Verapamil Hydrochloride

Tablet · Oral, Intravenous

Prescription (Rx) Calcium Channel Blocker 3 recalls

Uses

Verapamil hydrochloride sustained-release capsules are indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including this drug. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy.

Dosage and administration

Essential Hypertension The dose of verapamil hydrochloride sustained-release capsules should be individualized by titration. The usual daily dose of sustained-release verapamil, verapamil hydrochloride sustained-release capsules, in clinical trials has been 240 mg given by mouth once daily in the morning. However, initial doses of 120 mg a day may be warranted in patients who may have an increased response to verapamil (e.g., elderly, small people, etc.). Upward titration should be based on therapeutic efficacy and safety evaluated approximately 24 hours after dosing. The antihypertensive effects of verapamil hydrochloride sustained-release capsules are evident within the first week of therapy. If adequate response is not obtained with 120 mg of verapamil hydrochloride sustained-release capsules, the dose may be titrated upward in the following manner: (a) 180 mg in the morning. (b) 240 mg in the morning. (c) 360 mg in the morning. (d) 480 mg in the morning. Verapamil hydrochloride sustained-release capsules are for once-a-day administration. When switching from immediate-release verapamil to verapamil hydrochloride sustained-release capsules, the same total daily dose of verapamil hydrochloride sustained-release capsules can be used. As with immediate-release verapamil, dosages of verapamil hydrochloride sustained-release capsules should be individualized and titration may be needed in some patients. Sprinkling the Capsule Contents on Food Verapamil hydrochloride sustained-release capsules may also be administered by carefully opening the capsule and sprinkling the pellets on a spoonful of applesauce. The applesauce should be swallowed immediately without chewing and followed with a glass of cool water to ensure complete swallowing of the pellets. The applesauce used should not be hot, and it should be soft enough to be swallowed without chewing. Any pellet/applesauce mixture should be used immediately and not stored for future use. Subdividing the contents of a verapamil hydrochloride sustained-release capsule is not recommended.

Contraindications

Verapamil HCl is contraindicated in: Severe left ventricular dysfunction. (See WARNINGS . ) Hypotension (less than 90 mm Hg systolic pressure) or cardiogenic shock. Sick sinus syndrome (except in patients with a functioning artificial ventricular pacemaker). Second- or third-degree AV block (except in patients with a functioning artificial ventricular pacemaker). Patients with atrial flutter or atrial fibrillation and an accessory bypass tract (e.g., Wolff-Parkinson-White, Lown-Ganong-Levine syndromes). (See WARNINGS . ) Patients with known hypersensitivity to verapamil hydrochloride.

Warnings

Heart Failure Verapamil has a negative inotropic effect which, in most patients, is compensated by its afterload reduction (decreased systemic vascular resistance) properties without a net impairment of ventricular performance. In clinical experience with 4,954 patients, 87 (1.8%) developed congestive heart failure or pulmonary edema. Verapamil should be avoided in patients with severe left ventricular dysfunction (e.g., ejection fraction less than 30% or moderate to severe symptoms of cardiac failure) and in patients with any degree of ventricular dysfunction if they are receiving a beta-adrenergic blocker. (See DRUG INTERACTIONS . ) Patients with milder ventricular dysfunction should, if possible, be controlled with optimum doses of digitalis and/or diuretics before verapamil treatment (note interactions with digoxin under: PRECAUTIONS ). Hypotension Occasionally, the pharmacologic action of verapamil may produce a decrease in blood pressure below normal levels which may result in dizziness or symptomatic hypotension. The incidence of hypotension observed in 4,954 patients enrolled in clinical trials was 2.5%. In hypertensive patients, decreases in blood pressure below normal are unusual. Tilt table testing (60 degrees) was not able to induce orthostatic hypotension. Elevated Liver Enzymes Elevations of transaminases with and without concomitant elevations in alkaline phosphatase and bilirubin have been reported. Such elevations have sometimes been transient and may disappear even in the face of continued verapamil treatment. Several cases of hepatocellular injury related to verapamil have been proven by rechallenge; half of these had clinical symptoms (malaise, fever, and/or right upper quadrant pain) in addition to elevations of SGOT, SGPT and alkaline phosphatase. Periodic monitoring of liver function in patients receiving verapamil is therefore prudent. Accessory Bypass Tract (Wolff-Parkinson-White or Lown-Ganong-Levine) Some patients with paroxysmal and/or chronic atrial flutter or atrial fibrillation and a coexisting accessory AV pathway have developed increased antegrade conduction across the accessory pathway bypassing the AV node, producing a very rapid ventricular response or ventricular fibrillation after receiving intravenous verapamil (or digitalis). Although a risk of this occurring with oral verapamil has not been established, such patients receiving oral verapamil may be at risk and its use in these patients is contraindicated. (See CONTRAINDICATIONS . ) Treatment is usually DC-cardioversion. Cardioversion has been used safely and effectively after oral verapamil. Atrioventricular Block The effect of verapamil on AV conduction and the SA node may lead to asymptomatic first-degree AV block and transient bradycardia, sometimes accompanied by nodal escape rhythms. PR interval prolongation is correlated with verapamil plasma concentrations, especially during the early titration phase of therapy. Higher degrees of AV block, however, were infrequently (0.8%) observed. Marked first-degree block or progressive development to second- or third-degree AV block requires a reduction in dosage or, in rare instances, discontinuation of verapamil HCl and institution of appropriate therapy depending upon the clinical situation. Patients with Hypertrophic Cardiomyopathy (IHSS) In 120 patients with hypertrophic cardiomyopathy (most of them refractory or intolerant to propranolol) who received therapy with verapamil at doses up to 720 mg/day, a variety of serious adverse effects were seen. Three patients died in pulmonary edema; all had severe left ventricular outflow obstruction and a past history of left ventricular dysfunction. Eight other patients had pulmonary edema and/or severe hypotension; abnormally high (over 20 mm Hg) capillary wedge pressure and a marked left ventricular outflow obstruction were present in most of these patients. Concomitant administration of quinidine (see Drug Interactions ) preceded the severe hypotension in 3 of the 8 patients (2 of whom developed pulmonary edema). Sinus bradycardia occurred in 11% of the patients, second-degree AV block in 4% and sinus arrest in 2%. It must be appreciated that this group of patients had a serious disease with a high mortality rate. Most adverse effects responded well to dose reduction and only rarely did verapamil have to be discontinued.

