quinine

Antimalarials

Oral Administration

Administer with food to minimize gastrointestinal adverse effects.

Severe

torsade de pointes / Rapid / 0-1.0
ventricular fibrillation / Early / 0-1.0
hearing loss / Delayed / 10.0
seizures / Delayed / Incidence not known
suicidal ideation / Delayed / Incidence not known
coma / Early / Incidence not known
optic neuritis / Delayed / Incidence not known
night blindness / Delayed / Incidence not known
visual impairment / Early / Incidence not known
optic atrophy / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
vasculitis / Delayed / Incidence not known
exfoliative dermatitis / Delayed / Incidence not known
erythema multiforme / Delayed / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
thrombotic thrombocytopenic purpura (TTP) / Delayed / Incidence not known
pancytopenia / Delayed / Incidence not known
disseminated intravascular coagulation (DIC) / Delayed / Incidence not known
lupus-like symptoms / Delayed / Incidence not known
aplastic anemia / Delayed / Incidence not known
hemolytic anemia / Delayed / Incidence not known
agranulocytosis / Delayed / Incidence not known
hemolytic-uremic syndrome / Delayed / Incidence not known
coagulopathy / Delayed / Incidence not known
pulmonary edema / Early / Incidence not known
interstitial nephritis / Delayed / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known
ventricular tachycardia / Early / Incidence not known
AV block / Early / Incidence not known
bradycardia / Rapid / Incidence not known
cardiac arrest / Early / Incidence not known
atrial fibrillation / Early / Incidence not known

Moderate

blurred vision / Early / 10.0
peripheral vasodilation / Rapid / 10.0
confusion / Early / Incidence not known
aphasia / Delayed / Incidence not known
dystonic reaction / Delayed / Incidence not known
esophagitis / Delayed / Incidence not known
ataxia / Delayed / Incidence not known
photophobia / Early / Incidence not known
scotomata / Delayed / Incidence not known
bullous rash / Early / Incidence not known
erythema / Early / Incidence not known
contact dermatitis / Delayed / Incidence not known
neutropenia / Delayed / Incidence not known
hypoprothrombinemia / Delayed / Incidence not known
hemolysis / Early / Incidence not known
bleeding / Early / Incidence not known
leukopenia / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
hypoglycemia / Early / Incidence not known
dyspnea / Early / Incidence not known
jaundice / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
palpitations / Early / Incidence not known
chest pain (unspecified) / Early / Incidence not known
premature ventricular contractions (PVCs) / Early / Incidence not known
orthostatic hypotension / Delayed / Incidence not known
sinus tachycardia / Rapid / Incidence not known
hypotension / Rapid / Incidence not known
QT prolongation / Rapid / Incidence not known
infertility / Delayed / Incidence not known

Mild

vertigo / Early / 10.0
vomiting / Early / 10.0
dizziness / Early / 10.0
tinnitus / Delayed / 10.0
abdominal pain / Early / 10.0
diarrhea / Early / 10.0
nausea / Early / 10.0
diaphoresis / Early / 10.0
headache / Early / 10.0
anorexia / Delayed / Incidence not known
restlessness / Early / Incidence not known
tremor / Early / Incidence not known
diplopia / Early / Incidence not known
urticaria / Rapid / Incidence not known
photosensitivity / Delayed / Incidence not known
maculopapular rash / Early / Incidence not known
fever / Early / Incidence not known
pruritus / Rapid / Incidence not known
ecchymosis / Delayed / Incidence not known
petechiae / Delayed / Incidence not known
myalgia / Early / Incidence not known
weakness / Early / Incidence not known
syncope / Early / Incidence not known

Muscle cramps

Both the FDA and the manufacturer warn against the off-label use of quinine for leg cramps. When used as approved by the FDA in the treatment of chloroquine-resistant malaria, a life-threatening illness, the risks associated with quinine use are justified. However, in the off-label use to prevent or treat nocturnal leg muscle cramps, the risks associated with quinine use, and the absence of evidence regarding its efficacy for such use, outweigh any potential benefit for this benign, self-limiting condition. Quinine has a narrow margin between an effective dose and a toxic dose. The dosing for FDA-approved use is supported by data to maximize the safety and efficacy of the product; the dosing for unapproved drugs and unapproved indications has not been reviewed and approved by FDA. Since 1969, FDA has received 665 reports of adverse events with serious outcomes associated with quinine use, including 93 deaths. Quinine-containing drugs are associated with serious side effects, severe hypersensitivity reactions, and the potential for serious drug interactions (see Contraindications/Precautions, Adverse Reactions, and Drug Interactions).

Qualaquin

Rx

Antimalarial; occurs naturally in the bark of the cinchona tree; more toxic and potent antimalarial than quinidine; FDA ruled that it lacked evidence of effectiveness for relief of nocturnal muscle cramps; non-prescription forms are no longer available but prescription forms are still available.

For the treatment of malaria. For the treatment of uncomplicated malaria due to P. falciparum. Oral dosage Adults

648 mg PO every 8 hours for 3 days, in general, or 7 days for Southeast Asia. Guidelines recommend for chloroquine-resistant infections and for infections of unknown resistance; may also use for chloroquine-sensitive infections if necessary. Use in combination with doxycycline, tetracycline, or clindamycin.

Adolesents 16 to 17 years

648 mg PO every 8 hours for 3 days, in general, or 7 days for Southeast Asia. Guidelines recommend for chloroquine-resistant infections and for infections of unknown resistance; may also use for chloroquine-sensitive infections if necessary. Use in combination with doxycycline, tetracycline, or clindamycin.

Children and Adolescents 1 to 15 years†

10 mg/kg/dose (Max: 648 mg/dose) PO every 8 hours for 3 days, in general, or 7 days for Southeast Asia. Guidelines recommend for chloroquine-resistant infections and for infections of unknown resistance; may also use for chloroquine-sensitive infections if necessary. Use in combination with doxycycline (8 years and older), tetracycline (8 years and older), or clindamycin.

For the treatment of severe malaria† prior to the availability of IV artesunate. Oral dosage Adults

648 mg PO every 8 hours. Discontinue when IV artesunate therapy is started.

Children and Adolescents

10 mg/kg/dose (Max: 648 mg/dose) PO every 8 hours. Discontinue when IV artesunate therapy is started.

For the treatment of uncomplicated malaria due to P. vivax†, P. ovale†, P. malariae†, or P. knowlesi†. Oral dosage Adults

648 mg PO every 8 hours for 3 days. Guidelines recommend for chloroquine-resistant infections and for infections of unknown resistance; may also use for chloroquine-sensitive infections if necessary. Use in combination with doxycycline, tetracycline, or clindamycin; for P. vivax or P. ovale infections add primaquine phosphate.

Children and Adolesents

10 mg/kg/dose (Max: 648 mg/dose) PO every 8 hours for 3 days. Guidelines recommend for chloroquine-resistant infections and for infections of unknown resistance; may also use for chloroquine-sensitive infections if necessary. Use in combination with doxycycline (8 years and older), tetracycline (8 years and older), or clindamycin; for P. vivax or P. ovale infections add primaquine phosphate.

For the treatment of severe malaria† due to P. falciparum after IV artesunate therapy is completed. Oral dosage Adults

648 mg PO every 8 hours for 3 days, in general, or 7 days for Southeast Asia plus doxycycline or clindamycin (pregnant persons).

Children and Adolescents

10 mg/kg/dose (Max: 648 mg/dose) PO every 8 hours for 3 days, in general, or 7 days for Southeast Asia plus doxycycline (8 years or older) or clindamycin (younger than 8 years or pregnant persons).

For the treatment of severe malaria† due to P. vivax, P. ovale, P. malariae, or P. knowlesi after IV artesunate therapy is completed. Oral dosage Adults

648 mg PO every 8 hours for 3 days plus doxycycline or clindamycin (pregnant persons).

Children and Adolescents

10 mg/kg/dose (Max: 648 mg/dose) PO every 8 hours for 3 days plus doxycycline (8 years or older) or clindamycin (younger than 8 years or pregnant persons).

For the treatment of babesiosis†. For the treatment of babesiosis† in immunocompetent ambulatory patients with mild to moderate disease and hospitalized patients with acute, severe disease in combination with clindamycin. Oral dosage Adults

648 mg PO every 8 hours for 7 to 10 days as an alternative. Clindamycin plus quinine is preferred when parasitemia and symptoms have failed to abate after the initiation of atovaquone plus azithromycin.

Children and Adolescents

8 mg/kg/dose (Max: 648 mg/dose) PO every 8 hours for 7 to 10 days as an alternative. Clindamycin plus quinine is preferred when parasitemia and symptoms have failed to abate after the initiation of atovaquone plus azithromycin.

For the treatment of babesiosis† in immunocompromised ambulatory patients with mild to moderate disease and hospitalized patients with acute, severe disease in combination with clindamycin. Oral dosage Adults

648 mg PO every 8 hours for at least 7 to 10 days as an alternative; duration may need to be extended in these patients. Clindamycin plus quinine is preferred when parasitemia and symptoms have failed to abate after the initiation of atovaquone plus azithromycin.

Children and Adolescents

8 mg/kg/dose (Max: 648 mg/dose) PO every 8 hours for at least 7 to 10 days as an alternative; duration may need to be extended in these patients. Clindamycin plus quinine is preferred when parasitemia and symptoms have failed to abate after the initiation of atovaquone plus azithromycin.

For the treatment of babesiosis† in highly immunocompromised patients in combination with clindamycin. Oral dosage Adults

648 mg PO every 8 hours for at least 6 weeks, including 2 final weeks during which parasites are no longer detected on peripheral blood smear as an alternative. Clindamycin plus quinine is preferred when parasitemia and symptoms have failed to abate after the initiation of atovaquone plus azithromycin.

Children and Adolescents

8 mg/kg/dose (Max: 648 mg/dose) PO every 8 hours for at least 6 weeks, including 2 final weeks during which parasites are no longer detected on peripheral blood smear as an alternative. Clindamycin plus quinine is preferred when parasitemia and symptoms have failed to abate after the initiation of atovaquone plus azithromycin.

For the treatment of refractory or relapsed babesiosis† as part of combination therapy. Oral dosage Adults

648 mg PO every 8 hours as part of combination therapy with atovaquone plus azithromycin plus clindamycin.

Children and Adolescents

8 mg/kg/dose (Max: 648 mg/dose) PO every 8 hours as part of combination therapy with atovaquone plus azithromycin plus clindamycin.

†Indicates off-label use

Hepatic Impairment

Avoid use in patients with severe hepatic impairment (Child-Pugh C). Dosage adjustments are not required for mild to moderate hepatic impairment (Child-Pugh A and B); however, these patients should be closely monitored for quinine-associated adverse effects.

Renal Impairment

For patients with severe chronic renal impairment, FDA-labeling recommends 648 mg PO once, then 324 mg PO every 12 hours; creatinine clearance is not specified.
 
Alternately, in cases of severe malaria, do not reduce the dose or interval for renal impairment. In other cases:
CrCl more than 50 mL/minute: No dosage adjustment needed.
CrCl 10 to 50 mL/minute: Extend dosing interval to every 8 to 12 hours.
CrCl less than 10 mL/minute: Extend dosing interval to every 24 hours.
 
Chronic Intermittent Hemodialysis
In patients receiving dialysis, dose after dialysis. In cases of severe malaria, do not reduce the dose or interval.
 
Peritoneal Dialysis
648 mg PO every 24 hours. In cases of severe malaria, do not reduce the dose or interval.
 
Continuous Renal Replacement Therapy
648 mg PO every 8 to 12 hours. In cases of severe malaria, do not reduce the dose or interval.

