Professional Information

Verapamil Hydrochloride

Pronouncation: (ver-AP-a-mil HYE-droe-KLOR-ide)
Class: Calcium channel blocking agent

Trade Names:
Calan
- Tablets 40 mg
- Tablets 80 mg
- Tablets 120 mg

Trade Names:
Calan SR
- Tablets, sustained-release 120 mg
- Tablets, sustained-release 180 mg
- Tablets, sustained-release 240 mg

Trade Names:
Covera-HS
- Tablets, extended-release 180 mg
- Tablets, extended-release 240 mg

Trade Names:
Isoptin
- Tablets 40 mg
- Tablets 80 mg
- Tablets 120 mg

Trade Names:
Isoptin SR
- Tablets, sustained-release 120 mg
- Tablets, sustained-release 180 mg
- Tablets, sustained-release 240 mg

Trade Names:
Verelan
- Capsules, sustained-release 120 mg
- Capsules, sustained-release 180 mg
- Capsules, sustained-release 240 mg
- Capsules, sustained-release 360 mg

Trade Names:
Verelan PM
- Capsules, sustained-release 100 mg
- Capsules, sustained-release 200 mg
- Capsules, sustained-release 300 mg

Trade Names:
Verapamil
- Injection 2.5 mg/mL

Alti-Verapamil (Canada)
APO-Verap (Canada)
Chronovera (Canada)
Gen-Verapamil (Canada)
Gen-Verapamil SR (Canada)
Isoptin I.V. (Canada)
Novo-Veramil (Canada)
Novo-Veramil SR (Canada)
Nu-Verap (Canada)

Pharmacology

Feedback for Verapamil Hydrochloride

As a treatment for...	Avg User Ratings [?]
High Blood Pressure	1 comments Rate it!	10
Cluster Headaches	2 comments Rate it!	9.7
Supraventricular Tachycardia	0 comments Rate it!	9.0

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Inhibits movement of calcium ions across cell membrane, resulting in depression of mechanical contraction of myocardial and vascular smooth muscle and depression of impulse formation (automaticity) and conduction velocity.

Pharmacokinetics

Distribution

Rapid early distribution phase (t _½ about 4 min).

Metabolism

Rapidly metabolized. Extensive metabolism in the liver with 12 metabolites having been identified, most only in trace amounts. Major metabolites are N- and O-dealkylated products of verapamil.

Elimination

Terminal elimination t _½ is about 2 to 5 h. About 70% of dose is excreted in the urine and 16% more in feces within 5 days. About 3% to 4% is excreted as unchanged drug.

Special Populations

Elderly

Elimination t _½ may be prolonged.

Indications and Usage

Oral Immediate-release

Treatment of vasospastic (Prinzmetal variant), chronic stable (classic effort–associated), and unstable (crescendo, preinfarction) angina; adjunctive treatment with digitalis to control ventricular rate at rest and during stress in atrial flutter or fibrillation; prophylaxis of repetitive paroxysmal supraventricular tachycardia; management of essential hypertension.

Oral Sustained-release

Management of essential hypertension. Management of angina pectoris ( Covera HS only)

Parenteral

Rapid conversion of paroxysmal supraventricular tachycardia to sinus rhythm; temporary control of rapid ventricular rate in atrial flutter or fibrillation.

Unlabeled Uses

Treatment of migraine and cluster headaches; treatment of hypertrophic cardiomyopathy.

Contraindications

Hypersensitivity to verapamil; sick sinus syndrome or second- or third-degree AV block except with functioning pacemaker; hypotension (less than 90ߙmm Hg systolic); severe left ventricular dysfunction; cardiogenic shock and severe CHF, unless secondary to supraventricular tachycardia amenable to verapamil; patients with atrial flutter or fibrillation and accessory bypass tract. IV verapamil should not be used concomitantly (within few hours) of IV beta-adrenergic blocking agents or in ventricular tachycardia.

Dosage and Administration

Angina Pectoris
Adults

PO 80 to 120 mg 3 times daily. Start with 40 or 80 mg 3 times daily. Base upward titration on therapeutic efficacy and safety evaluated approximately 8 h after dosing. Dosage may be increased daily or weekly. Covera-HS : 180 to 540 mg once daily at bedtime.

Arrhythmias
Adults

PO In digitalized patients, with chronic atrial fibrillation, the dose ranges from 240 to 320 mg/day divided into 3 or 4 times a day dosing. Dosage for prophylaxis of paroxysmal supraventricular tachycardia in nondigitalized patients ranges from 240 to 480 mg daily divided into 3 or 4 times a day dosing. In general, maximum effects for any given dosage will be apparent during the first 48 h of therapy.

Essential Hypertension
Adults

PO 40 to 160 mg 3 times daily. Base upward titration on therapeutic efficacy, assessed at the end of the dosing interval. The antihypertensive effects are evident within the first week of therapy.