Precautions

PRECAUTIONS THE CONTENTS OF THE VERAPAMIL HYDROCHLORIDE SUSTAINED-RELEASE CAPSULES SHOULD NOT BE CRUSHED OR CHEWED. VERAPAMIL HYDROCHLORIDE SUSTAINED-RELEASE CAPSULES ARE TO BE SWALLOWED WHOLE OR THE ENTIRE CONTENTS OF THE CAPSULE SPRINKLED ONTO APPLESAUCE (see DOSAGE AND ADMINISTRATION ). General Use in Patients with Impaired Hepatic Function Since verapamil is highly metabolized by the liver, it should be administered cautiously to patients with impaired hepatic function. Severe liver dysfunction prolongs the elimination half-life of immediate-release verapamil to about 14 to 16 hours; hence, approximately 30% of the dose given to patients with normal liver function should be administered to these patients. Careful monitoring for abnormal prolongation of the PR interval or other signs of excessive pharmacologic effects (see OVERDOSAGE ) should be carried out. Use in Patients with Attenuated (Decreased) Neuromuscular Transmission It has been reported that verapamil decreases neuromuscular transmission in patients with Duchenne's muscular dystrophy, and that verapamil prolongs recovery from the neuromuscular blocking agent vecuronium and causes a worsening of myasthenia gravis. It may be necessary to decrease the dosage of verapamil when it is administered to patients with attenuated neuromuscular transmission. Use in Patients with Impaired Renal Function About 70% of an administered dose of verapamil is excreted as metabolites in the urine. Until further data are available, verapamil should be administered cautiously to patients with impaired renal function. These patients should be carefully monitored for abnormal prolongation of the PR interval or other signs of overdosage. (See OVERDOSAGE . ) Information for Patients When the sprinkle method of administration is prescribed, details of the proper technique should be explained to the patient. (See DOSAGE AND ADMINISTRATION .) Drug-Drug Interactions Drug Interactions: Effects of other drugs on verapamil pharmacokinetics In vitro metabolic studies indicate that verapamil is metabolized by cytochrome P450, CYP3A4, CYP1A2, and CYP2C. Clinically significant interactions have been reported with inhibitors of CYP3A4 (e.g., erythromycin, ritonavir) causing elevation of plasma levels of verapamil while inducers of CYP3A4 (e.g., rifampin) have caused a lowering of plasma levels of verapamil. Hypotension, bradyarrhythmias, and lactic acidosis have been observed in patients receiving concurrent telithromycin, an antibiotic in the ketolide class of antibiotics. Ivabradine Concurrent use of verapamil increases exposure to ivabradine and may exacerbate bradycardia and conduction disturbances. Avoid concomitant use of ivabradine and verapamil. HMG-CoA Reductase Inhibitors The use of HMG-CoA reductase inhibitors that are CYP3A4 substrates in combination with verapamil has been associated with reports of myopathy/rhabdomyolysis. Co-administration of multiple doses of 10 mg of verapamil with 80 mg simvastatin resulted in exposure to simvastatin 2.5-fold that following simvastatin alone. Limit the dose of simvastatin in patients on verapamil to 10 mg daily. Limit the daily dose of lovastatin to 40 mg. Lower starting and maintenance doses of other CYP3A4 substrates (e.g., atorvastatin) may be required as verapamil may increase the plasma concentration of these drugs. Beta Blockers Concomitant therapy with beta-adrenergic blockers and verapamil may result in additive negative effects on heart 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 excess bradycardia and AV block, including complete heart block, when the combination has been used for the treatment of hypertension. For hypertensive patients, the risk of combined therapy may outweigh the potential benefits. The combination should be used only with caution and close monitoring. 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 clearance has been reported when verapamil and metoprolol were administered together. A similar effect has not been observed when verapamil and atenolol are given together. Clonidine Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of clonidine concurrently with verapamil. Monitor heart rate in patients receiving concomitant verapamil and clonidine. Digitalis Consider reducing digoxin dose when verapamil and digoxin are to be given together. Monitor digoxin level periodically during therapy. 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 pharmacokinetics is magnified. Verapamil may reduce total body clearance and extrarenal clearance of digoxin by 27% and 29%, respectively. If digoxin toxicity is suspected, suspend or discontinue digoxin therapy. In previous clinical trials with other verapamil formulations related to the control of ventricular response in patients taking digoxin 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.