Abiraterone: (Moderate) Use abiraterone, a CYP2C8 inhibitor, and quinine, a CYP2C8 substrate, together cautiously, as levels of quinine may be increased. Monitor closely for signs of quinine toxicity such as visual impairment, hypoglycemia, and cardiac arrhythmias. Additionally, quinine may inhibit drugs metabolized by CYP3A4, such as abiraterone, causing increased abiraterone levels.
Acalabrutinib: (Major) Decrease the acalabrutinib dose to 100 mg PO once daily if coadministered with quinine. Coadministration may result in increased acalabrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Acalabrutinib is a CYP3A4 substrate; quinine is a moderate CYP3A4 inhibitor. In physiologically based pharmacokinetic (PBPK) simulations, the Cmax and AUC values of acalabrutinib were increased by 2- to almost 3-fold when acalabrutinib was coadministered with moderate CYP3A inhibitors.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with quinine may alter dihydrocodeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage adjustment of dihydrocodeine until stable drug effects are achieved. Discontinuation of quinine could alter dihydrocodeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If quinine is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Quinine is a moderate inhibitor of CYP3A4 and CYP2D6. CYP3A4 inhibitors may increase dihydrocodeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (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.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (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.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (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.
Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with quinine may alter codeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. 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 adjustment of codeine until stable drug effects are achieved. Discontinuation of quinine could alter codeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If quinine is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Quinine is a moderate inhibitor of CYP3A4 and CYP2D6. CYP3A4 inhibitors may increase codeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
Acetaminophen; Dextromethorphan: (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.
Acetaminophen; Dextromethorphan; Doxylamine: (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.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (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.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (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.
Acetaminophen; Dextromethorphan; Phenylephrine: (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.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (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.
Acetaminophen; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of quinine is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP2D6 and CYP3A4 substrate, and coadministration with CYP2D6 and CYP3A4 inhibitors like quinine can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced with a combined CYP2D6 and CYP3A4 inhibitor. If quinine is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Acetaminophen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of quinine is necessary. If quinine is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a moderate inhibitor like quinine can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If quinine is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Adagrasib: (Major) Avoid concomitant use of adagrasib and quinine due to the potential for increased quinine exposure and additive risk for QT/QTc prolongation and torsade de pointes (TdP). If use is necessary, monitor for quinine-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. Quinine is a CYP3A substrate, adagrasib is a strong CYP3A inhibitor, and both medications have been associated with QT interval prolongation. Coadministration of another strong CYP3A inhibitor increased the exposure of quinine by 45%.
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 quinine, may decrease adefovir elimination by competing for common renal tubular transport systems, therefore increasing serum concentrations of either adefovir and/or quinine.
Alfuzosin: (Major) Concurrent use of quinine and alfuzosin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Based on electrophysiology studies performed by the manufacturer, alfuzosin also has a slight effect to prolong the QT interval. The QT prolongation appeared less with alfuzosin 10 mg than with 40 mg. In addition, concentrations of alfuzosin may be increased with concomitant use of quinine. Alfuzosin is a CYP3A4 substrate and quinine is a CYP3A4 inhibitor.
Alosetron: (Moderate) Alosetron is metabolized by hepatic cytochrome P450 enzymes. Inhibitors of these enzymes, such as quinine, may decrease the clearance of alosetron and increase the systemic exposure of alosetron. Clinically, increased systemic exposure to alosetron may cause or worsen constipation, which might lead to serious adverse effects.
Alprazolam: (Major) Avoid coadministration of alprazolam and quinine due to the potential for elevated alprazolam concentrations, which may cause prolonged sedation and respiratory depression. If coadministration is necessary, consider reducing the dose of alprazolam as clinically appropriate and monitor for an increase in alprazolam-related adverse reactions. Lorazepam, oxazepam, or temazepam may be safer alternatives if a benzodiazepine must be administered in combination with quinine, as these benzodiazepines are not oxidatively metabolized. Alprazolam is a CYP3A4 substrate and quinine is a weak CYP3A4 inhibitor. Coadministration with another weak CYP3A4 inhibitor increased alprazolam maximum concentration by 82%, decreased clearance by 42%, and increased half-life by 16%.
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 quinine has not been studied. Coadministration of quinine 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.
Amiodarone: (Major) Concurrent use of quinine and amiodarone should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Amiodarone, a Class III antiarrhythmic agent, is also associated with a well-established risk of QT prolongation and TdP. Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. In addition, concentrations of both drugs may be increased during concomitant use. Amiodarone is a CYP3A4 substrate and P-glycoprotein (P-gp) inhibitor and quinine is a CYP3A4 inhibitor and P-gp substrate.
Amisulpride: (Major) Avoid coadministration of amisulpride and quinine due to the potential for additive QT prolongation and torsade de pointes (TdP). Amisulpride causes dose- and concentration- dependent QT prolongation. Quinine has been associated with QT prolongation and rare cases of TdP.
Amitriptyline: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). In addition, quinine is an inhibitor of CYP2D6. Avoid concurrent use of quinine with other drugs that prolong the QT and are CYP2D6 substrates. Coadministration may result in elevated plasma concentrations of the interacting drug, causing increased risk for adverse events, such as QT prolongation. Drugs that prolong the QT and are substrates for CYP2D6 include tricyclic antidepressants.
Amlodipine: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as quinine, are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
Amlodipine; Atorvastatin: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as quinine, are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required. (Moderate) Patients receiving concomitant atorvastatin and quinine should be monitored closely for muscle pain or weakness. Lower starting doses of atorvastatin should be considered while patients are receiving quinine. Atorvastatin is a CYP3A4 substrate; therefore, quinine has the potential to inhibit the metabolism of atorvastatin leading to an increased potential of rhabdomyolysis.
Amlodipine; Benazepril: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as quinine, are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
Amlodipine; Celecoxib: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as quinine, are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
Amlodipine; Olmesartan: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as quinine, are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
Amlodipine; Valsartan: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as quinine, are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as quinine, are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
Amoxapine: (Moderate) Concentrations of amoxapine may be increased with concomitant use of quinine. Amoxapine is a CYP2D6 substrate and quinine is a CYP2D6 inhibitor.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Concurrent use of quinine with clarithromycin should be avoided due to the risk for QT prolongation and torsade de pointes (TdP). Both quinine and clarithromycin have been associated with prolongation of the QT interval. In addition, because both clarithromycin and quinine are substrates and inhibitors of CYP3A4; coadministration may result in elevated plasma concentration of both drugs, causing an increased risk for adverse events.
Antacids: (Major) Antacids may delay or decrease the absorption of quinine.
Apalutamide: (Major) Monitor for lack of quinine efficacy if coadministration with apalutamide is necessary. Quinine is a CYP3A4, CYP2C19, CYP2C9, and P-glycoprotein (P-gp) substrate. Apalutamide is a strong CYP3A4 and CYP2C19 inducer, as well as a weak inducer of CYP2C9 and P-gp. Coadministration with another strong CYP3A4 inducer that also induces multiple other enzymes decreased the quinine AUC by 75% to 85%.
Apomorphine: (Major) Concurrent use of quinine and apomorphine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Aprepitant, Fosaprepitant: (Major) Avoid the concomitant use of quinine with aprepitant, fosaprepitant due to substantially increased exposure of aprepitant; increased quinine or decreased aprepitant exposure may also occur. If coadministration cannot be avoided, use caution and monitor for quinine- and aprepitant-related adverse effects for several days after administration of a multi-day aprepitant regimen, as well as a possible change in aprepitant efficacy. Quinine is a moderate CYP3A4 inhibitor and aprepitant is a CYP3A4 substrate. Coadministration of daily oral aprepitant (230 mg, or 1.8 times the recommended single dose) with a moderate CYP3A4 inhibitor, diltiazem, increased the aprepitant AUC 2-fold with a concomitant 1.7-fold increase in the diltiazem AUC; clinically meaningful changes in ECG, heart rate, or blood pressure beyond those induced by diltiazem alone did not occur. Additionally, quinine is a moderate CYP3A4 inducer in vitro and aprepitant is a CYP3A4 substrate. When a single dose of aprepitant (375 mg, or 3 times the maximum recommended dose) was administered on day 9 of a 14-day rifampin regimen (a strong CYP3A4 inducer), the AUC of aprepitant decreased approximately 11-fold and the mean terminal half-life decreased by 3-fold. The manufacturer of aprepitant recommends avoidance of administration with strong CYP3A4 inducers, but does not provide guidance for low-to-moderate inducers. Finally, quinine is also 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 additionally increase plasma concentrations of quinine. 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: (Major) Concomitant use of aripiprazole and quinine increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and increases aripiprazole exposure and risk for side effects. 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. Additionally, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form. For aripiprazole oral dosage forms, administer a quarter of the usual dose. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 200 mg/month or from 300 mg to 160 mg/month. Aripiprazole is CYP2D6 and CYP3A substrate, quinine is a moderate CYP2D6 and weak CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation. (Major) Concomitant use of aripiprazole and quinine 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.
Arsenic Trioxide: (Major) Concurrent use of quinine and arsenic trioxide should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. QT prolongation should also be expected with the administration of arsenic trioxide. TdP and complete atrioventricular block have been reported.
Artemether; Lumefantrine: (Major) Concurrent use of quinine and artemether; lumefantrine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Consider ECG monitoring if quinine must be used with or after artemether; lumefantrine treatment. Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Administration of artemether; lumefantrine is also associated with prolongation of the QT interval. Further, concentrations of both drugs may be elevated with concomitant use. Artemether; lumefantrine is an inhibitor and quinine is a substrate/inhibitor of the CYP2D6 isoenzyme; therefore, coadministration may lead to increased quinine concentrations. Additionally, artemether; lumefantrine is a substrate and quinine is a substrate/inhibitor of the CYP3A4 isoenzyme; therefore, concomitant use may lead to increased concentrations.
Articaine; Epinephrine: (Moderate) Coadministration of articaine with oxidizing agents, such as quinine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue articaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Asenapine: (Major) Concurrent use of quinine and asenapine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Asenapine has also been associated with QT prolongation. In addition, concentrations of asenapine may be increased with concomitant use of quinine. Asenapine is a CYP3A4 and CYP2D6 substrate and quinine is an inhibitor of both enzymes.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with quinine may alter codeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. 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 adjustment of codeine until stable drug effects are achieved. Discontinuation of quinine could alter codeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If quinine is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Quinine is a moderate inhibitor of CYP3A4 and CYP2D6. CYP3A4 inhibitors may increase codeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Use caution if using citric acid and quinine concomitantly. Urinary alkalinizing agents may increase plasma quinine concentrations because quinine is reabsorbed when the urine is alkaline. (Moderate) Use caution if using sodium bicarbonate and quinine concomitantly. Urinary alkalinizing agents may increase plasma quinine concentrations because quinine is reabsorbed when the urine is alkaline.
Aspirin, ASA; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of quinine is necessary. If quinine is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a moderate inhibitor like quinine can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If quinine is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Atazanavir: (Major) Anti-retroviral protease inhibitors can inhibit the metabolism of CYP3A4 substrates such as quinine. In theory, this interaction could potentially result in drug accumulation and quinine toxicity. Monitor for potential quinine toxicity and decrease quinine dosage if needed.
Atazanavir; Cobicistat: (Major) Anti-retroviral protease inhibitors can inhibit the metabolism of CYP3A4 substrates such as quinine. In theory, this interaction could potentially result in drug accumulation and quinine toxicity. Monitor for potential quinine toxicity and decrease quinine dosage if needed. (Moderate) Concurrent administration of cobicistat with quinine may elevate the concentrations of both drugs; thereby increasing the potential for adverse events. CYP3A4 is the major enzyme responsible for quinine metabolism. Other isoenzymes, including CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP2E1, have some role in the metabolism of quinine; however, the extent of involvement of each of these differs depending on methodology used in the studies. Quinine is also a substrate of P-glycoprotein (P-gp) drug transporter. Cobicistat is a strong inhibitor of CYP3A4, and an inhibitor of CYP2D6 and P-gp. Quinine may inhibit CYP3A4, while cobicistat is metabolized by CYP3A4.
Atomoxetine: (Major) QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Both atomoxetine and quinine are considered drugs with a possible risk of torsade de pointes (TdP); therefore, the combination should be used cautiously and with close monitoring. In addition, because atomoxetine is primarily metabolized by CYP2D6, concurrent use of CYP2D6 inhibitors such as quinine may theoretically increase the risk of atomoxetine-induced adverse effects. Monitor for adverse effects, such as dizziness, drowsiness, nervousness, insomnia, and cardiac effects (e.g., hypertension, increased pulse rate, QT prolongation).
Atorvastatin: (Moderate) Patients receiving concomitant atorvastatin and quinine should be monitored closely for muscle pain or weakness. Lower starting doses of atorvastatin should be considered while patients are receiving quinine. Atorvastatin is a CYP3A4 substrate; therefore, quinine has the potential to inhibit the metabolism of atorvastatin leading to an increased potential of rhabdomyolysis.
Atorvastatin; Ezetimibe: (Moderate) Patients receiving concomitant atorvastatin and quinine should be monitored closely for muscle pain or weakness. Lower starting doses of atorvastatin should be considered while patients are receiving quinine. Atorvastatin is a CYP3A4 substrate; therefore, quinine has the potential to inhibit the metabolism of atorvastatin leading to an increased potential of rhabdomyolysis.
Atracurium: (Major) Avoid concomitant use of neuromuscular blockers and quinine. Quinine may enhance the action of neuromuscular blockers. In 1 patient who received a neuromuscular blocker during an operative procedure, subsequent administration of quinine 1,800 mg 3 hours later resulted in respiratory depression.
Avanafil: (Major) Avanafil is a substrate of and primarily metabolized by CYP3A4. Studies have shown that drugs that inhibit CYP3A4 can increase avanafil exposure. Patients taking moderate CYP3A4 inhibitors including quinine, should take avanafil with caution and adhere to a maximum recommended adult avanafil dose of 50 mg/day.
Azithromycin: (Major) Concomitant use of quinine 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) If concomitant administration of barbiturates and quinine cannot be avoided, frequently monitor the barbiturate concentration. Also, monitor closely for increased barbiturate-associated adverse events such as excessive drowsiness, difficulty breathing, or confusion. A single quinine 600 mg dose increased the mean plasma Cmax and AUC of a barbiturate by 53% and 81%, respectively, in 8 healthy subjects. In addition, barbiturates are CYP3A4 inducers and may decrease plasma quinine concentrations.
Bedaquiline: (Major) Bedaquiline has 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. Coadministration with other QT prolonging drugs may result in additive or synergistic prolongation of the QT interval. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with bedaquiline include quinine. Quinine may also inhibit the CYP3A4 metabolism of bedaquiline, resulting in increased bedaquiline systemic exposure (AUC) and potentially more adverse reactions, such as QT prolongation and hepatotoxicity.
Benzhydrocodone; Acetaminophen: (Moderate) Concurrent use of benzhydrocodone with quinine may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Consider a dose reduction of benzhydrocodone until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals. Discontinuation of quinine in a patient taking benzhydrocodone may decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. If quinine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Benzhydrocodone is a prodrug for hydrocodone. Hydrocodone is a substrate for CYP3A4 and CYP2D6. Quinine is an inhibitor of CYP3A4 and CYP2D6.
Berotralstat: (Major) Reduce the berotralstat dose to 110 mg PO once daily in patients chronically taking quinine. Concurrent use may increase berotralstat exposure and the risk of adverse effects. Additionally, monitor for quinine-related adverse reactions as concurrent use may increase quinine exposure. Berotralstat is a P-gp substrate and moderate CYP3A4 inhibitor; quinine is a CYP3A4 substrate and P-gp inhibitor. Coadministration with another P-gp inhibitor increased berotralstat exposure by 69%.
Betrixaban: (Major) Avoid betrixaban use in patients with severe renal impairment receiving quinine. Reduce betrixaban dosage to 80 mg PO once followed by 40 mg PO once daily in all other patients receiving quinine. Bleeding risk may be increased; monitor patients closely for signs and symptoms of bleeding. Betrixaban is a substrate of P-gp; quinine inhibits P-gp.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and quinine 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) Concomitant administration of quinine and tetracycline may result in higher quinine plasma concentrations. It is recommended that patients be monitored closely for quinine-associated adverse reactions if tetracycline is given with quinine.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and quinine 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) Concomitant administration of quinine and tetracycline may result in higher quinine plasma concentrations. It is recommended that patients be monitored closely for quinine-associated adverse reactions if tetracycline is given with quinine.
Brexpiprazole: (Major) Because brexpiprazole is primarily metabolized by CYP3A4 and CYP2D6, the manufacturer recommends that the brexpiprazole dose be reduced to 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. Quinine is a moderate inhibitor of both CYP3A4 and CYP2D6. If these agents are used in combination, the patient should be carefully monitored for brexpiprazole-related adverse reactions.
Brimonidine; Timolol: (Minor) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme, including timolol.
Bromocriptine: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of quinine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may alter bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; quinine is both a moderate inhibitor and inducer of CYP3A4. The net effect on CYP3A4 substrates is unclear. Administration of bromocriptine with a moderate inhibitor of CYP3A4 increased the bromocriptine mean AUC and Cmax by 3.7-fold and 4.6-fold, respectively.
Brompheniramine; Dextromethorphan; Phenylephrine: (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.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (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.
Bupivacaine Liposomal: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as quinine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as quinine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine; Epinephrine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as quinine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine; Lidocaine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as quinine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Concomitant use of systemic lidocaine and quinine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; quinine inhibits CYP3A4. Additionally, coadministration of lidocaine with oxidizing agents, such as quinine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine; Meloxicam: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as quinine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Buprenorphine: (Major) Buprenorphine should be avoided in combination with quinine. Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP) and should be avoided in combination with other drugs that prolong the QT interval. 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. In addition, the plasma concentrations of buprenorphine, a CYP3A4 substrate, may be increased when administered concurrently with quinine, a CYP3A4 inhibitor, further increasing the risk of toxicity. If co-administration is necessary, monitor patients for QT prolongation, respiratory depression and sedation at frequent intervals and consider dose adjustments until stable drug effects are achieved. The effect of CYP3A4 inhibitors on buprenorphine implants has not been studied.
Buprenorphine; Naloxone: (Major) Buprenorphine should be avoided in combination with quinine. Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP) and should be avoided in combination with other drugs that prolong the QT interval. 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. In addition, the plasma concentrations of buprenorphine, a CYP3A4 substrate, may be increased when administered concurrently with quinine, a CYP3A4 inhibitor, further increasing the risk of toxicity. If co-administration is necessary, monitor patients for QT prolongation, respiratory depression and sedation at frequent intervals and consider dose adjustments until stable drug effects are achieved. The effect of CYP3A4 inhibitors on buprenorphine implants has not been studied.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of codeine with quinine may alter codeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. 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 adjustment of codeine until stable drug effects are achieved. Discontinuation of quinine could alter codeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If quinine is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Quinine is a moderate inhibitor of CYP3A4 and CYP2D6. CYP3A4 inhibitors may increase codeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concomitant use of codeine with quinine may alter codeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. 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 adjustment of codeine until stable drug effects are achieved. Discontinuation of quinine could alter codeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If quinine is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Quinine is a moderate inhibitor of CYP3A4 and CYP2D6. CYP3A4 inhibitors may increase codeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
Cabotegravir; Rilpivirine: (Major) Concurrent use of quinine and rilpivirine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation. In addition, concentrations of rilpivirine may be increased with concomitant use of quinine. Rilpivirine is a CYP3A4 substrate and quinine is a CYP3A4 inhibitor.
Cabozantinib: (Minor) Monitor for an increase in quinine-related adverse reactions if coadministration with cabozantinib is necessary; a dose adjustment of quinine may be necessary. Quinine 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) Antacids may delay or decrease the absorption of quinine.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Major) Antacids may delay or decrease the absorption of quinine.
Calcium Carbonate; Magnesium Hydroxide: (Major) Antacids may delay or decrease the absorption of quinine.
Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Major) Antacids may delay or decrease the absorption of quinine.
Calcium Carbonate; Simethicone: (Major) Antacids may delay or decrease the absorption of quinine.
Calcium; Vitamin D: (Major) Antacids may delay or decrease the absorption of quinine.
Carbamazepine: (Major) If concomitant administration of carbamazepine and quinine cannot be avoided, frequently monitor carbamazepine concentration. Also, monitor closely for increased carbamazepine-associated adverse events such as excessive drowsiness, loss of balance or difficulty walking straight, severe headaches, blurred or double vision, vomiting, or nystagmus. A single quinine 600 mg dose increased the mean plasma Cmax and AUC of carbamazepine by 56% and 104%, respectively, in 8 healthy subjects. In addition, carbamazepine is a CYP3A4 inducer and may decrease plasma quinine concentrations.
Carbonic anhydrase inhibitors: (Moderate) Use caution if using carbonic anhydrase inhibitors and quinine concomitantly. Urinary alkalinizing agents may increase plasma quinine concentrations because quinine is reabsorbed when the urine is alkaline.
Cardiac glycosides: (Major) Coadministration of digoxin and quinine increases the AUC of digoxin by 33%. Both digoxin and quinine are substrates for P-glycoprotein (P-gp). Measure serum digoxin concentrations before initiating quinine. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 15-30% or by modifying the dosing frequency and continue monitoring. Lower doses of quinine may have no effect on digitalis clearance.
Cariprazine: (Major) Cariprazine and its active metabolites are extensively metabolized by CYP3A4. Quinine is a moderate inhibitor of CYP3A4 and may reduce the hepatic metabolism of CYP3A4 substrates, although the impact of moderate CYP3A4 inhibitors on cariprazine metabolism has not been studied. Monitoring for adverse effects, such as CNS effects and extrapyramidal symptoms, is advisable during coadministration.
Carvedilol: (Minor) Inhibitors of the hepatic CYP450 isozyme CYP 2D6, such as quinine, may inhibit the hepatic oxidative metabolism of carvedilol. The clinical significance of this pharmacokinetic interaction is unclear.
Celecoxib; Tramadol: (Moderate) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme including tramadol.
Ceritinib: (Major) Avoid coadministration of quinine with ceritinib due to the risk of QT prolongation; plasma concentrations of quinine may also increase. Quinine is a CYP3A4 substrate that is associated with QT prolongation and rare cases of torsade de pointes (TdP). Ceritinib is a strong CYP3A4 inhibitor that causes concentration-dependent QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased the mean AUC of quinine by 45%.
Chlordiazepoxide; Amitriptyline: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). In addition, quinine is an inhibitor of CYP2D6. Avoid concurrent use of quinine with other drugs that prolong the QT and are CYP2D6 substrates. Coadministration may result in elevated plasma concentrations of the interacting drug, causing increased risk for adverse events, such as QT prolongation. Drugs that prolong the QT and are substrates for CYP2D6 include tricyclic antidepressants.
Chloroprocaine: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as quinine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Chloroquine: (Major) Avoid coadministration of chloroquine with quinine 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. Quinine has been associated with QT prolongation and rare cases of TdP.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with quinine may alter codeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. 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 adjustment of codeine until stable drug effects are achieved. Discontinuation of quinine could alter codeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If quinine is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Quinine is a moderate inhibitor of CYP3A4 and CYP2D6. CYP3A4 inhibitors may increase codeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
Chlorpheniramine; Dextromethorphan: (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.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (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.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (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.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with quinine may alter dihydrocodeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage adjustment of dihydrocodeine until stable drug effects are achieved. Discontinuation of quinine could alter dihydrocodeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If quinine is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Quinine is a moderate inhibitor of CYP3A4 and CYP2D6. CYP3A4 inhibitors may increase dihydrocodeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
Chlorpheniramine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of quinine is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP2D6 and CYP3A4 substrate, and coadministration with CYP2D6 and CYP3A4 inhibitors like quinine can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced with a combined CYP2D6 and CYP3A4 inhibitor. If quinine is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Chlorpromazine: (Major) Concurrent use of quinine and chlorpromazine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Chlorpromazine has also been associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. In addition, concentrations of chlorpromazine may be increased with concomitant use of quinine. Chlorpromazine is a CYP2D6 substrate and quinine is a CYP2D6 inhibitor.
Cimetidine: (Minor) Cimetidine reduced the hepatic clearance of quinine and prolonged its half-life. Peak quinine serum concentrations were not affected. The clinical significance of this pharmacokinetic interaction is unclear.
Ciprofloxacin: (Major) Concomitant use of quinine 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) Concurrent use is contraindicated. Cisapride is metabolized by the hepatic cytochrome P450 enzyme system, specifically the CYP3A4 isoenzyme. Postmarketing surveillance reports have documented QT prolongation and ventricular arrhythmias, including torsade de pointes (TdP) and death, when known and potent inhibitors of CYP3A4 are coadministered with cisapride. Quinine has the potential to inhibit the metabolism of cisapride through CYP3A4. In addition, quinine has been associated with QT prolongation and rare cases of TdP.
Cisatracurium: (Major) Avoid concomitant use of neuromuscular blockers and quinine. Quinine may enhance the action of neuromuscular blockers. In 1 patient who received a neuromuscular blocker during an operative procedure, subsequent administration of quinine 1,800 mg 3 hours later resulted in respiratory depression.
Citalopram: (Major) Concurrent use of quinine and citalopram should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If concurrent therapy is considered essential, ECG monitoring is recommended. Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Citalopram also causes dose-dependent QT interval prolongation. In addition, concentrations of citalopram may be increased with concomitant use of quinine. Citalopram is a CYP3A4 and CYP2D6 substrate and quinine is an inhibitor of both enzymes.
Citric Acid; Potassium Citrate; Sodium Citrate: (Moderate) Use caution if using citric acid and quinine concomitantly. Urinary alkalinizing agents may increase plasma quinine concentrations because quinine is reabsorbed when the urine is alkaline. (Moderate) Use caution if using potassium citrate and quinine concomitantly. Urinary alkalinizing agents may increase plasma quinine concentrations because quinine is reabsorbed when the urine is alkaline.
Clarithromycin: (Major) Concurrent use of quinine with clarithromycin should be avoided due to the risk for QT prolongation and torsade de pointes (TdP). Both quinine and clarithromycin have been associated with prolongation of the QT interval. In addition, because both clarithromycin and quinine are substrates and inhibitors of CYP3A4; coadministration may result in elevated plasma concentration of both drugs, causing an increased risk for adverse events.
Clobazam: (Moderate) A dosage reduction of clobazam may be necessary during co-administration of quinine. Metabolism of N-desmethylclobazam, the active metabolite of clobazam, occurs primarily through CYP2C19 and quinine is an inhibitor of CYP2C19 in vitro. Extrapolation from pharmacogenomic data indicates that concurrent use of clobazam with moderate or potent inhibitors of CYP2C19 may result in up to a 5-fold increase in exposure to N-desmethylclobazam. Adverse effects, such as sedation, lethargy, ataxia, or insomnia may be potentiated.
Clofarabine: (Moderate) Concomitant use of clofarabine, a substrate of OCT1 and OCT2, and quinine, an inhibitor of OCT1 and OCT2, 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 and OCT2 inhibitors.
Clofazimine: (Major) Concomitant use of clofazimine and quinine 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: (Major) Quinine has been associated with QT prolongation and rar

