Verapamil Hydrochloride

Animal studies suggest concomitant intravenous use of verapamil and dantrolene sodium may result in cardiovascular collapse.

Concurrent use increases ivabradine exposure and may exacerbate bradycardia and conduction disturbances. Avoid co-administration.

Concomitant use may result in exaggerated hypotensive response. In rare instances with severe cardiomyopathy or recent MI, serious adverse effects have occurred.

Beta-blocker with variable effects when combined with verapamil. Risk of excessive bradycardia and AV block. Use with caution and close monitoring.

Sinus bradycardia resulting in hospitalization and pacemaker insertion reported. Monitor heart rate during concurrent use.

Verapamil reduces total body clearance by 27% and extrarenal clearance by 29%. Maintenance and digitalization doses should be reduced.

Verapamil increases serum digoxin levels by 50-75% in first week, risking digitalis toxicity. Dose reduction and careful monitoring required.

In rare instances, including when patients with severe cardiomyopathy, congestive heart failure, or recent myocardial infarction were given intravenous beta-adrenergic blocking agents or disopyramide concomitantly with intravenous verapamil, serious adverse effects have occurred.

CYP3A4 inhibitor causing elevation of verapamil plasma levels, resulting in hypotension and bradyarrhythmias.

Increased sensitivity to lithium effects (neurotoxicity) reported with concomitant verapamil-lithium therapy. Serum lithium levels may increase, decrease, or remain unchanged. Careful monitoring required.

CYP3A4 substrate combination associated with myopathy/rhabdomyolysis. Limit lovastatin dose to 40 mg daily.

Beta-blocker with decreased clearance when given with verapamil, resulting in additive negative effects on heart rate and AV conduction.

Serious adverse effects reported in rare instances with intravenous beta-blockers and intravenous verapamil, especially in severe cardiomyopathy, heart failure, or recent MI. May result in exaggerated hypotensive response.

In one study involving 15 patients treated with high doses of propranolol (median dose: 480 mg/day; range: 160 to 1,280 mg/day) for severe angina, with preserved left ventricular function (ejection fraction greater than 35%), the hemodynamic effects of additional therapy with verapamil hydrochloride were assessed using invasive methods. These modest cardiodepressant effects persisted for greater than 6 but less than 30 hours after abrupt withdrawal of beta-blockers and were closely related to plasma levels of propranolol. In other studies, verapamil did not generally induce significant negative inotropic, chronotropic, or dromotropic effects in patients with preserved left ventricular function receiving low or moderate doses of propranolol (less than or equal to 320 mg/day); in some patients, however, combined therapy did produce such effects.

Rifampin therapy may markedly reduce oral verapamil bioavailability.

CYP3A4 inhibitor causing elevation of verapamil plasma levels, resulting in hypotension and bradyarrhythmias.

CYP3A4 substrate combination associated with myopathy/rhabdomyolysis. Verapamil increases simvastatin exposure 2.5-fold. Limit simvastatin dose to 10 mg daily.

Concurrent use has resulted in hypotension, bradyarrhythmias, and lactic acidosis.

Beta-blocker causing additive negative effects on heart rate, AV conduction, and cardiac contractility. Asymptomatic bradycardia and wandering atrial pacemaker reported.

Both inhalation anesthetics and verapamil depress cardiovascular activity by decreasing calcium ion movement. Concurrent use requires careful titration to avoid excessive cardiovascular depression.

Coadministration has led to increased bleeding times greater than observed with aspirin alone in few reported cases.

Verapamil inhibits alcohol elimination, resulting in elevated ethanol levels.

CYP3A4 substrate; verapamil may increase plasma concentration. Lower starting and maintenance doses may be required.

Verapamil may increase carbamazepine concentrations, producing side effects such as diplopia, headache, ataxia, or dizziness.

Acute studies show clearance of verapamil either reduced or unchanged; chronic interaction not fully studied.

Verapamil therapy may increase serum levels of cyclosporin.

May significantly increase verapamil concentrations (AUC increased 28-36%, Cmax increased 40-57%), though clinical consequences not expected.

Phenobarbital therapy may increase verapamil clearance.

Concomitant administration of verapamil and prazosin resulted in exaggerated hypotensive response in one study.

Verapamil has been used concomitantly with digitalis without evidence of serious negative drug interactions.

The absorption of verapamil can be reduced by the cyclophosphamide, oncovin, procarbazine, prednisone (COPP) and the vindesine, adriamycin, cisplatin (VAC) cytotoxic drug regimens.

The absorption of verapamil can be reduced by the cyclophosphamide, oncovin, procarbazine, prednisone (COPP) and the vindesine, adriamycin, cisplatin (VAC) cytotoxic drug regimens.

Mammalian target of rapamycin (mTOR) inhibitors: In a study of 25 healthy volunteers with co-administration of verapamil with sirolimus, whole blood sirolimus C max and AUC were increased 130% and 120%, respectively.