Side effects

Serious adverse reactions are uncommon when verapamil HCl therapy is initiated with upward dose titration within the recommended single and total daily dose. See WARNINGS for discussion of heart failure, hypotension, elevated liver enzymes, AV block, and rapid ventricular response. Reversible (upon discontinuation of verapamil) non-obstructive, paralytic ileus has been infrequently reported in association with the use of verapamil. In clinical trials involving 285 hypertensive patients on verapamil hydrochloride sustained-release capsules for greater than 1 week the following adverse reactions were reported in greater than 1.0% of the patients: Constipation 7.4% Headache 5.3% Dizziness 4.2% Lethargy 3.2% Dyspepsia 2.5% Rash 1.4% Ankle Edema 1.4% Sleep Disturbance 1.4% Myalgia 1.1% In clinical trials of other formulations of verapamil HCl (N=4,954) the following reactions have occurred at rates greater than 1.0%: Constipation 7.3% Dizziness 3.3% Nausea 2.7% Hypotension 2.5% Edema 1.9% Headache 2.2% Rash 1.2% CHF/Pulmonary Edema 1.8% Fatigue 1.7% Bradycardia (HR<50/min) 1.4% AV block-total 1°, 2°, 3° 1.2% 2° and 3° 0.8% Flushing 0.6% Elevated Liver Enzymes (See WARNINGS ) In clinical trials related to the control of ventricular response in digitalized patients who had atrial fibrillation or atrial flutter, ventricular rate below 50/min at rest occurred in 15% of patients and asymptomatic hypotension occurred in 5% of patients. The following reactions, reported in 1.0% or less of patients, occurred under conditions (open trials, marketing experience) where a causal relationship is uncertain; they are listed to alert the physician to a possible relationship: Cardiovascular: angina pectoris, atrioventricular dissociation, chest pain, claudication, myocardial infarction, palpitations, purpura (vasculitis), syncope. Digestive System: diarrhea, dry mouth, gastrointestinal distress, gingival hyperplasia. Hemic and Lymphatic: ecchymosis or bruising. Nervous System: cerebrovascular accident, confusion, equilibrium disorders, extrapyramidal symptoms, insomnia, muscle cramps, paresthesia, psychotic symptoms, shakiness, somnolence. Respiratory: dyspnea. Skin: arthralgia and rash, exanthema, hair loss, hyperkeratosis, maculae, sweating, urticaria, Stevens-Johnson syndrome, erythema multiforme. Special Senses: blurred vision, tinnitus. Urogenital: gynecomastia, impotence, increased urination, spotty menstruation. Treatment of Acute Cardiovascular Adverse Reactions The frequency of cardiovascular adverse reactions which require therapy is rare; hence, experience with their treatment is limited. Whenever severe hypotension or complete AV block occurs following oral administration of verapamil, the appropriate emergency measures should be applied immediately, e.g., intravenously administered isoproterenol HCl, levarterenol bitartrate, atropine (all in the usual doses), or calcium gluconate (10% solution). In patients with hypertrophic cardiomyopathy (IHSS), alpha-adrenergic agents (phenylephrine, metaraminol bitartrate or methoxamine) should be used to maintain blood pressure, and isoproterenol and levarterenol should be avoided. If further support is necessary, inotropic agents (dopamine or dobutamine) may be administered. Actual treatment and dosage should depend on the severity and the clinical situation and the judgment and experience of the treating physician. To report SUSPECTED ADVERSE EVENTS, contact Teva at 1-888-838-2872 or FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch for voluntary reporting of adverse reactions.

Drug interactions

Drug Interactions: Effects of other drugs on verapamil pharmacokinetics In vitro metabolic studies indicate that verapamil is metabolized by cytochrome P450, CYP3A4, CYP1A2, and CYP2C. Clinically significant interactions have been reported with inhibitors of CYP3A4 (e.g., erythromycin, ritonavir) causing elevation of plasma levels of verapamil while inducers of CYP3A4 (e.g., rifampin) have caused a lowering of plasma levels of verapamil. Hypotension, bradyarrhythmias, and lactic acidosis have been observed in patients receiving concurrent telithromycin, an antibiotic in the ketolide class of antibiotics. Ivabradine Concurrent use of verapamil increases exposure to ivabradine and may exacerbate bradycardia and conduction disturbances. Avoid concomitant use of ivabradine and verapamil. HMG-CoA Reductase Inhibitors The use of HMG-CoA reductase inhibitors that are CYP3A4 substrates in combination with verapamil has been associated with reports of myopathy/rhabdomyolysis. Co-administration of multiple doses of 10 mg of verapamil with 80 mg simvastatin resulted in exposure to simvastatin 2.5-fold that following simvastatin alone. Limit the dose of simvastatin in patients on verapamil to 10 mg daily. Limit the daily dose of lovastatin to 40 mg. Lower starting and maintenance doses of other CYP3A4 substrates (e.g., atorvastatin) may be required as verapamil may increase the plasma concentration of these drugs. Beta Blockers Concomitant therapy with beta-adrenergic blockers and verapamil may result in additive negative effects on heart 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 excess bradycardia and AV block, including complete heart block, when the combination has been used for the treatment of hypertension. For hypertensive patients, the risk of combined therapy may outweigh the potential benefits. The combination should be used only with caution and close monitoring. 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 clearance has been reported when verapamil and metoprolol were administered together. A similar effect has not been observed when verapamil and atenolol are given together. Clonidine Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of clonidine concurrently with verapamil. Monitor heart rate in patients receiving concomitant verapamil and clonidine. Digitalis Consider reducing digoxin dose when verapamil and digoxin are to be given together. Monitor digoxin level periodically during therapy. 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 pharmacokinetics is magnified. Verapamil may reduce total body clearance and extrarenal clearance of digoxin by 27% and 29%, respectively. If digoxin toxicity is suspected, suspend or discontinue digoxin therapy. In previous clinical trials with other verapamil formulations related to the control of ventricular response in patients taking digoxin 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 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. Antiarrhythmic Agents Disopyramide: Until data on possible interactions between verapamil and disopyramide phosphate 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 atrioventricular conduction. 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 electrophysiological 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 interactions. Alcohol: Verapamil has been found to significantly inhibit ethanol elimination resulting in elevated blood ethanol concentrations that may prolong the intoxicating effects of alcohol. (See CLINICAL PHARMACOLOGY - Pharmacokinetics and Metabolism. )

