine: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
Primaquine: (Major) Due to the potential for QT interval prolongation with primaquine, caution is advised with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with primaquine include quinidine.
Primidone: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
Probenecid; Colchicine: (Major) Avoid concomitant use of colchicine and quinidine due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and quinidine is a P-gp inhibitor.
Procainamide: (Major) According to the manufacturer of procainamide, use with other Class 1A agents, such as quinidine, is contraindicated; however, the manufacturer also states such use may be reserved for patients with serious arrhythmias unresponsive to a single drug if under close observation. Quinidine should only be used with extreme caution with procainamide, due to the potential for QT prolongation and similar effects on the cardiac action potential. Coadministration of quinidine may increase serum concentrations of procainamide, possibly by competing for pathways of renal clearance.
Procarbazine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with procarbazine, an antineoplastic agent with monoamine oxidase inhibitor (MAOI) activity. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Prochlorperazine: (Minor) Prochlorperazine is associated with a possible risk for QT prolongation. Theoretically, prochlorperazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with prochlorperazine include: quinidine (including dextromethorphan; quinidine).
Promethazine: (Contraindicated) Quinidine (including dextromethorphan; quinidine) administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6, such as promethazine, as the effects on the QT interval may be increased during concurrent use of these agents.
Promethazine; Dextromethorphan: (Contraindicated) Quinidine (including dextromethorphan; quinidine) administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6, such as promethazine, as the effects on the QT interval may be increased during concurrent use of these agents.
Promethazine; Phenylephrine: (Contraindicated) Quinidine (including dextromethorphan; quinidine) administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6, such as promethazine, as the effects on the QT interval may be increased during concurrent use of these agents.
Propafenone: (Contraindicated) Class IA antiarrhythmics are associated with QT prolongation and ventricular arrhythmias including torsades de pointes (TdP), and concurrent use with propafenone is not recommended by the manufacturer. Before switching from another antiarrhythmic drug to propafenone therapy, Class IA antiarrhythmics and Class III antiarrhythmics generally should be withheld for at least five half-lives prior to initiating propafenone. Quinidine is a CYP2D6 inhibitor with potential to inhibit propafenone metabolism, and coadministration is contraindicated. Small doses of quinidine completely inhibit the CYP2D6 hydroxylation metabolic pathway, with the result that extensive metabolizers become poor metabolizers. Coadministration with quinidine markedly decreases propafenone clearance in extensive metabolizers, and increases plasma propafenone concentrations by 2 to 3-fold at steady-state. Steady-state plasma concentrations increased more than 2-fold for propafenone, and decreased 50% for 5-OH-propafenone. (Minor) Use of dextromethorphan with propafenone might increase dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. In vitro studies suggest that propafenone inhibits CYP2D6, but clinically relevant interactions have not been reported due to this potential action. Dextromethorphan is a CYP2D6 substrate.
Propantheline: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
Propranolol: (Major) Patients receiving combined therapy with quinidine and propranolol should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block and heart failure, Reduce the beta-blocker dosage if necessary. Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, such as propranolol. Quinidine is a known inhibitor of CYP2D6, and may additionally impair the hepatic clearance of propanolol (CYP2D6 substrate); patients should be monitored for excess beta-blockade.
Propranolol; Hydrochlorothiazide, HCTZ: (Major) Patients receiving combined therapy with quinidine and propranolol should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block and heart failure, Reduce the beta-blocker dosage if necessary. Quinidine may have additive effects (e.g., reduced heart rate, hypotension) on cardiovascular parameters when used together with beta-blockers, such as propranolol. Quinidine is a known inhibitor of CYP2D6, and may additionally impair the hepatic clearance of propanolol (CYP2D6 substrate); patients should be monitored for excess beta-blockade.
Protriptyline: (Major) TCAs should be used cautiously and with close monitoring with cardiac drugs known to prolong the QT interval such as quinidine. The need to coadminister TCAs with protriptyline should be done with a careful assessment of risk versus benefit; consider alternative therapy to the TCA. The dosage of protriptyline may need to be reduced if these drugs are coadministered. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). This pharmacologic property of the TCAs is of concern in patients with significant cardiac histories or treated with selected cardiac agents. Cases of long QT syndrome and torsade de pointes tachycardia have been described with TCA use, but rarely occur when TCAs are used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of TCAs in combination with other QT-prolonging drugs. One study reported the common occurrence of overlapping prescriptions for 2 or more drugs with potential for QT-prolonging effects; antidepressants were involved in nearly 50% of the cases, but there are little data to document safety of the combined therapies. Certain cardiac drugs prolong repolarization at therapeutic or elevated plasma concentrations, and the addition of other drugs may increase the risk of QT prolongation and torsades de pointes via pharmacokinetic or pharmacodynamic interactions.
Pyridostigmine: (Moderate) Quinidine can potentiate the effects of depolarizing and nondepolarizing neuromuscular blockers. Recurrent paralysis may occur if quinidine injection is administered during recovery from use of nondepolarizing muscle relaxants. Consider the possible effect from quinidine when administering anticholinesterase agents such as pyridostigmine to antagonize neuromuscular blockade induced by nondepolarizing muscle relaxants.
Quetiapine: (Major) Concomitant use of quinidine and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quinidine: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of quinidine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and quinidine is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Quinine: (Contraindicated) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). In addition, quinine is an inhibitor of CYP3A4. Avoid concurrent use of quinine with other drugs that prolong the QT and are CYP3A4 substrates, such as quinidine. Coadministration may result in an elevated quinidine plasma concentration, causing an increased risk for adverse events, such as QT prolongation. Further, both quinine and quinidine are cinchona alkaloids; the possibility of cinchonism is increased if these drugs are administered concomitantly (Moderate) Although clinical drug interaction studies have not been performed, antimalarial doses of quinine (greater than or equal to 600 mg/day in adults) may inhibit the metabolism of CYP2D6 substrates such as dextromethorphan and may result in increased dextromethorphan exposure. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Quizartinib: (Major) Concomitant use of quizartinib and quinidine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ranolazine: (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include ranolazine.
