VERAPAMIL
HYDROCHLORIDE
INJECTION, USP
Rx Only

Verapamil HCl is a calcium antagonist or slow channel inhibitor. Verapamil Hydrochloride is available in 5 mg/2 mL single dose vials (for intravenous administration). Each mL contains Verapamil HCI 2.5 mg, Sodium Chloride 8.5 mg and Water for Injection q.s. pH adjusted with Hydrochloric Acid and/or Sodium Hydroxide. The pH of the solution is between 4 and 6.5. Protect spans from light. Sterile, nonpyrogenic.

The structural formula of Verapamil HCI is given below:

Verapamil HCI is an almost white, crystalline powder, practically free of odor, with a bitter taste. It is soluble in water, chloroform and methanol. Verapamil HCI is not chemically related to other antiarrhythmic drugs.

Intravenous Verapamil HCI is indicated for the following:

• Rapid conversion to sinus rhythm of paroxysmal supraventricular tachycardias, including those associated with accessory bypass tracts (Wolff-Parkinson-White [W-P-W] and Lown-Ganong-Levine [L-G-L] syndromes). When clinically advisable, appropriate vagal maneuvers (e.g., Valsalva maneuver) should be attempted prior to verapamil hydrochloride 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 [W-P-W] and Lown-Ganong-Levine [L-G-L] syndromes).

In controlled studies in the United States, about 60% of patients with supraventricular tachycardia converted to normal sinus rhythm within 10 minutes after intravenous verapamil. Uncontrolled studies reported in the world literature describe a conversion rate of about 80%. About 70% of patients with atrial flutter and/or fibrillation with a fast ventricular rate respond with a decrease in ventricular rate of at least 20%. Conversion of atrial flutter or fibrillation to sinus rhythm is uncommon (about 10%) after verapamil and may reflect the spontaneous conversion rate, since the conversion rate after placebo was similar. Slowing of the ventricular rate in patients with atrial fibrillation/flutter lasts 30 to 60 minutes after a single injection.

Because a small fraction (<1%) of patients treated with verapamil respond with life-threatening adverse responses (rapid ventricular rate In atrial flutter/fibrillation and an accessory bypass tract, marked hypotension, or extreme bradycardia/asystole - see Contraindications and Warnings), the initial use of intravenous verapamil should, if possible, be in a treatment setting with monitoring and resuscitation facilities, including DC-cardioversion capability (see Suggested Treatment of Acute Cardiovascular Adverse Reactions). As familiarity with the patient's response is gained, use in an office setting may be acceptable.

Cardioversion has been used safely and effectively after intravenous verapamil.

Intravenous Verapamil HCI is contraindicated in:

• Severe hypotension or cardiogenic shock.
• Second- or third-degree AV block (except in patients with a functioning artificial ventricular pacemaker).
• Sick sinus syndrome (except in patients with a functioning artificial ventricular pacemaker).
• Severe congestive heart failure (unless secondary to a supraventricular tachycardia amenable to verapamil therapy.)
• Patients receiving intravenous beta adrenergic blocking drugs (e.g., propranolol). Intravenous verapamil and intravenous beta adrenergic blocking drugs should not be administered in close proximity to each other (within a few hours), since both may have a depressant effect on myocardial contractility and AV conduction.
• Patients with atrial flutter or atrial fibrillation and an accessory bypass tract (i.e. Wolff-Parkinson-White, Lown-Ganong-Levine syndromes) are at risk to develop ventricular tachyarrhythmia including ventricular fibrillation if verapamil is administered. Therefore, the use of verapamil in these patients is contraindicated.
• Ventricular Tachycardia. Administration of intravenous verapamil to patients with wide-complex ventricular-tachycardia (QRS ≥ 0.12 sec) can result in marked hemodynamic deterioration and ventricular fibrillation. Proper pretherapy diagnosis and differentiation from wide-complex supraventricular tachycardia is imperative in the emergency room setting.
• Known hypersensitivity to verapamil hydrochloride.

VERAPAMIL HYDROCHLORIDE SHOULD BE GIVEN AS A SLOW INTRAVENOUS INJECTION OVER AT LEAST A TWO MINUTE PERIOD OF TIME. (See DOSAGE AND ADMINISTRATION)

The following reactions were reported with intravenous Verapamil HCI used in controlled U.S. clinical trials involving 324 patients.

Treatment of overdosage should be supportive and individualized. Beta-adrenergic stimulation and/or parenteral administration of calcium solutions may increase calcium ion flux across the slow channel, and have been effectively used in treatment of deliberate overdosage with oral Verapamil HCI. Verapamil cannot be removed by hemodialysis. Clinically significant hypotensive reactions or high degree AV block should be treated with vasopressor agents or cardiac pacing, respectively. Asystole should be handled by the usual measures including isoproterenol hydrochloride, other vasopressor agents or cardiopulmonary resuscitation (see Treatment of Cardiovascular Adverse Reactions.)

DOSAGE AND ADMINISTRATION (For Intravenous Use Only)

VERAPAMIL HYDROCHLORIDE SHOULD BE GIVEN AS A SLOW INTRAVENOUS INJECTION OVER AT LEAST A TWO MINUTE PERIOD OF TIME UNDER CONTINUOUS ELECTROCARDIOGRAPHIC AND BLOOD PRESSURE MONITORING.

The recommended intravenous doses of verapamil are as follows:

Note: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Verapamil is physically compatible and chemically stable for at least 24 hours at 25°C protected from light in most common large volume parenteral solutions. Admixing verapamil hydrochloride with albumin, amphotericin B, hydralazine HCI and trimethoprim with sulfamethoxazole should be avoided. Verapamil hydrochloride will precipitate in any solution with a pH above 6.

HOW SUPPLIED: Verapamil Hydrochloride Injection, USP (2.5 mg/mL)

0517-5402-25      2 mL Single Dose Vial (5 mg/2 mL)      packaged in 25

Store at controlled room temperature 15°-30°C (59°-86°F) (See USP). Protect from light.

IN0501
Rev. 1/03

AMERICAN
REGENT, INC.
SHIRLEY, NY 11967