Sustained-release capsules, Verelan PM

100 to 400 mg once daily at bedtime. Upward titration should be based on therapeutic efficacy and safety evaluated approximately 24 h after dosing. The antihypertensive effects are evident within the first week of therapy. If an adequate response is not obtained with 200 mg, the dose may be titrated to 300 mg each evening then, if needed, to 400 mg each evening.

Verelan sustained-release capsules

120 to 480 mg once daily in the morning. Upward titration should be based on therapeutic efficacy and safety evaluated approximately 24 h after dosing. The antihypertensive effects are evident within the first week of therapy.

Sustained-release tablets, Calan SR

120 to 480 mg. Daily doses of 240 mg or less are given each morning. Daily doses of 360 mg are given as 180 morning and evening or 240 mg each morning plus 120 mg each evening. Daily doses of 480 mg are administered as 240 mg every 12 h.

Covera-HS

180 to 540 mg once daily at bedtime.

Supraventricular Tachycardia, Atrial Flutter or Fibrillation
Adults

IV Initial dose 5 to 10 mg (0.075 to 0.15 mg/kg) IV bolus over at least 2 min. Give 10 mg (0.15 mg/kg) 30 min after the first dose if initial response is not adequate. An optimal interval for subsequent IV doses has not been determined; individualize for each patient.

Older patients

IV Administer the dose over at least 3 min to minimize risk of untoward drug effects.

1 to 15 yr of age

IV 0.1 to 0.3 mg/kg administered as an IV bolus over at least 2 min (max, 5 mg). Give 0.1 to 0.3 mg/kg 30 min after first dose if initial response is not adequate (max, 10 mg as a single dose). An optimal interval for subsequent IV doses has not been determined; individualize for each patient.

0 to 1 yr of age

IV 0.1 to 0.2 mg/kg administered as an IV bolus over at least 2 min under continuous ECG monitoring. Give 0.1 mg to 0.2 mg 30 min after the first dose under continuous ECG monitoring if the initial response is not adequate. An optimal interval for subsequent IV doses has not been determined; individualize for each patient.

General Advice

Sustained-release capsules, Verelan capsules: Administer once daily at bedtime.
Sustained-release capsules, Verelan capsules, Verelan PM : Alternatively, may be administered by opening the capsule and sprinkling the beads onto 1 tablespoonful of applesauce. The applesauce should be swallowed immediately without chewing and followed by a glass of cool water. The applesauce should not be hot and should be soft enough to swallow without chewing.
Parenteral: Administer as a slow IV injection over at least 2 min.
Parenteral: Discard unused amounts of solution immediately following withdrawal of any portion of the contents.
Incompatibilities: Do not mix IV product with sodium lactate in PVC bags, albumin, amphotericin B, hydralazine, aminophylline, sodium bicarbonate, nafcillin, or trimethoprim-sulfamethoxazole. Do not mix in solution with pH above 6.

Storage/Stability

Covera-HS : Store at 68° to 77°F. Protect from light. Sustained-release capsules: Store at 68° to 77°F. Protect from moisture. Tablets, Calan tablets: Store at 59° to 86°F. Protect from light. Sustained-release tablets, Calan SR capsules, Verelan PM capsules: Store at 59° to 86°F. Protect from light and moisture. Verelan capsules: Store at 68° to 77°F. Protect from light and moisture. Parenteral: Store at 68° to 77°F. Protect from light.

Drug Interactions

Alcohol

Alcohol blood levels may be elevated, prolonging the intoxicating effects.

Antineoplastic regimens (cyclophosphamide, oncovin, prednisone, and procarbazine or vindesine, adriamycin, and cisplatin)

These regimens can reduce verapamil absorption.

Aspirin

Risk of bleeding may be increased compared with aspirin alone.

Barbiturates (eg, phenobarbital)

Verapamil Cl may be increased, reducing plasma concentrations.

Beta-blockers

May result in increased hypotension and adverse reactions because of additive depressant effects on myocardial contractility or AV conduction.

Buspirone

Pharmacologic and adverse reactions may be increased by verapamil.

Calcium salts

Clinical effects and toxicities of verapamil may be reversed.

Carbamazepine

Increased carbamazepine serum levels.

Cyclosporine

Increased cyclosporine levels may result.

CYP3A4 inducers (eg, rifampin)

Verapamil plasma levels may be reduced, decreasing the pharmacologic effect.

CYP3A4 inhibitors (eg, erythromycin, ritonavir)

Verapamil plasma levels may be elevated, increasing the pharmacologic effects and adverse reactions.

Digitalis glycosides

Increased serum digoxin or digitoxin levels may occur.

Disopyramide

Do not use 48 h before or 24 h after verapamil.

Dofetilide

Risk of life-threatening ventricular arrhythmias, including torsades de pointes, may be increased. Coadministration with verapamil is contraindicated.

Doxorubicin

Doxorubicin serum concentrations may be elevated.

Flecainide

May prolong AV conduction.

Grapefruit juice

Verapamil plasma concentrations may be elevated.

Lithium

Coadminister with verapamil with caution because of variable effects.

Nondepolarizing muscle relaxants

Enhanced muscle relaxant effects and prolonged respiratory depression may occur.