Rasagiline: (Contraindicated) Dextromethorphan prescription products are contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Allow at least 14 days after stopping dextromethorphan before starting an MAOI, including rasagiline. Brief episodes of psychosis or bizarre behavior have also been reported with this combination. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotoninergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites.
Relugolix: (Major) Avoid concomitant use of relugolix and oral quinidine. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects; QT prolongation may also occur. If concomitant use is unavoidable, administer quinidine at least six hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate that may prolong the QT/QTc interval. Quinidine is a P-gp inhibitor that is associated with QT prolongation and torsade de pointes (TdP).
Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of relugolix and oral quinidine. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects; QT prolongation may also occur. If concomitant use is unavoidable, administer quinidine at least six hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate that may prolong the QT/QTc interval. Quinidine is a P-gp inhibitor that is associated with QT prolongation and torsade de pointes (TdP).
Ribociclib: (Major) Avoid coadministration of ribociclib with quinidine due to an increased risk for QT prolongation and torsade de pointes (TdP). Systemic exposure of quinidine may be increased resulting in an increase in quinidine-related adverse reactions. Ribociclib is a strong CYP3A4 inhibitor that has been shown to prolong the QT interval in a concentration-dependent manner. Quinidine is a CYP3A4 substrate that has also been associated with QT prolongation and torsade de pointes (TdP). Concomitant use may increase the risk for QT prolongation.
Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with quinidine due to an increased risk for QT prolongation and torsade de pointes (TdP). Systemic exposure of quinidine may be increased resulting in an increase in quinidine-related adverse reactions. Ribociclib is a strong CYP3A4 inhibitor that has been shown to prolong the QT interval in a concentration-dependent manner. Quinidine is a CYP3A4 substrate that has also been associated with QT prolongation and torsade de pointes (TdP). Concomitant use may increase the risk for QT prolongation.
Rifabutin: (Moderate) Rifabutin is an inducer of the cytochrome P-450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of quinidine.
Rifampin: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Inducers of CYP3A4 may increase hepatic elimination of quinidine. Rifampin is a potent inducer of this isoenzyme. Quinidine concentrations should be monitored closely after rifampin is added to the treatment regimen. No special precautions appear necessary if rifampin is begun several weeks before quinidine is added but quinidine doses may require adjustment if it is added or discontinued during quinidine therapy.
Rifapentine: (Moderate) Monitor for decreased efficacy of quinidine if coadministration with rifapentine is necessary. Concomitant use may result in decreased plasma concentrations of quinidine. Quinidine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Rifaximin: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with quinidine is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and quinidine is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
Rilpivirine: (Major) Rilpivirine should be used cautiously with Class IA antiarrhythmics (disopyramide, procainamide, quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval.
Riluzole: (Major) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and quinidine. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Rimegepant: (Major) Avoid a second dose of rimegepant within 48 hours if coadministered with quinidine; concurrent use may increase rimegepant exposure. Rimegepant is a P-gp substrate and quinidine is a P-gp inhibitor.
Risperidone: (Major) Concomitant use of risperidone and fixed-dose combination quinidine; dextromethorphan is contraindicated. Avoid concomitant use of risperidone and quinidine alone if possible; use increases the risk for QT/QTc prolongation and torsade de pointes (TdP) and is expected to increase risperidone exposure. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Additionally, monitor for an increase in risperidone-related adverse effects and reduce risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, an anticipatory dosage decrease may be considered prior to initiation of quinidine. Risperidone is a CYP2D6 substrate, and quinidine is a strong CYP2D6 inhibitor. Concomitant use with other strong CYP2D6 inhibitors increased risperidone overall exposure by 2.5- to 9-fold.
Ritlecitinib: (Moderate) Monitor ECG and for quinidine-related adverse reactions if coadministration with ritlecitinib is necessary. Concomitant use may result in increased plasma concentrations of quinidine. Quinidine is a CYP3A substrate and ritlecitinib is a moderate CYP3A inhibitor.
Ritonavir: (Major) Coadministration of HIV treatment doses of ritonavir and quinidine is contraindicated due to the potential for serious or life-threatening reactions, such as cardiac arrhythmias. Cautious consideration may be given to administering quinidine with boosting doses of ritonavir. Ritonavir is an inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as quinidine, should be expected with concurrent use.
Rivaroxaban: (Minor) Coadministration of rivaroxaban and quinidine may result in increases in rivaroxaban exposure and may increase bleeding risk. Quinidine is an inhibitor of P-glycoprotein (P-gp), and rivaroxaban is a substrate of P-gp. If these drugs are administered concurrently, monitor the patient for signs and symptoms of bleeding.
Rocuronium: (Moderate) Concomitant use of neuromuscular blockers and quinidine may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Rolapitant: (Moderate) Rolapitant increases exposure to dextromethorphan. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Rolapitant is a moderate CYP2D6 inhibitor with a prolonged effect; the inhibitory effect of rolapitant is expected to persist beyond 28 days for an unknown duration. During drug interaction studies, exposure (AUC) to dextromethorphan following a single dose of rolapitant increased close to 3-fold on Days 8 and Day 22. The inhibition of CYP2D6 persisted on Day 28 with a 2.3-fold increase in dextromethorphan exposure (AUC), the last time point measured. (Moderate) Use caution if quinidine and rolapitant are used concurrently, and monitor for quinidine-related adverse effects, including QT prolongation. Quinidine is a P-glycoprotein (P-gp) substrate, where an increase in exposure may significantly increase adverse effects; rolapitant is a P-gp inhibitor. When rolapitant was administered with another P-gp substrate, digoxin, the day 1 Cmax and AUC were increased by 70% and 30%, respectively; the Cmax and AUC on day 8 were not studied.
