Sular

Dihydropyridine Calcium Channel Blockers

Oral Administration

Avoid grapefruit juice before or after drug administration to avoid significant increases in nisoldipine bioavailability.
Avoid administering nisoldipine with high-fat meals, which can lead to excessive peak drug concentrations.

Oral Solid Formulations

Sular extended-release tablet: Swallow whole; do not crush, break, bite, or chew. Administer on an empty stomach (1 hour before or 2 hours after a meal).

Severe

exfoliative dermatitis / Delayed / 0-1.0
azotemia / Delayed / 0-1.0
stroke / Early / 0-1.0
atrial fibrillation / Early / 0-1.0
myocardial infarction / Delayed / 0-1.0
AV block / Early / 0-1.0
visual impairment / Early / 0-1.0
angioedema / Rapid / 0-1.0
heart failure / Delayed / Incidence not known

Moderate

peripheral edema / Delayed / 7.0-29.0
palpitations / Early / 3.0-3.0
chest pain (unspecified) / Early / 2.0-2.0
skin ulcer / Delayed / 0-1.0
elevated hepatic enzymes / Delayed / 0-1.0
hepatomegaly / Delayed / 0-1.0
supraventricular tachycardia (SVT) / Early / 0-1.0
sinus tachycardia / Rapid / 0-1.0
dyspnea / Early / 0-1.0
hypotension / Rapid / 0-1.0
orthostatic hypotension / Delayed / 0-1.0
hypokalemia / Delayed / 0-1.0
leukopenia / Delayed / 0-1.0
impotence (erectile dysfunction) / Delayed / 0-1.0
anemia / Delayed / 0-1.0
gingival hyperplasia / Delayed / 0-1.0
peripheral vasodilation / Rapid / Incidence not known

Mild

headache / Early / 22.0-22.0
dizziness / Early / 3.0-7.0
pharyngitis / Delayed / 5.0-5.0
flushing / Rapid / 4.0-4.0
sinusitis / Delayed / 3.0-3.0
nausea / Early / 2.0-2.0
rash / Early / 2.0-2.0
alopecia / Delayed / 0-1.0
skin discoloration / Delayed / 0-1.0
maculopapular rash / Early / 0-1.0
diaphoresis / Early / 0-1.0
acne vulgaris / Delayed / 0-1.0
urticaria / Rapid / 0-1.0
pruritus / Rapid / 0-1.0
skin irritation / Early / 0-1.0
syncope / Early / 0-1.0
paresthesias / Delayed / 0-1.0
diarrhea / Early / 0-1.0
arthralgia / Delayed / 0-1.0
dysgeusia / Early / 0-1.0
myalgia / Early / 0-1.0
dyspepsia / Early / 0-1.0
increased urinary frequency / Early / 0-1.0
muscle cramps / Delayed / 0-1.0
tinnitus / Delayed / 0-1.0
asthenia / Delayed / Incidence not known
fatigue / Early / Incidence not known
xerosis / Delayed / Incidence not known
gynecomastia / Delayed / Incidence not known

Sular

Rx

Long-acting, oral, dihydropyridine calcium-channel blocker; similar to nifedipine, but has greater affinity and selectivity for vascular smooth muscle, produces 5-10 times greater peripheral vasodilation, and has a longer half-life allowing QD dosing; approved for HTN; off-label for angina; 10 mg nisoldipine as effective as amlodipine 5 mg as a once daily dose for HTN.

For the treatment of hypertension. Oral dosage - Extended-release tablets Adults

Initially, 17 mg PO once daily. Titrate daily dose based on clinical response by 8.5 mg at intervals of at least 1 week. The usual dosage is 17—34 mg once daily. Blood pressure response increases over the 8.5—34 mg daily dosage range, however, the incidence of peripheral edema and possibly dizziness is also increased. Doses greater than 34 mg per day are not recommended.

Geriatric

Initiate therapy at 8.5 mg PO once daily. Adjust dosage based on clinical response, up to 34 mg/day.

For the treatment of ischemic heart disease including variant angina† (Prinzmetal's angina) and stable angina† pectoris. Oral dosage - Extended-release tablets Adults

Initially, 17—34 mg PO once daily is the usual effective dose range for stable angina. The dosage range is 8.5—34 mg PO once daily.

Geriatric

Initiate therapy at 8.5 mg PO once daily. Adjust dosage based on clinical response, up to 34 mg/day.

†Indicates off-label use

Hepatic Impairment

Initiate at 8.5 mg PO once daily. Monitor blood pressure closely and adjust dose based on clinical response.

Renal Impairment

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
 
Intermittent hemodialysis:
Nisoldipine is highly protein bound and is not likely to be significantly removed by hemodialysis.

