indication

For the treatment of chronic stable angina (classic effort-associated angina).

pharmacology

Bepridil is a calcium channel blocker that has well characterized anti-anginal properties and known but poorly characterized type 1 anti-arrhythmic and anti-hypertensive properties. It is not related chemically to other calcium channel blockers such as diltiazem hydrochloride, nifedipine and verapamil hydrochloride.

mechanism of action

Bepridil has inhibitory effects on both the slow calcium (L-type) and fast sodium inward currents in myocardial and vascular smooth muscle, interferes with calcium binding to calmodulin, and blocks both voltage and receptor operated calcium channels. Bepridil inhibits the transmembrane influx of calcium ions into cardiac and vascular smooth muscle. This has been demonstrated in isolated myocardial and vascular smooth muscle preparations in which both the slope of the calcium dose response curve and the maximum calcium-induced inotropic response were significantly reduced by bepridil. In cardiac myocytes in vitro, bepridil was shown to be tightly bound to actin. Bepridil regularly reduces heart rate and arterial pressure at rest and at a given level of exercise by dilating peripheral arterioles and reducing total peripheral resistance (afterload) against which the heart works.

toxicity

There has been one experience with overdosage in which a patient inadvertently took a single dose of 1600 mg of bepridil. The patient was observed for 72 hours in intensive care, but no significant adverse experiences were noted.

biotransformation

Hepatic.

absorption

Rapidly and completely absorbed after oral administration.

half life

24-50 hours

drug interactions

Amprenavir: Amprenavir may increase the effect and toxicity of bepridil.

Artemether: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Astemizole: Increased risk of cardiotoxicity and arrhythmias

Atazanavir: Atazanavir may increase the effect and toxicity of bepridil.

Cisapride: Increased risk of cardiotoxicity and arrhythmias

Fosamprenavir: Amprenavir increases the effect and toxicity of bepridil

Gatifloxacin: Increased risk of cardiotoxicity and arrhythmias

Grepafloxacin: Increased risk of cardiotoxicity and arrhythmias

Levofloxacin: Increased risk of cardiotoxicity and arrhythmias

Lumefantrine: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Moxifloxacin: Increased risk of cardiotoxicity and arrhythmias

Ritonavir: Ritonavir increases the effect and toxicity of bepridil

Sparfloxacin: Increased risk of cardiotoxicity and arrhythmias

Terfenadine: Increased risk of cardiotoxicity and arrhythmias

Tipranavir: Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Bepridil. Concomitant therapy is contraindicated.