Romidepsin: (Major) Romidepsin is a substrate for P-glycoprotein (P-gp). Quinidine is an inhibitor of P-gp. Concurrent administration of romidepsin with an inhibitor of P-gp may cause an increase in systemic romidepsin concentrations. Use caution when concomitant administration of these agents is necessary. In addition, romidepsin has been reported to prolong the QT interval. Quinidine also prolongs the QT interval. If romidepsin and quinidine must be coadministered, appropriate cardiovascular monitoring precautions should be considered, such as the monitoring of electrolytes and ECGs at baseline and periodically during treatment.
Rufinamide: (Minor) Rufinamide is not metabolized through hepatic CYP isozymes; however, it is a weak inducer of CYP3A4. In theory, decreased exposure of drugs that are extensively metabolized by CYP3A4, such as quinidine, may occur during concurrent use with rufinamide.
Safinamide: (Contraindicated) Dextromethorphan prescription products are contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Allow at least 14 days after stopping dextromethorphan before starting an MAOI, including safinamide. Brief episodes of psychosis or bizarre behavior have also been reported with this combination. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotoninergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites.
Saquinavir: (Contraindicated) Concurrent use of quinidine or quinidine-containing products (e.g., dextromethorphan; quinidine) and saquinavir boosted with ritonavir is contraindicated due to the risk of life threatening cardiac arrhythmias such as torsade de pointes (TdP). Saquinavir boosted with ritonavir is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of quinidine. Concurrent administration may result in large increases in quinidine serum concentrations, which could cause fatal cardiac arrhythmias. Additionally, saquinavir boosted with ritonavir causes dose-dependent QT and PR prolongation; avoid use with other drugs that may prolong the QT or PR interval, such quinidine.
Sarilumab: (Moderate) Monitor quinidine levels and adjust the dose of quinidine as appropriate if coadministration with sarilumab is necessary. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as quinidine, may have fluctuations in drug levels and therapeutic effect when sarilumab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Quinidine is a CYP3A4 substrate and narrow therapeutic index drug.
Scopolamine: (Moderate) The reduction in GI motility produced by scopolamine may increase the absorption of some drugs, including quinidine, resulting in increased anticholinergic effects. Increased monitoring is advised in patients receiving this combination.
Secobarbital: (Major) Quinidine is eliminated primarily via hepatic metabolism, primarily by the CYP3A4 isoenzyme. Administration of other hepatic enzyme inducers, such as barbiturates, can accelerate quinidine elimination and decrease its serum concentrations. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Quinidine concentrations should be monitored closely after one of these agents is added. No special precautions appear necessary if these agents are begun several weeks before quinidine is added but quinidine doses may require adjustment if one of these agents is added or discontinued during quinidine therapy.
Secukinumab: (Moderate) If secukinumab is initiated or discontinued in a patient taking quinidine, monitor for altered patient response to quinidine; quinidine dose adjustments may be needed. The formation of CYP450 enzymes may be altered by increased concentrations of cytokines during chronic inflammation. Thus, the formation of CYP450 enzymes could be normalized during secukinumab administration. In theory, clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as quinidine.
Selegiline: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor) or in patients who have taken an selegiline within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of selegiline. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan.
Selpercatinib: (Major) Monitor ECGs more frequently for QT prolongation if coadministration of selpercatinib with quinidine is necessary due to the risk of additive QT prolongation. Concentration-dependent QT prolongation has been observed with selpercatinib therapy. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP).
Serotonin-Receptor Agonists: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant dextromethorphan and serotonin-receptor agonists use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Sertraline: (Major) Concomitant use of sertraline and quinidine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with sertraline is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 2 times the maximum recommended dose. (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with sertraline. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. In addition, sertraline inhibits CYP2D6 and may increase systemic dextromethorphan exposure. Increased dextromethorphan concentrations may result in adverse effects consistent with the serotonin syndrome.
Sevoflurane: (Major) Halogenated anesthetics should be used cautiously with class IA antiarrhythmics (disopyramide, procainamide, quinidine). Halogenated anesthetics can prolong the QT interval and class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP).
Sildenafil: (Moderate) Sildenafil is metabolized principally by the hepatic isoenzymes CYP3A4 and CYP2C9. Inhibitors of these isoenzymes, such as quinidine, may reduce sildenafil clearance. Increased systemic exposure to sildenafil may result in an increase in sildenafil-induced adverse effects.
Siltuximab: (Moderate) Monitor quinidine levels and adjust the dose of quinidine as appropriate if coadministration with siltuximab is necessary. Inhibition of IL-6 signaling by siltuximab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as quinidine, may have fluctuations in drug levels and therapeutic effect when siltuximab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping siltuximab. In vitro, siltuximab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Quinidine is a CYP3A4 substrate and narrow therapeutic index drug.
Siponimod: (Major) In general, do not initiate treatment with sip onimod in patients receiving quinidine due to the potential for QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Quinidine administration is associated with QT prolongation and torsade de pointes.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of quinidine. Coadministration may increase sirolimus concentrations and the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and quinidine is a P-gp inhibitor.
Sodium Stibogluconate: (Major) Concomitant use of sodium stibogluconate and quinidine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sofosbuvir; Velpatasvir: (Moderate) Use caution when administering velpatasvir with quinidine. Taking these medications together may increase the plasma concentrations of both drugs, potentially resulting in adverse events. Both drugs are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp).
Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Plasma concentrations of quinidine, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with voxilaprevir, a P-gp inhibitor. Monitor patients for increased side effects if these drugs are administered concurrently. (Moderate) Use caution when administering velpatasvir with quinidine. Taking these medications together may increase the plasma concentrations of both drugs, potentially resulting in adverse events. Both drugs are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp).
Solifenacin: (Moderate) Class IA antiarrhythmics (disopymide, procainamide, and quinidine) should be used cautiously and with close monitoring with solifenacin. Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation. In addition, coadministration may result in additive anticholinergic effects. Anticholinergic agents administered concurrently with disopyramide, procainamide, or quinidine may produce additive antivagal effects on AV nodal conduction.
Sorafenib: (Major) Avoid coadministration of sorafenib with quinidine due to the risk of additive QT prolongation. If concomitant use is unavoidable, monitor electrocardiograms and correct electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Sorafenib is associated with QTc prolongation.
Sotalol: (Major) Sotalol administration is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Drugs that prolong the QT interval should be used with extreme caution in combination with sotalol. Ventricular tachycardia, including torsade de pointes and monomorphic ventricular tachycardia can occur with excessive prolongation of the QT interval. Examples of agents that may prolong the QT interval include: Class IA antiarrhythmics (disopyramide, procainamide, quinidine). Before initiating sotalol, the previous Class I antiarrhythmic therapy should be withdrawn under careful monitoring for a minimum of (2-3) plasma half-lives for the discontinued drug.
Spironolactone: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
St. John's Wort, Hypericum perforatum: (Major) St. John's Wort appears to induce several isoenzymes of the hepatic cytochrome P450 enzyme system, including CYP3A4. Coadministration of St. John's wort could decrease the efficacy of some medications metabolized by this enzyme, such as quinidine. Clinicians should observe patients closely if St. John's wort is used. (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with St. John's Wort. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Stiripentol: (Moderate) Consider a dose adjustment of quinidine when coadministered with stiripentol. Coadministration may alter plasma concentrations of quinidine resulting in an increased risk of adverse reactions and/or decreased efficacy. Quinidine is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Streptogramins: (Moderate) Coadministration of quinidine with dalfopristin; quinupristin may result in elevated quinidine plasma concentrations. If these drugs are used together, closely monitor for signs of quinidine-related adverse events. Quinidine is a substrate of CYP3A; dalfopristin; quinupristin is a weak CYP3A inhibitor.
Succinylcholine: (Moderate) Concomitant use of neuromuscular blockers and quinidine may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Sunitinib: (Major) Monitor patients for QT prolongation if coadministration of quinidine with sunitinib is necessary. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including TdP.
Tacrolimus: (Major) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). As the risk of TdP is increased with greater QT prolongation, avoid use of quinidine with another drug that prolongs the QT interval such as tacrolimus. It should be noted that the manufacturer of tacrolimus recommends reducing the tacrolimus dose, close monitoring of tacrolimus whole blood concentrations, and monitoring for QT prolongation when coadministrating tacrolimus with other substrates and/or inhibitors of CYP3A4 that also have the potential to prolong the QT interval such as quinidine. Tacrolimus and quinidine are both metabolized by cytochrome P450 3A4.
Tadalafil: (Moderate) Tadalafil is metabolized predominantly by the hepatic isoenzyme CYP3A4. Inhibitors of CYP3A4, such as quinidine, may reduce tadalafil clearance. Increased systemic exposure to tadalafil may result in an increase in tadalafil-induced adverse effects, including hypotension.
Talazoparib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with quinidine is necessary. Talazoparib is a P-gp substrate and quinidine is a P-gp inhibitor.
Tamoxifen: (Major) Coadministration of quinidine with tamoxifen may result in additive QT prolongation and decreased efficacy of tamoxifen. When administered as quinidine; dextromethorphan, coadministration with tamoxifen is contraindicated. Quinidine is a CYP2D6 inhibitor that is associated with QT prolongation and torsade de pointes (TdP). Tamoxifen is a CYP2D6 substrate that has also been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have also been described when tamoxifen is used at lower doses. Tamoxifen is metabolized by CYP2D6 to endoxifen and 4-hydroxytamoxifen, both of which are minor metabolites but have 100-fold greater affinity for the estrogen receptor and 30- to 100-fold greater potency in suppressing estrogen-dependent cell proliferation than tamoxifen. In one study, the mean steady-state endoxifen plasma concentration was significantly reduced in patients taking CYP2D6 inhibitors compared to those not taking concomitant CYP2D6 inhibitors. In another study, the mean steady-state plasma concentration of endoxifen in CYP2D6 normal metabolizers who were not receiving CYP2D6 inhibitors were 3.6-fold higher compared to normal metabolizers who were receiving strong CYP2D6 inhibitors; plasma levels in CYP2D6 normal metabolizers receiving strong CYP2D6 inhibitors were similar to levels observed in CYP2D6 poor metabolizers taking no CYP2D6 inhibitors. Some studies have shown that the efficacy of tamoxifen may be reduced when concomitant drugs decrease the levels of potent active metabolites; however, others have failed to demonstrate such an effect. The clinical significance is not well established.
Tamsulosin: (Moderate) Use caution when administering tamsulosin with a strong CYP2D6 inhibitor such as quinidine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure. If concomitant use in necessary, monitor patient closely for increased side effects.
Tedizolid: (Minor) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with tedizolid. Tedizolid is an antibiotic that is also a weak, reversible, non-selective MAO inhibitor in vitro. In theory, tedizolid has potential to interact with serotonergic agents, but interactions are thought to be unlikely. In clinical interaction studies with a related antibiotic (linezolid), interactions with dextromethorphan were studied, but serotonin syndrome or adverse effects were not reported. No drug-drug interaction precautions with dextromethorphan are specifically mentioned in the tedizolid label. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Teduglutide: (Moderate) Teduglutide may increase absorption of quinidine because of it's pharmacodynamic effect of improving intestinal absorption. Careful monitoring and possible dose adjustment of quinidine is recommended.