e cases of torsade de pointes (TdP). In addition, quinine is an inhibitor of CYP2D6. Avoid concurrent use of quinine with other drugs that prolong the QT and are CYP2D6 substrates. Coadministration may result in elevated plasma concentrations of the interacting drug, causing increased risk for adverse events, such as QT prolongation. Drugs that prolong the QT and are substrates for CYP2D6 include tricyclic antidepressants.
Clozapine: (Major) Both clozapine and quinine are associated with a possible risk for QT prolongation and torsade de pointes (TdP). Avoid concurrent use if possible. In addition, quinine is an inhibitor of CYP2D6 and CYP3A4, two of the isoenzymes responsible for the metabolism of clozapine. Elevated plasma concentrations of clozapine occurring through inhibition of CYP2D6 or CYP3A4 may potentially increase the risk of life-threatening arrhythmias, sedation, anticholinergic effects, seizures, orthostasis, or other adverse effects. According to the manufacturer of clozapine, monitor for adverse reactions and consider reducing the clozapine dose during concomitant use of inhibitors of CYP2D6 or CYP3A4. If the inhibitor is discontinued, monitor for lack of clozapine effectiveness and consider increasing the clozapine dose if necessary.
Cobicistat: (Moderate) Concurrent administration of cobicistat with quinine may elevate the concentrations of both drugs; thereby increasing the potential for adverse events. CYP3A4 is the major enzyme responsible for quinine metabolism. Other isoenzymes, including CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP2E1, have some role in the metabolism of quinine; however, the extent of involvement of each of these differs depending on methodology used in the studies. Quinine is also a substrate of P-glycoprotein (P-gp) drug transporter. Cobicistat is a strong inhibitor of CYP3A4, and an inhibitor of CYP2D6 and P-gp. Quinine may inhibit CYP3A4, while cobicistat is metabolized by CYP3A4.
Cobimetinib: (Major) Avoid the concurrent use of cobimetinib with quinine due to altered cobimetinib exposure. Cobimetinib is a CYP3A substrate in vitro, and quinine is both a moderate inhibitor and a moderate in vitro inducer of CYP3A. In healthy subjects (n = 15), coadministration of a single 10 mg dose of cobimetinib with itraconazole (200 mg once daily for 14 days), a strong CYP3A4 inhibitor, increased the mean cobimetinib AUC by 6.7-fold (90% CI, 5.6 to 8) and the mean Cmax by 3.2-fold (90% CI, 2.7 to 3.7). Additionally, based on simulations, cobimetinib exposure would decrease by 73% when coadministered with a moderate CYP3A inducer. Exposure to cobimetinib may be affected unpredictably if coadministered with quinine.
Codeine: (Moderate) Concomitant use of codeine with quinine may alter codeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. 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 adjustment of codeine until stable drug effects are achieved. Discontinuation of quinine could alter codeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If quinine is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Quinine is a moderate inhibitor of CYP3A4 and CYP2D6. CYP3A4 inhibitors may increase codeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with quinine may alter codeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. 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 adjustment of codeine until stable drug effects are achieved. Discontinuation of quinine could alter codeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If quinine is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Quinine is a moderate inhibitor of CYP3A4 and CYP2D6. CYP3A4 inhibitors may increase codeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with quinine may alter codeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. 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 adjustment of codeine until stable drug effects are achieved. Discontinuation of quinine could alter codeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If quinine is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Quinine is a moderate inhibitor of CYP3A4 and CYP2D6. CYP3A4 inhibitors may increase codeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with quinine may alter codeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. 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 adjustment of codeine until stable drug effects are achieved. Discontinuation of quinine could alter codeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If quinine is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Quinine is a moderate inhibitor of CYP3A4 and CYP2D6. CYP3A4 inhibitors may increase codeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
Codeine; Promethazine: (Moderate) Concomitant use of codeine with quinine may alter codeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. 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 adjustment of codeine until stable drug effects are achieved. Discontinuation of quinine could alter codeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If quinine is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Quinine is a moderate inhibitor of CYP3A4 and CYP2D6. CYP3A4 inhibitors may increase codeine-related adverse effects while CYP2D6 inhibitors may reduce efficacy.
Colchicine: (Major) Avoid concomitant use of colchicine and quinine 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 quinine is a P-gp inhibitor.
Conivaptan: (Moderate) Monitor for quinine-related adverse reactions if coadministration with conivaptan is necessary. Concurrent use may increase quinine exposure. Quinine is a substrate of CYP3A and conivaptan is a moderate CYP3A inhibitor.
Crizotinib: (Major) Avoid coadministration of crizotinib with quinine due to the risk of QT prolongation; exposure to quinine drugs may also increase. Crizotinib is a CYP3A substrate and moderate inhibitor that has been associated with concentration-dependent QT prolongation. Quinine is a CYP3A4 substrate that has also been associated with QT prolongation and rare cases of torsade de pointes (TdP).
Cyclosporine: (Moderate) Quinine is a substrate of P-glycoprotein (PGP), and cyclosporine is a PGP substrate and inhibitor. Therefore, quinine concentrations could be increased with coadministration. Monitor patients for increased side effects of quinine if these drugs are given together.
Dacarbazine, DTIC: (Moderate) Concurrent administration of daclatasvir, a CYP3A4 substrate, with quinine, a moderate CYP3A4 inhibitor, may increase daclatasvir serum concentrations. In addition, the therapeutic effects of quinine, a P-glycoprotein (P-gp) substrate, may be increased by daclatasvir, a P-gp inhibitor. If these drugs are administered together, monitor patients for adverse effects, such as headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions.
Dapagliflozin; Saxagliptin: (Moderate) Monitor patients for hypoglycemia if saxagliptin and quinine are used together. The metabolism of saxagliptin is primarily mediated by CYP3A4/5; saxagliptin plasma concentrations may increase in the presence of moderate CYP 3A4/5 inhibitors such as quinine.
Dapsone: (Moderate) Coadministration of dapsone with quinine may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Darunavir: (Major) Anti-retroviral protease inhibitors can inhibit the metabolism of CYP3A4 substrates such as quinine. In theory, this interaction could potentially result in drug accumulation and quinine toxicity. Monitor for potential quinine toxicity and decrease quinine dosage if needed.
Darunavir; Cobicistat: (Major) Anti-retroviral protease inhibitors can inhibit the metabolism of CYP3A4 substrates such as quinine. In theory, this interaction could potentially result in drug accumulation and quinine toxicity. Monitor for potential quinine toxicity and decrease quinine dosage if needed. (Moderate) Concurrent administration of cobicistat with quinine may elevate the concentrations of both drugs; thereby increasing the potential for adverse events. CYP3A4 is the major enzyme responsible for quinine metabolism. Other isoenzymes, including CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP2E1, have some role in the metabolism of quinine; however, the extent of involvement of each of these differs depending on methodology used in the studies. Quinine is also a substrate of P-glycoprotein (P-gp) drug transporter. Cobicistat is a strong inhibitor of CYP3A4, and an inhibitor of CYP2D6 and P-gp. Quinine may inhibit CYP3A4, while cobicistat is metabolized by CYP3A4.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Anti-retroviral protease inhibitors can inhibit the metabolism of CYP3A4 substrates such as quinine. In theory, this interaction could potentially result in drug accumulation and quinine toxicity. Monitor for potential quinine toxicity and decrease quinine dosage if needed. (Moderate) Concurrent administration of cobicistat with quinine may elevate the concentrations of both drugs; thereby increasing the potential for adverse events. CYP3A4 is the major enzyme responsible for quinine metabolism. Other isoenzymes, including CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP2E1, have some role in the metabolism of quinine; however, the extent of involvement of each of these differs depending on methodology used in the studies. Quinine is also a substrate of P-glycoprotein (P-gp) drug transporter. Cobicistat is a strong inhibitor of CYP3A4, and an inhibitor of CYP2D6 and P-gp. Quinine may inhibit CYP3A4, while cobicistat is metabolized by CYP3A4.
Dasatinib: (Major) Concurrent use of quinine and dasatinib should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. In vitro studies have shown that dasatinib also has the potential to prolong cardiac ventricular repolarization (prolong QT interval).
Deflazacort: (Major) Avoid concomitant use of deflazacort and quinine. Concurrent use may significantly alter concentrations of 21-desDFZ, the active metabolite of deflazacort, resulting in loss of efficacy and/or increased risk of toxicity. Deflazacort is a CYP3A4 substrate; quinine is a mixed inducer/inhibitor of CYP3A. The net effect on CYP3A4 substrates is unknown. Administration of deflazacort with multiple doses of rifampin (a strong CYP3A4 inducer) resulted in geometric mean exposures that were approximately 95% lower compared to administration alone. Administration of deflazacort with clarithromycin, a strong CYP3A4 inhibitor, increased total exposure to 21-desDFZ by about 3-fold.
Degarelix: (Major) Avoid concurrent use of quinine with degarelix due to the risk of QT prolongation. Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Androgen deprivation therapy (i.e., degarelix) may also prolong the QT/QTc interval.
Desflurane: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including halogenated anesthetics.
Desipramine: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). In addition, quinine is an inhibitor of CYP2D6. Avoid concurrent use of quinine with other drugs that prolong the QT and are CYP2D6 substrates. Coadministration may result in elevated plasma concentrations of the interacting drug, causing increased risk for adverse events, such as QT prolongation. Drugs that prolong the QT and are substrates for CYP2D6 include tricyclic antidepressants.
Deutetrabenazine: (Major) Avoid concurrent use of quinine with deutetrabenazine. Quinine has been associated with QT prolongation and rare cases of 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.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (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.
Dexmedetomidine: (Major) Concomitant use of dexmedetomidine and quinine 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: (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.
Dextromethorphan; Bupropion: (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.
Dextromethorphan; Diphenhydramine; Phenylephrine: (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.
Dextromethorphan; Guaifenesin: (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.
Dextromethorphan; Guaifenesin; Phenylephrine: (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.
Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: (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.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (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.
Dextromethorphan; Quinidine: (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.
Diltiazem: (Moderate) Monitor patients for increased side effects of quinine if administered with diltiazem; quinine concentrations could be increased with coadministration. Quinine is a substrate of CYP3A4, and diltiazem is a CYP3A4 inhibitor.
Disopyramide: (Major) Concurrent use of quinine and disopyramide should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Both drugs have been associated with prolongation of the QT interval and rare cases of TdP. In addition, concentrations of disopyramide may be increased with concomitant use of quinine. Disopyramide is a CYP3A4 substrate and quinine is a CYP3A4 inhibitor.
Dofetilide: (Contraindicated) Coadministration of dofetilide and quinine is contraindicated as concurrent use may increase the risk QT prolongation and torsades de pointes (TdP). Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Quinine has been associated with QT prolongation and rare cases of TdP.
Dolasetron: (Major) Concurrent use of quinine and dolasetron should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Dolasetron has also been associated with a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Use of dolasetron injection for the prevention of chemotherapy-induced nausea and vomiting is contraindicated because the risk of QT prolongation is higher with the doses required for this indication; when the injection is used at lower doses (i.e., those approved for post-operative nausea and vomiting) or when the oral formulation is used, the risk of QT prolongation is lower and caution is advised. In addition, concentrations of dolasetron may be increased with concomitant use of quinine. Dolasetron is a CYP3A4 and CYP2D6 substrate and quinine is an inhibitor of both enzymes.
Dolutegravir; Rilpivirine: (Major) Concurrent use of quinine and rilpivirine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation. In addition, concentrations of rilpivirine may be increased with concomitant use of quinine. Rilpivirine is a CYP3A4 substrate and quinine is a CYP3A4 inhibitor.
Donepezil: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with donepezil include quinine. In addition, concomitant use of quinine and donepezil may result in increased donepezil concentrations. Quinine is an inhibitor of CYP2D6 and CYP3A4, the two isoenzymes involved in the metabolism of donepezil.
Donepezil; Memantine: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with donepezil include quinine. In addition, concomitant use of quinine and donepezil may result in increased donepezil concentrations. Quinine is an inhibitor of CYP2D6 and CYP3A4, the two isoenzymes involved in the metabolism of donepezil. (Moderate) Memantine is excreted in part by renal tubular secretion. Competition of memantine for excretion with other drugs that are also eliminated by tubular secretion, such as quinine, could result in elevated serum concentrations of one or both drugs.
Dorzolamide; Timolol: (Minor) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme, including timolol.
Doxepin: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). In addition, quinine is an inhibitor of CYP2D6. Avoid concurrent use of quinine with other drugs that prolong the QT and are CYP2D6 substrates. Coadministration may result in elevated plasma concentrations of the interacting drug, causing increased risk for adverse events, such as QT prolongation. Drugs that prolong the QT and are substrates for CYP2D6 include tricyclic antidepressants.
Doxercalciferol: (Moderate) Cytochrome P450 enzyme inhibitors, such as quinine, 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 quinine with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Quinine is a CYP3A4, CYP2D6, and P-glycoprotein (P-gp) inhibitor; doxorubicin is a major substrate of CYP3A4, CYP2D6, and P-gp. Concurrent use of CYP3A4, CYP2D6, or P-gp inhibitors with doxorubicin has resulted in clinically significant interactions.
Doxorubicin: (Major) Avoid coadministration of quinine with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Quinine is a CYP3A4, CYP2D6, and P-glycoprotein (P-gp) inhibitor; doxorubicin is a major substrate of CYP3A4, CYP2D6, and P-gp. Concurrent use of CYP3A4, CYP2D6, or P-gp inhibitors with doxorubicin has resulted in clinically significant interactions.
Dronabinol: (Moderate) Use caution if coadministration of dronabinol with quinine is necessary, and monitor for changes in the efficacy or adverse effect profile of dronabinol (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate. Quinine is a moderate inhibitor and inducer (in vitro) of CYP3A4. Concomitant use may result in altered plasma concentrations of dronabinol.
Dronedarone: (Contraindicated) Concomitant use of dronedarone with other drugs that prolong the QTc, such as quinine, may induce torsade de pointes (TdP) and is contraindicated. 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.
Droperidol: (Major) Concurrent use of quinine and droperidol should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Droperidol administration is also associated with an established risk for QT prolongation and 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. In addition, concentrations of droperidol may be increased with concomitant use of quinine. Droperidol is a CYP3A4 substrate and quinine is a CYP3A4 inhibitor.
Dutasteride; Tamsulosin: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of quinine. Tamsulosin is extensively metabolized by CYP2D6 and CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Therefore, concomitant use with drugs that inhibit both CYP2D6 and CYP3A4, such as quinine, should be avoided.
Duvelisib: (Moderate) Monitor for increased toxicity of duvelisib and quinine during coadministration. Coadministration may increase the exposure of both drugs. Duvelisib is a substrate and moderate inhibitor of CYP3A; quinine is also a substrate and moderate inhibitor of CYP3A.
Efavirenz: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP, such as efavirenz. In addition, concurrent use may alter the systemic concentration of efavirenz and decrease the concentration of quinine. Efavirenz is a CYP3A4 substrate and inducer, while quinine is a CYP3A4 substrate, inducer, and inhibitor.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP, such as efavirenz. In addition, concurrent use may alter the systemic concentration of efavirenz and decrease the concentration of quinine. Efavirenz is a CYP3A4 substrate and inducer, while quinine is a CYP3A4 substrate, inducer, and inhibitor.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP, such as efavirenz. In addition, concurrent use may alter the systemic concentration of efavirenz and decrease the concentration of quinine. Efavirenz is a CYP3A4 substrate and inducer, while quinine is a CYP3A4 substrate, inducer, and inhibitor.
Elbasvir; Grazoprevir: (Major) If possible, avoid concurrent administration of elbasvir with quinine. Use of these drugs together may cause changes in the plasma concentrations of elbasvir, which could result in decreased virologic response or adverse reactions (i.e., hepatotoxicity). Quinine is an inhibitor and inducer of CYP3A; elbasvir is a substrate of CYP3A. (Major) If possible, avoid concurrent administration of grazoprevir with quinine. Use of these drugs together may cause changes in the plasma concentrations of grazoprevir, which could result in decreased virologic response or adverse reactions (i.e., hepatotoxicity). Quinine is an inhibitor and inducer of CYP3A; grazoprevir is a substrate of CYP3A. In addition, concentrations of quinine (also a CYP3A substrate) may be increased when given with grazoprevir (a weak CYP3A inhibitor).
Eletriptan: (Moderate) Monitor for increased eletriptan-related adverse effects if coadministered with quinine. Systemic concentrations of eletriptan may be increased. Eletriptan is a substrate for CYP3A4, and quinine is a moderate CYP3A4 inhibitor. Coadministration of other moderate CYP3A4 inhibitors increased the eletriptan AUC by 2 to 4-fold.
Elexacaftor; tezacaftor; ivacaftor: (Major) Adjust the tezacaftor; ivacaftor dosing schedule when coadministered with quinine; coadministration may increase tezacaftor; ivacaftor exposure and adverse reactions. When combined, dose 1 tezacaftor; ivacaftor combination tablet every other day in the morning and 1 ivacaftor tablet every other day in the morning on alternate days (i.e., tezacaftor/ivacaftor tablet on Day 1 and ivacaftor tablet on Day 2). The evening dose of ivacaftor should not be taken. Both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate); quinine is a moderate CYP3A inhibitor. Coadministration of a moderate CYP3A inhibitor increased ivacaftor exposure 3-fold. Simulation suggests a moderate inhibitor may increase tezacaftor exposure 2-fold. (Major) If quinine and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to once daily. Ivacaftor is a CYP3A substrate and quinine is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased ivacaftor exposure by 3-fold.
Eliglustat: (Contraindicated) Coadministration of quinine and eliglustat is contraindicated. Quinine is a CYP2D6 and CYP3A4 inhibitor associated with QT prolongation and rare cases of torsade de points (TdP); its use should be avoided with other drugs that prolong the QT interval. Eliglustat is a CYP2D6 and CYP3A substrate that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Coadministration of quinine and eliglustat may result in additive effects on the QT interval and significantly increased plasma concentrations of eliglustat, further increasing the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias).
Eltrombopag: (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inducers of CYP1A2, such as quinine, on the systemic exposure of eltrombopag has not been established. Monitor patients for a decrease in the efficacy of eltrombopag if these drugs are coadministered.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Coadministration of elvitegravir with quinine is not recommended as there is a potential for altered elvitegravir concentrations and reduced quinine concentrations. Changes antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Elvitegravir is a substrate of CYP3A4, and quinine may induce or inhibit CYP3A4. Elvitegravir also induces CYP2C9, and quinine is partially metabolized by CYP2C9. (Moderate) Concurrent administration of cobicistat with quinine may elevate the concentrations of both drugs; thereby increasing the potential for adverse events. CYP3A4 is the major enzyme responsible for quinine metabolism. Other isoenzymes, including CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP2E1, have some role in the metabolism of quinine; however, the extent of involvement of each of these differs depending on methodology used in the studies. Quinine is also a substrate of P-glycoprotein (P-gp) drug transporter. Cobicistat is a strong inhibitor of CYP3A4, and an inhibitor of CYP2D6 and P-gp. Quinine may inhibit CYP3A4, while cobicistat is metabolized by CYP3A4.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of elvitegravir with quinine is not recommended as there is a potential for altered elvitegravir concentrations and reduced quinine concentrations. Changes antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Elvitegravir is a substrate of CYP3A4, and quinine may induce or inhibit CYP3A4. Elvitegravir also induces CYP2C9, and quinine is partially metabolized by CYP2C9. (Moderate) Concurrent administration of cobicistat with quinine may elevate the concentrations of both drugs; thereby increasing the potential for adverse events. CYP3A4 is the major enzyme responsible for quinine metabolism. Other isoenzymes, including CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP2E1, have some role in the metabolism of quinine; however, the extent of involvement of each of these differs depending on methodology used in the studies. Quinine is also a substrate of P-glycoprotein (P-gp) drug transporter. Cobicistat is a strong inhibitor of CYP3A4, and an inhibitor of CYP2D6 and P-gp. Quinine may inhibit CYP3A4, while cobicistat is metabolized by CYP3A4.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Concurrent use of quinine and rilpivirine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation. In addition, concentrations of rilpivirine may be increased with concomitant use of quinine. Rilpivirine is a CYP3A4 substrate and quinine is a CYP3A4 inhibitor.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Major) Concurrent use of quinine and rilpivirine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation. In addition, concentrations of rilpivirine may be increased with concomitant use of quinine. Rilpivirine is a CYP3A4 substrate and quinine is a CYP3A4 inhibitor.