Pregnancy

Pregnancy Pregnancy Category C . Reproduction studies have been performed in rabbits and rats at oral doses up to 1.5 (15 mg/kg/day) and 6 (60 mg/kg/day) times the maximum recommended human daily dose, respectively, and have revealed no evidence of teratogenicity. In the rat, however, this multiple of the human dose was embryocidal and retarded fetal growth and development, probably because of adverse maternal effects reflected in reduced weight gains of the dams. This oral dose has also been shown to cause hypotension in rats. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Verapamil crosses the placental barrier and can be detected in umbilical vein blood at delivery.

Pediatric use

Pediatric Use Safety and efficacy of verapamil in children below the age of 18 years have not been established.

Geriatric use

Geriatric Use Clinical studies of verapamil did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Aging may affect the pharmacokinetics of verapamil. Elimination half-life may be prolonged in the elderly (see CLINICAL PHARMACOLOGY, Pharmacokinetics and Metabolism ). Verapamil is highly metabolized by the liver, and about 70% of the administered dose is excreted as metabolites in the urine. Clinical circumstances, some of which may be more common in the elderly, such as hepatic or renal impairment, should be considered (see PRECAUTIONS, General ). In general, lower initial doses of verapamil hydrochloride sustained-release capsules may be warranted in the elderly (see DOSAGE AND ADMINISTRATION ).

Overdosage

There is no specific antidote for verapamil overdosage; treatment should be supportive. Delayed pharmacodynamic consequences may occur with sustained-release formulations, and patients should be observed for at least 48 hours, preferably under continuous hospital care. Reported effects include hypotension, bradycardia, cardiac conduction defects, arrhythmias, hyperglycemia, and decreased mental status. In addition, there have been literature reports of non-cardiogenic pulmonary edema in patients taking large overdoses of verapamil (up to approximately 9g). In acute overdosage, gastrointestinal decontamination with cathartics and whole bowel irrigation should be considered. Calcium, inotropes (i.e., isoproterenol, dopamine, and glucagon), atropine, vasopressors (i.e., norepinephrine, and epinephrine), and cardiac pacing have been used with variable results to reverse hypotension and myocardial depression. In a few reported cases, overdose with calcium channel blockers that was initially refractory to atropine became more responsive to this treatment when the patients received large doses (close to 1g/hour for more than 24 hours) of calcium chloride. Calcium chloride is preferred to calcium gluconate since it provides 3 times more calcium per volume. Asystole should be handled by the usual measures including cardiopulmonary resuscitation. Verapamil cannot be removed by hemodialysis.

Description

Verapamil hydrochloride sustained-release capsules are calcium ion influx inhibitors (slow channel blockers or calcium ion antagonists). Verapamil hydrochloride sustained-release capsules are available for oral administration as a 360 mg hard gelatin capsule (lavender cap/yellow body), a 240 mg hard gelatin capsule (dark blue cap/yellow body), a 180 mg hard gelatin capsule (light grey cap/yellow body), and a 120 mg hard gelatin capsule (yellow cap/yellow body). These pellet-filled capsules provide a sustained-release of the drug in the gastrointestinal tract. The structural formula of verapamil HCl is given below: C 27 H 38 N 2 O 4
• HCl M.W. 491.07 Chemical name: Benzeneacetonitrile, α-[3-[[2-(3,4-dimethoxyphenyl)-ethyl]methylamino]propyl]-3,4-dimethoxy-α-(1-methylethyl) monohydrochloride. Verapamil HCl is an almost white, crystalline powder, practically free of odor, with a bitter taste. It is soluble in water, chloroform and methanol. Verapamil HCl is not structurally related to other cardioactive drugs. In addition to verapamil HCl the verapamil hydrochloride sustained-release capsules contain the following inactive ingredients: fumaric acid, talc, sugar spheres, povidone, shellac, gelatin, FD&C red #40, yellow iron oxide, titanium dioxide, methylparaben, propylparaben, silicon dioxide, and sodium lauryl sulfate. In addition, the verapamil hydrochloride sustained-release capsules 240 mg and 360 mg capsules contain FD&C blue #1 and D&C red #28; and the verapamil hydrochloride sustained-release capsules 180 mg contain black iron oxide. verapamil hydrochloride structural formula

Mechanism of action

Mechanism of Action Essential Hypertension Verapamil HCl exerts antihypertensive effects by decreasing systemic vascular resistance, usually without orthostatic decreases in blood pressure or reflex tachycardia; bradycardia (rate less than 50 beats/minute is uncommon). Verapamil HCl regularly reduces arterial pressure at rest and at a given level of exercise by dilating peripheral arterioles and reducing the total peripheral resistance (afterload) against which the heart works.

