Brands, Medical Use, Clinical Data
- Vasodilator Agents
- Antiarrhythmic Agents
- Calcium-channel blocking agents
- Capsule (sustained-release)
- Tablet (extended-release)
Brands / Synonyms
Apo-Verap; Arpamyl; Berkatens; Calan; Calan SR; Cardiagutt; Cardibeltin; Cordilox; Covera-HS; Dignover; Dilacoran; Drosteakard; Geangin; Iproveratril; Isoptimo; Isoptin; Isoptin SR; Novo-Veramil; NU-Verap; Quasar; Securon; Tarka; Univer; Vasolan; Veracim; Veramex; Verapamil; Verapamil HCl; Verapamil [Usan:Ban:Inn]; Verapamilo [Inn-Spanish]; Verapamilum [Inn-Latin]; Veraptin; Verelan; Verelan PM; Verexamil
For the treatment of hypertension and angina.
Verapamil, a class IV antiarrhythmic agent, is used as a calcium-channel blocking (CCB) agent for the treatment of angina, hypertension, and for supraventricular tachyarrhythmias.
Mechanism of Action
Possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, verapamil, like diltiazem, inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes. The resultant inhibition of the contractile processes of the myocardial smooth muscle cells leads to dilation of the coronary and systemic arteries,improved oxygen delivery to the myocardial tissue, and decreased total peripheral resistance, systemic blood pressure, and afterload.
LD50=8 mg/kg (i.v. in mice)
Biotrnasformation / Drug Metabolism
Verapamil HCl is contraindicated in:
1. Severe left ventricular dysfunction .
2. Hypotension (systolic pressure less than 90 mm Hg) or cardiogenic shock.
3. Sick sinus syndrome (except in patients with a functioning artificial ventricular pacemaker).
4. Second- or third-degree AV block (except in patients with a functioning artificial ventricular
5. Patients with atrial flutter or atrial fibrillation and an accessory bypass tract (e.g.,
Wolff-Parkinson-White, Lown-Ganong-Levine syndromes).
6. Patients with known hypersensitivity to verapamil HCl.
Verapamil undergoes biotransformation by predominantly CYP3A4, however CYP1A2 and members of the CYP2C subfamily
are involved in its metabolism. Coadministration of verapamil with other drugs metabolized by the above-mentioned
enzymes may alter the bioavailability of either verapmail and/or the other drugs. Therefore, coadministration of
narrow therapeutic index drugs with similar metabolic pathwyas as verapamil should be carefully monitored. Similarly,
verapamil plasma levels in patients with hepatic cysfuction whould be carefully monitored, due to decreased clearanc
of verapmil in these patients.
Alcohol: Verapamil has been found to inhibit ethanol elimination significantly, resulting in
elevated blood ethanol concentrations that may prolong the intoxicating effects of alcohol .
Antineoplastic Agents: Verapamil can increase the efficacy of doxorubicin both in tissue culture
systems and in patients. It raises the serum doxorubicin levels. The absorption of verapamil can be reduced by the
cyclophosphamide, oncovin, procarbazine, prednisone (COPP) and the vindesine, adriamycin, cisplatin (VAC) cytotoxic
drug regimens. Concomitant administration of R verapamil can decrease the clearance of paclitaxel.
Aspirin: In a few reported cases, coadministration of verapamil with aspirin has led to increased
bleeding times greater than observed with aspirin alone.
Beta-Blockers: Controlled studies in small numbers of patients suggest that the concomitant use of
verapamil and oral beta-adrenergic blocking agents may be beneficial in certain patients with chronic stable angina
or hypertension, but available information is not sufficient to predict with confidence the effects of concurrent
treatment in patients with left ventricular dysfunction or cardiac conduction abnormalities. Concomitant therapy with
beta-adrenergic blockers and verapamil may result in additive negative effects on hear rate, atrioventricular
conduction and/or cardiac contractility.
The combination of sustained-release verapamil and beta-adrenergic blocking agents has not been studied. However,
there have been reports of excessive bradycardia and AV block, including complete heart block, when the combination
has been used for the treatment of hypertension. For hypertensive patients, the risks of combined therapy may
outweigh the potential benefits. The combination should be used only with caution and close monitoring.
In one study involving 15 patients treated with high doses of propranolol (median dose, 480 mg/day; range 160 to
1280 mg/day) for severe angina, with preserved left ventricular function (ejection fraction greater than 35%), the
hemodynamic effects of additional therapy with verapamil HCl were assessed using invasive methods. The addition of
verapamil to high-dose beta-blockers induced modest negative inotropic and chronotropic effects that were not severe
enough to limit short-term (48 hours) combination therapy in this study. 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. The primary verapamil/beta-blocker interaction in this study appeared to be
hemodynamic rather than electrophysiologic.