Other antihypertensive agents

Additive hypotension.

Paclitaxel, theophylline

Cl of these agents may be reduced by verapamil, increasing plasma levels.

Prazosin

Increased prazosin serum levels may result.

Quinidine

Hypotension, bradycardia, ventricular tachycardia, AV block, and pulmonary edema may occur.

Rifampin

Loss of effectiveness of oral verapamil may occur.

Simvastatin

Plasma levels may be elevated by verapamil, increasing the risk of toxicity (eg, rhabdomyolysis).

St. John's wort

Verapamil plasma concentrations may be reduced, decreasing the efficacy.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Abnormal ECG, hypotension (3%); angina pectoris, AV dissociation, chest pain, CHF/pulmonary edema, claudication, hypertension, MI, palpitation, purpura, syncope (2% or less); AV block, bradycardia (1%).

Hypotension (2%); bradycardia, severe tachycardia (1%).

CNS

Headache (12%); dizziness (3%); asthenia, cerebrovascular accident, confusion, equilibrium disorders, extrapyramidal symptoms, fatigue, insomnia, paresthesia, psychotic symptoms, shakiness, somnolence (2% or less).

Dizziness, headache (1%).

Dermatologic

Erythema multiforme, exanthema, hair loss, hyperkeratosis, macules, rash, sweating, Stevens-Johnson syndrome, urticaria (2% or less).

EENT

Pharyngitis, rhinitis (3%); blurred vision, tinnitus (2% or less).

GI

Constipation (9%); dyspepsia, nausea (3%); diarrhea, dry mouth, GI distress, gingival hyperplasia (2% or less).

Nausea (1%).

Genitourinary

Gynecomastia, impotence, increased urination, spotty menstruation (2% or less).

Hematologic-Lymphatic

Ecchymosis or bruising (2% or less).

Metabolic-Nutritional

Galactorrhea/hyperprolactinemia (2% or less).

Musculoskeletal

Arthralgia, muscle cramps (2% or less).

Respiratory

Sinusitis (3%); dyspnea (2% or less).

Miscellaneous

Infection (12%); flu-syndrome, peripheral edema (4%); accidental injury, aggravated allergy, edema, pain (2% or less).

Precautions

Pregnancy

Category C .

Lactation

Excreted in breast milk.

Children

Oral

Safety and efficacy not established.

Parenteral

Controlled studies have not been conducted in children, but uncontrolled experience with IV administration to children and newborns indicates that results of treatment are similar to those in adults. Use with caution.

Elderly

Since elimination may be prolonged in elderly patients, lower doses may be warranted.

Renal Function

Use with caution.

Hepatic Function

Use with caution.

Cardiac conduction

May be associated with variety of cardiac conduction abnormalities including first-, second-, or third-degree AV block; bradycardia; asystole; severe hypotension; nodal escape rhythms; PR prolongation; and ventricular tachycardia in patients with atrial flutter/fibrillation and Wolff-Parkinson-White syndrome caused by antegrade conduction.

Duchenne muscular dystrophy

May decrease neuromuscular transmission in patients with Duchenne muscular dystrophy and prolong recovery from neuromuscular blocking agent vecuronium.

Heart failure

Verapamil has a negative inotropic effect and should be avoided in patients with severe left ventricular dysfunction.

Hepatic enzymes

Elevated transaminases with or without elevations in alkaline phosphatase and bilirubin have been reported.

Hypertrophic cardiomyopathy

Serious adverse effects were seen in patients with hypertrophic cardiomyopathy who received oral verapamil.

Hypotension

Decreased BP may occur, resulting in dizziness or symptomatic hypotension.

Increased intracranial pressure

IV verapamil has increased intracranial pressure in patients with supratentorial tumors at time of anesthesia induction.

Neuromuscular transmission

Use with caution in patients with decreased neuromuscular transmission. Verapamil causes worsening of myasthenia gravis.

Premature ventricular contractions

May occur after IV use; consider possibility with oral use.

Overdosage

Symptoms

Arrhythmias, bradycardia, cardiac conduction defects, decreased mental status, hyperglycemia, hypotension, noncardiogenic pulmonary edema.

Patient Information

Tell patient if dose is missed to take as soon as possible. If several hours have passed or if it is nearing time for next dose, tell patient not to double dose to catch up unless advised by health care provider.
If more than one dose is missed, tell patient to contact health care provider.
Caution patient not to change dose unless directed by health care provider.
Advise patient not to suddenly stop taking medication.
Remind patient to brush and floss teeth and see dentist regularly.
Instruct patient to report any irregular heartbeat, shortness of breath, swelling of hands and feet, pronounced dizziness, constipation, nausea, or hypotension.
Advise patient to avoid use of alcohol and nonprescription medications without consulting health care provider first.
Instruct patient to limit caffeine consumption.
Advise patient that drug may cause dizziness and to use caution while driving or performing other tasks requiring mental alertness until effects of drug have stabilized.
Stress to patient the importance of compliance in all areas of treatment regimen: diet, exercise, stress reduction, and drug therapy.