How supplied

Verapamil hydrochloride sustained-release capsules are supplied in four dosage strengths: 120 mg - Two-piece, size 2 hard gelatin capsule (yellow cap/yellow body), printed with 60274 and 120 mg in black ink, supplied as follows: NDC 0591-2880-01 - Bottle of 100s 180 mg - Two-piece, size 1 elongated hard gelatin capsule (light grey cap/yellow body), printed with 60274 and 180 mg in black ink, supplied as follows: NDC 0591-2882-01 - Bottle of 100s 240 mg - Two-piece, size 0 hard gelatin capsule (dark blue cap/yellow body), printed with 60274 and 240 mg in black ink, supplied as follows: NDC 0591-2884-01 - Bottle of 100s 360 mg - Two-piece, size 00 hard gelatin capsule (lavender cap/yellow body), printed with 60274 and 360 mg in black ink, supplied as follows: NDC 0591-2886-01 - Bottle of 100s Store at Controlled Room Temperature 20° to 25°C (68° to 77°F). [See USP]. Avoid excessive heat. Brief digressions above 25°C, while not detrimental, should be avoided. Protect from moisture. Dispense in tight, light-resistant container as defined in USP.

Storage

Store at Controlled Room Temperature 20° to 25°C (68° to 77°F). [See USP]. Avoid excessive heat. Brief digressions above 25°C, while not detrimental, should be avoided. Protect from moisture. Dispense in tight, light-resistant container as defined in USP.

Patient information

Information for Patients When the sprinkle method of administration is prescribed, details of the proper technique should be explained to the patient. (See DOSAGE AND ADMINISTRATION .)

Label text from the FDA structured product label by Teva Pharmaceuticals Inc (revised Sep 22, 2025). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Verapamil Hydrochloride NDC products (132)