Telavancin: (Major) Class IA antiarrhythmics (disopyramide, procainamide, quinidine) should be used cautiously with telavancin. Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP) and telavancin has been associated with QT prolongation.
Telmisartan; Amlodipine: (Moderate) Monitor for increased quinidine adverse reactions if coadministered with amlodipine. Taking these drugs together may increase quinidine plasma concentrations, potentially resulting in adverse events. Amlodipine is a weak CYP3A4 inhibitor; quinidine is a substrate of CYP3A4 with a narrow therapeutic index. In addition, quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Temsirolimus: (Moderate) Monitor for an increase in temsirolimus- and quinidine-related adverse reactions if coadministration is necessary. Both drugs are P-glycoprotein (P-gp) substrates and inhibitors. Concomitant use is likely to lead to increased concentrations of both temsirolimus and quinidine.
Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as quinidine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Terazosin: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Terbinafine: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of terbinafine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and terbinafine is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Tetrabenazine: (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include tetrabenazine.
Thiazide diuretics: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Thioridazine: (Contraindicated) Because of the potential for torsade de pointes (TdP), concurrent use of quinidine and thioridazine is contraindicated. Class IA antiarrhythmics and thioridazine are associated with a well-established risk of QT prolongation and TdP. Thioridazine is considered contraindicated for use with agents that may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
Ticagrelor: (Moderate) Coadministration of ticagrelor and quinidine may result in increased exposure to ticagrelor which may increase the bleeding risk. Ticagrelor is a P-glycoprotein (P-gp) substrate and quinidine is a P-gp inhibitor. Based on drug information data with cyclosporine, no dose adjustment is recommended by the manufacturer of ticagrelor. Use combination with caution and monitor for evidence of bleeding.
Timolol: (Major) In general, patients receiving combined therapy with quinidine and beta-blockers should be monitored for potential hypotension, orthostasis, bradycardia and/or AV block, and heart failure. Reduce the beta-blocker dosage if necessary. Quinidine may have additive effects on cardiovascular parameters when used together with beta-blockers, such as timolol. Decreased heart rate (bradycardia) has been reported during combination timolol and quinidine therapy. Additive hypotension is also possible. Additionally, quinidine is a known inhibitor of CYP2D6, and may impair the hepatic clearance of timolol (CYP2D6 substrate). Patients should be monitored for excess beta-blockade. Quinidine has been reported to potentiate timolol-induced bradycardia even after use of ophthalmic timolol.
Tipranavir: (Contraindicated) Concurrent use of quinidine and tipranavir is contraindicated due to the potential for serious and/or life-threatening cardiac arrhythmias. Tipranavir inhibits the CYP3A4 metabolism of quinidine, resulting in elevated quinidine serum concentrations. (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of tipranavir is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and tipranavir is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Tocilizumab: (Moderate) Monitor quinidine levels and adjust the dose of quinidine as appropriate if coadministration with tocilizumab is necessary. Inhibition of IL-6 signaling by tocilizumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as quinidine, may have fluctuations in drug levels and therapeutic effect when tocilizumab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping tocilizumab. In vitro, tocilizumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Quinidine is a CYP3A4 substrate and narrow therapeutic index drug. (Minor) Concomitant use of tocilizumab and dextromethorphan may lead to a decrease in the efficacy of dextromethorphan; clinical significance of this interaction is not known or established. Inhibition of IL-6 signaling by tocilizumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. This effect on CYP450 enzyme activity may persist for several weeks after stopping tocilizumab. A 5% decrease in dextromethorphan exposure and a 29% decrease in its metabolite, dextrorphan was noted 1 week after a single tocilizumab infusion. In vitro, tocilizumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Dextromethorphan is a CYP2D6 substrate.
Tolterodine: (Major) Use tolterodine and quinidine concomitantly with caution and close monitoring. Quinidine can inhibit the hepatic CYP2D6 isoenzyme, which may decrease the metabolism of tolterodine. It is not known if dosage adjustments in tolterodine would be needed as the result of this interaction. In addition, tolterodine is associated with dose-dependent prolongation of the QT interval, especially in poor metabolizers of CYP2D6, and quinidine (including dextromethorphan; quinidine) is associated with an established risk of QT prolongation. In addition, the anticholinergic effects of quinidine may be significant and may be enhanced when combined with tolterodine. Anticholinergic agents administered concurrently with quinidine may produce additive antivagal effects on AV nodal conduction.
Topotecan: (Major) Avoid coadministration of quinidine with oral topotecan due to increased topotecan exposure; quinidine may be administered with intravenous topotecan. Oral topotecan is a substrate of P-glycoprotein (P-gp) and quinidine is a P-gp inhibitor. Oral administration within 4 hours of another P-gp inhibitor increased the dose-normalized AUC of topotecan lactone and total topotecan 2-fold to 3-fold compared to oral topotecan alone.
Toremifene: (Major) Avoid coadministration of quinidine with toremifene if possible due to the risk of additive QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia or hypomagnesemia prior to administration of toremifene. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. Quinidine administration is also associated with QT prolongation and torsade de pointes (TdP).
