Verapamil Hydrochloride
FDA Drug Information • Also known as: Verapamil Hydrochloride, Verelan Pm
- Brand Names
- Verapamil Hydrochloride, Verelan Pm
- Route
- ORAL
- Dosage Form
- CAPSULE, DELAYED RELEASE PELLETS
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
DESCRIPTION Verapamil hydrochloride is a calcium antagonist or slow-channel inhibitor. Verapamil hydrochloride injection, USP is a sterile, nonpyrogenic solution containing verapamil hydrochloride USP 2.5 mg/mL and sodium chloride USP 8.5 mg/mL in water for injection USP. The solution contains no bacteriostat or antimicrobial agent and is intended for single-dose intravenous administration. May contain hydrochloric acid NF or sodium hydroxide NF for pH adjustment; pH is 4.0 to 6.0. The chemical name of verapamil hydrochloride USP is benzeneacetonitrile, α-[3-[{2-(3,4-dimethoxyphenyl)ethyl} methylamino] propyl]-3,4-dimethoxy-α-(1-methylethyl) monohydrochloride. Verapamil hydrochloride USP is a white or practically white crystalline powder. It is practically odorless and has a bitter taste. It is soluble in water; freely soluble in chloroform; sparingly soluble in alcohol; practically insoluble in ether. It has the following structural formula: Molecular weight: 491.06 Molecular formula: C 27 H 38 N 2 O 4
What Is Verapamil Hydrochloride Used For?
INDICATIONS AND USAGE Verapamil hydrochloride injection, USP 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 hydrochloride. 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 faster 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 hydrochloride 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 hydrochloride 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 verapamil hydrochloride injection should, if possible, be in a treatment setting with monitoring and resuscitation facilities, including D.C.-cardioversion capability (see ADVERSE REACTIONS , 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 verapamil hydrochloride injection.
Dosage and Administration
DOSAGE AND ADMINISTRATION FOR INTRAVENOUS USE ONLY. VERAPAMIL HYDROCHLORIDE INJECTION SHOULD BE GIVEN AS A SLOW INTRAVENOUS INJECTION OVER AT LEAST A TWO-MINUTE PERIOD OF TIME UNDER CONTINUOUS ELECTROCARDIOGRAPHIC (ECG) AND BLOOD PRESSURE MONITORING. The recommended intravenous doses of verapamil hydrochloride injection are as follows: Adult: Initial dose − 5 to 10 mg (0.075 to 0.15 mg/kg body weight) given as an intravenous bolus over at least 2 minutes. Repeat dose − 10 mg (0.15 mg/kg body weight) 30 minutes after the first dose if the initial response is not adequate. An optimal interval for subsequent intravenous doses has not been determined, and should be individualized for each patient. Older patients − The dose should be administered over at least 3 minutes to minimize the risk of untoward drug effects. Pediatric: Initial dose: 0 to 1 year: 0.1 to 0.2 mg/kg body weight (usual single dose range: 0.75 to 2 mg) should be administered as an intravenous bolus over at least 2 minutes under continuous ECG monitoring . 1 to 15 years: 0.1 to 0.3 mg/kg body weight (usual single dose range: 2 to 5 mg) should be administered as an intravenous bolus over at least 2 minutes. Do not exceed 5 mg . Repeat dose: 0 to 1 year: 0.1 to 0.2 mg/kg body weight (usual single dose range: 0.75 to 2 mg) 30 minutes after the first dose if the initial response is not adequate ( under continuous ECG monitoring ). An optimal interval for subsequent intravenous doses has not been determined, and should be individualized for each patient. 1 to 15 years: 0.1 to 0.3 mg/kg body weight (usual single dose range: 2 to 5 mg) 30 minutes after the first dose if the initial response is not adequate. Do not exceed 10 mg as a single dose. An optimal interval for subsequent intravenous doses has not been determined, and should be individualized for each patient. Note: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Use only if solution is clear and vial seal is intact. Unused amount of solution should be discarded immediately following withdrawal of any portion of contents. For stability reasons this product is not recommended for dilution with sodium lactate injection, USP in polyvinyl chloride bags. 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 injection with albumin, amphotericin B, hydralazine hydrochloride and trimethoprim with sulfamethoxazole should be avoided. Verapamil hydrochloride injection will precipitate in any solution with a pH above 6.0.