Encorafenib: (Major) Avoid coadministration of encorafenib and quinine due to increased encorafenib exposure and QT prolongation. If concurrent use cannot be avoided, reduce the encorafenib dose to one-half of the dose used prior to the addition of quinine. Monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. If quinine is discontinued, the original encorafenib dose may be resumed after 3 to 5 elimination half-lives of quinine. Encorafenib is a CYP3A4 substrate that has been associated with dose-dependent QT prolongation; quinine is a moderate CYP3A4 inhibitor that has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Coadministration of a moderate CYP3A4 inhibitor with a single 50 mg dose of encorafenib (0.1 times the recommended dose) increased the encorafenib AUC and Cmax by 2-fold and 45%, respectively.
Entecavir: (Major) Both entecavir and quinine are secreted by active tubular secretion. In theory, coadministration of entecavir with quinine 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 quinine due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP).
Enzalutamide: (Moderate) Monitor for lack of quinine efficacy if coadministration with enzalutamide is necessary. Quinine is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased quinine exposure by 75% to 85%.
Eplerenone: (Major) Do not exceed an eplerenone dose of 25 mg PO once daily if given concurrently with a CYP3A4 inhibitor in a post-myocardial infarction patient with heart failure. In patients with hypertension receiving a concurrent CYP3A4 inhibitor, initiate eplerenone at 25 mg PO once daily; the dose may be increased to a maximum of 25 mg PO twice daily for inadequate blood pressure response. In addition, measure serum creatinine and serum potassium within 3 to 7 days of initiating a CYP3A4 inhibitor and periodically thereafter. Eplerenone is a CYP3A4 substrate. Quinine is a CYP3A4 inhibitor. Coadministration with moderate CYP3A4 inhibitors increased eplerenone exposure by 100% to 190%. Increased eplerenone concentrations may lead to a risk of developing hyperkalemia and hypotension.
Eribulin: (Major) Concurrent use of quinine and eribulin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If these drugs must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Eribulin has also been associated with QT prolongation.
Erlotinib: (Major) Avoid coadministration of erlotinib with quinine if possible due to the risk of decreased erlotinib efficacy. If concomitant use is unavoidable, increase the dose of erlotinib by 50 mg increments at 2-week intervals as tolerated, to a maximum of 300 mg. Erlotinib is primarily metabolized by CYP3A4, and to a lesser extent by CYP1A2. Quinine is a CYP1A2 inducer. Coadministration may decrease plasma concentrations of erlotinib.
Erythromycin: (Major) Concurrent use of quinine with erythromycin should be avoided due to the risk for QT prolongation and torsade de pointes (TdP). Both quinine and erythromycin have been associated with prolongation of the QT interval. In addition, because quinine is a substrate of CYP3A4 and erythromycin is an inhibitor of CYP3A4; coadministration may result in elevated quinine serum concentrations, causing an increased risk for adverse events.
Escitalopram: (Moderate) The plasma concentration of escitalopram, a CYP2C19 and CYP3A4 substrate, may be increased when administered concurrently with quinine, a CYP2C19 and CYP3A4 inhibitor. If these drugs are used together, monitor for escitalopram-associated adverse reactions.
Etonogestrel: (Minor) Coadministration of etonogestrel and moderate CYP3A4 inhibitors such as quinine may increase the serum concentration of etonogestrel.
Etonogestrel; Ethinyl Estradiol: (Minor) Coadministration of etonogestrel and moderate CYP3A4 inhibitors such as quinine may increase the serum concentration of etonogestrel.
Etravirine: (Moderate) Quinine is a substrate of P-glycoprotein (PGP) and CYP3A4, and etravirine is a PGP inhibitor and CYP3A4 inducer. Therefore, quinine concentrations could be altered with coadministration. Monitor patients for effectiveness and increased adverse effects of quinine if these drugs are given together.
Everolimus: (Moderate) Monitor everolimus whole blood trough concentrations as appropriate and watch for everolimus-related adverse reactions if coadministration with quinine is necessary. The dose of everolimus may need to be reduced. Everolimus is a P-glycoprotein (P-gp) substrate and quinine is a P-gp inhibitor. Coadministration with P-gp inhibitors may decrease the efflux of everolimus from intestinal cells and increase everolimus blood concentrations.
Ezetimibe; Simvastatin: (Moderate) Patients receiving concomitant simvastatin and quinine should be monitored closely for muscle pain or weakness. Simvastatin is a CYP3A4 substrate; therefore, quinine has the potential to inhibit the metabolism of simvastatin leading to an increased potential of rhabdomyolysis. Lower starting doses of simvastatin should be considered while patients are receiving quinine. Discontinue simvastatin if marked creatine phosphokinase (CPK) elevation occurs or myopathy (defined as muscle aches or muscle weakness in conjunction with CPK values greater than 10 times the upper limit of normal) is diagnosed or suspected.
Fedratinib: (Moderate) Monitor for increased adverse events of quinine if administered with fedratinib. Concurrent use may increase quinine exposure. Fedratinib is a moderate CYP3A4 inhibitor and quinine is a CYP3A4 substrate.
Fenofibric Acid: (Minor) At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19 and a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C19 and CYP2C9 substrates, such as quinine, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 and CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of quinine during coadministration with fenofibric acid.
Fentanyl: (Moderate) Consider a reduced dose of fentanyl with frequent monitoring for respiratory depression and sedation if concurrent use of quinine is necessary. If quinine is discontinued, consider increasing the fentanyl dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Fentanyl is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like quinine can increase fentanyl exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of fentanyl. If quinine is discontinued, fentanyl plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to fentanyl.
Finerenone: (Moderate) Monitor serum potassium during initiation or dose adjustment of either finerenone or quinine; a finerenone dosage reduction may be necessary. Concomitant use may increase finerenone exposure and the risk of hyperkalemia. Finerenone is a CYP3A substrate and quinine is a weak CYP3A inhibitor. Coadministration with another weak CYP3A inhibitor increased overall exposure to finerenone by 21%.
Fingolimod: (Major) Concurrent use of quinine and fingolimod should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Fingolimod initiation results in decreased heart rate and may prolong the QT interval. After the first fingolimod dose, overnight monitoring with continuous ECG in a medical facility is advised for patients taking QT prolonging drugs with a known risk of TdP, such as quinine. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia.
Flecainide: (Major) Flecainide clearance can be modestly inhibited by quinine, increasing flecainide serum concentrations. Quinine is a CYP2D6 inhibitor, and flecainide is a CYP2D6 substrate. Additionally, both drugs are associated with prolongation of the QT internal. Until more data are available, concomitant use of these two drugs should be avoided whenever possible.
Flibanserin: (Contraindicated) The concomitant use of flibanserin and moderate CYP3A4 inhibitors, such as quinine, is contraindicated. Moderate CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a moderate CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a moderate CYP3A4 inhibitor following flibanserin use, start the moderate CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Fluconazole: (Contraindicated) Concurrent use of fluconazole and quinine is contraindicated due to the risk of life-threatening arrhythmias such as torsade de pointes (TdP). Both fluconazole and quinine have been associated with QT prolongation and rare cases of TdP. In addition, fluconazole is an inhibitor of CYP3A4 and quinine is a CYP3A4 substrate. Coadministration may result in an elevated quinine plasma concentrations, causing an increased risk for adverse events, such as QT prolongation.
Fluoxetine: (Major) Concomitant use of quinine and fluoxetine 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.
Fluphenazine: (Major) Concurrent use of quinine and fluphenazine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Fluphenazine, a phenothiazine, is also associated with a possible risk for QT prolongation and/or TdP.
Fluvoxamine: (Major) It is recommended to avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP. Quinine has been associated with QT prolongation and rare cases of torsade de pointes. Cases of QT prolongation and TdP have been reported during postmarketing use of fluvoxamine.
Food: (Major) Clinicians should be aware that some food and beverage products contain quinine. Tonic water commonly contains quinine and may have additive effects when taken with quinine medications. One study reported that the concentrations of quinine in tonic water are not significant enough to result in drug interactions with CYP2D6 substrates.
Fosamprenavir: (Moderate) Monitor for quinine-related adverse reactions if coadministration with fosamprenavir is necessary. Concurrent use may increase quinine exposure. Quinine 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 quinine. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Quinine has also been associated with QT prolongation and rare cases of TdP. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
Fosphenytoin: (Minor) Concomitant administration of fosphenytoin with quinine may decrease plasma quinine concentrations. Fosphenytoin is a CYP3A4 inducer, and quinine is a CYP3A4 substrate.
Fostemsavir: (Major) Avoid concurrent use of quinine with fostemsavir. Quinine has been associated with QT prolongation and rare cases of 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 quinine 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 quinine is a 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.
Gemfibrozil: (Moderate) Coadministration may result in a significant increase in quinine exposure. A dose reduction of quinine may be required if used concomitantly with gemfibrozil. Use quinine and gemfibrozil together with caution. Quinine is a substrate of CYP2C8, and gemfibrozil is a strong CYP2C8 inhibitor.
Gemifloxacin: (Major) Concurrent use of quinine and gemifloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Gemifloxacin may also prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 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) Avoid coadministration of gemtuzumab ozogamicin with quinine due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin. Quinine has been associated with QT prolongation and rare cases of TdP.
Gilteritinib: (Major) Avoid concomitant use of quinine with gilteritinib due to the potential for additive QT prolongation. Gilteritinib has been associated with QT prolongation. Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP).
Glasdegib: (Major) Avoid coadministration of glasdegib with quinine due to the potential for additive QT prolongation. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP).
Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of glecaprevir and quinine as coadministration may increase serum concentrations of quinine and increase the risk of adverse effects. Quinine is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and quinine as coadministration may increase serum concentrations of quinine and increase the risk of adverse effects. Quinine is a substrate of P-glycoprotein (P-gp); pibrentasvir is an inhibitor of P-gp.
Goserelin: (Major) Avoid coadministration of quinine with goserelin due to the risk of QT prolongation and torsade de pointes (TdP). Quinine has been associated with QT prolongation and rare cases of TdP. Androgen deprivation therapy (i.e., goserelin) may also prolong the QT/QTc interval.
Granisetron: (Major) Concurrent use of quinine and granisetron should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Granisetron has also been associated with QT prolongation. In addition, concentrations of granisetron may be increased with concomitant use of quinine. Granisetron is a CYP3A4 substrate and quinine is a CYP3A4 inhibitor.
Grapefruit juice: (Moderate) Quinine pharmacokinetics were not affected by grapefruit juice in a study of 10 healthy volunteers who were administered 5 days of grapefruit juice prior to receiving a single 600 mg quinine dose. However, there is a case report in which a 19 year old patient with known asymptomatic long QT syndrome developed torsade de pointes (TdP) after ingesting excessive amounts of grapefruit juice and quinine-containing tonic water. The TdP stopped 48 hours after discontinuing these drinks. Use of quinine and grapefruit juice should be done with caution, especially with large or multiple doses of quinine or if co-administered in patients with potential cardiac abnormalities.
Guaifenesin; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of quinine is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP2D6 and CYP3A4 substrate, and coadministration with CYP2D6 and CYP3A4 inhibitors like quinine can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced with a combined CYP2D6 and CYP3A4 inhibitor. If quinine is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Guanfacine: (Major) Quinine may significantly alter guanfacine plasma concentrations. Guanfacine is primarily metabolized by CYP3A4. Quinine is a moderate inhibitor of CYP3A4; in vitro data suggests it may also moderately induce CYP3A4. The net effect of this potential interaction is unclear, but guanfacine dosage adjustments, most likely a dose decrease, may be required. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if used with a moderate to strong CYP3A4 inhibitor, the guanfacine dosage should be decreased to half of the recommended dose and the patient should be closely monitored for alpha-adrenergic effects (e.g., hypotension, drowsiness, bradycardia). However, if used with a moderate to strong CYP3A4 inducer, labeling recommends to consider doubling the recommended dose of guanfacine ER; if the inducer is added in a patient already receiving guanfacine, this escalation should occur over 1 to 2 weeks. If the inducer or inhibitor is discontinued, guanfacine ER should return to its recommended dose (with downward titration occurring over 1 to 2 weeks). Specific recommendations for immediate-release (IR) guanfacine are not available.
Halogenated Anesthetics: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including halogenated anesthetics.
Haloperidol: (Major) Concurrent use of quinine and haloperidol should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. QT prolongation and TdP have also been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Further, quinine is a substrate of CYP3A4 and an inhibitor of CYP2D6 and CYP3A4, the isoenzymes responsible for the metabolism of haloperidol. Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and inhibitors of CYP3A4 or CYP2D6. Elevated haloperidol concentrations occurring through inhibition of CYP2D6 or CYP3A4 may increase the risk of adverse effects, including QT prolongation.
Histrelin: (Major) Avoid coadministration of quinine with histrelin due to the risk of QT prolongation and torsade de pointes (TdP). Quinine has been associated with QT prolongation and rare cases of TdP. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval.
Homatropine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of quinine is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP2D6 and CYP3A4 substrate, and coadministration with CYP2D6 and CYP3A4 inhibitors like quinine can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced with a combined CYP2D6 and CYP3A4 inhibitor. If quinine is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of quinine is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP2D6 and CYP3A4 substrate, and coadministration with CYP2D6 and CYP3A4 inhibitors like quinine can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced with a combined CYP2D6 and CYP3A4 inhibitor. If quinine is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocodone; Ibuprofen: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of quinine is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP2D6 and CYP3A4 substrate, and coadministration with CYP2D6 and CYP3A4 inhibitors like quinine can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced with a combined CYP2D6 and CYP3A4 inhibitor. If quinine is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical depen dence to hydrocodone.
Hydrocodone; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of quinine is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP2D6 and CYP3A4 substrate, and coadministration with CYP2D6 and CYP3A4 inhibitors like quinine can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced with a combined CYP2D6 and CYP3A4 inhibitor. If quinine is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydroxychloroquine: (Major) Concomitant use of quinine 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 quinine 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.
Ibritumomab Tiuxetan: (Moderate) Alkalinization of the urine by alkalinizing agents can decrease the renal clearance of quinine. Increased plasma levels of quinine following reduced clearance can increase the risk of quinine-induced toxicity.
Ibuprofen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of quinine is necessary. If quinine is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a moderate inhibitor like quinine can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If quinine is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Ibutilide: (Major) Concurrent use of quinine and ibutilide should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Ibutilide administration can also cause QT prolongation and TdP; proarrhythmic events should be anticipated.
Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with quinine, a CYP3A substrate, as quinine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Ifosfamide: (Moderate) Monitor for a decrease in the efficacy of ifosfamide if coadministration with quinine is necessary. Ifosfamide is metabolized by CYP3A4 to its active alkylating metabolites. Quinine is a moderate CYP3A4 inhibitor. Coadministration may decrease plasma concentrations of these active metabolites, decreasing the effectiveness of ifosfamide treatment.
Iloperidone: (Major) Concurrent use of quinine and iloperidone should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Iloperidone has also been associated with QT prolongation; however, TdP has not been reported. In addition, concentrations of iloperidone may be increased with concomitant use of quinine. Iloperidone is a CYP3A4 and CYP2D6 substrate and quinine is an inhibitor of both enzymes.
Imipramine: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). In addition, quinine is an inhibitor of CYP2D6. Avoid concurrent use of quinine with other drugs that prolong the QT and are CYP2D6 substrates. Coadministration may result in elevated plasma concentrations of the interacting drug, causing increased risk for adverse events, such as QT prolongation. Drugs that prolong the QT and are substrates for CYP2D6 include tricyclic antidepressants.
Indinavir: (Major) Anti-retroviral protease inhibitors can inhibit the metabolism of CYP3A4 substrates such as quinine. In theory, this interaction could potentially result in drug accumulation and quinine toxicity. Monitor for potential quinine toxicity and decrease quinine dosage if needed.
Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with quinine 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. Quinine has been associated with QT prolongation and rare cases of TdP.
Isavuconazonium: (Major) Concomitant use of isavuconazonium with quinine may result in increased serum concentrations of quinine and altered concentrations of isavuconazonium. Quinine is a substrate/inhibitor/inducer of the hepatic isoenzyme CYP3A4 and substrate of the drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of CYP3A4 and an inhibitor of P-gp. Caution and close monitoring are advised if these drugs are used together.
Isoflurane: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including halogenated anesthetics.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Rifampin is a potent inducer of the cytochrome P-450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of quinine. Dosages of quinine may need to be adjusted while the patient is receiving rifampin.
Isoniazid, INH; Rifampin: (Major) Rifampin is a potent inducer of the cytochrome P-450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of quinine. Dosages of quinine may need to be adjusted while the patient is receiving rifampin.
Itraconazole: (Moderate) Monitor patients for increased quinine-related adverse effects if coadministration of itraconazole is necessary. Quinine is a substrate of P-glycoprotein (P-gp) and CYP3A4, and itraconazole is a P-gp and CYP3A4 inhibitor. Therefore, quinine concentrations could be increased with coadministration.
Ivacaftor: (Major) If quinine and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to once daily. Ivacaftor is a CYP3A substrate and quinine is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased ivacaftor exposure by 3-fold.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with quinine due to increased plasma concentrations of ivosidenib and QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. Ivosidenib is a CYP3A4 substrate that has been associated with QTc prolongation and ventricular arrhythmias. Quinine is a moderate CYP3A4 inhibitor that has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Coadministration with another moderate CYP3A4 inhibitor is predicted to increase the ivosidenib single-dose AUC to 173% of control based on physiologically-based pharmacokinetic modeling, with no change in Cmax. Multiple doses of the moderate CYP3A4 inhibitor are predicted to increase the ivosidenib steady-state AUC to 152% of control and AUC to 190% of control.
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and quinine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Concomitant use may also increase the exposure of quinine, further increasing the risk for adverse effects. Quinine is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor. Coadministration with ketoconazole increased the exposure of quinine by 45% and decreased the clearance by 31%.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Concurrent use of quinine with clarithromycin should be avoided due to the risk for QT prolongation and torsade de pointes (TdP). Both quinine and clarithromycin have been associated with prolongation of the QT interval. In addition, because both clarithromycin and quinine are substrates and inhibitors of CYP3A4; coadministration may result in elevated plasma concentration of both drugs, causing an increased risk for adverse events.
Lanthanum Carbonate: (Major) Oral compounds known to interact with antacids, like quinine sulfate, should not be taken within 2 hours of dosing with lanthanum carbonate. If these agents are used concomitantly, space the dosing intervals appropriately. Monitor serum concentrations and clinical condition.
Lapatinib: (Major) Avoid coadministration of quinine with lapatinib due to the risk of QT prolongation and torsade de pointes (TdP); exposure to both drugs may also increase. Lapatinib is a P-glycoprotein (P-gp) substrate/inhibitor as well as a CYP3A4 substrate/weak inhibitor. It has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and TdP have been reported in postmarketing experience with lapatinib. Quinine is also a P-gp substrate/inhibitor and CYP3A4 substrate, that has also been associated with QT prolongation and rare cases of TdP.
Ledipasvir; Sofosbuvir: (Moderate) Caution and close monitoring of quinine-associated adverse reactions is advised with concomitant administration of ledipasvir. Quinine is a substrate of the drug transporter P-glycoprotein (P-gp); ledipasvir is a P-gp inhibitor. Taking these drugs together may increase quinine plasma concentrations.
Lefamulin: (Major) Avoid coadministration of lefamulin with quinine 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. Quinine is a P-gp and moderate CYP3A4 inhibitor that has been associated with QT prolongation and rare cases of torsade de pointes (TdP).
