bepridil hydrochloride
Vascor

Available forms
Available by prescription only
Tablets: 200 mg, 300 mg, 400 mg

Indications and dosages
 Treatment of chronic stable angina (classic effort-related angina) in patients who are unresponsive or inadequately responsive to other antianginals. Adults: Initially, 200 mg P.O. daily; after 10 days, adjust dosage based on patient tolerance and response. Most common maintenance dosage is 300 mg daily. Maximum daily dose is 400 mg.

Pharmacodynamics
Antianginal action: Precise mechanism of action is unknown. Drug inhibits calcium ion influx into cardiac and vascular smooth muscle and also inhibits the sodium inward influx, resulting in reductions in the maximal upstroke velocity and amplitude of the action potential. It’s believed to reduce heart rate and arterial pressure by dilating peripheral arterioles and reducing total peripheral resistance (afterload). The effects are dose-dependent. Bepridil has dose-related class I antiarrhythmic properties affecting electrophysiologic changes, such as prolongation of QT and QTc intervals.

Pharmacokinetics
Absorption: Rapidly and completely absorbed after oral administration.
Distribution: Over 99% of drug is bound to plasma proteins.
Metabolism: Metabolized in the liver.
Excretion: Elimination is biphasic. Bepridil has a distribution half-life of 2 hours. Over 10 days, 70% is excreted in urine, 22% in feces as metabolites. Terminal half-life after multiple dosing averages 42 hours (range, 26 to 64 hours).

Contraindications and precautions
Contraindicated in patients hypersensitive to drug and in those with uncompensated cardiac insufficiency, sick sinus syndrome or second- or third-degree AV block (unless pacemaker is present); hypotension (below 90 mm Hg systolic); congenital QT interval prolongation; or history of serious ventricular arrhythmias. Also contraindicated in those receiving other drugs that prolong QT interval.
 Use cautiously in patients with left bundle-branch block, sinus bradycardia, impaired renal or hepatic function, or heart failure. Drug isn’t recommended for patients within 3 months of an MI.

Interactions
Drug-drug. Beta blockers: Cause excessive bradycardia and conduction abnormalities. Monitor patient closely.
Digoxin: Causes modest increases in steady-state serum digoxin levels. Monitor serum digoxin levels.
Potassium-wasting diuretics: Hypokalemia may occur, which increases risk of serious ventricular arrhythmias. Monitor serum potassium levels closely.
Procainamide, quinidine, tricyclic antidepressants:
Cause additive prolongation of QT interval. Avoid use together.

Adverse reactions
CNS: dizziness, drowsiness, nervousness, headache, insomnia, paresthesia, asthenia, tremor.
CV: edema, flushing, palpitations, tachycardia, ventricular arrhythmias, including torsades de pointes, ventricular tachycardia, ventricular fibrillation.
EENT: tinnitus.
GI: nausea, diarrhea, constipation, abdominal discomfort, dry mouth, anorexia.
Hematologic: agranulocytosis.
Hepatic: abnormal liver function.
Respiratory: dyspnea.
Skin: rash.
Other: flu syndrome.

Effects on lab test results
• May increase ALT levels.

Overdose and treatment
Exaggerated adverse reactions have been observed, especially clinically significant hypotension, high-degree AV block, and ventricular tachycardia.
 Treat with appropriate supportive measures, including gastric lavage, beta-adrenergic stimulation, parenteral calcium solutions, vasopressor agents, and cardioversion, as needed. Close observation in a cardiac care facility for a minimum of 48 hours is recommended.

Special considerations
 ALERT Careful patient selection and monitoring are essential. Use the following selection criteria: Diagnosis of chronic stable angina with failure to respond or inadequate response to other therapies, QTc interval of less than 0.44 second, absence of hypokalemia, hypotension, severe left ventricular dysfunction, serious ventricular arrhythmias, unpacked sick sinus syndrome, second- or third-degree AV block, and no use of other drugs that prolong the QT interval.
• Monitor serum potassium level and correct hypokalemia before starting therapy. Use potassium-sparing diuretics for patients who need diuretic therapy.
• Monitor QTc interval before and during therapy. Reduced dose is required if QTc prolongation is greater than 0.52 second or increases more than 25%. If prolongation of QTc interval persists, discontinue bepridil.
• Beta blockers, nitrates, digoxin, insulin, and oral antidiabetics may be used with bepridil.
• Use cautiously in patients with renal or hepatic disorders. No clinical data are available.
• Assess patient for development of cough or dyspnea; consider pulmonary infiltrates or fibroses as a potential cause.
• Food doesn’t interfere with absorption of bepridil. Food may alleviate or prevent nausea.
Breast-feeding patients
• Drug appears in breast milk; risk-benefit must be assessed.
Pediatric patients
• Safety and efficacy in children younger than age 18 haven’t been established.
Geriatric patients
• Recommended starting dose is same as in younger adult patients; however, more frequent monitoring may be required.

Patient education
• Instruct patient to recognize signs and symptoms of hypokalemia and the importance of compliance with prescribed potassium supplements.
• Tell patient to report signs or symptoms of infection, such as sore throat and fever.
• Instruct patient to take drug with food or at bedtime if nausea occurs.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use