Acebutolol: (Moderate) Concurrent use of nisoldipine with acebutolol can be beneficial (i.e., inhibition of vasodilation-induced reflex tachycardia by beta-blockade); however, the additive negative inotropic and/or chronotropic effects can cause adverse effects, especially in patients with compromised ventricular function or conduction defects (e.g., sinus bradycardia or AV block).
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Acetaminophen; Dichloralphenazone; Isometheptene: (Major) Isometheptene has sympathomimetic properties. Patients taking antihypertensive agents may need to have their therapy modified. Careful blood pressure monitoring is recommended.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Acetaminophen; Ibuprofen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Acetaminophen; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Acetaminophen; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Acrivastine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Adagrasib: (Major) Avoid coadministration of nisoldipine with adagrasib due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A substrate and adagrasib is a CYP3A inhibitor. Coadministration with another CYP3A inhibitor increased the AUC of nisoldipine by 30% to 45%.
Adenosine: (Moderate) Use adenosine with caution in the presence of calcium-channel blockers due to the potential for additive or synergistic depressant effects on the sinoatrial and atrioventricular nodes.
Aldesleukin, IL-2: (Moderate) Calcium channel blockers may potentiate the hypotension seen with aldesleukin, IL 2.
Alemtuzumab: (Moderate) Alemtuzumab may cause hypotension. Careful monitoring of blood pressure and hypotensive symptoms is recommended especially in patients with ischemic heart disease and in patients on antihypertensive agents.
Alfentanil: (Moderate) Monitor patients for bradycardia and hypotension when alfentanil is coadministered with nisoldipine. Alfentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with alfentanil is increased in patients receiving nisoldipine.
Alfuzosin: (Moderate) The concomitant administration of alpha-blockers with other antihypertensive agents can cause additive hypotensive effects. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
Alprostadil: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, like calcium channel blockers, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
Amifostine: (Major) Patients receiving calcium-channel blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped for 24 hours before chemotherapy doses of amifostine, patients should not receive amifostine.
Aminolevulinic Acid: (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
Amiodarone: (Major) Avoid coadministration of nisoldipine with amiodarone 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 amiodarone is a CYP3A4 inhibitor.
Amlodipine; Celecoxib: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Amobarbital: (Major) Coadministration of nisoldipine with CYP3A4 inducers like the barbiturates should be avoided and alternative antihypertensive therapy should be considered. Coadministration of a strong CYP3A4 inducer with nisoldipine in epileptic patients lowered the nisoldipine plasma concentrations to undetectable levels. Barbiturates (e.g., phenobarbital, primidone) may also decrease the oral bioavailability of nisoldipine via increased hepatic drug clearance.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid coadministration of nisoldipine with clarithromycin, particularly in geriatric patients, due to increased plasma concentrations of nisoldipine. If the use of a macrolide antibiotic is necessary in a patient receiving nisoldipine therapy, azithromycin is the preferred agent. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A4 substrate and clarithromycin is a CYP3A4 inhibitor. A retrospective, case crossover study, found the risk of hospitalization due to hypotension or shock to be significantly increased in geriatric patients exposed to clarithromycin during concurrent calcium-channel blocker therapy (OR 3.7, 95% CI 2.3-6.1). Concurrent use of azithromycin was not associated with an increased risk of hypotension (OR 1.5, 95% CI 0.8-2.8).
Amphetamine; Dextroamphetamine Salts: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
Apalutamide: (Major) Avoid coadministration of nisoldipine with apalutamide due to decreased plasma concentrations of nisoldipine. Nisoldipine is a CYP3A4 substrate and enzalutamide is a apalutamide CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Apomorphine: (Moderate) Use of calcium-channel blockers and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination.
Apraclonidine: (Minor) Apraclonidine had minimal effects on heart rate and blood pressure during clinical studies in patients with glaucoma. However, it is theoretically possible that additive blood pressure reductions could occur when apraclonidine is combined with the use of antihypertensive agents. Use caution during concurrent use, especially in patients with severe, uncontrolled cardiovascular disease, including hypertension.
Aprepitant, Fosaprepitant: (Major) Avoid coadministration of nisoldipine with multi-day regimens of oral aprepitant due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use. Nisoldipine is a CYP3A4 substrate and aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a CYP3A4 inhibitor. When administered as a single oral or single intravenous dose, the inhibitory effect of aprepitant on CYP3A4 is weak and did not result in a clinically significant increase in the AUC of a sensitive substrate.
Aripiprazole: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Armodafinil: (Major) Avoid coadministration of nisoldipine with armodafinil due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and armodafinil is a weak CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Articaine; Epinephrine: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
Asciminib: (Major) Avoid coadministration of nisoldipine with asciminib due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A substrate and asciminib is a CYP3A inhibitor. Coadministration with another CYP3A inhibitor increased the AUC of nisoldipine by 30% to 45%.
Asenapine: (Moderate) Secondary to alpha-blockade, asenapine can produce vasodilation that may result in additive effects during concurrent use of antihypertensive agents. The potential reduction in blood pressure can precipitate orthostatic hypotension and associated dizziness, tachycardia, and syncope. If concurrent use of asenapine and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
Aspirin, ASA; Butalbital; Caffeine: (Major) Coadministration of nisoldipine with CYP3A4 inducers like the barbiturates should be avoided and alternative antihypertensive therapy should be considered. Coadministration of a strong CYP3A4 inducer with nisoldipine in epileptic patients lowered the nisoldipine plasma concentrations to undetectable levels. Barbiturates (e.g., phenobarbital, primidone) may also decrease the oral bioavailability of nisoldipine via increased hepatic drug clearance.
Atazanavir: (Major) Avoid coadministration of nisoldipine with protease inhibitors due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A substrate and protease inhibitors are moderate to strong CYP3A inhibitors. Coadministration with another CYP3A inhibitor increased the AUC of nisoldipine by 30% to 45%.
Atazanavir; Cobicistat: (Major) Avoid coadministration of nisoldipine with cobicistat 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 cobicistat is a strong CYP3A4 inhibitor. (Major) Avoid coadministration of nisoldipine with protease inhibitors due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A substrate and protease inhibitors are moderate to strong CYP3A inhibitors. Coadministration with another CYP3A inhibitor increased the AUC of nisoldipine by 30% to 45%.
Atenolol: (Moderate) Concurrent use of nisoldipine with atenolol can be beneficial (i.e., inhibition of vasodilation-induced reflex tachycardia by beta-blockade); however, the additive negative inotropic and/or chronotropic effects can cause adverse effects, especially in patients with compromised ventricular function or conduction defects (e.g., sinus bradycardia or AV block). Pharmacokinetic interactions between nisoldipine and atenolol are variable and not significant.
Atenolol; Chlorthalidone: (Moderate) Concurrent use of nisoldipine with atenolol can be beneficial (i.e., inhibition of vasodilation-induced reflex tachycardia by beta-blockade); however, the additive negative inotropic and/or chronotropic effects can cause adverse effects, especially in patients with compromised ventricular function or conduction defects (e.g., sinus bradycardia or AV block). Pharmacokinetic interactions between nisoldipine and atenolol are variable and not significant.
Avacopan: (Major) Avoid coadministration of nisoldipine with avacopan due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A substrate and avacopan is a CYP3A inhibitor. Coadministration with another CYP3A inhibitor increased the AUC of nisoldipine by 30% to 45%.
Baclofen: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
Barbiturates: (Major) Coadministration of nisoldipine with CYP3A4 inducers like the barbiturates should be avoided and alternative antihypertensive therapy should be considered. Coadministration of a strong CYP3A4 inducer with nisoldipine in epileptic patients lowered the nisoldipine plasma concentrations to undetectable levels. Barbiturates (e.g., phenobarbital, primidone) may also decrease the oral bioavailability of nisoldipine via increased hepatic drug clearance.
Belumosudil: (Major) Avoid coadministration of nisoldipine with belumosudil due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A substrate and belumosudil is a CYP3A inhibitor. Coadministration with another CYP3A inhibitor increased the AUC of nisoldipine by 30% to 45%.
Belzutifan: (Major) Avoid coadministration of nisoldipine with belzutifan as concurrent use may decrease nisoldipine exposure and efficacy. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A substrate and belzutifan is a CYP3A inducer. Coadministration with a strong CYP3A inducer lowered nisoldipine plasma concentrations to undetectable levels.
Benzphetamine: (Minor) Benzphetamine might increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
Berotralstat: (Major) Avoid coadministration of nisoldipine with berotralstat 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 berotralstat is a CYP3A4 inhibitor. Coadministration with another CYP3A4 inhibitor increased the AUC of nisoldipine by 30% to 45%.
Betaxolol: (Moderate) Concurrent use of nisoldipine with betaxolol can be beneficial (i.e., inhibition of vasodilation-induced reflex tachycardia by beta-blockade); however, the additive negative inotropic and/or chronotropic effects can cause adverse effects, especially in patients with compromised ventricular function or conduction defects (e.g., sinus bradycardia or AV block).
Bexarotene: (Major) Avoid coadministration of nisoldipine with bexarotene due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and bexarotene is a CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Bicalutamide: (Major) Avoid coadministration of nisoldipine with bicalutamide 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 bicalutamide is a weak CYP3A4 inhibitor.
Bisoprolol: (Moderate) Concurrent use of nisoldipine with bisoprolol can be beneficial (i.e., inhibition of vasodilation-induced reflex tachycardia by beta-blockade); however, the additive negative inotropic and/or chronotropic effects can cause adverse effects, especially in patients with compromised ventricular function or conduction defects (e.g., sinus bradycardia or AV block).
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent use of nisoldipine with bisoprolol can be beneficial (i.e., inhibition of vasodilation-induced reflex tachycardia by beta-blockade); however, the additive negative inotropic and/or chronotropic effects can cause adverse effects, especially in patients with compromised ventricular function or conduction defects (e.g., sinus bradycardia or AV block).
Bortezomib: (Moderate) Patients on antihypertensive agents receiving bortezomib treatment may require close monitoring of their blood pressure and dosage adjustment of their medication. During clinical trials of bortezomib, hypotension was reported in roughly 12 percent of patients.
Bosentan: (Major) Avoid coadministration of nisoldipine with bosentan due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and bosentan is a CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Brigatinib: (Moderate) Avoid coadministration of nisoldipine with brigatinib as concurrent use may decrease nisoldipine exposure and efficacy. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and brigatinib is a CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Brimonidine; Timolol: (Moderate) Concurrent use of nisoldipine with timolol can be beneficial (i.e., inhibition of vasodilation-induced reflex tachycardia by beta-blockade); however, the additive negative inotropic and/or chronotropic effects can cause adverse effects, especially in patients with compromised ventricular function or conduction defects (e.g., sinus bradycardia or AV block).
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Brompheniramine; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Brompheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Bupivacaine; Epinephrine: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
Bupivacaine; Meloxicam: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Butabarbital: (Major) Coadministration of nisoldipine with CYP3A4 inducers like the barbiturates should be avoided and alternative antihypertensive therapy should be considered. Coadministration of a strong CYP3A4 inducer with nisoldipine in epileptic patients lowered the nisoldipine plasma concentrations to undetectable levels. Barbiturates (e.g., phenobarbital, primidone) may also decrease the oral bioavailability of nisoldipine via increased hepatic drug clearance.
Butalbital; Acetaminophen: (Major) Coadministration of nisoldipine with CYP3A4 inducers like the barbiturates should be avoided and alternative antihypertensive therapy should be considered. Coadministration of a strong CYP3A4 inducer with nisoldipine in epileptic patients lowered the nisoldipine plasma concentrations to undetectable levels. Barbiturates (e.g., phenobarbital, primidone) may also decrease the oral bioavailability of nisoldipine via increased hepatic drug clearance.