NDCStrength & formLabelerType
50090-7311Verapamil Hydrochloride 120 mg/1
Tablet
A-S Medication SolutionsANDA
50090-5253Verapamil Hydrochloride 180 mg/1
Tablet
A-S Medication SolutionsANDA
50090-4582Verapamil Hydrochloride 240 mg/1
Tablet, Film Coated, Extended Release
A-S Medication SolutionsANDA
50090-4013Verapamil Hydrochloride 120 mg/1
Tablet
A-S Medication SolutionsANDA
50090-1400Verapamil Hydrochloride 120 mg/1
Tablet, Film Coated, Extended Release
A-S Medication SolutionsANDA
0591-0404Verapamil Hydrochloride 40 mg/1
Tablet, Film Coated
Actavis Pharma, Inc.ANDA
0591-0345Verapamil Hydrochloride 120 mg/1
Tablet, Film Coated
Actavis Pharma, Inc.ANDA
0591-0343Verapamil Hydrochloride 80 mg/1
Tablet, Film Coated
Actavis Pharma, Inc.ANDA
70121-1585Verapamil Hydrochloride 2.5 mg/mL
Injection, Solution
Amneal Pharmaceuticals LLCANDA
70121-1586Verapamil Hydrochloride 2.5 mg/mL
Injection, Solution
Amneal Pharmaceuticals LLCANDA
71610-405Verapamil Hydrochloride 180 mg/1
Tablet
Aphena Pharma Solutions - Tennessee, LLCANDA
71610-268Verapamil Hydrochloride 240 mg/1
Tablet, Film Coated, Extended Release
Aphena Pharma Solutions - Tennessee, LLCANDA
72485-109Verapamil Hydrochloride 10 mg/4mL
Injection
Armas Pharmaceuticals Inc.ANDA
72485-108Verapamil Hydrochloride 5 mg/2mL
Injection
Armas Pharmaceuticals Inc.ANDA
42291-853Verapamil Hydrochloride 40 mg/1
Tablet
AvKAREANDA
42291-854Verapamil Hydrochloride 80 mg/1
Tablet
AvKAREANDA
42291-855Verapamil Hydrochloride 120 mg/1
Tablet
AvKAREANDA
43066-031Verapamil Hydrochloride 2.5 mg/mL
Injection, Solution
Baxter Healthcare CorporationANDA
43066-035Verapamil Hydrochloride 2.5 mg/mL
Injection, Solution
Baxter Healthcare CorporationANDA
71335-1258Verapamil Hydrochloride 180 mg/1
Tablet
Bryant Ranch PrepackANDA
71335-1004Verapamil Hydrochloride 120 mg/1
Tablet
Bryant Ranch PrepackANDA
63629-4337Verapamil Hydrochloride 120 mg/1
Tablet, Film Coated
Bryant Ranch PrepackANDA
71335-2375Verapamil Hydrochloride 120 mg/1
Tablet
Bryant Ranch PrepackANDA
71335-1394Verapamil Hydrochloride 240 mg/1
Tablet
Bryant Ranch PrepackANDA
71335-2087Verapamil Hydrochloride 40 mg/1
Tablet, Film Coated
Bryant Ranch PrepackANDA
72162-2232Verapamil Hydrochloride 80 mg/1
Tablet
Bryant Ranch PrepackANDA
71209-047Verapamil Hydrochloride 180 mg/1
Tablet, Extended Release
Cadila Pharmaceuticals LimitedANDA
71209-048Verapamil Hydrochloride 240 mg/1
Tablet, Extended Release
Cadila Pharmaceuticals LimitedANDA
71209-104Verapamil Hydrochloride 120 mg/1
Tablet, Extended Release
Cadila Pharmaceuticals LimitedANDA
65145-113Verapamil Hydrochloride 2.5 mg/mL
Injection, Solution
Caplin Steriles LimitedANDA
65145-114Verapamil Hydrochloride 2.5 mg/mL
Injection, Solution
Caplin Steriles LimitedANDA
62135-745Verapamil Hydrochloride 120 mg/1
Tablet
Chartwell RX, LLCANDA
62135-744Verapamil Hydrochloride 80 mg/1
Tablet
Chartwell RX, LLCANDA
62135-743Verapamil Hydrochloride 40 mg/1
Tablet
Chartwell RX, LLCANDA
55150-343Verapamil Hydrochloride 2.5 mg/mL
Injection, Solution
Eugia US LLCANDA
55150-342Verapamil Hydrochloride 2.5 mg/mL
Injection, Solution
Eugia US LLCANDA
65219-384Verapamil Hydrochloride 2.5 mg/mL
Injection
FRESENIUS KABI USA, LLCANDA
68083-447Verapamil Hydrochloride 2.5 mg/mL
Injection
Gland Pharma LimitedANDA
68083-448Verapamil Hydrochloride 2.5 mg/mL
Injection
Gland Pharma LimitedANDA
68462-293Verapamil Hydrochloride 180 mg/1
Tablet, Film Coated, Extended Release
Glenmark Pharmaceuticals Inc., USAANDA
68462-260Verapamil Hydrochloride 240 mg/1
Tablet, Film Coated, Extended Release
Glenmark Pharmaceuticals Inc., USAANDA
68462-292Verapamil Hydrochloride 120 mg/1
Tablet, Film Coated, Extended Release
Glenmark Pharmaceuticals Inc., USAANDA
51407-964Verapamil Hydrochloride 120 mg/1
Tablet
Golden State Medical Supply, Inc.ANDA
51407-963Verapamil Hydrochloride 80 mg/1
Tablet
Golden State Medical Supply, Inc.ANDA
51407-962Verapamil Hydrochloride 40 mg/1
Tablet
Golden State Medical Supply, Inc.ANDA
0404-9966Verapamil Hydrochloride 2.5 mg/mL
Injection, Solution
Henry Schein, Inc.ANDA
0404-9967Verapamil Hydrochloride 2.5 mg/mL
Injection, Solution
Henry Schein, Inc.ANDA
0404-9968Verapamil Hydrochloride 2.5 mg/mL
Injection, Solution
Henry Schein, Inc.ANDA
23155-912Verapamil Hydrochloride 2.5 mg/mL
Injection
Heritage Pharmaceuticals Inc. d/b/a Avet Pharmaceuticals Inc.ANDA
23155-911Verapamil Hydrochloride 2.5 mg/mL
Injection
Heritage Pharmaceuticals Inc. d/b/a Avet Pharmaceuticals Inc.ANDA
23155-486Verapamil Hydrochloride 120 mg/1
Tablet
Heritage Pharmaceuticals Inc. d/b/a Avet Pharmaceuticals Inc.ANDA