Tramadol: (Moderate) As quinidine is a potent inhibitor of CYP2D6 and tramadol is partially metabolized by CYP2D6, concurrent therapy may decrease tramadol metabolism. This interaction may result in decreased tramadol efficacy and/or increased tramadol-induced risks of serotonin syndrome or seizures. The analgesic activity of tramadol is due to the activity of both the parent drug and the O-desmethyltramadol metabolite (M1), and M1 formation is dependent on CYP2D6. Therefore, use of tramadol with a CYP2D6-inhibitor may alter tramadol efficacy. In addition, inhibition of CYP2D6 metabolism is expected to result in reduced metabolic clearance of tramadol. This in turn may increase the risk of tramadol-related adverse events including serotonin syndrome and seizures. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Tramadol; Acetaminophen: (Moderate) As quinidine is a potent inhibitor of CYP2D6 and tramadol is partially metabolized by CYP2D6, concurrent therapy may decrease tramadol metabolism. This interaction may result in decreased tramadol efficacy and/or increased tramadol-induced risks of serotonin syndrome or seizures. The analgesic activity of tramadol is due to the activity of both the parent drug and the O-desmethyltramadol metabolite (M1), and M1 formation is dependent on CYP2D6. Therefore, use of tramadol with a CYP2D6-inhibitor may alter tramadol efficacy. In addition, inhibition of CYP2D6 metabolism is expected to result in reduced metabolic clearance of tramadol. This in turn may increase the risk of tramadol-related adverse events including serotonin syndrome and seizures. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Trandolapril; Verapamil: (Major) Pharmacokinetic and pharmacodynamic interactions exist between quinidine and verapamil. Oral verapamil has been shown to reduce the clearance and metabolism of oral quinidine. Quinidine half-life increased and plasma concentrations were higher after verapamil. No changes in quinidine protein binding were observed. In addition to the pharmacokinetic interaction which may potentiate quinidine's clinical effects, both quinidine and verapamil can cause hypotension. When quinidine and verapamil are coadministered in doses that are each well tolerated as monotherapy, hypotension attributable to additive peripheral (alpha)-blockade is sometimes reported. Concurrent use of verapamil and quinidine in patients with hypertrophic cardiomyopathy or arrhythmias can cause significant hypotension. It is recommended to avoid combined therapy with verapamil and quinidine in patients with hypertrophic cardiomyopathy. Quinidine and verapamil may also have additive negative inotropic effects. Concurrent use of verapamil and quinidine should be monitored carefully for electrophysiologic and hemodynamic effects.
Tranylcypromine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking a monoamine oxidase inhibitor (MAOI) or in patients who have taken an MAOI within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of an MAOI. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotonergic agents, a sufficient amount of time must be allowed for clearance of the serotonergic agent and its active metabolites.
Trazodone: (Major) Concomitant use of trazodone and quinidine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Treprostinil: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Triamterene: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Triclabendazole: (Major) Concomitant use of triclabendazole and quinidine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Tricyclic antidepressants: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with tricyclic antidepressants. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Trifluoperazine: (Minor) Trifluoperazine and quinidine should be used cautiously due to the potential for QT prolongation. Trifluoperazine, a phenothiazine, has a possible risk for QT prolongation. Quinidine is associated with a well-established risk of QT prolongation and torsade de pointes (TdP).
Trihexyphenidyl: (Moderate) The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
Trimipramine: (Contraindicated) Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions. Quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Tricyclic antidepressants are associated with a possible risk of QT prolongation, particularly at high dosages or in overdose, and are substrates for CYP2D6.
Triptorelin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving quinidine. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
Trospium: (Major) Trospium is eliminated by active tubular secretion and has the potential for pharmacokinetic interactions with other drugs that are eliminated by active tubular secretion, such as quinidine. In theory, coadministration of trospium with quinidine may increase the serum concentrations of trospium or quinidine due to competition for the drug elimination pathway.
Tucatinib: (Moderate) Monitor for quinidine-related adverse reactions if coadministration with tucatinib is necessary. Concurrent use may increase quinidine exposure. Quinidine is a CYP3A4 substrate and tucatinib is a strong CYP3A4 inhibitor.
Ubrogepant: (Major) Limit the initial and second dose of ubrogepant to 50 mg if coadministered with quinidine. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a substrate of the P-gp drug transporter; quinidine is a P-gp inhibitor.
Valbenazine: (Major) Consider reducing the dose of valbenazine, based on tolerability, during co-administration with a strong CYP2D6 inhibitor, such as quinidine. QT prolongation is not clinically significant at valbenazine concentrations expected with recommended dosing; however, concentrations of the active metabolite of valbenazine may be higher in patients taking a strong CYP2D6 inhibitor and QT prolongation may become clinically significant.
Vandetanib: (Major) Avoid coadministration of vandetanib with quinidine due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Quinidine administration is also associated with QT prolongation and TdP.
Vardenafil: (Major) Vardenafil should be avoided in patients taking Class IA antiarrhythmics (disopyramide, procainamide, and quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsade de pointes (TdP). Therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. The effect of vardenafil on the QT interval should be considered when prescribing the drug.
Vecuronium: (Moderate) Concomitant use of neuromuscular blockers and quinidine may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Vemurafenib: (Major) Vemurafenib has been associated with QT prolongation. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). If vemurafenib and quinidine must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Also, quinidine is also a CYP3A4 substrate and a P-glycoprotein (P-gp) substrate/inhibitor. Vemurafenib is a CYP3A4 substrate/inducer, and a P-gp substrate/inhibitor. Quinidine concentrations may be increased or decreased and vemurafenib concentrations may be increased during concurrent use. (Minor) Use of dextromethorphan with vemurafenib increases dextromethorphan exposure. Vemurafenib is a weak CYP2D6 inhibitor and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor. Coadministration of vemurafenib and dextromethorphan increased the AUC of dextromethorphan by 47% and the dextromethorphan Cmax by 36%.