Butalbital; Acetaminophen; Caffeine: (Major) Coadministration of nisoldipine with CYP3A4 inducers like the barbiturates should be avoided and alternative antihypertensive therapy should be considered. Coadministration of a strong CYP3A4 inducer with nisoldipine in epileptic patients lowered the nisoldipine plasma concentrations to undetectable levels. Barbiturates (e.g., phenobarbital, primidone) may also decrease the oral bioavailability of nisoldipine via increased hepatic drug clearance.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Coadministration of nisoldipine with CYP3A4 inducers like the barbiturates should be avoided and alternative antihypertensive therapy should be considered. Coadministration of a strong CYP3A4 inducer with nisoldipine in epileptic patients lowered the nisoldipine plasma concentrations to undetectable levels. Barbiturates (e.g., phenobarbital, primidone) may also decrease the oral bioavailability of nisoldipine via increased hepatic drug clearance.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Coadministration of nisoldipine with CYP3A4 inducers like the barbiturates should be avoided and alternative antihypertensive therapy should be considered. Coadministration of a strong CYP3A4 inducer with nisoldipine in epileptic patients lowered the nisoldipine plasma concentrations to undetectable levels. Barbiturates (e.g., phenobarbital, primidone) may also decrease the oral bioavailability of nisoldipine via increased hepatic drug clearance.
Cabergoline: (Moderate) Cabergoline should be used cautiously with antihypertensive agents, including nisoldipine. Cabergoline has been associated with hypotension. Initial doses of cabergoline higher than 1 mg may produce orthostatic hypotension. It may be advisable to monitor blood pressure.
Calcium: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Carbamazepine: (Major) Avoid coadministration of nisoldipine with carbamazepine due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Carbidopa; Levodopa: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Carbidopa; Levodopa; Entacapone: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Cariprazine: (Moderate) Orthostatic vital signs should be monitored in patients who are at risk for hypotension, such as those receiving cariprazine in combination with antihypertensive agents. Atypical antipsychotics may cause orthostatic hypotension and syncope, most commonly during treatment initiation and dosage increases. Patients should be informed about measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning, or rising slowly from a seated position. Consider a cariprazine dose reduction if hypotension occurs.
Carteolol: (Moderate) Concurrent use of nisoldipine with carteolol can be beneficial (i.e., inhibition of vasodilation-induced reflex tachycardia by beta-blockade); however, the additive negative inotropic and/or chronotropic effects can cause adverse effects, especially in patients with compromised ventricular function or conduction defects (e.g., sinus bradycardia or AV block).
Carvedilol: (Moderate) Concurrent use of nisoldipine with carvedilol can be beneficial (i.e., inhibition of vasodilation-induced reflex tachycardia by beta-blockade); however, the additive negative inotropic and/or chronotropic effects can cause adverse effects, especially in patients with compromised ventricular function or conduction defects (e.g., sinus bradycardia or AV block).
Celecoxib: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Celecoxib; Tramadol: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Cenobamate: (Major) Avoid coadministration of nisoldipine with cenobamate as concurrent use may decrease nisoldipine exposure and efficacy. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and cenobamate is a moderate CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Ceritinib: (Major) Avoid coadministration of nisoldipine with ceritinib 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 ceritinib is a strong CYP3A4 inhibitor.
Cetirizine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Chloramphenicol: (Major) Avoid coadministration of nisoldipine with chloramphenicol 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 chloramphenicol is a strong CYP3A4 inhibitor.
Chloroprocaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Chlorpheniramine; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Chlorpheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Cimetidine: (Moderate) Avoid coadministration of nisoldipine with cimetidine due to increased plasma concentrations of nisoldipine. Coadministration of cimetidine and nisoldipine increased nisoldipine exposure by 30% to 45%. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A4 substrate and cimetidine is a weak CYP3A4 inhibitor.
Ciprofloxacin: (Major) Avoid coadministration of nisoldipine with ciprofloxacin 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 ciprofloxacin is a CYP3A4 inhibitor.
Clarithromycin: (Major) Avoid coadministration of nisoldipine with clarithromycin, particularly in geriatric patients, due to increased plasma concentrations of nisoldipine. If the use of a macrolide antibiotic is necessary in a patient receiving nisoldipine therapy, azithromycin is the preferred agent. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A4 substrate and clarithromycin is a CYP3A4 inhibitor. A retrospective, case crossover study, found the risk of hospitalization due to hypotension or shock to be significantly increased in geriatric patients exposed to clarithromycin during concurrent calcium-channel blocker therapy (OR 3.7, 95% CI 2.3-6.1). Concurrent use of azithromycin was not associated with an increased risk of hypotension (OR 1.5, 95% CI 0.8-2.8).
Clobazam: (Major) Avoid coadministration of nisoldipine with clobazam due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and clobazam is a mild CYP3A4 inducer. Coadministration with a CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Clozapine: (Major) Clozapine used concomitantly with the antihypertensive agents can increase the risk and severity of hypotension by potentiating the effect of the antihypertensive drug.
Cobicistat: (Major) Avoid coadministration of nisoldipine with cobicistat 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 cobicistat is a strong CYP3A4 inhibitor.
Cocaine: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Codeine; Phenylephrine; Promethazine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Co-Enzyme Q10, Ubiquinone: (Moderate) Co-enzyme Q10, ubiquinone (CoQ10) may lower blood pressure. CoQ10 use in combination with antihypertensive agents may lead to additional reductions in blood pressure in some individuals. Patients who choose to take CoQ10 concurrently with antihypertensive medications should receive periodic blood pressure monitoring. Patients should be advised to inform their prescriber of their use of CoQ10.
Conivaptan: (Major) Avoid coadministration of nisoldipine with conivaptan due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A substrate and conivaptan is a CYP3A inhibitor. Coadministration with another CYP3A inhibitor increased the AUC of nisoldipine by 30% to 45%.
Crizotinib: (Major) In general, coadministration of nisoldipine with crizotinib should be avoided due to increased nisoldipine exposure. Crizotinib is a moderate CYP3A inhibitor and nisoldipine is a CYP3A substrate.
Cyclosporine: (Major) Avoid coadministration of nisoldipine with cyclosporine 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 cyclosporine is a CYP3A4 inhibitor.
Dabrafenib: (Major) Avoid the concomitant use of dabrafenib and nisoldipine; decreased nisoldipine concentrations and loss of efficacy may occur. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of nisoldipine efficacy. Dabrafenib is a moderate CYP3A4 inducer and nisoldipine is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
Dalfopristin; Quinupristin: (Major) Avoid coadministration of nisoldipine with dalfopristin; quinupristin due to increased plasma concentrations of nisoldipine. Nisoldipine is a CYP3A4 substrate and dalfopristin; quinupristin is a weak CYP3A4 inhibitor.
Danazol: (Major) Avoid coadministration of nisoldipine with danazol 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 danazol is a CYP3A4 inhibitor.
Dantrolene: (Moderate) Concurrent use with skeletal muscle relaxants and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
Darunavir: (Major) Avoid coadministration of nisoldipine with protease inhibitors due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A substrate and protease inhibitors are moderate to strong CYP3A inhibitors. Coadministration with another CYP3A inhibitor increased the AUC of nisoldipine by 30% to 45%.
Darunavir; Cobicistat: (Major) Avoid coadministration of nisoldipine with cobicistat 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 cobicistat is a strong CYP3A4 inhibitor. (Major) Avoid coadministration of nisoldipine with protease inhibitors due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A substrate and protease inhibitors are moderate to strong CYP3A inhibitors. Coadministration with another CYP3A inhibitor increased the AUC of nisoldipine by 30% to 45%.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid coadministration of nisoldipine with cobicistat 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 cobicistat is a strong CYP3A4 inhibitor. (Major) Avoid coadministration of nisoldipine with protease inhibitors due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A substrate and protease inhibitors are moderate to strong CYP3A inhibitors. Coadministration with another CYP3A inhibitor increased the AUC of nisoldipine by 30% to 45%.
Deferasirox: (Major) Avoid coadministration of nisoldipine with deferasirox due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and deferasirox is a weak CYP3A4 inducer. Coadministration with a CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Delavirdine: (Major) Avoid coadministration of nisoldipine with delavirdine 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 delavirdine is a CYP3A4 inhibitor.
Desloratadine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Desogestrel; Ethinyl Estradiol: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Dexamethasone: (Major) Avoid coadministration of nisoldipine with dexamethasone as concurrent use may decrease nisoldipine exposure and efficacy. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A substrate and dexamethasone is a CYP3A inducer. Coadministration with a strong CYP3A inducer lowered nisoldipine plasma concentrations to undetectable levels.
Dexbrompheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Dexmedetomidine: (Moderate) Concomitant administration of dexmedetomidine and calcium-channel blockers could lead to additive hypotension and bradycardia; use together with caution. Dexmedetomidine can produce bradycardia or AV block and should be used cautiously in patients who are receiving antihypertensive drugs that may lower the heart rate such as calcium-channel blockers.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Dextromethorphan; Quinidine: (Moderate) Quinidine may decrease the bioavailability of nisoldipine by 26% without affecting the peak concentration. Monitoring serum quinidine concentrations is prudent following the addition or discontinuation of nisoldipine.
Diazoxide: (Moderate) Additive hypotensive effects can occur with the concomitant administration of diazoxide with other antihypertensive agents. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly. The manufacturer advises that IV diazoxide should not be administered to patients within 6 hours of receiving other antihypertensive agents.
Diclofenac: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Diclofenac; Misoprostol: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Diethylpropion: (Major) Diethylpropion has vasopressor effects and may limit the benefit of calcium-channel blockers. Although leading drug interaction texts differ in the potential for an interaction between diethylpropion and this group of antihypertensive agents, these effects are likely to be clinically significant and have been described in hypertensive patients on these medications.
Diflunisal: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Digoxin: (Moderate) The manufacturer of Sular reports that there are no significant interactions between nisoldipine core-coat and warfarin or digoxin. However, in a study of chronic coadministration of immediate release nisoldipine and digoxin in 10 patients with heart failure, nisoldipine was shown to elevate trough digoxin plasma concentrations by about 15%. A structurally related dihydropyridine, nifedipine, has been reported to increase digoxin levels up to 45%. In individual patients, significant elevation of digoxin plasma levels could occur with nisoldipine coadministration; monitoring of digoxin levels is advised.
Diphenhydramine; Ibuprofen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Diphenhydramine; Naproxen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Diphenhydramine; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Dorzolamide; Timolol: (Moderate) Concurrent use of nisoldipine with timolol can be beneficial (i.e., inhibition of vasodilation-induced reflex tachycardia by beta-blockade); however, the additive negative inotropic and/or chronotropic effects can cause adverse effects, especially in patients with compromised ventricular function or conduction defects (e.g., sinus bradycardia or AV block).
Dronedarone: (Major) In general, coadministration of nisoldipine with dronedarone should be avoided due to increased nisoldipine exposure. Dronedarone is a moderate CYP3A inhibitor and nisoldipine is a sensitive CYP3A substrate.
Drospirenone; Ethinyl Estradiol: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Duloxetine: (Moderate) Orthostatic hypotension and syncope have been reported during duloxetine administration. The concurrent administration of antihypertensive agents and duloxetine may increase the risk of hypotension. Monitor blood pressure if the combination is necessary.
Dutasteride; Tamsulosin: (Moderate) The concomitant administration of tamsulosin with other antihypertensive agents can cause additive hypotensive effects. In addition, diltiazem, nicardipine, and verapamil may increase tamsulosin plasma concentrations via CYP3A4 inhibition. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
Duvelisib: (Major) Avoid coadministration of nisoldipine with duvelisib due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a sensitive CYP3A substrate and duvelisib is a moderate CYP3A inhibitor.
Efavirenz: (Major) Avoid coadministration of nisoldipine with efavirenz due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and efavirenz is a CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of nisoldipine with efavirenz due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and efavirenz is a CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of nisoldipine with efavirenz due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and efavirenz is a CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Elagolix: (Major) Avoid coadministration of nisoldipine with elagolix due to decreased plasma concentrations of nisoldipine. Nisoldipine is a CYP3A4 substrate and enzalutamide is a elagolix weak to moderate CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Elagolix; Estradiol; Norethindrone acetate: (Major) Avoid coadministration of nisoldipine with elagolix due to decreased plasma concentrations of nisoldipine. Nisoldipine is a CYP3A4 substrate and enzalutamide is a elagolix weak to moderate CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetec

table levels.
Elbasvir; Grazoprevir: (Moderate) Administering nisoldipine with elbasvir; grazoprevir may result in elevated nisoldipine plasma concentrations. Nisoldipine is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
Elexacaftor; tezacaftor; ivacaftor: (Major) Avoid coadministration of nisoldipine with ivacaftor 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 ivacaftor is a CYP3A4 inhibitor.
Eluxadoline: (Major) Avoid coadministration of nisoldipine with eluxadoline 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 eluxadoline is a weak CYP3A4 inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid coadministration of nisoldipine with cobicistat 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 cobicistat is a strong CYP3A4 inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of nisoldipine with cobicistat 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 cobicistat is a strong CYP3A4 inhibitor.
Empagliflozin: (Moderate) Administer antidiabetic agents with caution in patients receiving calcium-channel blockers. These drugs may cause hyperglycemia leading to a temporary loss of glycemic control in patients receiving antidiabetic agents. Close observation and monitoring of blood glucose is necessary to maintain adequate glycemic control.
Empagliflozin; Linagliptin: (Moderate) Administer antidiabetic agents with caution in patients receiving calcium-channel blockers. These drugs may cause hyperglycemia leading to a temporary loss of glycemic control in patients receiving antidiabetic agents. Close observation and monitoring of blood glucose is necessary to maintain adequate glycemic control.
Empagliflozin; Linagliptin; Metformin: (Moderate) Administer antidiabetic agents with caution in patients receiving calcium-channel blockers. These drugs may cause hyperglycemia leading to a temporary loss of glycemic control in patients receiving antidiabetic agents. Close observation and monitoring of blood glucose is necessary to maintain adequate glycemic control.
Empagliflozin; Metformin: (Moderate) Administer antidiabetic agents with caution in patients receiving calcium-channel blockers. These drugs may cause hyperglycemia leading to a temporary loss of glycemic control in patients receiving antidiabetic agents. Close observation and monitoring of blood glucose is necessary to maintain adequate glycemic control.
Encorafenib: (Moderate) Coadministration of encorafenib with nisoldipine may result in increased toxicity or decreased efficacy of nisoldipine. Nisoldipine is a sensitive CYP3A4 substrate. In vitro studies with encorafenib showed time-dependent inhibition of CYP3A4 and induction of CYP3A4. The clinical relevance of the in vivo effect of encorafenib on CYP3A4 is not established.
Enzalutamide: (Major) Avoid coadministration of nisoldipine with enzalutamide due to decreased plasma concentrations of nisoldipine. Nisoldipine is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Ephedrine: (Major) The cardiovascular effects of sympathomimetics, such as ephedrine, may reduce the antihypertensive effects produced by calcium-channel blockers. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Ephedrine; Guaifenesin: (Major) The cardiovascular effects of sympathomimetics, such as ephedrine, may reduce the antihypertensive effects produced by calcium-channel blockers. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Epinephrine: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
Epirubicin: (Moderate) Close cardiac monitoring is recommended throughout therapy in patients receiving concomitant therapy with epirubicin and calcium-channel blockers. Individuals receiving these medications together are at increased risk of developing heart failure.
Eplerenone: (Moderate) Nisoldipine can have additive hypotensive effects with other antihypertensive agents. This additive effect can be desirable, but the patient should be monitored carefully and the dosage should be adjusted based on clinical response.
Epoprostenol: (Moderate) Calcium-channel blockers can have additive hypotensive effects with other antihypertensive agents. This additive effect can be desirable, but the patient should be monitored carefully and the dosage should be adjusted based on clinical response.
Erythromycin: (Major) Avoid administration of erythromycin and nisoldipine, particularly in geriatric patients. Coadministration has been associated with an increased risk of hypotension and shock. Azithromycin may be preferred if the use of a macrolide antibiotic is necessary in a patient receiving nisoldipine therapy. If coadministration is unavoidable, monitor blood pressure and heart rate. Nisoldipine is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor.
Eslicarbazepine: (Major) Avoid coadministration of nisoldipine with eslicarbazepine due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and eslicarbazepine is a CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Esmolol: (Moderate) Concurrent use of nisoldipine with esmolol can be beneficial (i.e., inhibition of vasodilation-induced reflex tachycardia by beta-blockade); however, the additive negative inotropic and/or chronotropic effects can cause adverse effects, especially in patients with compromised ventricular function or conduction defects (e.g., sinus bradycardia or AV block).
Estradiol: (Minor) Estrogens can induce fluid retention and may increase blood pressure in some patients; patients who are receiving antihypertensive agents concurrently with hormone therapy should be monitored for antihypertensive effectiveness.
Ethinyl Estradiol; Norelgestromin: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Ethinyl Estradiol; Norethindrone Acetate: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Ethinyl Estradiol; Norgestrel: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Ethynodiol Diacetate; Ethinyl Estradiol: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Etodolac: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Etomidate: (Major) The depression of cardiac contractility, conductivity, and automaticity as well as the vascular dilation associated with general anesthetics may be potentiated by calcium-channel blockers. Alternatively, general anesthetics can potentiate the hypotensive effects of calcium-channel blockers. When used concomitantly, anesthetics and calcium-channel blockers should be titrated carefully to avoid excessive cardiovascular depression.
Etonogestrel; Ethinyl Estradiol: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Etravirine: (Major) Avoid coadministration of nisoldipine with etravirine due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and etravirine is a CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Everolimus: (Major) Avoid coadministration of nisoldipine with everolimus due to increased plasma concentrations of nisoldipine. Nisoldipine is a CYP3A4 substrate and everolimus is a weak CYP3A4 inhibitor.
Fedratinib: (Major) Avoid coadministration of nisoldipine with fedratinib 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 fedratinib is a CYP3A4 inhibitor.
Fenoprofen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Fentanyl: (Moderate) Monitor patients for bradycardia and hypotension when fentanyl is coadministered with nisoldipine. Fentanyl may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with fentanyl is increased in patients receiving nisoldipine.
Fexofenadine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Fish Oil, Omega-3 Fatty Acids (Dietary Supplements): (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Fluconazole: (Major) Avoid coadministration of nisoldipine with fluconazole 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 fluconazole is a CYP3A4 inhibitor.
Fluoxetine: (Major) Avoid coadministration of nisoldipine with fluoxetine 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 fluoxetine is a CYP3A4 inhibitor.
Flurbiprofen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Fluvoxamine: (Major) Avoid coadministration of nisoldipine with fluvoxamine 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 fluvoxamine is a CYP3A4 inhibitor.
Fosamprenavir: (Major) Avoid coadministration of nisoldipine with protease inhibitors due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A substrate and protease inhibitors are moderate to strong CYP3A inhibitors. Coadministration with another CYP3A inhibitor increased the AUC of nisoldipine by 30% to 45%.
Fosphenytoin: (Major) Coadministration of nisoldipine with fosphenytoin should be avoided and alternative antihypertensive therapy should be considered. Coadministration of phenytoin with nisoldipine in epileptic patients lowered the nisoldipine plasma concentrations to undetectable levels.
Fostamatinib: (Major) Avoid coadministration of nisoldipine with fostamatinib due to increased plasma concentrations of nisoldipine. Nisoldipine is a CYP3A4 substrate and fostamatinib is a weak CYP3A4 inhibitor.
General anesthetics: (Major) The depression of cardiac contractility, conductivity, and automaticity as well as the vascular dilation associated with general anesthetics may be potentiated by calcium-channel blockers. Alternatively, general anesthetics can potentiate the hypotensive effects of calcium-channel blockers. When used concomitantly, anesthetics and calcium-channel blockers should be titrated carefully to avoid excessive cardiovascular depression.
Ginkgo, Ginkgo biloba: (Moderate) Ginkgo biloba appears to inhibit the metabolism of calcium-channel blockers, perhaps by inhibiting the CYP3A4 isoenzyme. A non-controlled pharmacokinetic study in healthy volunteers found that the concurrent administration of ginkgo with nifedipine resulted in a 53% increase in nifedipine peak concentrations. More study is needed regarding ginkgo's effects on CYP3A4 and whether clinically significant drug interactions result.
Ginseng, Panax ginseng: (Moderate) Ginseng appears to inhibit the metabolism of calcium-channel blockers, perhaps by inhibiting the CYP3A4 isoenzyme. A non-controlled pharmacokinetic study in healthy volunteers found that the concurrent administration of ginseng with nifedipine resulted in a 30% increase in nifedipine peak concentrations. More study is needed regarding ginseng's effects on CYP3A4 and whether clinically significant drug interactions result.
Glycerol Phenylbutyrate: (Major) Avoid coadministration of nisoldipine with glycerol phenylbutyrate as concurrent use may decrease nisoldipine exposure and efficacy. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A substrate and glycerol phenylbutyrate is a CYP3A inducer. Coadministration with a strong CYP3A inducer lowered nisoldipine plasma concentrations to undetectable levels.
Grapefruit juice: (Major) Grapefruit juice contains compounds that inhibit cytochrome P-450 CYP3A4 isozymes in the gut wall. Grapefruit juice can increase the serum concentrations and oral bioavailability of nisoldipine. Concomitant ingestion of grapefruit juice with nisoldipine should be avoided since coadministration may result in an increase in Cmax and AUC.
Guaifenesin; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Haloperidol: (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
Hydrocodone; Ibuprofen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Hydrocodone; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Ibuprofen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Ibuprofen; Famotidine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Ibuprofen; Oxycodone: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Ibuprofen; Pseudoephedrine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Idelalisib: (Major) Avoid coadministration of nisoldipine with idelalisib 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 idelalisib is a strong CYP3A4 inhibitor.
Iloperidone: (Moderate) Secondary to alpha-blockade, iloperidone can produce vasodilation that may result in additive effects during concurrent use with antihypertensive agents. The potential reduction in blood pressure can precipitate orthostatic hypotension and associated dizziness, tachycardia, and syncope. If concurrent use of iloperidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
Iloprost: (Moderate) Calcium-channel blockers can have additive hypotensive effects with other antihypertensive agents. This additive effect can be desirable, but the patient should be monitored carefully and the dosage should be adjusted based on clinical response.
Imatinib: (Major) Avoid coadministration of nisoldipine with imatinib 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 imatinib is a CYP3A4 inhibitor.
Indinavir: (Major) Avoid coadministration of nisoldipine with protease inhibitors due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A substrate and protease inhibitors are moderate to strong CYP3A inhibitors. Coadministration with another CYP3A inhibitor increased the AUC of nisoldipine by 30% to 45%.
Indomethacin: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Intravenous Lipid Emulsions: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Isavuconazonium: (Major) Avoid coadministration of nisoldipine with isavuconazonium 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 isavuconazonium is a CYP3A4 inhibitor.
Isocarboxazid: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with calcium-channel blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
Isoflurane: (Major) The depression of cardiac contractility, conductivity, and automaticity as well as the vascular dilation associated with general anesthetics may be potentiated by calcium-channel blockers. Alternatively, general anesthetics can potentiate the hypotensive effects of calcium-channel blockers. When used concomitantly, anesthetics and calcium-channel blockers should be titrated carefully to avoid excessive cardiovascular depression.
