bepridil (Vascor, Angopril, Cordium)
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Introduction
Tradename: Vascor.
Indications
- chronic stable angina
- should be reserved for patients that have failed other anti-anginal therapy
- may be use alone or in combination with beta-blockers &/or nitrates
Contraindications
- history of serious ventricular arrhythmias
- sick sinus syndrome
- 2nd or 3rd degree AV block except with functioning ventricular pacemaker
- hypotension (systolic blood pressure < 90 mm Hg)
- uncompensated congestive heart failure
- congenital QT prolongation
- concurrent administration of other agents that prolong the QT interval
Caution:
- left bundle branch block
- sinus bradycardia
- hepatic or renal insufficiency
- recent myocardial infarction: no data; not recommended
Dosage
start 200 mg PO QD, max 400 mg QD
Tabs: 200, 300, 400 mg.
Pharmacokinetics
- rapidly & completely absorbed after oral administration
- absorption unaffected by food
- time to peak serum concentration after oral administration is 2-3 hours
- average maximum concentration is 2300 ng/mL (300 mg)
- > 99% bound to plasma proteins
- metabolized by liver by cyt P450 3A4
- metabolites excreted in urine (70%) & feces (22%)
- elimination is biphasic
- terminal 1/2life is 26-64 hours
- clearance of bepridil in patients with angina is lower than than in healthy patients
- crosses placenta
elimination via liver
1/2life = 26-64 hours terminal
protein binding = >99 %
Monitor
Adverse effects
- common (> 10%)
- less common (1-10%)
- cardiac
- hematologic
- respiratory
- non cardiac, non infective pulmonary interstitial infiltrates
- pulmonary fibrosis
- other
- fever, flu-like syndrome, flatulence, increased appetite, dry mouth, arthritis, drowsiness, insomnia, vertigo, akisthisia, fainting, depression, behavorial effects, rash, sweating, blurred vision, tinnitus, dysgeusia, impotence, elevation of serum transaminases, uterine hypotonia
- drug adverse effects of calcium channel blockers
- drug adverse effects of renin-angiotensin-aldosterone system inhibitors (RAAS inhibitors)
- drug adverse effects of antihypertensive agents
Drug interactions
- K+ depleting agents: furosemide
- drugs which increase the QT interval including quinidine, procainamide tricyclic antidepressants (TCA)
- any drug that inhibits cyt P450 3A4 may increase levels of bepridil
- any drug that induces cyt P450 3A4 may diminish levels of bepridil
- drug interaction(s) of calcium channel blockers with ARBs
- drug interaction(s) of calcium channel blockers with ACE inhibitors
- drug interaction(s) of calcium channel blockers with diuretics
- drug interaction(s) of calcium channel blockers with erythromycin
- drug interaction(s) of calcium channel blockers with clarithromycin
- drug interaction(s) of renin-angiotensin-aldosterone inhibitors with trimethoprim-sulfamethoxazole
- drug interaction(s) of beta-adrenergic receptor antagonists with calcium channel blockers
- drug interaction(s) of NSAIDs & antihypertensives
Mechanism of action
- anti-anginal properties
- poorly characterized anti-arrhythmic & antihypertensive properties
- inhibits both slow Ca+2 & fast Na+ inward channels in myocardial & vascular smooth muscle
- interferes with calcium binding to calmodulin
- negative inotropic effects
- bradycardic effects
- does NOT cause bronchoconstriction
- not chemically-related to other Ca+2 channel blockers