23155-059Verapamil Hydrochloride 40 mg/1
Tablet
Heritage Pharmaceuticals Inc. d/b/a Avet Pharmaceuticals Inc.ANDA
23155-026Verapamil Hydrochloride 80 mg/1
Tablet
Heritage Pharmaceuticals Inc. d/b/a Avet Pharmaceuticals Inc.ANDA
51662-1398Verapamil Hydrochloride 2.5 mg/mL
Injection, Solution
HF Acquisition Co LLC, DBA HealthFirstANDA
51662-1686Verapamil Hydrochloride 2.5 mg/mL
Injection, Solution
HF Acquisition Co LLC, DBA HealthFirstANDA
51662-1685Verapamil Hydrochloride 2.5 mg/mL
Injection, Solution
HF Acquisition Co LLC, DBA HealthFirstANDA
51662-1549Verapamil Hydrochloride 2.5 mg/mL
Injection, Solution
HF Acquisition Co LLC, DBA HealthFirstANDA
51662-1270Verapamil Hydrochloride 2.5 mg/mL
Injection, Solution
HF Acquisition Co. LLC, DBA HealthFirstANDA
0409-4011Verapamil Hydrochloride 2.5 mg/mL
Injection, Solution
Hospira, Inc.ANDA
0409-1144Verapamil Hydrochloride 2.5 mg/mL
Injection, Solution
Hospira, Inc.ANDA
70756-606Verapamil Hydrochloride 2.5 mg/mL
Injection, Solution
Lifestar Pharma LLCANDA
70756-605Verapamil Hydrochloride 2.5 mg/mL
Injection, Solution
Lifestar Pharma LLCANDA
71872-7203Verapamil Hydrochloride 5 mg/2mL
Injection
Medical Purchasing Solutions, LLCANDA
71872-7183Verapamil Hydrochloride 2.5 mg/mL
Injection
Medical Purchasing Solutions, LLCANDA
71872-7291Verapamil Hydrochloride 2.5 mg/mL
Injection, Solution
Medical Purchasing Solutions, LLCANDA
71872-7243Verapamil Hydrochloride 2.5 mg/mL
Injection, Solution
Medical Purchasing Solutions, LLCANDA
71872-7210Verapamil Hydrochloride 5 mg/2mL
Injection
Medical Purchasing Solutions, LLCANDA
71872-7356Verapamil Hydrochloride 2.5 mg/mL
Injection, Solution
Medical Purchasing Solutions, LLC.ANDA
42571-313Verapamil Hydrochloride 2.5 mg/mL
Injection
Micro Labs LimitedANDA
51079-917Verapamil Hydrochloride 120 mg/1
Capsule, Extended Release
Mylan Institutional Inc.ANDA
0378-6440Verapamil Hydrochloride 240 mg/1
Capsule, Extended Release
Mylan Pharmaceuticals Inc.ANDA
0378-6380Verapamil Hydrochloride 180 mg/1
Capsule, Extended Release
Mylan Pharmaceuticals Inc.ANDA
0378-6320Verapamil Hydrochloride 120 mg/1
Capsule, Extended Release
Mylan Pharmaceuticals Inc.ANDA
75834-158Verapamil Hydrochloride 180 mg/1
Tablet, Film Coated, Extended Release
Nivagen Pharmaceuticals, Inc.ANDA
75834-159Verapamil Hydrochloride 240 mg/1
Tablet, Film Coated, Extended Release
Nivagen Pharmaceuticals, Inc.ANDA
75834-320Verapamil Hydrochloride 120 mg/1
Tablet, Film Coated, Extended Release
Nivagen Pharmaceuticals, Inc.ANDA
51655-315Verapamil Hydrochloride 120 mg/1
Tablet
Northwind Health Company, LLCANDA
51655-734Verapamil Hydrochloride 180 mg/1
Tablet
Northwind Health Company, LLCANDA
51655-956Verapamil Hydrochloride 240 mg/1
Tablet, Film Coated, Extended Release
Northwind Health Company, LLCANDA
51655-957Verapamil Hydrochloride 120 mg/1
Tablet, Film Coated
Northwind Health Company, LLCANDA
51655-959Verapamil Hydrochloride 180 mg/1
Tablet, Film Coated, Extended Release
Northwind Health Company, LLCANDA
51655-984Verapamil Hydrochloride 240 mg/1
Tablet
Northwind Health Company, LLCANDA
66267-212Verapamil Hydrochloride 240 mg/1
Tablet, Film Coated, Extended Release
NuCare Pharmaceuticals, Inc.ANDA
68071-5257Verapamil Hydrochloride 180 mg/1
Tablet
NuCare Pharmaceuticals,Inc.ANDA
68071-4635Verapamil Hydrochloride 120 mg/1
Tablet
NuCare Pharmaceuticals,Inc.ANDA
68071-3434Verapamil Hydrochloride 80 mg/1
Tablet
NuCare Pharmaceuticals,Inc.ANDA
68071-3435Verapamil Hydrochloride 240 mg/1
Tablet
NuCare Pharmaceuticals,Inc.ANDA
68071-3436Verapamil Hydrochloride 180 mg/1
Tablet
NuCare Pharmaceuticals,Inc.ANDA
68071-3446Verapamil Hydrochloride 120 mg/1
Tablet, Film Coated, Extended Release
NuCare Pharmaceuticals,Inc.ANDA
72789-416Verapamil Hydrochloride 180 mg/1
Tablet, Film Coated, Extended Release
PD-Rx Pharmaceuticals, Inc.ANDA
55289-723Verapamil Hydrochloride 240 mg/1
Tablet, Film Coated, Extended Release
PD-Rx Pharmaceuticals, Inc.ANDA
68788-8696Verapamil Hydrochloride 120 mg/1
Tablet
Preferred Pharmaceuticals Inc.ANDA
68788-8338Verapamil Hydrochloride 120 mg/1
Tablet
Preferred Pharmaceuticals Inc.ANDA
68788-6328Verapamil Hydrochloride 120 mg/1
Tablet, Film Coated, Extended Release
Preferred Pharmaceuticals Inc.ANDA
68788-9790Verapamil Hydrochloride 240 mg/1
Tablet, Film Coated, Extended Release
Preferred Pharmaceuticals, Inc.ANDA
63187-849Verapamil Hydrochloride 120 mg/1
Tablet, Film Coated, Extended Release
Proficient Rx LPANDA
71205-607Verapamil Hydrochloride 180 mg/1
Tablet
Proficient Rx LPANDA
71205-129Verapamil Hydrochloride 120 mg/1