Isoniazid, INH: (Major) Avoid coadministration of nisoldipine with isoniazid 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 isoniazid is a CYP3A4 inhibitor.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid coadministration of nisoldipine with isoniazid 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 isoniazid is a CYP3A4 inhibitor. (Major) Avoid coadministration of nisoldipine with rifampin due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Isoniazid, INH; Rifampin: (Major) Avoid coadministration of nisoldipine with isoniazid 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 isoniazid is a CYP3A4 inhibitor. (Major) Avoid coadministration of nisoldipine with rifampin due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Isoproterenol: (Moderate) The pharmacologic effects of isoproterenol may cause an increase in blood pressure. If isoproterenol is used concomitantly with antihypertensives, the blood pressure should be monitored as the administration of isoproterenol can compromise the effectiveness of antihypertensive agents.
Isosorbide Dinitrate, ISDN: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
Isosorbide Mononitrate: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
Istradefylline: (Major) Avoid coadministration of nisoldipine with istradefylline 40 mg daily 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; istradefylline administered as 40 mg daily is a weak CYP3A4 inhibitor. There was no effect on drug exposure when istradefylline 20 mg daily was coadministered with a sensitive CYP3A4 substrate.
Itraconazole: (Contraindicated) Nisoldipine is contraindicated for use during and for 2 weeks after itraconazole therapy. Itraconazole is an inhibitor of cytochrome P450 3A4, which significantly increases nisoldipine exposure. Calcium-channel blockers can have a negative inotropic effect that may be additive to those of itraconazole. Edema has been reported in patients receiving itraconazole and dihydropyridine calcium-channel blockers concomitantly.
Ivacaftor: (Major) Avoid coadministration of nisoldipine with ivacaftor 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 ivacaftor is a CYP3A4 inhibitor.
Ivosidenib: (Major) Avoid coadministration of nisoldipine with ivosidenib due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a sensitive CYP3A4 substrate and ivosidenib is a CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Ketamine: (Major) The depression of cardiac contractility, conductivity, and automaticity as well as the vascular dilation associated with general anesthetics may be potentiated by calcium-channel blockers. Alternatively, general anesthetics can potentiate the hypotensive effects of calcium-channel blockers. When used concomitantly, anesthetics and calcium-channel blockers should be titrated carefully to avoid excessive cardiovascular depression.
Ketoconazole: (Major) Avoid coadministration of nisoldipine with ketoconazole 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 ketoconazole is a CYP3A4 inhibitor. Coadministration with ketoconazole increased the AUC of nisoldipine by 24-fold.
Ketoprofen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Ketorolac: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Labetalol: (Moderate) Concurrent use of nisoldipine with labetalol can be beneficial (i.e., inhibition of vasodilation-induced reflex tachycardia by beta-blockade); however, the additive negative inotropic and/or chronotropic effects can cause adverse effects, especially in patients with compromised ventricular function or conduction defects (e.g., sinus bradycardia or AV block).
Lacosamide: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as calcium-channel blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Lanreotide: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., calcium-channel blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the calcium-channel blocker dose if necessary.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of nisoldipine with clarithromycin, particularly in geriatric patients, due to increased plasma concentrations of nisoldipine. If the use of a macrolide antibiotic is necessary in a patient receiving nisoldipine therapy, azithromycin is the preferred agent. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A4 substrate and clarithromycin is a CYP3A4 inhibitor. A retrospective, case crossover study, found the risk of hospitalization due to hypotension or shock to be significantly increased in geriatric patients exposed to clarithromycin during concurrent calcium-channel blocker therapy (OR 3.7, 95% CI 2.3-6.1). Concurrent use of azithromycin was not associated with an increased risk of hypotension (OR 1.5, 95% CI 0.8-2.8).
Lapatinib: (Major) Avoid coadministration of nisoldipine with lapatinib 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 lapatinib is a CYP3A4 inhibitor.
Larotrectinib: (Major) Avoid coadministration of nisoldipine with larotrectinib due to increased plasma concentrations of nisoldipine. Nisoldipine is a CYP3A4 substrate and larotrectinib is a weak CYP3A4 inhibitor.
Lasmiditan: (Moderate) Monitor heart rate if lasmiditan is coadministered with calcium-channel blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to another heart rate lowering drug decreased heart rate by an additional 5 beats per minute.
Lefamulin: (Major) Avoid coadministration of nisoldipine with oral lefamulin 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 oral lefamulin is a CYP3A4 inhibitor; an interaction is not expected with intravenous lefamulin.
Lenacapavir: (Major) Avoid coadministration of nisoldipine with lenacapavir due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A substrate and lenacapavir is a CYP3A inhibitor. Coadministration with another CYP3A inhibitor increased the AUC of nisoldipine by 30% to 45%.
Lesinurad: (Major) Avoid coadministration of nisoldipine with lesinurad due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and lesinurad is a CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Lesinurad; Allopurinol: (Major) Avoid coadministration of nisoldipine with lesinurad due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and lesinurad is a CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Letermovir: (Major) Avoid concurrent administration of letermovir and nisoldipine, as taking these drugs together may increase nisoldipine concentrations and risk for adverse events. The magnitude of this interaction may be increased in patients who are also receiving cyclosporine. Nisoldipine is a sensitive substrate of CYP3A4. Letermovir is a moderate CYP3A4 inhibitor. The combined effect of letermovir and cyclosporine on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor.
Levodopa: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Levoketoconazole: (Major) Avoid coadministration of nisoldipine with ketoconazole 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 ketoconazole is a CYP3A4 inhibitor. Coadministration with ketoconazole increased the AUC of nisoldipine by 24-fold.
Levonorgestrel; Ethinyl Estradiol: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Lidocaine; Epinephrine: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
Lisdexamfetamine: (Minor) Lisdexamfetamine might increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
Lithium: (Moderate) Monitor for neurologic adverse reactions during concomitant use of lithium and calcium channel blockers. Concomitant use may increase the risk of neurologic adverse reactions, such as ataxia, tremors, nausea, vomiting, diarrhea, and/or tinnitus.
Lonafarnib: (Major) Avoid coadministration of nisoldipine with lonafarnib 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 lonafarnib is a CYP3A4 inhibitor. Coadministration with another CYP3A4 inhibitor increased the AUC of nisoldipine by 30% to 45%.
Lopinavir; Ritonavir: (Major) Avoid coadministration of nisoldipine with protease inhibitors due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A substrate and protease inhibitors are moderate to strong CYP3A inhibitors. Coadministration with another CYP3A inhibitor increased the AUC of nisoldipine by 30% to 45%.
Loratadine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Lorlatinib: (Major) Avoid coadministration of nisoldipine with lorlatinib due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and lorlatinib is a moderate CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of nisoldipine with ivacaftor 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 ivacaftor is a CYP3A4 inhibitor.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of nisoldipine with lumacaftor; ivacaftor due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and lumacaftor; ivacaftor is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Lurasidone: (Moderate) Due to the antagonism of lurasidone at alpha-1 adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents. If concurrent use of lurasidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
Maribavir: (Major) Avoid coadministration of nisoldipine with maribavir due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A substrate and maribavir is a CYP3A inhibitor. Coadministration with another CYP3A inhibitor increased the AUC of nisoldipine by 30% to 45%.
Mavacamten: (Major) Avoid coadministration of nisoldipine with mavacamten as concurrent use may decrease nisoldipine exposure and efficacy. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A substrate and mavacamten is a CYP3A inducer. Coadministration with a strong CYP3A inducer lowered nisoldipine plasma concentrations to undetectable levels.
Meclofenamate Sodium: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Mefenamic Acid: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Melatonin: (Moderate) Monitor blood pressure during concomitant calcium-channel blocker and melatonin use. Melatonin may impair the efficacy of calcium-channel blockers. In a placebo-controlled study, melatonin evening ingestion led to significant increases in blood pressure (6.5 mmHg systolic and 4.9 mmHg diastolic) and heart rate (3.9 bpm) throughout the day in patients taking a calcium channel blocker Melatonin appeared to antagonize the antihypertensive effects of the calcium channel blocker.
Meloxicam: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Methamphetamine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
Methohexital: (Major) Coadministration of nisoldipine with CYP3A4 inducers like the barbiturates should be avoided and alternative antihypertensive therapy should be considered. Coadministration of a strong CYP3A4 inducer with nisoldipine in epileptic patients lowered the nisoldipine plasma concentrations to undetectable levels. Barbiturates (e.g., phenobarbital, primidone) may also decrease the oral bioavailability of nisoldipine via increased hepatic drug clearance.
Methoxsalen: (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
Methylphenidate Derivatives: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Metoprolol: (Moderate) Concurrent use of nisoldipine with metoprolol can be beneficial (i.e., inhibition of vasodilation-induced reflex tachycardia by beta-blockade); however, the additive negative inotropic and/or chronotropic effects can cause adverse effects, especially in patients with compromised ventricular function or conduction defects (e.g., sinus bradycardia or AV block).
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent use of nisoldipine with metoprolol can be beneficial (i.e., inhibition of vasodilation-induced reflex tachycardia by beta-blockade); however, the additive negative inotropic and/or chronotropic effects can cause adverse effects, especially in patients with compromised ventricular function or conduction defects (e.g., sinus bradycardia or AV block).
Mifepristone: (Major) Avoid coadministration of nisoldipine with mifepristone 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 mifepristone is a CYP3A4 inhibitor.
Milrinone: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Mitapivat: (Major) Avoid coadministration of nisoldipine with mitapivat as concurrent use may decrease nisoldipine exposure and efficacy. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A substrate and mitapivat is a weak CYP3A inducer. Coadministration with a strong CYP3A inducer lowered nisoldipine plasma concentrations to undetectable levels.
Mitotane: (Major) Avoid coadministration of nisoldipine with mitotane due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and mititane is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Mobocertinib: (Major) Avoid coadministration of nisoldipine with mobocertinib as concurrent use may decrease nisoldipine exposure and efficacy. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A substrate and mobocertinib is a weak CYP3A inducer. Coadministration with a strong CYP3A inducer lowered nisoldipine plasma concentrations to undetectable levels.
Modafinil: (Major) Avoid coadministration of nisoldipine with modafinil due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and modafinil is a CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Nabumetone: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Nadolol: (Moderate) Concurrent use of nisoldipine with nadolol can be beneficial (i.e., inhibition of vasodilation-induced reflex tachycardia by beta-blockade); however, the additive negative inotropic and/or chronotropic effects can cause adverse effects, especially in patients with compromised ventricular function or conduction defects (e.g., sinus bradycardia or AV block).
Nafcillin: (Major) Avoid coadministration of nisoldipine with nafcillin due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and nafcillin is a CYP3A4 inducer in vitro. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Naproxen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Naproxen; Esomeprazole: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Naproxen; Pseudoephedrine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Nebivolol: (Moderate) Concurrent use of nisoldipine with nebivolol can be beneficial (i.e., inhibition of vasodilation-induced reflex tachycardia by beta-blockade); however, the additive negative inotropic and/or chronotropic effects can cause adverse effects, especially in patients with compromised ventricular function or conduction defects (e.g., sinus bradycardia or AV block).
Nebivolol; Valsartan: (Moderate) Concurrent use of nisoldipine with nebivolol can be beneficial (i.e., inhibition of vasodilation-induced reflex tachycardia by beta-blockade); however, the additive negative inotropic and/or chronotropic effects can cause adverse effects, especially in patients with compromised vent ricular function or conduction defects (e.g., sinus bradycardia or AV block).