Side Effects (Adverse Reactions)
ADVERSE REACTIONS The following reactions were reported with verapamil hydrochloride injection used 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%). Occasional cases of seizures during verapamil injection have been reported. Gastrointestinal: Nausea (0.9%); abdominal discomfort (0.6%). In rare cases of hypersensitive patients, broncho/laryngeal spasm accompanied by itch and urticaria has been reported. The following reactions have been reported at low frequency: emotional depression, rotary nystagmus, sleepiness, vertigo, muscle fatigue, diaphoresis, and respiratory failure. Suggested Treatment of Acute Cardiovascular Adverse Reactions* The frequency of these adverse reactions was quite low, and experience with their treatment has been limited. Adverse Reaction Proven Effective Treatment Supportive Treatment 1. Symptomatic hypotension requiring treatment Dopamine intravenous Calcium chloride intravenous Norepinephrine bitartrate intravenous Metaraminol bitartrate intravenous Isoproterenol hydrochloride intravenous Intravenous fluids Trendelenburg position 2. Bradycardia, AV block, Asystole Isoproterenol hydrochloride intravenous Calcium chloride intravenous Norepinephrine bitartrate intravenous Atropine intravenous Cardiac pacing Intravenous fluids (slow drip) 3. Rapid ventricular rate (due to antegrade conduction in flutter/fibrillation with W-P-W or L-G-L syndromes) DC-cardioversion (high energy may be required) Procainamide intravenous Lidocaine intravenous Intravenous fluids (slow drip) * Actual treatment and dosage should depend on the severity of the clinical situation and the judgment and experience of the treating physician.
Warnings and Precautions
WARNINGS VERAPAMIL HYDROCHLORIDE SHOULD BE GIVEN AS A SLOW INTRAVENOUS INJECTION OVER AT LEAST A TWO-MINUTE PERIOD OF TIME (see DOSAGE AND ADMINISTRATION ). Hypotension: Verapamil hydrochloride injection 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% to 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 intravenous pharmacologic treatment (norepinephrine bitartrate, metaraminol bitartrate, or 10% calcium gluconate). All recovered without sequelae. Extreme Bradycardia/Asystole: Verapamil hydrochloride affects the AV and SA nodes and rarely may produce second- or third-degree AV block, bradycardia, and, in extreme cases, asystole. This is more likely to occur in patients with a sick sinus syndrome (SA nodal disease), which is more common in older patients. Bradycardia associated with sick sinus syndrome was reported in 0.3% of the patients treated in controlled double-blind trials in the U.S. The total incidence of bradycardia (ventricular rate less than 60 beats/min) was 1.2% in these studies. Asystole in patients other than those with sick sinus syndrome is usually of short duration (few seconds or less), with spontaneous return to AV nodal or normal sinus rhythm. If this does not occur promptly, appropriate treatment should be initiated immediately. (See ADVERSE REACTIONS and Suggested Treatment of Acute Cardiovascular Adverse Reactions .) Heart Failure: When heart failure is not severe or rate related, it should be controlled with digitalis glycosides and diuretics, as appropriate, before verapamil is used. In patients with moderately severe to severe cardiac dysfunction (pulmonary wedge pressure above 20 mm Hg, ejection fraction less than 30%), acute worsening of heart failure may be seen. Concomitant Antiarrhythmic Therapy: Digitalis: Verapamil hydrochloride injection has been used concomitantly with digitalis preparations without the occurrence of serious adverse effects. However, since both drugs slow AV conduction, patients should be monitored for AV block or excessive bradycardia. Procainamide: Verapamil hydrochloride injection has been administered to a small number of patients receiving oral procainamide without the occurrence of serious adverse effects. Quinidine: Verapamil hydrochloride injection has been administered to a small number of patients receiving oral quinidine without the occurrence of serious adverse effects. However, three patients have been described in whom the combination resulted in an exaggerated hypotensive response presumably from the combined ability of both drugs to antagonize the...
Contraindications
CONTRAINDICATIONS Verapamil hydrochloride injection 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 (e.g., 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.
Overdosage
OVERDOSAGE Treatment of overdosage should be supportive and individualized. Beta-adrenergic stimulation and/or parenteral administration of calcium injections may increase calcium ion flux across the slow channel, and have been effectively used in treatment of deliberate overdosage with oral verapamil hydrochloride. 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 ADVERSE REACTIONS : Suggested Treatment of Acute Cardiovascular Adverse Reactions ).
How Supplied
HOW SUPPLIED Verapamil hydrochloride injection, USP 2.5 mg/mL is a clear, colorless solution filled in a clear glass vial and is supplied in single-dose containers as follows: Strength NDC # Pack 5 mg/2 mL (2.5 mg/mL) 70710-1643-1 2 mL single-dose vial 70710-1643-5 Carton of 5 single-dose vials 70710-1643-7 Carton of 25 single-dose vials 10 mg/4 mL (2.5 mg/mL) 70710-1644-1 4 mL single-dose vial 70710-1644-5 Carton of 5 single-dose vials Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Protect from light by retaining in package until ready to use. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. Please address medical inquiries to Zydus Pharmaceuticals (USA) Inc. at [email protected] or Tel.: 1-877-993-8779. Manufactured by: Zydus Lifesciences Ltd. Vadodara, India. Distributed by: Zydus Pharmaceuticals (USA) Inc. Pennington, NJ 08534 Revised: 01/23
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.