Lemborexant: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with quinine as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; quinine is a weak CYP3A4 inhibitor. Coadministration of lemborexant with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Lenacapavir: (Moderate) Monitor for quinine-related adverse reactions if coadministration with lenacapavir is necessary. Concurrent use may increase quinine exposure. Quinine is a CYP3A substrate and lenacapavir is a moderate CYP3A inhibitor.
Lenvatinib: (Major) Avoid coadministration of lenvatinib with quinine due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Quinine has also been associated with QT prolongation and rare cases of torsade de pointes (TdP).
Letermovir: (Moderate) Plasma concentrations of quinine could increase when administered concurrently with letermovir. The magnitude of this interaction may be increased in patients who are also receiving cyclosporine. If these drugs are given together, closely monitor for quinine-related adverse events. Quinine is primarily metabolized by CYP3A4. Letermovir is moderate inhibitor of CYP3A4. When given with cyclosporine, the combined effect of letermovir and cyclosporine on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. In a drug interaction study, concurrent use with another strong CYP3A4 inhibitor increased quinine AUC by 45%, and decreased the mean oral clearance of quinine by 31%; no change in quinine dosage regimen was needed.
Leuprolide: (Major) Avoid coadministration of quinine with leuprolide due to the risk of QT prolongation and torsade de pointes (TdP). Quinine has been associated with QT prolongation and rare cases of TdP. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Leuprolide; Norethindrone: (Major) Avoid coadministration of quinine with leuprolide due to the risk of QT prolongation and torsade de pointes (TdP). Quinine has been associated with QT prolongation and rare cases of TdP. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Levamlodipine: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as quinine, are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
Levofloxacin: (Major) Concomitant use of quinine and levofloxacin 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.
Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and quinine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Concomitant use may also increase the exposure of quinine, further increasing the risk for adverse effects. Quinine is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor. Coadministration with ketoconazole increased the exposure of quinine by 45% and decreased the clearance by 31%.
Lidocaine: (Moderate) Concomitant use of systemic lidocaine and quinine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; quinine inhibits CYP3A4. Additionally, coadministration of lidocaine with oxidizing agents, such as quinine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Lidocaine; Epinephrine: (Moderate) Concomitant use of systemic lidocaine and quinine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; quinine inhibits CYP3A4. Additionally, coadministration of lidocaine with oxidizing agents, such as quinine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Lidocaine; Prilocaine: (Moderate) Coadministration of prilocaine with oxidizing agents, such as quinine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue prilocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Concomitant use of systemic lidocaine and quinine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; quinine inhibits CYP3A4. Additionally, coadministration of lidocaine with oxidizing agents, such as quinine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Lithium: (Major) Concomitant use of quinine 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: (Major) Avoid coadministration of lofexidine and quinine due to the potential for additive QT prolongation and torsade de pointes (TdP). Monitor the ECG for QT prolongation if coadministration is required. Lofexidine may prolong the QT interval, and TdP has been reported during postmarketing use. Quinine has been associated with QT prolongation and rare cases of TdP.
Lonafarnib: (Major) Avoid coadministration of lonafarnib and quinine; concurrent use may increase the exposure of both drugs and the risk of adverse effects. If coadministration is unavoidable, reduce to or continue lonafarnib at a dosage of 115 mg/m2; closely monitor patients for adverse reactions from both drugs. Resume previous lonafarnib dosage 14 days after discontinuing quinine. Lonafarnib is a sensitive CYP3A4 substrate and strong CYP3A4 inhibitor; quinine is a CYP3A4 substrate and weak CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the exposure of quinine by 45% and decreased the clearance by 31%.
Loperamide: (Major) Concomitant use of loperamide and quinine 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 quinine is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Loperamide; Simethicone: (Major) Concomitant use of loperamide and quinine 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 quinine is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with quinine 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. Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). (Major) Concomitant use of quinine and ritonavir should be avoided due to increased quinine concentrations. In a study of healthy patients who received a single oral 600 mg dose of quinine with the 15th dose of ritonavir (200 mg PO Q12h for 9 days), there was a 4-fold increase in the mean quinine AUC and Cmax and an increase in the mean quinine elimination half-life (13.4 h vs. 11.2 h) when compared to quinine administered alone. There were no significant changes in the ritonavir pharmacokinetics. Ritonavir is a potent CYP3A4 inhibitor and quinine is a CYP3A4 substrate.
Lovastatin: (Moderate) Lovastatin is a CYP3A4 substrate; therefore, quinine has the potential to inhibit the metabolism of lovastatin leading to an increased potential of rhabdomyolysis. Patients receiving concomitant lovastatin and quinine should be monitored closely for muscle pain or weakness. Lower starting doses of lovastatin should be considered while patients are receiving quinine.
Luliconazole: (Moderate) Theoretically, luliconazole may increase the side effects of quinine, which is a CYP2C19 and a CYP3A4 substrate. Monitor patients for adverse effects of quinine, such as QT prolongation and cinchonism. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Lumacaftor; Ivacaftor: (Major) If quinine and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to once daily. Ivacaftor is a CYP3A substrate and quinine is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased ivacaftor exposure by 3-fold. (Moderate) Lumacaftor; ivacaftor may reduce the efficacy of quinine by decreasing its systemic exposure. If used together, monitor patients closely for loss of quinine efficacy. Quinine is primarily metabolized by CYP3A4 and is also a substrate of CYP2C8, CYP2C9, CYP2C19, and the drug transporter P-glycoprotein (P-gp). Lumacaftor is a strong CYP3A inducer; in vitro data also suggest that lumacaftor; ivacaftor may induce CYP2C19 and induce and/or inhibit CYP2C8, CYP2C9, and P-gp.
Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may reduce the efficacy of quinine by decreasing its systemic exposure. If used together, monitor patients closely for loss of quinine efficacy. Quinine is primarily metabolized by CYP3A4 and is also a substrate of CYP2C8, CYP2C9, CYP2C19, and the drug transporter P-glycoprotein (P-gp). Lumacaftor is a strong CYP3A inducer; in vitro data also suggest that lumacaftor; ivacaftor may induce CYP2C19 and induce and/or inhibit CYP2C8, CYP2C9, and P-gp.
Lurasidone: (Major) Results of in vivo and in vitro drug interaction studies suggest that quinine has the potential to inhibit the metabolism of drugs that are substrates of CYP3A4. Because lurasidone is primarily metabolized by CYP3A4, concurrent use of quinine can theoretically lead to an increased risk of lurasidone-related adverse reactions.
Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as quinine. 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. Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP).
Maprotiline: (Major) Concurrent use of quinine and maprotiline should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Maprotiline has also been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. In addition, concentrations of maprotiline may be increased with concomitant use of quinine. Maprotiline is a CYP2D6 substrate and quinine is a CYP2D6 inhibitor.
Maraviroc: (Moderate) Use caution if coadministration of maraviroc with quinine is necessary as altered maraviroc concentrations may occur. Maraviroc is a substrate of CYP3A; quinine is an inhibitor and inducer of CYP3A4. Monitor for decreased efficacy and/or an increase in adverse effects with concomitant use.
Mefloquine: (Contraindicated) Due to the risk for QT prolongation and seizures, do not administer mefloquine until at least 12 hours after quinine discontinuation have passed. Both drugs have been associated with QT prolongation. In addition, quinine is an inhibitor of CYP3A4, and mefloquine is a CYP3A4 substrate. Coadministration has resulted in a 22% increase in mefloquine systemic exposure, causing an increased risk for adverse events, such as QT prolongation and seizures.
Memantine: (Moderate) Memantine is excreted in part by renal tubular secretion. Competition of memantine for excretion with other drugs that are also eliminated by tubular secretion, such as quinine, could result in elevated serum concentrations of one or both drugs.
Meperidine: (Moderate) Quinine inhibits CYP2D6 and may theoretically increase concentrations of drugs metabolized by this enzyme, such as meperidine. Because large increases in serum concentrations of meperidine may be associated with severe adverse reactions, caution is recommended during coadministration with quinine.
Mepivacaine: (Moderate) Coadministration of mepivacaine with oxidizing agents, such as quinine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue mepivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Metformin; Repaglinide: (Moderate) Repaglinide is partly metabolized by CYP3A4. Drugs that inhibit CYP3A4 may increase plasma concentrations of repaglinide. Quinine has been shown to be an inhibitor of CYP3A4. If these drugs are co-administered, dose adjustment of repaglinide may be necessary.
Metformin; Saxagliptin: (Moderate) Monitor patients for hypoglycemia if saxagliptin and quinine are used together. The metabolism of saxagliptin is primarily mediated by CYP3A4/5; saxagliptin plasma concentrations may increase in the presence of moderate CYP 3A4/5 inhibitors such as quinine.
Methadone: (Major) Concurrent use of quinine and methadone should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Methadone is also considered to be associated with an increased risk for QT prolongation and TdP, especially at higher doses (> 200 mg/day but averaging approximately 400 mg/day). Laboratory studies, both in vivo and in vitro, have demonstrated that methadone inhibits cardiac potassium channels and prolongs the QT interval. Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction. In addition, concentrations of methadone may be increased with concomitant use of quinine. Methadone is a CYP3A4 and CYP2D6 substrate and quinine is a CYP3A4/CYP2D6 inhibitor.
Methamphetamine: (Minor) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme. Caution is recommended when administering quinine with other CYP2D6 substrates, such as methamphetamine, that have a narrow therapeutic range or where large increases in serum concentrations may be associated with severe adverse reactions.
Metoprolol: (Moderate) Monitor for increased metoprolol adverse reactions including bradycardia and hypotension during coadministration. A dosage reduction for metoprolol may be needed based on response. Concurrent use may increase metoprolol exposure. Metoprolol is a CYP2D6 substrate; quinine is a CYP2D6 inhibitor.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for increased metoprolol adverse reactions including bradycardia and hypotension during coadministration. A dosage reduction for metoprolol may be needed based on response. Concurrent use may increase metoprolol exposure. Metoprolol is a CYP2D6 substrate; quinine is a CYP2D6 inhibitor.
Metronidazole: (Major) Concomitant use of metronidazole and quinine 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) Mexiletine is significantly metabolized by CYP2D6 isoenzymes. CYP2D6 inhibitors, such as quinine, could theoretically impair mexiletine metabolism; the clinical significance of such interactions is unknown.
Midazolam: (Minor) Quinine does not induce the metabolism of midazolam. In a study of 23 subjects receiving multiple doses of quinine for 7 days and a single dose of midazolam, the mean AUC and Cmax of midazolam and 1-hydroxymidazolam were not significantly affected.
Midostaurin: (Major) Avoid the concomitant use of midostaurin and quinine; both drugs have been reported to increase the QT interval. If coadministration cannot be avoided, consider obtaining electrocardiograms to monitor the QT interval. In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. QT prolongation has been reported with quinine therapy; rarely, potentially fatal cardiac arrhythmias (e.g., torsades de pointes and ventricular fibrillation) have occurred.
Mifepristone: (Major) Concurrent use of quinine and mifepristone should generally be avoided due to an increased risk for elevated concentrations of either drug and an increased risk for QT prolongation and torsade de pointes (TdP). Consider alternative drug therapy if possible. Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Mifepristone has also been associated with dose-dependent prolongation of the QT interval. In addition, both drugs are inhibitors and substrates of CYP3A4; coadministration may result in increased concentration of both drugs. Monitor for quinine-related "cinchonism". Monitor for adrenal suppression from Mifepristone. To minimize the risk for QT prolongation, the lowest effective dose of mifepristone should be used.
Mirabegron: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as quinine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Mirtazapine: (Major) Concomitant use of quinine 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.
Mitotane: (Major) Use caution if mitotane and quinine are used concomitantly, and monitor for decreased efficacy of quinine and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and quinine is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of quinine. Another strong CYP3A inducer, rifampin, has been shown to significantly decreases the AUC (75% to 85%) and Cmax (55%) of quinine, resulting in treatment failures; concomitant use should be avoided.
Mivacurium: (Major) Avoid concomitant use of neuromuscular blockers and quinine. Quinine may enhance the action of neuromuscular blockers. In 1 patient who received a neuromuscular blocker during an operative procedure, subsequent administration of quinine 1,800 mg 3 hours later resulted in respiratory depression.
Mobocertinib: (Major) Concomitant use of mobocertinib and quinine 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.
Moxifloxacin: (Major) Concurrent use of quinine and moxifloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Prolongation of the QT interval has also been reported with administration of moxifloxacin. Post-marketing surveillance has identified very rare cases of ventricular arrhythmias including 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.
Naldemedine: (Major) Monitor for potential naldemedine-related adverse reactions if coadministered with quinine. The plasma concentrations of naldemedine may be increased during concurrent use. Naldemedine is a CYP3A4 substrate; quinine is a moderate CYP3A4 inhibitor.
Naloxegol: (Major) Avoid concomitant administration of naloxegol and quinine due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A4 substrate; quinine is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased naloxegol exposure by approximately 3.4-fold.
Nanoparticle Albumin-Bound Sirolimus: (Major) Avoid concomitant use of sirolimus and quinine. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and quinine is a weak CYP3A and P-gp inhibitor.
Nebivolol: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with quinine. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as quinine, could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition; the clinical significance of this potential interaction is unknown, but an increase in adverse effects is possible.
Nebivolol; Valsartan: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with quinine. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as quinine, could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition; the clinical significance of this potential interaction is unknown, but an increase in adverse effects is possible.
Nelfinavir: (Major) Anti-retroviral protease inhibitors can inhibit the metabolism of CYP3A4 substrates such as quinine. In theory, this interaction could potentially result in drug accumulation and quinine toxicity. Monitor for potential quinine toxicity and decrease quinine dosage if needed.
Neostigmine: (Major) The actions of quinine on skeletal muscle are pharmacologically opposite to those of cholinesterase inhibitors. Therefore, quinine may interfere with the actions of cholinesterase inhibitors in treating such conditions as myasthenia gravis. This represents a pharmacodynamic interaction with cholinesterase inhibitors rather than a pharmacokinetic interaction.
Neostigmine; Glycopyrrolate: (Major) The actions of quinine on skeletal muscle are pharmacologically opposite to those of cholinesterase inhibitors. Therefore, quinine may interfere with the actions of cholinesterase inhibitors in treating such conditions as myasthenia gravis. This represents a pharmacodynamic interaction with cholinesterase inhibitors rather than a pharmacokinetic interaction.
Neratinib: (Major) Avoid concomitant use of quinine with neratinib due to an increased risk of neratinib-related toxicity. Neratinib is a CYP3A4 substrate and quinine is a moderate CYP3A4 inhibitor. The effect of moderate CYP3A4 inhibition on neratinib concentrations has not been studied; however, coadministration with a strong CYP3A4 inhibitor increased neratinib exposure by 481%. Because of the significant impact on neratinib exposure from strong CYP3A4 inhibition, the potential impact on neratinib safety from concomitant use with moderate CYP3A4 inhibitors should be considered as they may also significantly increase neratinib exposure.
Neuromuscular blockers: (Major) Avoid concomitant use of neuromuscular blockers and quinine. Quinine may enhance the action of neuromuscular blockers. In 1 patient who received a neuromuscular blocker during an operative procedure, subsequent administration of quinine 1,800 mg 3 hours later resulted in respiratory depression.
Niacin; Simvastatin: (Moderate) Patients receiving concomitant simvastatin and quinine should be monitored closely for muscle pain or weakness. Simvastatin is a CYP3A4 substrate; therefore, quinine has the potential to inhibit the metabolism of simvastatin leading to an increased potential of rhabdomyolysis. Lower starting doses of simvastatin should be considered while patients are receiving quinine. Discontinue simvastatin if marked creatine phosphokinase (CPK) elevation occurs or myopathy (defined as muscle aches or muscle weakness in conjunction with CPK values greater than 10 times the upper limit of normal) is diagnosed or suspected.
Nilotinib: (Major) Avoid the concomitant use of nilotinib and quinine; significant prolongation of the QT interval may occur. Sudden death and QT prolongation have been reported in patients who received nilotinib therapy. Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP).
Niraparib; Abiraterone: (Moderate) Use abiraterone, a CYP2C8 inhibitor, and quinine, a CYP2C8 substrate, together cautiously, as levels of quinine may be increased. Monitor closely for signs of quinine toxicity such as visual impairment, hypoglycemia, and cardiac arrhythmias. Additionally, quinine may inhibit drugs metabolized by CYP3A4, such as abiraterone, causing increased abiraterone levels.
Nirmatrelvir; Ritonavir: (Major) Concomitant use of quinine and ritonavir should be avoided due to increased quinine concentrations. In a study of healthy patients who received a single oral 600 mg dose of quinine with the 15th dose of ritonavir (200 mg PO Q12h for 9 days), there was a 4-fold increase in the mean quinine AUC and Cmax and an increase in the mean quinine elimination half-life (13.4 h vs. 11.2 h) when compared to quinine administered alone. There were no significant changes in the ritonavir pharmacokinetics. Ritonavir is a potent CYP3A4 inhibitor and quinine is a CYP3A4 substrate.
Nisoldipine: (Major) Avoid coadministration of nisoldipine with quinine due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A4 substrate and quinine is a CYP3A4 inhibitor.
Nortriptyline: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). In addition, quinine is an inhibitor of CYP2D6. Avoid concurrent use of quinine with other drugs that prolong the QT and are CYP2D6 substrates. Coadministration may result in elevated plasma concentrations of the interacting drug, causing increased risk for adverse events, such as QT prolongation. Drugs that prolong the QT and are substrates for CYP2D6 include tricyclic antidepressants.
Ofloxacin: (Major) Concomitant use of quinine and ofloxacin 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.
Olanzapine: (Major) Concurrent use of quinine and olanzapine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Limited data, including some case reports, suggest that olanzapine may also be associated with a significant prolongation of the QTc interval in rare instances. In addition, concentrations of olanzapine may be increased with concomitant use of quinine. Olanzapine is a CYP2D6 substrate and quinine is a CYP2D6 inhibitor.
Olanzapine; Fluoxetine: (Major) Concomitant use of quinine and fluoxetine 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. (Major) Concurrent use of quinine and olanzapine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Limited data, including some case reports, suggest that olanzapine may also be associated with a significant prolongation of the QTc interval in rare instances. In addition, concentrations of olanzapine may be increased with concomitant use of quinine. Olanzapine is a CYP2D6 substrate and quinine is a CYP2D6 inhibitor.
Olanzapine; Samidorphan: (Major) Concurrent use of quinine and olanzapine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Limited data, including some case reports, suggest that olanzapine may also be associated with a significant prolongation of the QTc interval in rare instances. In addition, concentrations of olanzapine may be increased with concomitant use of quinine. Olanzapine is a CYP2D6 substrate and quinine is a CYP2D6 inhibitor.
Oliceridine: (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 quinine is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and quinine may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If quinine 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 quinine is a moderate CYP2D6 inhibitor.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as quinine, are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
Omeprazole; Amoxicillin; Rifabutin: (Major) Rifabutin is an inducer of hepatic metabolism and may significantly accelerate quinine clearance and reduce its half-life. Higher doses of quinine may be required in patients receiving rifabutin.
Omeprazole; Sodium Bicarbonate: (Moderate) Use caution if using sodium bicarbonate and quinine concomitantly. Urinary alkalinizing agents may increase plasma quinine concentrations because quinine is reabsorbed when the urine is alkaline.
Ondansetron: (Major) Concurrent use of quinine and ondansetron should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Both drugs have been associated with prolongation of the QT interval and rare cases of TdP. In addition, concentrations of ondansetron may be increased with concomitant use of quinine. Ondansetron is a CYP3A4 and CYP2D6 substrate and quinine is an inhibitor of both enzymes.
Oritavancin: (Moderate) Coadministration of oritavancin and quinine may result in increases or decreases in quinine exposure and may increase side effects or decrease efficacy of quinine. Quinine is primarily metabolized by CYP3A4, but is also metabolized by CYP2D6, CYP2C9, and CYP2C19. Oritavancin weakly induces CYP3A4 and CYP2D6, while weakly inhibiting CYP2C9 and CYP2C19. If these drugs are administered concurrently, monitor the patient for signs of toxicity or lack of efficacy.