Nefazodone: (Major) Avoid coadministration of nisoldipine with nefazodone 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 nefazodone is a strong CYP3A4 inhibitor.
Nelfinavir: (Major) Avoid coadministration of nisoldipine with protease inhibitors due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A substrate and protease inhibitors are moderate to strong CYP3A inhibitors. Coadministration with another CYP3A inhibitor increased the AUC of nisoldipine by 30% to 45%.
Nesiritide, BNP: (Major) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents.
Netupitant, Fosnetupitant; Palonosetron: (Major) Avoid coadministration of nisoldipine with netupitant 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 netupitant is a CYP3A4 inhibitor.
Neuromuscular blockers: (Moderate) Concomitant use of neuromuscular blockers and calcium-channel blockers may prolong neuromuscular blockade.
Nevirapine: (Major) Avoid coadministration of nisoldipine with nevirapine as concurrent use may decrease nisoldipine exposure and efficacy. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A substrate and nevirapine is a CYP3A inducer. Coadministration with a strong CYP3A inducer lowered nisoldipine plasma concentrations to undetectable levels.
Niacin, Niacinamide: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents, especially calcium-channel blockers. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
Niacin; Simvastatin: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents, especially calcium-channel blockers. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
Nilotinib: (Major) Avoid coadministration of nisoldipine with nilotinib 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 nilotinib is a moderate CYP3A4 inhibitor.
Nirmatrelvir; Ritonavir: (Major) Avoid coadministration of nisoldipine with protease inhibitors due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A substrate and protease inhibitors are moderate to strong CYP3A inhibitors. Coadministration with another CYP3A inhibitor increased the AUC of nisoldipine by 30% to 45%.
Nitrates: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
Nitroglycerin: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
Nitroprusside: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
Nonsteroidal antiinflammatory drugs: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Norethindrone; Ethinyl Estradiol: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Norgestimate; Ethinyl Estradiol: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Odevixibat: (Major) Avoid coadministration of nisoldipine with odevixibat as concurrent use may decrease nisoldipine exposure and efficacy. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A substrate and odevixibat is a CYP3A inducer. Coadministration with a strong CYP3A inducer lowered nisoldipine plasma concentrations to undetectable levels.
Olanzapine: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Olanzapine; Fluoxetine: (Major) Avoid coadministration of nisoldipine with fluoxetine 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 fluoxetine is a CYP3A4 inhibitor. (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Olanzapine; Samidorphan: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Olutasidenib: (Major) Avoid coadministration of nisoldipine with olutasidenib as concurrent use may decrease nisoldipine exposure and efficacy. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A substrate and olutasidenib is a CYP3A inducer. Coadministration with a strong CYP3A inducer lowered nisoldipine plasma concentrations to undetectable levels.
Omaveloxolone: (Major) Avoid coadministration of nisoldipine with omaveloxolone as concurrent use may decrease nisoldipine exposure and efficacy. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A substrate and omaveloxolone is a CYP3A inducer. Coadministration with a strong CYP3A inducer lowered nisoldipine plasma concentrations to undetectable levels.
Omeprazole; Amoxicillin; Rifabutin: (Major) Avoid coadministration of nisoldipine with rifabutin due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and rifabutin is a CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Oritavancin: (Major) Avoid coadministration of nisoldipine with oritavancin due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and oritavancin is a weak CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Osilodrostat: (Major) Avoid coadministration of nisoldipine with osilodrostat 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 osilodrostat is a CYP3A4 inhibitor.
Oxaprozin: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Oxcarbazepine: (Major) Avoid coadministration of nisoldipine with oxcarbazepine due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and oxcarbazepine is a CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Oxymetazoline: (Major) The vasoconstricting actions of oxymetazoline, an alpha adrenergic agonist, may reduce the antihypertensive effects produced by calcium-channel blockers. If these drugs are used together, closely monitor for changes in blood pressure.
Pacritinib: (Major) Avoid coadministration of nisoldipine with pacritinib due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A substrate and pacritinib is a CYP3A inhibitor. Coadministration with another CYP3A inhibitor increased the AUC of nisoldipine by 30% to 45%.
Palbociclib: (Major) Avoid coadministration of nisoldipine with palbociclib 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 palbociclib is a CYP3A4 inhibitor.
Paliperidone: (Moderate) Paliperidone may cause orthostatic hypotension, thereby enhancing the hypotensive effects of antihypertensive agents. Orthostatic vital signs should be monitored in patients receiving paliperidone and calcium-channel blockers who are susceptible to hypotension.
Pasireotide: (Major) Pasireotide may cause a decrease in heart rate. Closely monitor patients who are also taking drugs associated with bradycardia such as calcium-channel blockers. Dose adjustments of calcium-channel blockers may be necessary.
Pazopanib: (Major) Avoid coadministration of nisoldipine with pazopanib 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 pazopanib is a weak CYP3A4 inhibitor.
Pentobarbital: (Major) Coadministration of nisoldipine with CYP3A4 inducers like the barbiturates should be avoided and alternative antihypertensive therapy should be considered. Coadministration of a strong CYP3A4 inducer with nisoldipine in epileptic patients lowered the nisoldipine plasma concentrations to undetectable levels. Barbiturates (e.g., phenobarbital, primidone) may also decrease the oral bioavailability of nisoldipine via increased hepatic drug clearance.
Pentoxifylline: (Moderate) Pentoxifylline has been used concurrently with antihypertensive drugs (beta blockers, diuretics) without observed problems. Small decreases in blood pressure have been observed in some patients treated with pentoxifylline; periodic systemic blood pressure monitoring is recommended for patients receiving concomitant antihypertensives. If indicated, dosage of the antihypertensive agents should be reduced.
Pexidartinib: (Major) Avoid coadministration of nisoldipine with pexidartinib as concurrent use may decrease nisoldipine exposure and efficacy. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and pexidartinib is a CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Phenelzine: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with calcium-channel blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
Phenobarbital: (Major) Coadministration of nisoldipine with CYP3A4 inducers like the barbiturates should be avoided and alternative antihypertensive therapy should be considered. Coadministration of a strong CYP3A4 inducer with nisoldipine in epileptic patients lowered the nisoldipine plasma concentrations to undetectable levels. Barbiturates (e.g., phenobarbital, primidone) may also decrease the oral bioavailability of nisoldipine via increased hepatic drug clearance.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Coadministration of nisoldipine with CYP3A4 inducers like the barbiturates should be avoided and alternative antihypertensive therapy should be considered. Coadministration of a strong CYP3A4 inducer with nisoldipine in epileptic patients lowered the nisoldipine plasma concentrations to undetectable levels. Barbiturates (e.g., phenobarbital, primidone) may also decrease the oral bioavailability of nisoldipine via increased hepatic drug clearance.
Phentermine; Topiramate: (Major) Avoid coadministration of nisoldipine with topiramate due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and topiramate is a weak CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Phenytoin: (Major) Coadministration of nisoldipine with phenytoin should be avoided and alternative antihypertensive therapy should be considered. Coadministration of phenytoin with nisoldipine in epileptic patients lowered the nisoldipine plasma concentrations to undetectable levels.
Photosensitizing agents (topical): (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
Pindolol: (Moderate) Concurrent use of nisoldipine with pindolol can be beneficial (i.e., inhibition of vasodilation-induced reflex tachycardia by beta-blockade); however, the additive negative inotropic and/or chronotropic effects can cause adverse effects, especially in patients with compromised ventricular function or conduction defects (e.g., sinus bradycardia or AV block).
Piroxicam: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Pirtobrutinib: (Major) Avoid coadministration of nisoldipine with pirtobrutinib due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A substrate and pirtobrutinib is a CYP3A inhibitor. Coadministration with another CYP3A inhibitor increased the AUC of nisoldipine by 30% to 45%.
Posaconazole: (Major) Avoid coadministration of nisoldipine with posaconazole 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 posaconazole is a CYP3A4 inhibitor.
Prazosin: (Moderate) Prazosin is well-known to produce a 'first-dose' phenomenon. Some patients develop significant hypotension shortly after administration of the first dose. The first dose response (acute postural hypotension) of prazosin may be exaggerated in patients who are receiving beta-adrenergic blockers, diuretics, or other antihypertensive agents. Concomitant administration of prazosin with other antihypertensive agents is not prohibited, however. This can be therapeutically advantageous, but lower dosages of each agent should be used. The use of alpha-blockers with verapamil can lead to excessive hypotension; In addition, verapamil has been reported to increase the AUC and Cmax of prazosin.
Prilocaine; Epinephrine: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
Primidone: (Major) Coadministration of nisoldipine with CYP3A4 inducers like the barbiturates should be avoided and alternative antihypertensive therapy should be considered. Coadministration of a strong CYP3A4 inducer with nisoldipine in epileptic patients lowered the nisoldipine plasma concentrations to undetectable levels. Barbiturates (e.g., phenobarbital, primidone) may also decrease the oral bioavailability of nisoldipine via increased hepatic drug clearance.
Procainamide: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
Promethazine; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Propofol: (Major) The depression of cardiac contractility, conductivity, and automaticity as well as the vascular dilation associated with general anesthetics may be potentiated by calcium-channel blockers. Alternatively, general anesthetics can potentiate the hypotensive effects of calcium-channel blockers. When used concomitantly, anesthetics and calcium-channel blockers should be titrated carefully to avoid excessive cardiovascular depression.
Propranolol: (Moderate) Concurrent use of nisoldipine with propranolol can be beneficial (i.e., inhibition of vasodilation-induced reflex tachycardia by beta-blockade); however, the additive negative inotropic and/or chronotropic effects can cause adverse effects, especially in patients with compromised ventricular function or conduction defects (e.g., sinus bradycardia or AV block). Pharmacokinetic interactions between nisoldipine and propranolol are variable and not significant. Propranolol attenuated the heart rate increase following the administration of immediate release nisoldipine.
Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent use of nisoldipine with propranolol can be beneficial (i.e., inhibition of vasodilation-induced reflex tachycardia by beta-blockade); however, the additive negative inotropic and/or chronotropic effects can cause adverse effects, especially in patients with compromised ventricular function or conduction defects (e.g., sinus bradycardia or AV block). Pharmacokinetic interactions between nisoldipine and propranolol are variable and not significant. Propranolol attenuated the heart rate increase following the administration of immediate release nisoldipine.
Protease inhibitors: (Major) Avoid coadministration of nisoldipine with protease inhibitors due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A substrate and protease inhibitors are moderate to strong CYP3A inhibitors. Coadministration with another CYP3A inhibitor increased the AUC of nisoldipine by 30% to 45%.
Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Pseudoephedrine; Triprolidine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Quinidine: (Moderate) Quinidine may decrease the bioavailability of nisoldipine by 26% without affecting the peak concentration. Monitoring serum quinidine concentrations is prudent following the addition or discontinuation of nisoldipine.
Quinine: (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.
Ranolazine: (Major) Avoid coadministration of nisoldipine with ranolazine 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 ranolazine is a weak CYP3A4 inhibitor.
Rasagiline: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with calcium-channel blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of an MAOI and a calcium-channel blocker.
Remifentanil: (Moderate) The risk of significant hypotension and/or bradycardia during therapy with remifentanil may be increased in patients receiving calcium-channel blockers due to additive hypotensive effects.
