No

Calcium Channel Blocker

Treatment of chronic stable angina; due to side effect profile, reserve for patients who have been intolerant of other antianginal therapy; bepridil may be used alone or in combination with nitrates or beta-blockers

C

History of serious ventricular or atrial arrhythmias (especially tachycardia or those associated with accessory conduction pathways), uncompensated cardiac insufficiency, congenital Q-T interval prolongation, patients taking other drugs that prolong the Q-T interval, history of hypersensitivity to bepridil or any component, calcium channel blockers, or adenosine; concurrent administration with ritonavir, amprenavir, or sparfloxacin

Use with great caution in patients with history of IHSS, second or third degree A-V block, cardiogenic shock; reserve for patients in whom other antianginals have failed. Carefully titrate dosages for patients with impaired renal or hepatic function; use caution when treating patients with congestive heart failure, significant hypotension, severe left ventricular dysfunction, hypertrophic cardiomyopathy (especially obstructive), concomitant therapy with beta-blockers or digoxin, edema, or increased intracranial pressure with cranial tumors; do not abruptly withdraw (may cause chest pain); elderly may experience hypotension and constipation more readily.

>10%:

Central nervous system: Dizziness

Gastrointestinal: Nausea, dyspepsia

1% to 10%:

Cardiovascular: Bradycardia, edema, palpitations

Central nervous system: Nervousness, headache (7% to 13%), drowsiness, psychiatric disturbances (<2%), insomnia (2% to 3%)

Dermatologic: Rash ( less than or equal to 2%)

Endocrine & metabolic: Sexual dysfunction

Gastrointestinal: Diarrhea, anorexia, xerostomia, constipation, abdominal pain, dyspepsia, flatulence

Neuromuscular & skeletal: Weakness (6.5% to 14%), tremor (<9%), paresthesia (2.5%)

Ocular: Blurred vision

Otic: Tinnitus

Respiratory: Rhinitis, dyspnea ( less than or equal to 8.7%), cough ( less than or equal to 2%)

Miscellaneous ( less than or equal to 2%): Flu syndrome, diaphoresis

<1%: Ventricular premature contractions, hypertension, syncope, prolonged Q-T intervals, fever, altered behavior, akathisia, abnormal taste, arthritis, pharyngitis

The primary cardiac symptoms of calcium blocker overdose include hypotension and bradycardia. The hypotension is caused by peripheral vasodilation, myocardial depression, and bradycardia. Bradycardia results from sinus bradycardia, second- or third-degree atrioventricular block, or sinus arrest with junctional rhythm. Intraventricular conduction is usually not affected so QRS duration is normal (verapamil does prolong the P-R interval and bepridil prolongs the Q-T and may cause ventricular arrhythmias, including torsade de pointes).

In a few reported cases, overdose with calcium channel blockers has been associated with hypotension and bradycardia, initially refractory to atropine but becoming more responsive to this agent when larger doses (approaching 1 g/hour for more than 24 hours) of calcium chloride was administered.

CYP3A3/4 enzyme substrate

Bepridil and cyclosporine may increase cyclosporine levels (other calcium channel blockers have been shown to interact)

Bepridil and digitalis glycoside may increase digitalis glycoside levels

Use with ritonavir, amprenavir and other protease inhibitors may increase risk of bepridil and sparfloxacin toxicity, especially its cardiotoxicity

Coadministration with beta-blocking agents may result in increased depressant effects on myocardial contractility or A-V conduction

Severe hypotension or increased fluid volume requirements may occur with concomitant fentanyl

Bepridil, a type 4 calcium antagonist, possesses characteristics of the traditional calcium antagonists, inhibiting calcium ion from entering the "slow channels" or select voltage-sensitive areas of vascular smooth muscle and myocardium during depolarization and producing a relaxation of coronary vascular smooth muscle and coronary vasodilation. However, bepridil may also inhibit fast sodium channels (inward), which may account for some of its side effects (eg, arrhythmias); a direct bradycardia effect of bepridil has been postulated via direct action on the S-A node.

Onset of action: 1 hour

Absorption: Oral: 100%

Distribution: Protein binding: >99%

Metabolism: Hepatic

Bioavailability: 60%

Half-life: 24 hours

Time to peak: 2-3 hours

Elimination: Metabolites renally excreted

Adults: Oral: Initial: 200 mg/day, then adjust dose at 10-day intervals until optimal response is achieved; usual dose: 300 mg/day; maximum daily dose: 400 mg

EKG and serum electrolytes, blood pressure, signs and symptoms of congestive heart failure; elderly may need very close monitoring due to underlying cardiac and organ system defects

1-2 ng/mL

aminotransferases, CPK, LDH

May cause nervousness; rare reports of akathisia

Concurrent use with beta-blockers may decrease AV nodal conduction

No information available to require special precautions

Other drugs of this class can cause gingival hyperplasia (ie, nifedipine) but there have been no reports for bepridil

Take as directed (may be taken with food to reduce gastric side effects). Do not discontinue without consulting prescriber. Regular EKGs and follow-up with prescriber may be required. If taking potassium supplements or potassium-sparing diuretics, serum potassium monitoring will be required. May cause dizziness, shakiness, visual disturbances, or headache; use caution when driving or engaging in tasks that require alertness until response to drug is known. Report irregular or pounding heartbeat, respiratory difficulty, swelling of hands or feet, unresolved headache, dizziness, constipation, or any unusual bleeding or bruising. Pregnancy precautions: Inform prescriber if you are or intend to be pregnant.

EKG required; patient should be hospitalized during initiation or escalation of therapy

Tablet, as hydrochloride: 200 mg, 300 mg, 400 mg

Viallon A, Page Y, Lafond P, et al, "Bepridil and Torsade de Pointes: Are the Precautions of Use Respected?" Therapie, 1994, 49(5):431-4.

Zeller FP and Spinler SA, "Bepridil: A New Long-Acting Calcium Channel Blocking Agent," Drug Intell Clin Pharm, 1987, 21(6):487-92.