Tablet, Film Coated
Proficient Rx LPANDA
71205-017Verapamil Hydrochloride 240 mg/1
Tablet, Film Coated, Extended Release
Proficient Rx LPANDA
84549-605Verapamil Hydrochloride 2.5 mg/mL
Injection, Solution
ProPharma DistributionANDA
70518-0605Verapamil Hydrochloride 180 mg/1
Tablet, Film Coated, Extended Release
REMEDYREPACK INC.ANDA
70518-1326Verapamil Hydrochloride 240 mg/1
Tablet, Film Coated, Extended Release
REMEDYREPACK INC.ANDA
70518-4453Verapamil Hydrochloride 2.5 mg/mL
Injection, Solution
REMEDYREPACK INC.ANDA
70518-4513Verapamil Hydrochloride 180 mg/1
Tablet
REMEDYREPACK INC.ANDA
48433-145Verapamil Hydrochloride 120 mg/1
Capsule, Extended Release
Safecor Health LLCANDA
25021-312Verapamil Hydrochloride 2.5 mg/mL
Injection, Solution
Sagent PharmaceuticalsANDA
70069-273Verapamil Hydrochloride 2.5 mg/mL
Injection, Solution
Somerset Therapeutics, LLCANDA
70069-271Verapamil Hydrochloride 2.5 mg/mL
Injection, Solution
Somerset Therapeutics, LLCANDA
70069-272Verapamil Hydrochloride 2.5 mg/mL
Injection, Solution
Somerset Therapeutics, LLCANDA
70771-1953Verapamil Hydrochloride 120 mg/1
Tablet
Zydus Lifesciences LimitedANDA
70771-1954Verapamil Hydrochloride 180 mg/1
Tablet
Zydus Lifesciences LimitedANDA
70771-1955Verapamil Hydrochloride 240 mg/1
Tablet
Zydus Lifesciences LimitedANDA
70771-1602Verapamil Hydrochloride 2.5 mg/mL
Injection, Solution
Zydus Lifesciences LimitedANDA
70771-1601Verapamil Hydrochloride 2.5 mg/mL
Injection, Solution
Zydus Lifesciences LimitedANDA
68382-561Verapamil Hydrochloride 120 mg/1
Tablet
Zydus Pharmaceuticals (USA) Inc.ANDA
68382-563Verapamil Hydrochloride 240 mg/1
Tablet
Zydus Pharmaceuticals (USA) Inc.ANDA
68382-562Verapamil Hydrochloride 180 mg/1
Tablet
Zydus Pharmaceuticals (USA) Inc.ANDA
70710-1643Verapamil Hydrochloride 2.5 mg/mL
Injection, Solution
Zydus Pharmaceuticals USA Inc.ANDA
70710-1937Verapamil Hydrochloride 2.5 mg/mL
Injection, Solution
Zydus Pharmaceuticals USA Inc.ANDA
70710-1644Verapamil Hydrochloride 2.5 mg/mL
Injection, Solution
Zydus Pharmaceuticals USA Inc.ANDA
51754-0204Verapamil Hydrochloride 2.5 mg/mL
Injection
EXELA PHARMA SCIENCES, LLCNDA
51754-0203Verapamil Hydrochloride 2.5 mg/mL
Injection
EXELA PHARMA SCIENCES, LLCNDA
71872-7048Verapamil Hydrochloride 2.5 mg/mL
Injection
Medical Purchasing Solutions, LLCNDA
0591-2880Verapamil Hydrochloride 120 mg/1
Capsule, Delayed Release Pellets
Teva Pharmaceuticals IncNDA
62135-532Verapamil Hydrochloride 100 mg/1
Capsule, Extended Release
Chartwell RX, LLCNDA AUTHORIZED GENERIC
52536-886Verapamil Hydrochloride 360 mg/1
Capsule, Delayed Release
Wilshire Pharmaceuticals, Inc.NDA AUTHORIZED GENERIC
52536-884Verapamil Hydrochloride 240 mg/1
Capsule, Delayed Release
Wilshire Pharmaceuticals, Inc.NDA AUTHORIZED GENERIC
52536-882Verapamil Hydrochloride 180 mg/1
Capsule, Delayed Release
Wilshire Pharmaceuticals, Inc.NDA AUTHORIZED GENERIC
52536-880Verapamil Hydrochloride 120 mg/1
Capsule, Delayed Release
Wilshire Pharmaceuticals, Inc.NDA AUTHORIZED GENERIC
52536-487Verapamil Hydrochloride 300 mg/1
Capsule, Extended Release
Wilshire Pharmaceuticals, Inc.NDA AUTHORIZED GENERIC
52536-486Verapamil Hydrochloride 200 mg/1
Capsule, Extended Release
Wilshire Pharmaceuticals, Inc.NDA AUTHORIZED GENERIC
52536-485Verapamil Hydrochloride 100 mg/1
Capsule, Extended Release
Wilshire Pharmaceuticals, Inc.NDA AUTHORIZED GENERIC

Verapamil Hydrochloride recalls

Frequently asked questions

What is Verapamil Hydrochloride used for?

Verapamil hydrochloride sustained-release capsules are indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including this drug.…

What are the side effects of Verapamil Hydrochloride?

Serious adverse reactions are uncommon when verapamil HCl therapy is initiated with upward dose titration within the recommended single and total daily dose. See WARNINGS for discussion of heart failure, hypotension, elevated liver enzymes, AV block, and rapid ventricular response. Reversible (upon discontinuation of verapamil) non-obstructive, paralytic ileus has been infrequently reported in… See the full label for the complete list.

Who makes Verapamil Hydrochloride?

Verapamil Hydrochloride is listed by 46 labelers in the FDA NDC directory, including A-S Medication Solutions, Actavis Pharma, Inc., Amneal Pharmaceuticals LLC, Aphena Pharma Solutions - Tennessee, LLC.

Has Verapamil Hydrochloride been recalled?

The FDA enforcement database lists 3 recalls for Verapamil Hydrochloride, most recently D-0592-2024 (class iii): Cross contamination with other products.