Osilodrostat: (Major) Avoid concurrent use of quinine with osilodrostat due to the risk of QT prolongation. Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Osilodrostat is associated with dose-dependent QT prolongation.
Osimertinib: (Major) Avoid coadministration of quinine with osimertinib due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is necessary, monitor for an increase in quinine-related adverse reactions, periodically monitor ECGs for QT prolongation, and monitor electrolytes; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Quinine is a P-glycoprotein (P-gp) substrate that has been associated with QT prolongation and rare cases of TdP. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib, which is also a P-gp inhibitor.
Oxaliplatin: (Major) Avoid coadministration of quinine with oxaliplatin due to the risk of additive QT prolongation and torsade de pointes (TdP). Quinine has been associated with QT prolongation and rare cases of TdP. QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of quinine is necessary. If quinine is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a moderate inhibitor like quinine can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If quinine is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Ozanimod: (Major) In general, do not initiate ozanimod in patients taking quinine 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. Quinine has been associated with QT prolongation and rare cases of TdP.
Pacritinib: (Major) Concomitant use of pacritinib and quinine 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) Concurrent use of quinine and paliperidone should be avoided if possible due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Paliperidone has been associated with QT prolongation; TdP and ventricular fibrillation have been reported in the setting of overdose. According to the manufacturer of paliperidone, the drug should be avoided in combination with other agents that prolong the QT interval. However, if coadministration is necessary and the patient has known risk factors for cardiac disease or arrhythmias, close monitoring is essential.
Pancuronium: (Major) Avoid concomitant use of neuromuscular blockers and quinine. Quinine may enhance the action of neuromuscular blockers. In 1 patient who received a neuromuscular blocker during an operative procedure, subsequent administration of quinine 1,800 mg 3 hours later resulted in respiratory depression.
Panobinostat: (Major) The co-administration of panobinostat with quinine is not recommended; QT prolongation has been reported with both agents. Quinine is a CYP3A4 inhibitor and panobinostat is a CYP3A4 substrate. The panobinostat Cmax and AUC (0-48hr) values were increased by 62% and 73%, respectively, in patients with advanced cancer who received a single 20 mg-dose of panobinostat after taking 14 days of a strong CYP3A4 inhibitor. Although an initial panobinostat dose reduction is recommended in patients taking concomitant strong CYP3A4 inhibitors, no dose recommendations with mild or moderate CYP3A4 inhibitors are provided by the manufacturer. If concomitant use of quinine and panobinostat cannot be avoided, closely monitor electrocardiograms and for signs and symptoms of panobinostat toxicity such as cardiac arrhythmias, diarrhea, bleeding, infection, and hepatotoxicity. Hold panobinostat if the QTcF increases to >= 480 milliseconds during therapy; permanently discontinue if QT prolongation does not resolve.
Paroxetine: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with quinine is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and quinine is a moderate CYP2D6 inhibitor.
Pasireotide: (Major) Concurrent use of quinine and pasireotide should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Pasireotide may have additive effects on the prolongation of the QT interval.
Pazopanib: (Major) Concurrent use of quinine and pazopanib should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Pazopanib has also been reported to prolong the QT interval. In addition, both drugs are CYP3A4 inhibitors and substrates; coadministration may increase serum concentrations of both drugs. Dose adjustment of pazopanib may be necessary when coadministration of pazopanib and quinine is required.
Peginterferon Alfa-2b: (Major) Monitor for adverse effects associated with increased exposure to quinine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 and CYP2D6 inhibitor, while quinine is a substrate of both these enzymes.
Penicillamine: (Major) Do not use penicillamine concurrently with antimalarials due to an increased risk of severe hematologic and renal adverse reactions.
Penicillin G Benzathine; Penicillin G Procaine: (Moderate) Coadministration of penicillin G procaine with oxidizing agents, such as quinine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue penicillin G procaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Penicillin G Procaine: (Moderate) Coadministration of penicillin G procaine with oxidizing agents, such as quinine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue penicillin G procaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Pentamidine: (Major) Concurrent use of quinine and pentamidine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Pentamidine has also been associated with QT prolongation. In addition, concentrations of pentamidine may be increased with concomitant use of quinine. Pentamidine is a CYP2D6 substrate and quinine is a CYP2D6 inhibitor.
Perindopril; Amlodipine: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as quinine, are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
Perphenazine: (Major) Concurrent use of quinine and perphenazine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Perphenazine, a phenothiazine, is also associated with a possible risk for QT prolongation and/or TdP. In addition, concentrations of perphenazine may be increased with concomitant use of quinine. Perphenazine is a CYP2D6 substrate and quinine is a CYP2D6 inhibitor.
Perphenazine; Amitriptyline: (Major) Concurrent use of quinine and perphenazine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Perphenazine, a phenothiazine, is also associated with a possible risk for QT prolongation and/or TdP. In addition, concentrations of perphenazine may be increased with concomitant use of quinine. Perphenazine is a CYP2D6 substrate and quinine is a CYP2D6 inhibitor. (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). In addition, quinine is an inhibitor of CYP2D6. Avoid concurrent use of quinine with other drugs that prolong the QT and are CYP2D6 substrates. Coadministration may result in elevated plasma concentrations of the interacting drug, causing increased risk for adverse events, such as QT prolongation. Drugs that prolong the QT and are substrates for CYP2D6 include tricyclic antidepressants.
Phenytoin: (Minor) Concomitant administration of phenytoin with quinine may decrease plasma quinine concentrations. Phenytoin is a CYP3A4 inducer, and quinine is a CYP3A4 substrate.
Physostigmine: (Major) The actions of quinine on skeletal muscle are pharmacologically opposite to those of cholinesterase inhibitors. Therefore, quinine may interfere with the actions of cholinesterase inhibitors in treating such conditions as myasthenia gravis. This represents a pharmacodynamic interaction with cholinesterase inhibitors rather than a pharmacokinetic interaction.
Pimavanserin: (Major) 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 pimavanserin. Co-administration may result in an elevated plasma concentration of the interacting drug, causing an increased risk for adverse events, such as QT prolongation.
Pimozide: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of pimozide with other QT prolonging drugs, such as quinine, is contraindicated. In addition, pimozide is metabolized primarily through CYP3A4, and to a lesser extent CYP1A2 and CYP2D6. Quinine is an inhibitor of CYP3A4 and CYP2D6. Elevated pimozide concentrations occurring through inhibition of CYP3A4, CYP2D6, and/or CYP1A2 can lead to QT prolongation, ventricular arrhythmias, and sudden death.
Pitolisant: (Major) Avoid coadministration of pitolisant with quinine as concurrent use may increase the risk of QT prolongation. Pitolisant prolongs the QT interval. Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP).
Pomalidomide: (Moderate) Use pomalidomide and quinine together with caution; decreased pomalidomide exposure may occur resulting in reduced pomalidomide effectiveness. Pomalidomide is a CYP1A2 substrate and quinine is a CYP1A2 inducer.
Ponesimod: (Major) In general, do not initiate ponesimod in patients taking quinine 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. Quinine has been associated with QT prolongation and rare cases of TdP.
Posaconazole: (Contraindicated) Concurrent use of posaconazole and quinine is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of quinine. Further, quinine is an inhibitor of the drug efflux protein, P-glycoprotein (P-gp), for which posaconazole is a substrate and an inhibitor. This complex interaction may ultimately result in altered plasma concentrations of both posaconazole and quinine. 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 quinine.
Potassium Bicarbonate: (Moderate) Use caution if using citric acid and quinine concomitantly. Urinary alkalinizing agents may increase plasma quinine concentrations because quinine is reabsorbed when the urine is alkaline. (Moderate) Use caution if using potassium citrate and quinine concomitantly. Urinary alkalinizing agents may increase plasma quinine concentrations because quinine is reabsorbed when the urine is alkaline.
Potassium Chloride: (Moderate) Use caution if using potassium citrate and quinine concomitantly. Urinary alkalinizing agents may increase plasma quinine concentrations because quinine is reabsorbed when the urine is alkaline.
Potassium Citrate: (Moderate) Use caution if using potassium citrate and quinine concomitantly. Urinary alkalinizing agents may increase plasma quinine concentrations because quinine is reabsorbed when the urine is alkaline.
Potassium Citrate; Citric Acid: (Moderate) Use caution if using citric acid and quinine concomitantly. Urinary alkalinizing agents may increase plasma quinine concentrations because quinine is reabsorbed when the urine is alkaline. (Moderate) Use caution if using potassium citrate and quinine concomitantly. Urinary alkalinizing agents may increase plasma quinine concentrations because quinine is reabsorbed when the urine is alkaline.
Pralsetinib: (Major) Avoid concomitant use of quinine 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 quinine is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Praziquantel: (Major) In vitro and drug interactions studies suggest that the CYP3A4 isoenzyme is the major enzyme involved in praziquantel metabolism. Therefore, use of praziquantel with quinine, a CYP3A4 inducer and inhibitor, should be done with caution as concomitant use may produce therapeutically ineffective concentrations of praziquantel.
Prilocaine: (Moderate) Coadministration of prilocaine with oxidizing agents, such as quinine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue prilocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Prilocaine; Epinephrine: (Moderate) Coadministration of prilocaine with oxidizing agents, such as quinine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue prilocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
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 quinine.
Probenecid; Colchicine: (Major) Avoid concomitant use of colchicine and quinine 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 quinine is a P-gp inhibitor.
Procainamide: (Major) Concurrent use of quinine and procainamide should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Procainamide is also associated with a well-established risk of QT prolongation and TdP.
Prochlorperazine: (Major) Concurrent use of quinine and prochlorperazine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If coadministration is considered necessary, and the patient has known risk factors for cardiac disease or arrhythmia, then close monitoring is essential. Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Phenothiazines, such as prochlorperazine, have also been reported to prolong the QT interval.
Promethazine; Dextromethorphan: (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.
Propafenone: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). In addition, quinine is an inhibitor of both CYP3A4 and CYP2D6. Avoid concurrent use of quinine with other drugs that prolong the QT and are CYP3A4/CYP2D6 substrates. such as propafenone, which also may prolong the QT interval. Coadministration may result in an elevated plasma concentrations, as quinine inhibits CYP2D6 and may increase concentrations of drugs metabolized by this enzyme, such as propafenone. Also, quinine is a substrate of P-glycoprotein (P-gp) and propafenone is a P-gp inhibitor; therefore, quinine concentrations could be increased with coadministration. Caution is recommended. Monitor patients for increased side effects, such as fast, irregular heartbeat, if these drugs must be used together. Consider alternative therapy to quinine if possible.
Propranolol: (Minor) Propranolol is significantly metabolized by CYP2D6 isoenzymes. CYP2D6 inhibitors, such as quinine, could theoretically impair propranolol metabolism; the clinical significance of such interactions is unknown.
Propranolol; Hydrochlorothiazide, HCTZ: (Minor) Propranolol is significantly metabolized by CYP2D6 isoenzymes. CYP2D6 inhibitors, such as quinine, could theoretically impair propranolol metabolism; the clinical significance of such interactions is unknown.
Protriptyline: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). In addition, quinine is an inhibitor of CYP2D6. Avoid concurrent use of quinine with other drugs that prolong the QT and are CYP2D6 substrates. Coadministration may result in elevated plasma concentrations of the interacting drug, causing increased risk for adverse events, such as QT prolongation. Drugs that prolong the QT and are substrates for CYP2D6 include tricyclic antidepressants.
Pyridostigmine: (Major) The actions of quinine on skeletal muscle are pharmacologically opposite to those of cholinesterase inhibitors. Therefore, quinine may interfere with the actions of cholinesterase inhibitors in treating such conditions as myasthenia gravis. This represents a pharmacodynamic interaction with cholinesterase inhibitors rather than a pharmacokinetic interaction.
Quetiapine: (Major) Concurrent use of quinine and quetiapine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Limited data, including some case reports, suggest that quetiapine may also be associated with a significant prolongation of the QTc interval in rare instances. In addition, concentrations of quetiapine may be increased with concomitant use of quinine. Quetiapine is a CYP3A4 substrate and quinine is a CYP3A4 inhibitor.
Quinidine: (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
Quizartinib: (Major) Concomitant use of quizartinib and quinine 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.
Rabies Vaccine: (Major) If administered concurrently, antimalarials can impair the immunologic response to the rabies vaccine, thereby, decreasing its protective effect. If possible, administration of antimalarials should be avoided during use of the rabies vaccine for postexposure prophylaxis. When antimalarials must be administered to persons also receiving the rabies vaccine for postexposure prophylaxis, a serum rabies antibody titer should be obtained on day 14 (day of the 4th vaccination) to ensure an acceptable antibody response has been induced.
Ranolazine: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that prolong the QT, such as ranolazine. In addition, quinine is an inhibitor of both CYP3A4 and CYP2D6. Ranolazine is primarily metabolized by CYP3A. According to the manufacturer, the ranolazine dosage should be limited to 500 mg PO twice daily for patients receiving drugs known to be moderate CYP3A inhibitors. Conversely, ranolazine is a P-glycoprotein (P-gp) and CYP3A inhibitor, and quinine is a substrate for P-gp and CYP3A. Ranolazine may theoretically increase plasma concentrations of quinine and increase the risk for adverse effects, such as QT prolongation.
Relugolix: (Major) Avoid concomitant use of relugolix and oral quinine due to the risk of QT prolongation; relugolix exposure may also increase along with the risk of relugolix-related adverse effects. Relugolix therapy may be interrupted for up to 14 days if a short course of quinine is required; if treatment is interrupted for more than seven days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. If concomitant use is unavoidable, administer quinine at least six hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate that may prolong the QT/QTc interval. Quinine is a P-gp inhibitor that has also been associated with QT prolongation and rare cases of torsade de pointes (TdP).
Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of relugolix and oral quinine due to the risk of QT prolongation; relugolix exposure may also increase along with the risk of relugolix-related adverse effects. Relugolix therapy may be interrupted for up to 14 days if a short course of quinine is required; if treatment is interrupted for more than seven days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. If concomitant use is unavoidable, administer quinine at least six hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate that may prolong the QT/QTc interval. Quinine is a P-gp inhibitor that has also been associated with QT prolongation and rare cases of torsade de pointes (TdP).
Repaglinide: (Moderate) Repaglinide is partly metabolized by CYP3A4. Drugs that inhibit CYP3A4 may increase plasma concentrations of repaglinide. Quinine has been shown to be an inhibitor of CYP3A4. If these drugs are co-administered, dose adjustment of repaglinide may be necessary.
Ribociclib: (Major) Avoid coadministration of ribociclib with quinine due to an increased risk for QT prolongation and torsade de pointes (TdP). Additionally, the systemic exposure of quinine may be increased, resulting in an increase in treatment-related adverse reactions. Ribociclib is a strong CYP3A4 inhibitor that has been shown to prolong the QT interval in a concentration-dependent manner. Quinine is a CYP3A4 substrate that has also been associated with QT prolongation and rare cases of TdP. Concomitant use may increase the risk for QT prolongation.
Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with quinine due to an increased risk for QT prolongation and torsade de pointes (TdP). Additionally, the systemic exposure of quinine may be increased, resulting in an increase in treatment-related adverse reactions. Ribociclib is a strong CYP3A4 inhibitor that has been shown to prolong the QT interval in a concentration-dependent manner. Quinine is a CYP3A4 substrate that has also been associated with QT prolongation and rare cases of TdP. Concomitant use may increase the risk for QT prolongation.
Rifabutin: (Major) Rifabutin is an inducer of hepatic metabolism and may significantly accelerate quinine clearance and reduce its half-life. Higher doses of quinine may be required in patients receiving rifabutin.
Rifampin: (Major) Rifampin is a potent inducer of the cytochrome P-450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of quinine. Dosages of quinine may need to be adjusted while the patient is receiving rifampin.
Rifapentine: (Moderate) Monitor for decreased quinine efficacy if coadministration with rifapentine is necessary. Quinine is a CYP3A4 and CYP2C9 substrate; rifapentine is a strong CYP3A4 inducer and moderate CYP2C9 inducer. Coadministration with another strong CYP3A4 inducer that also induces multiple other enzymes decreased the quinine AUC by 75% to 85%.
Rifaximin: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with quinine 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 quinine is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
Rilpivirine: (Major) Concurrent use of quinine and rilpivirine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation. In addition, concentrations of rilpivirine may be increased with concomitant use of quinine. Rilpivirine is a CYP3A4 substrate and quinine is a CYP3A4 inhibitor.
Riluzole: (Moderate) Coadministration of riluzole with quinine may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and quinine is a CYP1A2 inducer.
Rimegepant: (Major) Avoid a second dose of rimegepant within 48 hours if coadministered with quinine; concurrent use may increase rimegepant exposure. Rimegepant is a P-gp substrate and quinine is a P-gp inhibitor.
Risperidone: (Major) Concurrent use of quinine and risperidone should be avoided if possible due to an increased risk for QT prolongation and torsade de pointes (TdP). If coadministration is required and the patient has risk factors for cardiac disease or arrhythmias, close monitoring is recommended.
Ritlecitinib: (Moderate) Monitor for quinine-related adverse reactions if coadministration with ritlecitinib is necessary. Concurrent use may increase quinine exposure. Quinine is a CYP3A substrate and ritlecitinib is a moderate CYP3A inhibitor.
Ritonavir: (Major) Concomitant use of quinine and ritonavir should be avoided due to increased quinine concentrations. In a study of healthy patients who received a single oral 600 mg dose of quinine with the 15th dose of ritonavir (200 mg PO Q12h for 9 days), there was a 4-fold increase in the mean quinine AUC and Cmax and an increase in the mean quinine elimination half-life (13.4 h vs. 11.2 h) when compared to quinine administered alone. There were no significant changes in the ritonavir pharmacokinetics. Ritonavir is a potent CYP3A4 inhibitor and quinine is a CYP3A4 substrate.
Rivaroxaban: (Minor) Coadministration of rivaroxaban and quinine may result in increases or decreases in rivaroxaban exposure and may increase bleeding risk or decrease efficacy of rivaroxaban. Quinine is an inhibitor and inducer of CYP3A4, and rivaroxaban is a substrate of CYP3A4. If these drugs are administered concurrently, monitor the patient for signs and symptoms of bleeding and lack of efficacy.
Rocuronium: (Major) Avoid concomitant use of neuromuscular blockers and quinine. Quinine may enhance the action of neuromuscular blockers. In 1 patient who received a neuromuscular blocker during an operative procedure, subsequent administration of quinine 1,800 mg 3 hours later resulted in respiratory depression.
Romidepsin: (Major) Concurrent use of quinine and romidepsin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If these drugs must be coadministered, appropriate cardiovascular monitoring precautions should be considered, such as the monitoring of electrolytes and ECGs at baseline and periodically during treatment. Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Romidepsin has also been reported to prolong the QT interval. In addition, concentrations of romidepsin may be increased with concomitant use of quinine. Romidepsin is a CYP3A4 substrate and quinine is a CYP3A4 inhibitor.
Ropivacaine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as quinine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Rufinamide: (Minor) The potential interaction between quinine and rufinamide is unpredictable. CYP isozymes 3A4 and, to a lesser extent, 2E1 are involved in quinine metabolism. In theory, plasma concentrations of CYP2E1 substrates may be increased due to the weak 2E1 inhibitory effects of rufinamide. Conversely, the weak CYP3A4 inducer effects of rufinamide may result in decreased exposure of drugs that are metabolized by this isozyme.
Saquinavir: (Contraindicated) Concurrent use of saquinavir boosted with ritonavir and quinine is contraindicated due to the potential for life threatening arrhythmias such as torsade de pointes (TdP). Saquinavir boosted with ritonavir is an inhibitor of CYP3A4 and of the drug efflux protein, P-glycoprotein (P-gp). Quinine is a substrate for P-gp, as well as a substrate and inhibitor of CYP3A4. These drugs used together may result in altered serum concentrations of both saquinavir and quinine, which could cause drug related adverse events. In addition, saquinavir boosted with ritonavir causes dose-depnedent QT prolongation; avoid use in combination with other drugs that may prolong the QT interval such as quinine.
Saxagliptin: (Moderate) Monitor patients for hypoglycemia if saxagliptin and quinine are used together. The metabolism of saxagliptin is primarily mediated by CYP3A4/5; saxagliptin plasma concentrations may increase in the presence of moderate CYP 3A4/5 inhibitors such as quinine.