Ribociclib: (Major) Avoid coadministration of nisoldipine with ribociclib due to increased plasma concentrations of nisoldipine. Nisoldipine is a sensitive CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor.
Ribociclib; Letrozole: (Major) Avoid coadministration of nisoldipine with ribociclib due to increased plasma concentrations of nisoldipine. Nisoldipine is a sensitive CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor.
Rifabutin: (Major) Avoid coadministration of nisoldipine with rifabutin due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and rifabutin is a CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Rifampin: (Major) Avoid coadministration of nisoldipine with rifampin due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Rifapentine: (Major) Avoid coadministration of nisoldipine with rifapentine due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Risperidone: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Ritlecitinib: (Major) Avoid coadministration of nisoldipine with ritlecitinib due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A substrate and ritlecitinib is a CYP3A inhibitor. Coadministration with another CYP3A inhibitor increased the AUC of nisoldipine by 30% to 45%.
Ritonavir: (Major) Avoid coadministration of nisoldipine with protease inhibitors due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A substrate and protease inhibitors are moderate to strong CYP3A inhibitors. Coadministration with another CYP3A inhibitor increased the AUC of nisoldipine by 30% to 45%.
Rucaparib: (Major) Avoid coadministration of nisoldipine with rucaparib due to the risk of increased plasma concentrations of nisoldipine. Nisoldipine is a CYP3A4 substrate and rucaparib is a weak CYP3A4 inhibitor.
Saquinavir: (Major) Avoid coadministration of nisoldipine with protease inhibitors due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A substrate and protease inhibitors are moderate to strong CYP3A inhibitors. Coadministration with another CYP3A inhibitor increased the AUC of nisoldipine by 30% to 45%.
Secobarbital: (Major) Coadministration of nisoldipine with CYP3A4 inducers like the barbiturates should be avoided and alternative antihypertensive therapy should be considered. Coadministration of a strong CYP3A4 inducer with nisoldipine in epileptic patients lowered the nisoldipine plasma concentrations to undetectable levels. Barbiturates (e.g., phenobarbital, primidone) may also decrease the oral bioavailability of nisoldipine via increased hepatic drug clearance.
Segesterone Acetate; Ethinyl Estradiol: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Selpercatinib: (Major) Avoid coadministration of nisoldipine with selpercatinib 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 selpercatinib is a weak CYP3A4 inhibitor. Coadministration with another CYP3A4 inhibitor increased the AUC of nisoldipine by 30% to 45%.
Sevoflurane: (Major) The depression of cardiac contractility, conductivity, and automaticity as well as the vascular dilation associated with general anesthetics may be potentiated by calcium-channel blockers. Alternatively, general anesthetics can potentiate the hypotensive effects of calcium-channel blockers. When used concomitantly, anesthetics and calcium-channel blockers should be titrated carefully to avoid excessive cardiovascular depression.
Silodosin: (Moderate) Monitor for adverse effects if silodosin is coadministered with nisoldipine. The incidence of dizziness and orthostatic hypotension were increased in patients also receiving antihypertensive medications in clinical trials.
Sincalide: (Moderate) Sincalide-induced gallbladder ejection fraction may be affected by calcium-channel blockers. False study results are possible in patients with drug-induced hyper- or hypo-responsiveness; thorough patient history is important in the interpretation of results.
Sodium Phenylbutyrate; Taurursodiol: (Major) Avoid coadministration of nisoldipine with taurursodiol as concurrent use may decrease nisoldipine exposure and efficacy. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A substrate and taurursodiol is a CYP3A inducer. Coadministration with a strong CYP3A inducer lowered nisoldipine plasma concentrations to undetectable levels.
Sotalol: (Moderate) Concurrent use of nisoldipine with sotalol can be beneficial (i.e., inhibition of vasodilation-induced reflex tachycardia by beta-blockade); however, the additive negative inotropic and/or chronotropic effects can cause adverse effects, especially in patients with compromised ventricular function or conduction defects (e.g., sinus bradycardia or AV block).
Sotorasib: (Major) Avoid coadministration of nisoldipine with sotorasib as concurrent use may decrease nisoldipine exposure and efficacy. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and sotorasib is a CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Spironolactone: (Major) Avoid coadministration of nisoldipine with spironolactone 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 spironolactone is a CYP3A4 inhibitor. Coadministration with another CYP3A4 inhibitor increased the AUC of nisoldipine by 30% to 45%.
Spironolactone; Hydrochlorothiazide, HCTZ: (Major) Avoid coadministration of nisoldipine with spironolactone 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 spironolactone is a CYP3A4 inhibitor. Coadministration with another CYP3A4 inhibitor increased the AUC of nisoldipine by 30% to 45%.
St. John's Wort, Hypericum perforatum: (Major) Avoid coadministration of nisoldipine with St. John's Word due to the possibility for decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and St. John's Word is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Stiripentol: (Moderate) Consider a dose adjustment of nisoldipine when coadministered with stiripentol. Coadministration may alter plasma concentrations of nisoldipine resulting in an increased risk of adverse reactions and/or decreased efficacy. Nisoldipine is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Streptogramins: (Major) Avoid coadministration of nisoldipine with dalfopristin; quinupristin due to increased plasma concentrations of nisoldipine. Nisoldipine is a CYP3A4 substrate and dalfopristin; quinupristin is a weak CYP3A4 inhibitor.
Sufentanil: (Moderate) Monitor patients for bradycardia and hypotension when sufentanil is coadministered with nisoldipine. Sufentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with sufentanil is increased in patients receiving nisoldipine.
Sulindac: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Sumatriptan; Naproxen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Tamsulosin: (Moderate) The concomitant administration of tamsulosin with other antihypertensive agents can cause additive hypotensive effects. In addition, diltiazem, nicardipine, and verapamil may increase tamsulosin plasma concentrations via CYP3A4 inhibition. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
Tazemetostat: (Major) Avoid coadministration of nisoldipine with tazemetostat as concurrent use may decrease nisoldipine exposure and efficacy. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and tazemetostat is a CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Tecovirimat: (Major) Avoid coadministration of nisoldipine with tecovirimat due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and tecovirimat is a weak CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Telotristat Ethyl: (Major) Avoid coadministration of nisoldipine with telotristat as concurrent use may decrease nisoldipine exposure and efficacy. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and telotristat is a CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Temsirolimus: (Moderate) Monitor for signs and symptoms of angioedema if temsirolimus is administered concomitantly with nisoldipine. Angioedema has been reported in patients taking mammalian target of rapamycin (mTOR) inhibitors in combination with another calcium channel blocker.
Tetrabenazine: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
Tetracaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of tetracaine and antihypertensive agents.
Tezacaftor; Ivacaftor: (Major) Avoid coadministration of nisoldipine with ivacaftor 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 ivacaftor is a CYP3A4 inhibitor.
Thalidomide: (Moderate) Thalidomide and other agents that slow cardiac conduction such as calcium-channel blockers should be used cautiously due to the potential for additive bradycardia.
Thiothixene: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Ticagrelor: (Major) Avoid coadministration of nisoldipine with ticagrelor 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 ticagrelor is a weak CYP3A4 inhibitor.
Timolol: (Moderate) Concurrent use of nisoldipine with timolol can be beneficial (i.e., inhibition of vasodilation-induced reflex tachycardia by beta-blockade); however, the additive negative inotropic and/or chronotropic effects can cause adverse effects, especially in patients with compromised ventricular function or conduction defects (e.g., sinus bradycardia or AV block).
Tipranavir: (Major) Avoid coadministration of nisoldipine with protease inhibitors due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A substrate and protease inhibitors are moderate to strong CYP3A inhibitors. Coadministration with another CYP3A inhibitor increased the AUC of nisoldipine by 30% to 45%.
Tolmetin: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Topiramate: (Major) Avoid coadministration of nisoldipine with topiramate due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and topiramate is a weak CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Tranylcypromine: (Major) Avoid concomitant use of calcium-channel blockers and tranylcypromine due to the risk of additive hypotension. Potential for this interaction persists for up to 10 days after discontinuation of tranylcypromine (or 4 to 5 half-lives after discontinuation of the calcium-channel blocker). If a medication-free interval is not feasible, initiate therapy at the lowest appropriate dose and monitor blood pressure closely.
Trazodone: (Minor) Due to additive hypotensive effects, patients receiving antihypertensive agents concurrently with trazodone may have excessive hypotension. Decreased dosage of the antihypertensive agent may be required when given with trazodone.
Trofinetide: (Major) Avoid coadministration of nisoldipine with trofinetide due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A substrate and trofinetide is a CYP3A inhibitor. Coadministration with another CYP3A inhibitor increased the AUC of nisoldipine by 30% to 45%.
Tucatinib: (Major) Avoid coadministration of nisoldipine with tucatinib 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 tucatinib is a strong CYP3A4 inhibitor.
Valdecoxib: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Vemurafenib: (Moderate) Vemurafenib is an inducer of CYP3A4 and decreased plasma concentrations of drugs metabolized by this enzyme, such as nisoldipine, could be expected with concurrent use. Use caution, and monitor therapeutic effects of nisoldipine when coadministered with vemurafenib.
Verteporfin: (Moderate) Use caution if coadministration of verteporfin with calcium channel blockers is necessary due to the risk of increased photosensitivity. Verteporfin is a light-activated drug used in photodynamic therapy; all patients treated with verteporfin will be photosensitive. Concomitant use with calcium channel blockers could enhance the rate of verteporfin uptake by the vascular endothelium, resulting in enhanced photosensitivity.
Viloxazine: (Major) Avoid coadministration of nisoldipine with viloxazine 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 viloxazine is a CYP3A4 inhibitor. Coadministration with another CYP3A4 inhibitor increased the AUC of nisoldipine by 30% to 45%.
Vonoprazan; Amoxicillin: (Major) Avoid coadministration of nisoldipine with vonoprazan due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A substrate and vonoprazan is a CYP3A inhibitor. Coadministration with another CYP3A inhibitor increased the AUC of nisoldipine by 30% to 45%.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of nisoldipine with clarithromycin, particularly in geriatric patients, due to increased plasma concentrations of nisoldipine. If the use of a macrolide antibiotic is necessary in a patient receiving nisoldipine therapy, azithromycin is the preferred agent. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A4 substrate and clarithromycin is a CYP3A4 inhibitor. A retrospective, case crossover study, found the risk of hospitalization due to hypotension or shock to be significantly increased in geriatric patients exposed to clarithromycin during concurrent calcium-channel blocker therapy (OR 3.7, 95% CI 2.3-6.1). Concurrent use of azithromycin was not associated with an increased risk of hypotension (OR 1.5, 95% CI 0.8-2.8). (Major) Avoid coadministration of nisoldipine with vonoprazan due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A substrate and vonoprazan is a CYP3A inhibitor. Coadministration with another CYP3A inhibitor increased the AUC of nisoldipine by 30% to 45%.
Voriconazole: (Major) Avoid coadministration of nisoldipine with voriconazole 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 voriconazole is a CYP3A4 inhibitor.
Voxelotor: (Major) Avoid coadministration of nisoldipine with voxelotor due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A substrate and voxelotor is a CYP3A inhibitor. Coadministration with another CYP3A inhibitor increased the AUC of nisoldipine by 30% to 45%.
Zafirlukast: (Major) Avoid coadministration of nisoldipine with zafirlukast 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 zafirlukast is a CYP3A4 inhibitor.
Zanubrutinib: (Major) Avoid coadministration of nisoldipine with zanubrutinib as concurrent use may decrease nisoldipine exposure and efficacy. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and zanubrutinib is a CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Ziprasidone: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.