Venetoclax: (Major) Reduce the dose of venetoclax by at least 50% and monitor for venetoclax toxicity (e.g., hematologic toxicity, GI toxicity, and tumor lysis syndrome) if coadministered with quinidine due to the potential for increased venetoclax exposure. Resume the original venetoclax dose 2 to 3 days after discontinuation of quinidine. Venetoclax is a P-glycoprotein (P-gp) substrate; quinidine is a P-gp inhibitor. Coadministration with a single dose of another P-gp inhibitor increased venetoclax exposure by 78% in a drug interaction study.
Venlafaxine: (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine includes venlafaxine. (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with venlafaxine. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
Verapamil: (Major) Pharmacokinetic and pharmacodynamic interactions exist between quinidine and verapamil. Oral verapamil has been shown to reduce the clearance and metabolism of oral quinidine. Quinidine half-life increased and plasma concentrations were higher after verapamil. No changes in quinidine protein binding were observed. In addition to the pharmacokinetic interaction which may potentiate quinidine's clinical effects, both quinidine and verapamil can cause hypotension. When quinidine and verapamil are coadministered in doses that are each well tolerated as monotherapy, hypotension attributable to additive peripheral (alpha)-blockade is sometimes reported. Concurrent use of verapamil and quinidine in patients with hypertrophic cardiomyopathy or arrhythmias can cause significant hypotension. It is recommended to avoid combined therapy with verapamil and quinidine in patients with hypertrophic cardiomyopathy. Quinidine and verapamil may also have additive negative inotropic effects. Concurrent use of verapamil and quinidine should be monitored carefully for electrophysiologic and hemodynamic effects.
Vilazodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with vilazodone. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Viloxazine: (Moderate) Monitor for an increase in dextromethorphan-related adverse effects if concomitant use of viloxazine is necessary. Concomitant use may increase dextromethorphan exposure; viloxazine is a weak CYP2D6 inhibitor and dextromethorphan is a CYP2D6 substrate.
Vincristine Liposomal: (Major) Quinidine inhibits P-glycoprotein (P-gp), and vincristine is a P-gp substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Vincristine: (Major) Quinidine inhibits P-glycoprotein (P-gp), and vincristine is a P-gp substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Voclosporin: (Major) Use caution if quinidine is coadministered with voclosporin due to the risk of additive QT prolongation. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP). Quinidine (including dextromethorphan; quinidine) and disopyramide are also associated with QT prolongation and TdP. There have been post-marketing reports of TdP occurring with the coadministration of clarithromycin and quinidine or disopyramide. If used concomitantly, monitor ECGs for QT prolongation and consider monitoring serum concentrations of quinidine or disopyramide.
Voriconazole: (Contraindicated) Quinidine (including dextromethorphan; quinidine) use is contraindicated with voriconazole according to recommendations made by the manufacturer of voriconazole. Voriconazole inhibits the CYP3A4 enzyme that is responsible for quinidine metabolism; elevated and toxic levels of quinidine may occur potentiating the risk for QT prolongation and cardiac arrhythmias (e.g., torsade de pointes).
Vorinostat: (Major) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Vorinostat therapy is associated with a risk of QT prolongation and should be used cautiously with quinidine.
Vortioxetine: (Major) The primary isoenzyme involved in the metabolim of vortioxetine is CYP2D6; therefore, the manufacturer recommends a reduction in the vortioxetine dose by one-half during co-administration with strong inhibitors of CYP2D6 such as quinidine. The vortioxetine dose should be increased to the original level when the CYP2D6 inhibitor is discontinued. (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with vortioxetine. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustments. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Voxelotor: (Moderate) Monitor ECG and for quinidine-related adverse reactions if coadministration with voxelotor is necessary. Concomitant use may result in increased plasma concentrations of quinidine. Quinidine is a CYP3A substrate and voxelotor is a moderate CYP3A inhibitor.
Warfarin: (Moderate) Quinidine may potentiate the anticoagulation effects of warfarin; bleeding has been reported. This interaction is probably due to additive hypoprothrombinemia associated with concomitant administration of warfarin and quinine or quinidine. Close monitoring of the INR is required when either of these agents is added to warfarin therapy.
Zafirlukast: (Minor) Zafirlukast inhibits the CYP3A4 isoenzymes and should be used cautiously in patients stabilized on drugs metabolized by CYP3A4, such as quinidine.
Ziprasidone: (Contraindicated) Concomitant use of ziprasidone and class 1A antiarrhythmics, such as quinidine, is contraindicated by the manufacturer of ziprasidone due to the potential for additive QT prolongation and torsade de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of TdP in patients with multiple confounding factors. Class 1A antiarrhythmics are associated with a well-established risk of QT prolongation and TdP.
Zonisamide: (Minor) Zonisamide is a weak inhibitor of P-glycoprotein (P-gp), and quinidine is a substrate of P-gp. There is theoretical potential for zonisamide to affect the pharmacokinetics of drugs that are P-gp substrates. Use caution when starting or stopping zonisamide or changing the zonisamide dosage in patients also receiving drugs which are P-gp substrates.

Nuedexta Oral Cap: 20-10mg

Adults

Dextromethorphan 40 mg/day PO; quinidine 20 mg/day PO.

Geriatric

Dextromethorphan 40 mg/day PO; quinidine 20 mg/day PO.

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

The mechanism by which dextromethorphan; quinidine exerts its therapeutic effect in pseudobulbar affect (PBA) is unknown. The quinidine component of the formulation is used to increase the systemic bioavailability of dextromethorphan through its effect as a CYP2D6 inhibitor. Dextromethorphan, a sigma-1 receptor agonist and uncompetitive NMDA receptor antagonist, is the pharmacologically active ingredient of this combination product.

