Verapamil Hydrochloride

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-Parkins On-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.

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.

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

You should not use verapamil if you are allergic to it, or if you have:

• certain serious heart conditions, especially "sick sinus syndrome" or "AV block" (unless you have a pacemaker);
• low blood pressure; or
• if you have recently had a heart attack.

To make sure you can safely take verapamil, tell your doctor if you have any of these other conditions:

• kidney disease;
• liver disease;
• congestive heart failure; or
• a nerve-muscle disorder such as myasthenia gravis or muscular dystrophy.

FDA pregnancy category C. It is not known whether verapamil will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

Verapamil can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

• Angina
• Atrial Fibrillation (AF, AFib)
• Mitral Valve Prolapse (MVP)
• Palpitations

Verapamil is in a group of drugs called calcium channel blockers. It works by relaxing the muscles of your heart and blood vessels.

Verapamil is used to treat hypertension (high blood pressure), angina (chest pain), and certain heart rhythm disorders.

Verapamil may also be used for other purposes not listed in this medication guide.

Calcium-channel blocking agent; nondihydropyridine.117 118 302 382

Contraindications

• Severe left ventricular dysfunctionb (unless heart failure is secondary to a supraventricular tachycardia amenable to verapamil therapy).382

• Severe hypotension (SBP <90 mm Hg) or cardiogenic shock.118 b

• Sick sinus syndrome (unless a functioning artificial ventricular pacemaker is present).118 b

• Second- or third-degree AV block (unless a functioning artificial ventricular pacemaker is present).118 b

• Atrial flutter or fibrillation associated with an accessory bypass tract (e.g., Wolff-Parkinson-White or Lown-Ganong-Levine syndrome).118 382 b

• Patients currently receiving, or having recently received (i.e., within a few hours of IV verapamil therapy), IV β-adrenergic blocker therapy.382

• Use of IV verapamil in patients with wide-complex ventricular tachycardia (QRS ≥0.12 seconds).382 (See Wide-Complex Ventricular Tachycardia under Cautions.)

• Known hypersensitivity to verapamil or any ingredient in the formulation.118 382 b

Warnings/Precautions

Warnings

Possible precipitation or acute worsening of heart failure.117 118 207 376

Avoid use in patients with severe left ventricular dysfunction (e.g., pulmonary wedge pressure >20 mm Hg, ejection fraction <30%),117 118 207 unless the heart failure is caused by a supraventricular tachycardia amenable to verapamil therapy382 b or in patients with moderate to severe symptoms of cardiac failure.

Avoid use in patients with any degree of ventricular dysfunction who are receiving a β-adrenergic blocker concomitantly.117 118 207 376 382

Adequate treatment (e.g., with a cardiac glycoside and/or diuretic) recommended prior to initiation of verapamil therapy in patients with milder ventricular dysfunction.117 118 207 376

Possibly marked hemodynamic deterioration and ventricular fibrillation associated with use of IV verapamil in patients with wide-complex ventricular tachycardia (QRS of ≥0.12 seconds); IV verapamil contraindicated in these patients.382

Possible hypotension;117 118 207 376 monitor BP carefully.b

Possible hepatocellular toxicity; monitor liver function tests periodically.117 118 207 376

Possible increases in serum AST/ALT concentrations with or without concomitant increases in alkaline phosphatase and bilirubin concentrations; may resolve despite continued therapy.117 118 207 376

Possible life-threatening ventricular fibrillation and/or cardiac arrest precipitated by accelerated AV conduction in patients with atrial flutter and/or fibrillation with an accessory bypass tract (Wolff-Parkinson-White or Lown-Ganong Levine syndrome); use contraindicated in these patients.117 118 207 376 382 b

Possible second- or third-degree AV block, bradycardia, or asystole, particularly in patients with sick sinus syndrome; use contraindicated in patients with sick sinus syndrome (unless a functioning artificial ventricular pacemaker is present).382

