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bepridil (Vascor, Angopril, Cordium)
Tradename: Vascor.
Indications:
1) chronic stable angina
2) should be reserved for patients that have failed other anti-anginal therapy
3) may be use alone or in combination with beta-blockers &/or nitrates
Contraindications:
1) history of serious ventricular arrhythmias
2) sick sinus syndrome
3) 2nd or 3rd degree AV block except with functioning ventricular pacemaker
4) hypotension (systolic blood pressure < 90 mm Hg)
5) uncompensated congestive heart failure
6) congenital QT prolongation
7) concurrent administration of other agents that prolong the QT interval
Caution:
1) left bundle branch block
2) sinus bradycardia
3) hepatic or renal insufficiency
4) recent myocardial infarction: no data; not recommended
Dosage: start 200 mg PO QD, max 400 mg QD.
Tabs: 200, 300, 400 mg.
Pharmacokinetics:
1) rapidly & completely absorbed after oral administration
2) absorption unaffected by food
3) time to peak serum concentration after oral administration is 2-3 hours
4) average maximum concentration is 2300 ng/mL (300 mg)
5) > 99% bound to plasma proteins
6) metabolized by liver by cyt P450 3A4
- metabolites excreted in urine (70%) & feces (22%)
7) elimination is biphasic
8) terminal 1/2life is 26-64 hours
9) clearance of bepridil in patients with angina is lower than than in healthy patients
10) crosses placenta
Monitor:
1) EKG: QTc
2) complete blood count (CBC)
Adverse effects:
1) common (> 10%)
- nausea, dyspepsia, dizziness
2) less common (1-10%)
- diarrhea, asthenia, nervousness, tremor
3) cardiac
a) ventricular arrhythmias
- prolongation of QT interval
- torsades de pointes
- hypokalemia & antecedent bradycardia increase risk
- ventricular fibrillation
b) congestive heart failure
4) hematologic
- agranulocytosis
5) respiratory
- non cardiac, non infective pulmonary interstitial infiltrates
- pulmonary fibrosis
6) 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 interactions:
1) K+ depleting agents: furosemide
2) drugs which increase the QT interval including quinidine, procainamide tricyclic antidepressants (TCA)
3) any drug that inhibits cyt P450 3A4 may increase levels of bepridil
4) any drug that induces cyt P450 3A4 may diminish levels of bepridil
Mechanism of action:
1) anti-anginal properties
2) poorly characterized anti-arrhythmic & antihypertensive properties
3) inhibits both slow Ca+2 & fast Na+ inward channels in myocardial & vascular smooth muscle
4) interferes with calcium binding to calmodulin
5) negative inotropic effects
6) bradycardic effects
7) does NOT cause bronchoconstriction
7) not chemically-related to other Ca+2 channel blockers
Interactions
drug interactions
drug adverse effects (more general classes)
Related
cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)
QT interval
General
calcium channel blocker (CCB)
Properties
MISC-INFO: elimination route LIVER
pregnancy-category C
safety in lactation -
1/2life 26-64 HOURS
protein-binding >99%
Database Correlations
PUBCHEM correlations
References
- The Pharmacological Basis of Therapeutics, 9th ed.
Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- Physician's Desk Reference (PDR) 51st edition, Medical
Economics, 1999