Dextromethorphan; quinidine is administered orally. Protein binding of dextromethorphan is 60% to 70%, and protein-binding of quinidine is 80% to 89%. Dextromethorphan is metabolized by CYP2D6 and quinidine is metabolized by CYP3A4. Dextromethorphan undergoes rapid and extensive hepatic metabolism to demethylated metabolites; however, quinidine affects dextromethorphan pharmacokinetics. Quinidine is a CYP2D6 inhibitor and it increases and prolongs the exposure to dextromethorphan in this product combination. Quinidine is metabolized by a series of hydroxylations in the liver to form two active quinidine derivatives; there are several different hydroxylated metabolites, including some with pharmacologic activity. The most important active metabolite is 3-hydroxy-quinidine (3HQ), which has at least half the pharmacologic activity of the parent compound with respect to cardiac effects such as QT prolongation. When the dextromethorphan; quinidine product was administered to extensive CYP2D6 metabolizers (normal metabolizers), the elimination half-lives of dextromethorphan and quinidine were 13 hours and 7 hours, respectively. Excretion of dextromethorphan is primarily by renal elimination of metabolites. Roughly 20% of the quinidine dose is excreted unchanged in the urine. Alkalinization of the urine can decrease renal elimination of quinidine to as little as 5%, while acidification will enhance quinidine excretion.
 
Affected Cytochrome P450 isoenzymes and drug transporters: CYP2D6 (dextromethorphan); CYP2D6, CYP3A4, P-glycoprotein (quinidine)
Dextromethorphan: Dextromethorphan is metabolized by CYP2D6. When dextromethorphan; quinidine is prescribed with potent CYP2D6 inhibitors (e.g., paroxetine), consideration should be given to initiating treatment with a lower dose. Dextromethorphan does not inhibit or induce CYP450 isoenzymes.
Quinidine: Quinidine is an inhibitor of CYP2D6 and may interact with drugs that are metabolized by this enzyme due to accumulation of the CYP2D6 substrate parent drug and/or failure of metabolite formation. Quinidine inhibited CYP2D6 with a half maximal inhibitory concentration (IC50) of less than 0.05 microM. Therapy with CYP2D6 substrates that have a relatively narrow therapeutic index should be initiated at a low dose if a patient is receiving quinidine concurrently; do not use quinidine with drugs that both prolong QT interval and are metabolized by CYP2D6. If dextromethorphan; quinidine is added to the treatment regimen of a patient already receiving a drug primarily metabolized by CYP2D6, the need for a dose modification of the original medication should be considered. In cases of prodrugs whose actions are mediated by the CYP2D6-produced metabolites (e.g., codeine and hydrocodone), it may not be possible to achieve the desired clinical benefits in the presence of quinidine due to quinidine-mediated inhibition of CYP2D6. Quinidine also inhibits P-glycoprotein (P-gp) transport and is a substrate for P-gp. Quinidine is primarily metabolized by the CYP3A4 enzyme, and inhibitors may cause clinically significant interactions with quinidine. Recommend ECG in patients taking concomitant moderate or strong CYP3A4 inhibitors with quinidine, particularly if the other drug is also known to prolong the QT interval.

Oral Route

After oral administration, maximum plasma concentrations of dextromethorphan and quinidine are reached in about 3 to 4 hours and 1 to 2 hours, respectively. There is a 20-fold increase in dextromethorphan exposure during co-administration with quinidine compared to dextromethorphan alone. Hence, the quinidine component of the formulation is used to increase the systemic bioavailability of dextromethorphan, the pharmacologically active ingredient. Food does not have a significant effect on exposure of dextromethorphan or quinidine; therefore, the drug may be taken without regard to meals. After twice daily administration of dextromethorphan; quinidine, the mean plasma Cmax of quinidine is within 1—3% of the concentration required for its antiarrhythmic effect.

Pregnancy

There are no adequate data on the developmental risk associated with dextromethorphan; quinidine use during human pregnancy. Due to a lack of pregnancy outcome data, dextromethorphan; quinidine should only be used during pregnancy when the benefits of treatment outweigh the potential risks to the fetus.[42280] In animal studies, the combination of dextromethorphan and quinidine was associated with developmental toxicity, including teratogenicity and embryolethality. Reduced skeletal ossification, decreased pup weight and survival, and developmental delays were observed in the offspring of rats given 1/50 mg/kg/day, or one-fiftieth of the recommended human dose of 40/20 mg/day on a mg/m2 basis, during organogenesis or throughout pregnancy and lactation. Embryolethality was observed in the offspring of rats given 50/100 mg/kg/day during organogenesis.[42280] In 1 case of in utero exposure to quinidine, the neonatal serum concentration of quinidine was equal to that of the mother, with no adverse effect noted in the neonate. The concentration of quinidine in the amniotic fluid was approximately 3 times higher than that in the serum.[28249] Retrospective and surveillance studies in humans have shown dextromethorphan to be relatively safe during the first trimester. However, the data are too limited to be conclusive.[26485] The effects of dextromethorphan; quinidine on labor and obstetric delivery are unknown.[42280]

Quinidine is excreted in human milk. It is not known whether dextromethorphan is excreted in human milk. There are no data on the effects dextromethorphan; quinidine on the breastfed infant or the effects on milk production.[42280] Based on the relatively low molecular weight of dextromethorphan, some transfer into breast milk is expected.[39683] During use of quinidine as an anti-arrhythmic, breast-feeding is generally not recommended because the drug is excreted in human milk at concentrations slightly lower than those found in maternal serum, and the reduced protein binding of quinidine in the neonate may increase the risk of toxicity at low total serum concentrations.[28249] Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for dextromethorphan; quinidine and any potential adverse effects on the breastfed infant from the drug product or the underlying maternal condition.[42280]