Segesterone Acetate; Ethinyl Estradiol: (Minor) Coadministration of segesterone, a CYP3A4 substrate and quinine, a moderate CYP3A4 inhibitor may increase the serum concentration of segesterone.
Selpercatinib: (Major) Avoid concurrent use of quinine with selpercatinib due to the risk of additive QT prolongation. Monitor ECGs more frequently for QT prolongation if coadministration is necessary. Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Concentration-dependent QT prolongation has been observed with selpercatinib therapy.
Sertraline: (Major) Concomitant use of sertraline and quinine 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.
Sevoflurane: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including halogenated anesthetics.
Sildenafil: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with quinine is necessary; a dose reduction of sildenafil may be necessary when prescribed for erectile dysfunction. Sildenafil is a sensitive CYP3A4 substrate and quinine is a moderate CYP3A4 inhibitor.
Simvastatin: (Moderate) Patients receiving concomitant simvastatin and quinine should be monitored closely for muscle pain or weakness. Simvastatin is a CYP3A4 substrate; therefore, quinine has the potential to inhibit the metabolism of simvastatin leading to an increased potential of rhabdomyolysis. Lower starting doses of simvastatin should be considered while patients are receiving quinine. Discontinue simvastatin if marked creatine phosphokinase (CPK) elevation occurs or myopathy (defined as muscle aches or muscle weakness in conjunction with CPK values greater than 10 times the upper limit of normal) is diagnosed or suspected.
Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving quinine due to the potential for QT prolongation and additive bradycardia. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Additionally, concomitant use of siponimod and quinine may increase siponimod exposure. If the patient is also receiving a drug regimen containing a moderate CYP2C9 inhibitor, use of siponimod is not recommended due to a significant increase in siponimod exposure. Siponimod is a CYP2C9 and CYP3A4 substrate; quinine is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP2C9/CYP3A4 dual inhibitor led to a 2-fold increase in the exposure of siponimod.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of quinine. Coadministration may increase sirolimus concentrations and the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and quinine is a weak CYP3A and P-gp inhibitor.
Sodium Acetate: (Moderate) Alkalinization of the urine by alkalinizing agents can decrease the renal clearance of quinine. Increased plasma levels of quinine following reduced clearance can increase the risk of quinine-induced toxicity.
Sodium Bicarbonate: (Moderate) Use caution if using citric acid and quinine concomitantly. Urinary alkalinizing agents may increase plasma quinine concentrations because quinine is reabsorbed when the urine is alkaline. (Moderate) Use caution if using sodium bicarbonate and quinine concomitantly. Urinary alkalinizing agents may increase plasma quinine concentrations because quinine is reabsorbed when the urine is alkaline.
Sodium Citrate; Citric Acid: (Moderate) Use caution if using citric acid and quinine concomitantly. Urinary alkalinizing agents may increase plasma quinine concentrations because quinine is reabsorbed when the urine is alkaline.
Sodium Stibogluconate: (Major) Concomitant use of sodium stibogluconate and quinine 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: (Major) Avoid coadministration of velpatasvir with quinine. Taking these drugs together may significantly alter velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy or adverse effects. Velpatasvir is a CYP3A4 substrate, while quinine is a mixed inducer/inhibitor or CYP3A4. Additionally, velpatasvir is an inhibitor of the drug transporter P-glycoprotein (P-gp). Coadministration with substrates of this transporter, such as quinine, may increase their exposure.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Avoid coadministration of velpatasvir with quinine. Taking these drugs together may significantly alter velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy or adverse effects. Velpatasvir is a CYP3A4 substrate, while quinine is a mixed inducer/inhibitor or CYP3A4. Additionally, velpatasvir is an inhibitor of the drug transporter P-glycoprotein (P-gp). Coadministration with substrates of this transporter, such as quinine, may increase their exposure. (Moderate) Plasma concentrations of quinine, 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.
Solifenacin: (Major) Avoid coadministration of quinine with solifenacin if possible due to the risk of QT prolongation and increased solfenacin exposure. If concomitant use is unavoidable, do not exceed more than solfenacin 5 mg per day in adults; do not exceed the initial starting dose in pediatric patients. Periodically monitor ECGs and electrolytes; an interruption of quinine therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Solifenacin is a CYP3A4 substrate and quinine is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold. Both drugs have been associated with dose- or concentration-dependent QT prolongation, and torsade de pointes (TdP) was reported in postmarketing experience with solifenacin although causality was not determined.
Sonidegib: (Major) Avoid the concomitant use of sonidegib and quinine; sonidegib exposure may be significantly increased resulting in increased risk of adverse events, particularly musculoskeletal toxicity. If concomitant use cannot be avoided, administer quinine for less than 14 days; monitor patients closely for adverse reactions (e.g., elevated serum creatine kinase and serum creatinine levels). Sonidegib is a CYP3A substrate and quinine is a moderate CYP3A4 inhibitor. Physiologic-based pharmacokinetic (PBPK) simulations indicate a moderate 3A4 inhibitor would increase the sonidegib AUC by 1.8-fold if administered for 14 days and by 2.8-fold if the moderate CYP3A inhibitor is administered with sonidegib for more than 14 days.
Sorafenib: (Major) Avoid coadministration of sorafenib with quinine due to the risk of additive QT prolongation. Sorafenib is associated with QTc prolongation. Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP).
Sotalol: (Major) Concomitant use of sotalol and quinine 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.
St. John's Wort, Hypericum perforatum: (Moderate) Quinine is a substrate of P-glycoprotein (PGP) and CYP3A4, and St. John's Wort, Hypericum perforatum is an inducer of PGP and CYP3A4. Monitor patients for decreased efficacy of quinine if these drugs are given together.
Succinylcholine: (Major) Avoid concomitant use of neuromuscular blockers and quinine. Quinine may enhance the action of neuromuscular blockers. In 1 patient who received a neuromuscular blocker during an operative procedure, subsequent administration of quinine 1,800 mg 3 hours later resulted in respiratory depression.
Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if quinine must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of quinine is necessary. If quinine is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a moderate CYP3A4 inhibitor like quinine can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If quinine is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Sunitinib: (Major) Avoid concurrent use of quinine with other drugs that may cause QT prolongation and torsade de pointes (TdP). Quinine has been associated with QT prolongation and rare cases of TdP. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including TdP.
Suvorexant: (Major) A dose reduction to 5 mg of suvorexant is recommended during concurrent use with quinine. The suvorexant dose may be increased to 10 mg if needed for efficacy. Suvorexant is a CYP3A4 substrate and quinine is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor increased the suvorexant AUC by 2-fold.
Tacrolimus: (Major) Concurrent use of quinine and tacrolimus should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Tacrolimus also causes QT prolongation. In addition, concentrations of tacrolimus may be increased with concomitant use of quinine. Tacrolimus is a CYP3A4 substrate and quinine is a CYP3A4 inhibitor. Reducing the tacrolimus dose, close monitoring of tacrolimus whole blood concentrations, and monitoring for QT prolongation is recommended when coadministrating tacrolimus with inhibitors of CYP3A4 that also have the potential to prolong the QT interval.
Talazoparib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with quinine is necessary. Talazoparib is a P-gp substrate and quinine is a P-gp inhibitor.
Tamoxifen: (Major) Concomitant use of tamoxifen and quinine 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.
Tamsulosin: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of quinine. Tamsulosin is extensively metabolized by CYP2D6 and CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Therefore, concomitant use with drugs that inhibit both CYP2D6 and CYP3A4, such as quinine, should be avoided.
Telavancin: (Major) Concurrent use of quinine and telavancin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Telavancin has also been associated with QT prolongation.
Telmisartan; Amlodipine: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as quinine, are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
Temsirolimus: (Major) Monitor for an increase in temsirolimus- and quinine-related adverse reactions if coadministration is necessary. Temsirolimus is a P-glycoprotein (P-gp) substrate and inhibitor. Quinine is also a P-gp substrate, as well as a weak P-gp inhibitor. Concomitant use is likely to lead to increased concentrations of quinine; exposure to temsirolimus may also increase.
Terbinafine: (Moderate) Caution is advised when administering terbinafine with quinine. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may alter the systemic exposure of both drugs. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is an inhibitor of CYP2D6 and is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP1A2, CYP2C19, and CYP3A4; quinine is a substrate of CYP2D6, an inhibitor of CYP2C19, an inducer of CYP1A2, and an inhibitor/inducer of CYP3A4. Monitor patients for adverse reactions and breakthrough fungal infections if these drugs are coadministered.
Teriflunomide: (Moderate) Use caution when administering teriflunomide and quinine concurrently. In vivo data suggest that teriflunomide is a weak inducer of CYP1A2 and an inhibitor of CYP2C8. Coadministration of teriflunomide with CYP1A2 and CYP2C8 substrates, such as quinine, may lead to increases in adverse effects or possible efficacy reduction.
Tetrabenazine: (Major) Concurrent use of quinine and tetrabenazine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Tetrabenazine causes a small increase in the corrected QT interval (QTc). In addition, concentrations of tetrabenazine may be increased with concomitant use of quinine. Tetrabenazine is a CYP2D6 substrate and quinine is a CYP2D6 inhibitor.
Tetracaine: (Moderate) Coadministration of tetracaine with oxidizing agents, such as quinine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue tetracaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Tetracycline: (Moderate) Concomitant administration of quinine and tetracycline may result in higher quinine plasma concentrations. It is recommended that patients be monitored closely for quinine-associated adverse reactions if tetracycline is given with quinine.
Tezacaftor; Ivacaftor: (Major) Adjust the tezacaftor; ivacaftor dosing schedule when coadministered with quinine; coadministration may increase tezacaftor; ivacaftor exposure and adverse reactions. When combined, dose 1 tezacaftor; ivacaftor combination tablet every other day in the morning and 1 ivacaftor tablet every other day in the morning on alternate days (i.e., tezacaftor/ivacaftor tablet on Day 1 and ivacaftor tablet on Day 2). The evening dose of ivacaftor should not be taken. Both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate); quinine is a moderate CYP3A inhibitor. Coadministration of a moderate CYP3A inhibitor increased ivacaftor exposure 3-fold. Simulation suggests a moderate inhibitor may increase tezacaftor exposure 2-fold. (Major) If quinine and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to once daily. Ivacaftor is a CYP3A substrate and quinine is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased ivacaftor exposure by 3-fold.
Theophylline, Aminophylline: (Major) The coadministration of theophylline, aminophylline with quinine may increase the Cmax and AUC of quinine and decrease the AUC of theophylline, aminophylline. This interaction may be due to the potential induction of the CYP1A2 isoenzyme by quinine as the CYP1A2 isoenzyme is the primary route of metabolism for theophylline, aminophylline. Coadministration does not require any dosage changes; however, side effects of quinine should be monitored and plasma concentrations of theophylline should be frequently monitored to ensure therapeutic concentrations.
Thioridazine: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Thioridazine is considered contraindicated for use with quinine, which when combined with thioridazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
Timolol: (Minor) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme, including timolol.
Tipranavir: (Major) Anti-retroviral protease inhibitors can inhibit the metabolism of CYP3A4 substrates such as quinine. In theory, this interaction could potentially result in drug accumulation and quinine toxicity. Monitor for potential quinine toxicity and decrease quinine dosage if needed.
Tobacco: (Major) Advise patients to avoid smoking tobacco while taking quinine. In healthy male smokers, the single dose AUC of quinine was reduced 44% and the Cmax was 18% lower than in non-smokers. Smoking has been observed to have less of an impact in patients receiving quinine for acute malaria. In malaria patients receiving a 7-day course of quinine, the AUC was reduced by 25% and the Cmax decreased 16.5% in smokers. Cigarette smoking did not appear to influence therapeutic outcomes; therefore, increasing the dose of quinine in smokers is not recommended.
Tolterodine: (Major) Concurrent use of quinine and tolterodine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Tolterodine has also been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. In a small portion of patients who poorly metabolize tolterodine via CYP2D6, the CYP3A4 pathway becomes important in tolterodine elimination. Quinine is an inhibitor of both CYP2D6 and CYP3A4; coadministation may result in increased tolterodine concentrations.
Tolvaptan: (Major) Avoid coadministration of quinine when tolvaptan is administered for hyponatremia. In patients with autosomal dominant polycystic kidney disease (ADPKD), reduce tolvaptan dosage if administered with quinine. In ADPKD patients receiving tolvaptan 90mg every morning and 30 mg every evening, reduce the dose to 45 mg every morning and 15 mg every evening; for those receiving tolvaptan 60 mg every morning and 30 mg every evening, reduce the dose to 30 mg every morning and 15 mg every evening; for those receiving tolvaptan 45 mg every morning and 15 mg every evening, reduce the dose to 15 mg every morning and 15 mg every evening. Consider additional dosage reduction if the reduced dose is not tolerated. Interrupt tolvaptan in ADPKD patients if the recommended reduced doses are not available in patients requiring short-term therapy of quinine. Tolvaptan is a sensitive CYP3A4 substrate; quinine is a moderate CYP3A4 inhibitor. Coadministration of another moderate CYP3A4 inhibitor increased the tolvaptan AUC by 200%.
Topotecan: (Major) Avoid coadministration of quinine with oral topotecan due to increased topotecan exposure; quinine may be administered with intravenous topotecan. Oral topotecan is a substrate of P-glycoprotein (P-gp) and quinine 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 quinine with toremifene due to the risk of additive QT prolongation. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. Quinine has also been associated with QT prolongation and rare cases of torsade de pointes (TdP).
Tramadol: (Moderate) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme including tramadol.
Tramadol; Acetaminophen: (Moderate) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme including tramadol.
Trandolapril; Verapamil: (Moderate) Quinine is a substrate of P-glycoprotein (PGP) and CYP3A4 and verapamil is a PGP and CYP3A4 inhibitor; therefore, quinine concentrations could be increased with coadministration. Additionally, verapamil is a CYP3A4 substrate and quinine can inhibit CYP3A4; therefore, verapamil concentrations could also be increased with coadministration. Monitor patients for increased side effects of quinine and verapamil if these drugs are given together.
Triclabendazole: (Major) Concomitant use of triclabendazole and quinine 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: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). In addition, quinine is an inhibitor of CYP2D6. Avoid concurrent use of quinine with other drugs that prolong the QT and are CYP2D6 substrates. Coadministration may result in elevated plasma concentrations of the interacting drug, causing increased risk for adverse events, such as QT prolongation. Drugs that prolong the QT and are substrates for CYP2D6 include tricyclic antidepressants.
Trifluoperazine: (Major) Concurrent use of quinine and trifluoperazine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Trifluoperazine, a phenothiazine, is also associated with a possible risk for QT prolongation and/or TdP.
Trimipramine: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). In addition, quinine is an inhibitor of CYP2D6. Avoid concurrent use of quinine with other drugs that prolong the QT and are CYP2D6 substrates. Coadministration may result in elevated plasma concentrations of the interacting drug, causing increased risk for adverse events, such as QT prolongation. Drugs that prolong the QT and are substrates for CYP2D6 include tricyclic antidepressants.
Triptorelin: (Major) Avoid coadministration of quinine with triptorelin due to the risk of QT prolongation and torsade de pointes (TdP). Quinine has been associated with QT prolongation and rare cases of TdP. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
Trospium: (Moderate) Both trospium and quinine are eliminated by active renal tubular secretion; coadministration has the potential to increase serum concentrations of trospium or quinine due to competition for the drug elimination pathway. Careful patient monitoring and dosage adjustment of trospium and/or quinine is recommended.
Tucatinib: (Moderate) Monitor for quinine-related adverse reactions if coadministration with tucatinib is necessary. Concurrent use may increase quinine exposure. Quinine 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 quinine. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a substrate of the P-gp drug transporter; quinine is a P-gp inhibitor.
Vandetanib: (Major) Avoid coadministration of vandetanib with quinine due to an increased risk of QT prolongation and torsade de pointes (TdP). Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Quinine has also been associated with QT prolongation and rare cases of TdP.
Vardenafil: (Major) Concomitant use of vardenafil and quinine 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.
Vecuronium: (Major) Avoid concomitant use of neuromuscular blockers and quinine. Quinine may enhance the action of neuromuscular blockers. In 1 patient who received a neuromuscular blocker during an operative procedure, subsequent administration of quinine 1,800 mg 3 hours later resulted in respiratory depression.
Vemurafenib: (Major) Concurrent use of quinine and vemurafenib should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If these drugs must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Both drugs have been associated with prolongation of the QT interval. In addition, both drugs are substrates of CYP3A4, quinine is a CYP3A4 inhibitor, and vemurafenib is a CYP3A4 inducer; coadministration may increase concentrations of vemurafenib and reduce concentrations of quinine.
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 quinine due to the potential for increased venetoclax exposure. Resume the original venetoclax dose 2 to 3 days after discontinuation of quinine. Venetoclax is a CYP3A4 and P-glycoprotein (P-gp) substrate; quinine is a CYP3A4 (moderate) and P-gp inhibitor. Coadministration with a single dose of another P-gp inhibitor increased venetoclax exposure by 78% in a drug interaction study.
Venlafaxine: (Moderate) Quinine inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme. Caution is recommended when administering quinine with other CYP2D6 substrates that have a narrow therapeutic range or where large increases in serum concentrations may be associated with severe adverse reactions, such as venlafaxine.
Verapamil: (Moderate) Quinine is a substrate of P-glycoprotein (PGP) and CYP3A4 and verapamil is a PGP and CYP3A4 inhibitor; therefore, quinine concentrations could be increased with coadministration. Additionally, verapamil is a CYP3A4 substrate and quinine can inhibit CYP3A4; therefore, verapamil concentrations could also be increased with coadministration. Monitor patients for increased side effects of quinine and verapamil if these drugs are given together.
Vincristine Liposomal: (Moderate) Quinine inhibits CYP3A4, and vincristine is a CYP3A substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Vincristine: (Moderate) Quinine inhibits CYP3A4, and vincristine is a CYP3A substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Vinorelbine: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with quinine is necessary. Vinorelbine is a CYP3A4 substrate and quinine is a moderate CYP3A4 inhibitor.
Voclosporin: (Major) Avoid concomitant use of quinine and voclosporin due to the risk of additive QT prolongation. Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Concurrent use of quinine with clarithromycin should be avoided due to the risk for QT prolongation and torsade de pointes (TdP). Both quinine and clarithromycin have been associated with prolongation of the QT interval. In addition, because both clarithromycin and quinine are substrates and inhibitors of CYP3A4; coadministration may result in elevated plasma concentration of both drugs, causing an increased risk for adverse events.
Vorapaxar: (Moderate) Use caution during concurrent use of vorapaxar and quinine. Quinine inhibits CYP3A and induced CYP3A4 in an in vitro study. Increased or decreased serum concentrations of vorapaxar are possible when vorapaxar, a CYP3A4 substrate, is coadministered with quinine. Increased exposure to vorapaxar may increase the risk of bleeding complications while decreased exposure to vorapaxar may reduce efficacy.
Voriconazole: (Major) Concurrent use of quinine and voriconazole should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Both drugs have been associated with prolongation of the QT interval and rare cases of TdP. Additionally, the systemic exposure of quinine may be increased, resulting in an increase in treatment-related adverse reactions. Voriconazole is a strong CYP3A4 inhibitor. Quinine is a CYP3A4 substrate.
Vorinostat: (Major) Concurrent use of quinine and vorinostat should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Vorinostat therapy is also associated with a risk of QT prolongation.
Voxelotor: (Moderate) Monitor for quinine-related adverse reactions if coadministration with voxelotor is necessary. Concurrent use may increase quinine exposure. Quinine is a CYP3A substrate and voxelotor is a moderate CYP3A inhibitor.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with quinine is necessary as concurrent use may increase or decrease the exposure of warfarin leading to increased bleeding risk or reduced efficacy. Quinine is a weak CYP3A4 inhibitor and warfarin is a CYP3A4 substrate. Quinine is also a CYP1A2 inducer and warfarin is a CYP1A2 substrate.
Ziprasidone: (Major) Concomitant use of ziprasidone and quinine should be avoided due to the potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. Quinine has been associated with QT prolongation and rare cases of TdP.
Zolpidem: (Moderate) It is advisable to closely monitor zolpidem tolerability and safety during concurrent use of quinine, a moderate CYP3A4 inhibitor, since CYP3A4 is the primary isoenzyme responsible for zolpidem metabolism. There is evidence of an increase in pharmacodynamics effects and systemic exposure of zolpidem during co-administration with some potent inhibitors of CYP3A4, such as azole antifungals.
Zonisamide: (Minor) Zonisamide is a weak inhibitor of P-glycoprotein (P-gp), and quinine 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.