Nisoldipine/Sular Oral Tab ER: 8.5mg, 17mg, 20mg, 25.5mg, 30mg, 34mg, 40mg

Adults

34 mg/day PO.

Elderly

34 mg/day PO.

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Mechanism of Action: Nisoldipine selectively vasodilates the arteriolar circulation and has little or no effect on venous circulation or the myocardium. Like other calcium-channel antagonists, nisoldipine inhibits the transmembrane influx of extracellular calcium through vascular smooth muscle by blocking calcium-specific ion channels. Serum calcium levels remain unchanged. The decrease in intracellular calcium inhibits the contractile processes of the smooth muscle cells, causing dilation of the coronary and systemic arteries. This results in increased myocardial oxygen delivery due to coronary vasodilation, and also results in reduced myocardial oxygen demand via decreased total peripheral resistance, reduced systemic blood pressure, and afterload reduction.Nisoldipine has no clinical effect on AV conduction and minimal direct negative inotropic effects at therapeutic doses. In patients with normal left venticular function, the negative inotropic effects of dihydropyridines are generally counterbalanced by afterload reduction and a transient reflex increase in heart rate. Nisoldipine did not worsen heart failure in patients with stable heart failure or asymptomatic left ventricular dysfunction; however, it has not been adequately studied in patients with severe heart failure. In general, calcium-channel blockers exert favorable effects on left ventricular hypertrophy, and do not worsen insulin resistance or exert detrimental effects on the lipid profile.

Nisoldipine is administered orally. The pharmacokinetics are linear within the therapeutic dose range. It is highly (> 99%) protein bound. Nisoldipine is a high clearance drug with a terminal elimination half life ranging from 7—12 hours. The predominant route of elimination is metabolism and renal excretion of its five metabolites. One hydroxylated metabolite is active, with 10% potency relative to nisoldipine. The exact metabolic pathway is unknown, however, other dihydropyridines are metabolized by the CYP3A4 isoenzyme. Coadministration of nisoldipine with grapefruit juice (a CYP3A4 inhibitor) resulted in an average three-fold (ranging up to 7-fold) increase in Cmax and a two-fold (ranging up to 5-fold) increase in AUC.
 
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4
Nisoldipine is a CYP3A4 substrate, and its metabolism may theoretically be affected by CYP3A4 inhibitors or inducers.

Oral Route

The Sular formulation contains an external coat and an internal core that contains slow release and fast release nisoldipine, respectively, designed for once daily administration. Nisoldipine is well absorbed into the gastrointestinal tract (GI), but its absolute bioavailability is only 5.5% due to first pass metabolism by the gut wall and liver. The highest rate of metabolism occurs in the proximal parts of the intestine. Coadministration of Sular with a high fat meal significantly increases nisoldipine release from the core-coat formulation and thereby increases peak plasma concentrations up to 300%; however the total drug exposure is decreased 25% because more drug is released proximally where extensive pre-systemic metabolism occurs. Peak nisoldipine plasma concentrations are reached 6—12 hours after dosing.

Pregnancy

Nisoldipine is classified as FDA pregnancy category C. There are no adequate and well controlled studies in pregnant women. According to the manufacturer, nisoldipine should be used only when the maternal benefits clearly outweigh the fetal risks.

According to the manufacturer, a decision should be made to discontinue nursing or to discontinue nisoldipine, taking into account the importance of the drug to the mother. It is not known whether nisoldipine is excreted into breast milk. The molecular weight of the drug is low enough that excretion of the drug into breast milk should be expected. The effect of this exposure on a nursing infant is unknown. Because neonatal myocardium is very sensitive to changes in calcium status, it may be prudent to avoid using nisoldipine in the breast-feeding mother until more safety data are available. The American Academy of Pediatrics (AAP) has not evaluated the use of nisoldipine in breast-feeding mothers; however, the AAP regards nifedipine as usually compatible with breast-feeding. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.