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. Therefore, if
combined therapy is used, close surveillance of clinical status should be carried out. Combined therapy should
usually be avoided in patients with atrio-ventricular conduction abnormalities and those with depressed left
Asymptomatic bradycardia (36 beats/min) with a wandering atrial pacemaker has been observed in a patient receiving
concomitant timolol (a beta-adrenergic blocker) eyedrops and oral verapamil.
A decrease in metoprolol and propranolol clearance has been observed when either drug is administered
concomitantly with verapamil. A variable effect has been seen when verapamil and atenolol were given together.
Digitalis: Clinical use of verapamil in digitalized patients has shown the combination to be well
tolerated if digoxin doses are properly adjusted. However, chronic verapamil treatment can increase serum digoxin
levels by 50% to 75% during the first week of therapy, and this can result in digitalis toxicity. In patients with
hepatic cirrhosis, the influence of verapamil on digoxin kinetics is magnified. Verapamil may reduce total body
clearance and extrarenal clearance of digitoxin by 27% and 29%, respectively. Maintenance and digitalization doses
should be reduced when verapamil is administered, and the patient should be reassessed to avoid over- or
underdigitalization. Whenever overdigitalization is suspected, the daily dose of digitalis should be reduced or
temporarily discontinued. On discontinuation of verapamil HCl use, the patient should be reassessed to avoid
underdigitalization. In previous clinical trials with other verapamil formulations related to the control of
ventricular response in digitalized patients who had atrial fibrillation or atrial flutter, ventricular rates below
50/min at rest occurred in 15% of patients, and asymptomatic hypotension occurred in 5% of patients.
Antihypertensive Agents: Verapamil administered concomitantly with oral antihypertensive agents
(e.g., vasodilators, angiotensin-converting enzyme inhibitors, diuretics, beta-blockers) will usually have an
additive effect on lowering blood pressure. Patients receiving these combinations should be appropriately monitored.
Concomitant use of agents that attenuate alpha-adrenergic function with verapamil may result in a reduction in blood
pressure that is excessive in some patients. Such an effect was observed in one study following the concomitant
administration of verapamil and prazosin.
Disopyramide: Until data on possible interactions between verapamil and disopyramide are obtained,
disopyramide should not be administered within 48 hours before or 24 hours after verapamil administration.
Flecainide: A study in healthy volunteers showed that the concomitant administration of flecainide
and verapamil may have additive effects on myocardial contractility, AV conduction, and repolarization. Concomitant
therapy with flecainide and verapamil may result in additive negative inotropic effect and prolongation of
Quinidine: In a small number of patients with hypertrophic cardiomyopathy (IHSS), concomitant use of
verapamil and quinidine resulted in significant hypotension. Until further data are obtained, combined therapy of
verapamil and quinidine in patients with hypertrophic cardiomyopathy should probably be avoided.
The electrophysiologic effects of quinidine and verapamil on AV conduction were studied in 8 patients. Verapamil
significantly counteracted the effects of quinidine on AV conduction. There has been a report of increased quinidine
levels during verapamil therapy.
Nitrates: Verapamil has been given concomitantly with short- and long-acting nitrates without any
undesirable drug interactions. The pharmacologic profile of both drugs and the clinical experience suggest beneficial
Cimetidine: The interaction between cimetidine and chronically administered verapamil has not been
studied. Variable results on clearance have been obtained in acute studies of healthy volunteers; clearance of
verapamil was either reduced or unchanged.
Lithium: Increased sensitivity to the effects of lithium (neurotoxicity) has been reported during
concomitant verapamil-lithium therapy; lithium levels have been observed sometimes to increase, sometimes to
decrease, and sometimes to be unchanged. Patients receiving both drugs must be monitored carefully.
Carbamazepine: Verapamil therapy may increase carbamazepine concentrations during combined therapy.
This may produce carbamazepine side effects such as diplopia, headache, ataxia, or dizziness.
Rifampin: Therapy with rifampin may markedly reduce oral verapamil bioavailability.
Phenobarbital: Phenobarbital therapy may increase verapamil clearance.
Cyclosporin: Verapamil therapy may increase serum levels of cyclosporin.
Theophylline: Verapamil may inhibit the clearance and increase the plasma levels of
Inhalation Anesthetics: Animal experiments have shown that inhalation anesthetics depress
cardiovascular activity by decreasing the inward movement of calcium ions. When used concomitantly, inhalation
anesthetics and calcium antagonists, such as verapamil, should each be titrated carefully to avoid excessive
Neuromuscular Blocking Agents: Clinical data and animal studies suggest that verapamil may
potentiate the activity of neuromuscular blocking agents (curare-like and depolarizing). It may be necessary to
decrease the dose of verapamil and/or the dose of the neuromuscular blocking agent when the drugs are used