Qualaquin/Quinine/Quinine Sulfate Oral Cap: 324mg

Adults

1,944 mg/day PO.

Geriatric

1,944 mg/day PO.

Adolescents

16 to 17 years: 1,944 mg/day PO.
13 to 15 years: Safety and efficacy have not been established; however, doses up to 30 mg/kg/day PO (Max: 1,944 mg/day) have been used off-label.

Children

Safety and efficacy have not been established; however, doses up to 30 mg/kg/day PO (Max: 1,944 mg/day) have been used off-label.

Infants

Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

Mechanism of Action: The drug's exact mechanism of antiprotozoal action in the treatment of malaria is not fully understood, but quinine concentrates in the parasitized erythrocytes and has a schizontocidal action. Quinine elevates the pH of parasitic acid vesicles and may upset molecular transport and phospholipase activity. It is active against the asexual erythrocytic forms of Plasmodium falciparum, P. malariae, P ovale, or P. vivax. Quinine does not provide a cure for malaria because it is not effective against exoerythrocytic forms of the parasite.Antimyotonic activity occurs through direct action on the muscle fiber, increasing the refractory period. It also decreases the excitability of the motor end-plate, reducing response to repeated nerve stimulation. Quinine also affects calcium distribution within the muscle fiber. Quinine has a curare-like action and counteracts the effects of neostigmine and physostigmine.Quinine produces cardiovascular effects similar to those of quinidine, but normal oral dosage levels have little effect in patients without cardiac dysfunction. Intravenous dosage, no longer used in the U.S., can produce severe hypotension. Quinine has been shown to prolong the Q-T interval.

Quinine is administered orally. Plasma levels are higher in patients with malaria because malaria can cause a decrease in hepatic function, with a consequent reduction in clearance. It distributes widely into liver, lungs, kidneys, and spleen, but the volume of distribution is lower in patients with malaria. There is some distribution into CSF, and the drug crosses the placenta and is excreted into breast milk. In healthy adults, about 70% is bound to plasma protein; binding is greater in patients with malaria. Plasma half-life is between 8—21 hours, and is lower in children and higher in patients with malaria. Acid urine increases the rate of excretion, which is largely of metabolites, with only a small amount as unchanged drug. Small amounts may be excreted in the feces.
 
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, P-gp
Quinine is extensively metabolized in the liver, mainly to hydroxy-metabolites. In vitro studies have shown the CYP3A4 isoenzyme is the major enzyme responsible for metabolism, and it is also a P-glycoprotein (P-gp) substrate. Other isoenzymes, including CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP2E1 have some role in the metabolism; however, the extent of involvement of each of these differs depending on methodology used in the in vitro studies. In vivo drug interactions have been observed with drugs that induce or inhibit the CYP3A4 isoenzyme. Similarly, other in vivo drug interactions have been reported with drugs that inhibit or induce CYP isoenzymes that may contribute to the metabolism of quinine such as CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP2E1. In vivo and in vitro drug interaction studies suggest that quinine has the potential to inhibit the metabolism of drugs that are substrates of CYP3A4 and CYP2D6, as well as inhibit the biliary excretion of some drugs. An in vitro study showed quinine increased the metabolic activities of CYP1A2 and CYP3A4.

Oral Route

Quinine is almost completely absorbed from the GI tract, and peak serum levels are achieved in about 1—3 hours.

Pregnancy

Guidelines support quinine use (in combination with clindamycin) for treatment of chloroquine-resistant P. falciparum malaria during all pregnancy trimesters. Prolonged experience in pregnant women over several decades has not identified a drug associated risk of major birth defects, miscarriage or adverse or maternal outcomes. Although quinine crosses the placenta with measurable blood concentrations in the fetus, fetal blood concentrations may not be therapeutic. Malaria during and after pregnancy increases the risk for adverse pregnancy and neonatal outcomes, including maternal anemia, severe malaria, spontaneous abortion, stillbirths, preterm delivery, low birth weight, intrauterine growth retardation, congenital malaria, and maternal and neonatal mortality. An increase in the incidence of low blood glucose concentrations, due to increased pancreatic secretion of insulin, has been reported with quinine use in pregnant women, especially in the third trimester. Monitor glucose concentrations in pregnant women during use. Vomiting, dizziness, nausea, and the perception of ringing or buzzing in the ears are commonly reported adverse reactions in pregnant women taking quinine. Pregnant women are also at risk for a rare triad of complications that includes massive hemolysis, hemoglobinemia, and hemoglobinuria. In doses several times higher than those used to treat malaria, quinine may cause uterine contractions; however, there is no evidence that quinine causes uterine contractions at the doses recommended for the treatment of malaria. Published data on over 1,000 pregnancy exposures to quinine did not show an increase in teratogenic effects over the background rate in the general population; however, most of these exposures were not in the first trimester. In studies in which over 893 pregnant women were treated with quinine for malaria in the first trimester, no quinine-associated increases in the incidence of congenital anomalies were observed compared with other antimalarial agents. An epidemiologic survey that included 104 mother-child pairs exposed to quinine during the first 4 months of pregnancy found no increased risk of structural birth defects. A study of women with P. falciparum malaria who were treated with oral quinine sulfate (10 mg/kg 3 times daily for 7 days) at any time in pregnancy reported no significant difference in the rate of stillbirths at more than 28 weeks of gestation in women treated with quinine compared with a control group without malaria or exposure to antimalarial drugs during pregnancy. The overall rate of congenital malformations was not different for women who were treated with quinine sulfate compared with the control group. The spontaneous abortion rate was higher in the control group (10.9%) than in women treated with quinine sulfate (3.5%) (OR 3.1; 95% CI 2.1 to 4.7). Deafness and optic nerve hypoplasia have been reported in children exposed in utero to maternal ingestion of high doses of quinine.[31403]

Quinine is excreted into breast milk. There are no data on the effects of quinine on the breast-fed infant or the effects on milk production. No toxicity was reported in infants in a single study where oral quinine sulfate (10 mg/kg every 8 hours for 1 to 10 days) was administered to 25 lactating women. Quinine concentrations in breast milk were approximately 31% of concentrations in maternal plasma. It is estimated that the breast-fed infant would receive less than 2 to 3 mg/day of quinine base (less than 0.4% of the maternal dose) via breast milk. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for quinine and any potential adverse effects on the breast-fed infant from quinine or the underlying maternal condition.[31403] Because the quantity of antimalarial drugs transferred in breast milk is insufficient to provide adequate protection against malaria, an infant who requires chemoprophylaxis must receive the recommended dosages of antimalarial drugs.