Possible first-degree AV block or progression to second- or third-degree AV block; generally responds to discontinuance of IV verapamil, reduction of oral verapamil dosage, or, in the case of increased ventricular response rate, to cardioversion.118 382 b

If severe AV block occurs, discontinue the drug and initiate appropriate treatment (e.g., IV atropine, isoproterenol, calcium) as needed.382 b

Possibly serious and sometimes fatal adverse cardiovascular effects (e.g., pulmonary edema, hypotension, second-degree AV block, sinus arrest) in patients with hypertrophic cardiomyopathy; use with caution in these patients.118 207 b

Possible precipitation of respiratory muscle failure with IV verapamil in patients with Duchenne’s muscular dystrophy; use with caution.382

Possible increased intracranial pressure with IV verapamil in patients with supratentorial tumors at the time of anesthesia induction; use caution and monitor carefully.382

General Precautions

Certain extended-release tablets (e.g., Covera-HS) are nondeformable; use with caution in patients with preexisting severe GI narrowing.349

When verapamil is used in fixed combination with trandolapril, consider the cautions, precautions, and contraindications associated with trandolapril.352

Specific Populations

Category C.117 118

Distributed into milk; discontinue nursing or the drug.117 118

Possibly severe adverse cardiovascular effects (e.g., refractory hypotension, cardiac arrest) following IV administration of verapamil in neonates and infants.382 If used in children, caution advised.382

Safety and efficacy of oral verapamil not established in children <18 years of age.117 118 207 302 362 376

Consider the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly.c Select dosage with caution;302 376 c titrate dosage carefully.c

Severe hepatic impairment prolongs elimination half-life of verapamil.118 207 (See Elimination: Special Populations, under Pharmacokinetics.) Dosage adjustments may be necessary.118 207 (See Hepatic Impairment under Dosage and Administration.)

Use with caution and with close monitoring for prolongation of the PR interval on ECG, BP changes, or other signs of overdosage.118 382 b

Use with caution and with close monitoring for prolongation of the PR interval on ECG, BP changes, or other signs of overdosage.117 118 382 b

Common Adverse Effects

Constipation,207 362 dizziness,207 362 382 nausea,207 362 382 hypotension,207 362 382 headache.207 362 382

Storage

Oral

Tightly closed container at room temperature (approximately 25°C); generally should be protected from light and moisture.117 118 207 302 362 376 Consult individual manufacturer's labeling for specific storage instructions.

Parenteral

15–30°C.382 Store ampuls and vials in carton to protect from light.382

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Will precipitate in any solution with a pH>6.382

• Inhibits calcium ion influx across membranes of myocardial cells and vascular smooth muscle, thereby inhibiting contractile processes of cardiac and vascular smooth muscle, with resultant dilation of main coronary and systemic arteries; dilation of systemic arteries results in decreased total peripheral resistance, systemic BP, and afterload of the heart.b

• Increases myocardial oxygen delivery in patients with Prinzmetal variant angina (vasospastic angina) by inhibiting spontaneous and ergonovine-induced coronary artery spasm.b

• Alleviates symptoms of unstable and chronic stable angina pectoris through reduction in afterload (at rest and with exercise) and its resultant decrease in oxygen consumption.b

• Unlike nifedipine, verapamil has substantial inhibitory effects on the cardiac conduction system and is considered a class IV antiarrhythmic agent.b

• May reduce resting heart rate and produce sinus arrest or SA block in patients with SA node disease (e.g., sick sinus syndrome).b (See Extreme Bradycardia/Asystole under Cautions.)

• Slows conduction and prolongs refractoriness in the AV node, thereby prolonging the AH (atria-His bundle) interval; this usually also results in PR interval prolongation on ECG and, rarely, second- or third-degree AV block (even in patients without preexisting conduction defects).b (See AV Block under Cautions.)

• Has little effect on the QT interval and minimal or no effects on antegrade or retrograde conduction of accessory bypass pathways.b

• Negative inotropic effects of the drug usually offset by reduced afterload; cardiac index not reduced except in patients with moderately severe or severe heart failure.b (See Cardiac Failure under Cautions.)