Verapamil

Verapamil is indicated for the treatment of supraventricular tachyarrhythmias, including: • Rapid conversion to sinus rhythm of paroxysmal supraventricular tachycardias, including those associated with accessory bypass tracts (Wolff-Parkinson-White [WPW] and Lown-Ganong-Levine [LGL] syndromes). When clinically advisable, appropriate vagal maneuvers (e.g., Valsalva maneuver) should be attempted prior to Verapamil administration. • Temporary control of rapid ventricular rate in atrial flutter or atrial fibrillation, except when the atrial flutter and/or atrial fibrillation are associated with accessory bypass tracts (Wolff-Parkinson-White [WPW] and Lown-Ganong-Levine [LGL] syndromes). In controlled studies in the U.S., about 60% of patients with supraventricular tachycardia converted to normal sinus rhythm within 10 minutes after intravenous Verapamil hydrochloride.

Verapamil inhibits the calcium ion (and possibly sodium ion) influx through slow channels into conductile and contractile myocardial cells and vascular smooth muscle cells. The antiarrhythmic effect of Verapamil appears to be due to its effect on the slow channel in cells of the cardiac conductile system. Electrical activity through the SA and AV nodes depends, to a significant degree, upon calcium influx through the slow channel. By inhibiting this influx, Verapamil slows AV conduction and prolongs the effective refractory period within the AV node in a rate-related manner. This effect results in a reduction of the ventricular rate in patients with atrial flutter and/or atrial fibrillation and a rapid ventricular response.

For intravenous use only. VERAPAMIL SHOULD BE GIVEN AS A SLOW INTRAVENOUS INJECTION OVER AT LEAST A TWO-MINUTE PERIOD OF TIME UNDER CONTINUOUS ECG AND BLOOD PRESSURE MONITORING. The recommended intravenous doses of Verapamil are as follows: Adult: Initial dose —5-10 mg (0.075-0.15 mg/kg body weight) given as an intravenous bolus. Repeat dose— 10 mg (0.15 mg/kg body weight) 30 minutes after the first dose if the initial response is not adequate. Older patients— The dose should be administered over at least 3 minutes to minimize the risk of untoward drug effects. Pediatric: Initial dose 0-1 year: 0.1-0.2 mg/kg body weight (usual single dose range: 0.75-2 mg) should be administered as an intravenous bolus. 1-15 years: 0.1-0.3 mg/kg body weight (usual single dose range: 2-5 mg) should be administered as an intravenous bolus.

Verapamil hydrochloride injection is contraindicated in: 1. Severe hypotension or cardiogenic shock 2. Second- or third-degree AV block (except in patients with a functioning artificial ventricular pacemaker) 3. Sick sinus syndrome (except in patients with a functioning artificial ventricular pacemaker) 4. Severe congestive heart failure (unless secondary to a supraventricular tachycardia amenable to Verapamil therapy) 5. Patients receiving intravenous beta-adrenergic blocking drugs (e.g., propranolol).

VERAPAMIL SHOULD BE GIVEN AS A SLOW INTRAVENOUS INJECTION OVER AT LEAST A TWO-MINUTE PERIOD OF TIME. Hypotension: Intravenous Verapamil often produces a decrease in blood pressure below baseline levels that is usually transient and asymptomatic but may result in dizziness. Systolic pressure less than 90 mm Hg and/or diastolic pressure less than 60 mm Hg was seen in 5%-10% of patients in controlled U.S. trials in supraventricular tachycardia and in about 10% of the patients with atrial flutter/fibrillation. The incidence of symptomatic hypotension observed in studies conducted in the U.S. was approximately 1.5%. Three of the five symptomatic patients required pharmacologic treatment (norepinephrine bitartrate IV, metaraminol bitartrate IV, or 10% calcium gluconate IV). All recovered without sequelae.

The following reactions were reported with intravenous Verapamil use in controlled U.S. clinical trials involving 324 patients: Cardiovascular: Symptomatic hypotension (1.5%), bradycardia (1.2%), severe tachycardia (1.0%). The worldwide experience in open clinical trials in more than 7,900 patients was similar. Central nervous system effects: Dizziness (1.2%), headache (1.2%). Although rare, cases of seizures during verapamil injection has been reported. Gastrointestinal: Nausea (0.9%), abdominal discomfort (0.6%). In rare cases of hypersensitivity, broncho/laryngeal spasm accompanied by itch and urticaria has been reported. The following reactions were reported in a few patients: emotional depression, rotary nystagmus, sleepiness, vertigo, muscle fatigue, or diaphoresis.