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propafenone (Rythmol, Baxarytmon)
Tradename: Rythmol.
Indications:
1) supraventricular arrhythmias
a) atrial fibrillation
b) atrial flutter
c) including Wolff-Parkinson-White (WPW) syndrome
2) AV nodal re-entry tachycardia
3) auxiliary pathway-mediated tachycardia
4) chemical cardioversion of atrial fibrillation
5) treatment of life-threatening ventricular arrhythmias
Contraindications:
- avoid in patients with impaired ventricular function in the setting of coronary artery disease
Dosage:
1) start 150 mg PO TID
2) max 900-1200 mg/day
3) dosage adjustment necessary with renal insufficiency
Tabs: 150, 225, 300 mg.
Pharmacokinetics:
1) well absorbed form GI tract
2) large 1st pass hepatic metabolism, thus oral bio- availability is variable
3) metabolism genetically variable; extensive vs slow metabolizers
4) time to peak serum concentrations: 2-3 hours
5) serum levels do not correlate with clinical response
6) 85-95% of drug bound to plasma proteins
7) metabolized by cyt P450 2D6
8) elimination 1/2life is 5-17 hours, depending upon metabolizer status
Adverse effects:
1) common (> 10%)
- dizziness, drowsiness, dry mouth
2) less common (1-10%)
- disturbance of taste (metallic & bitter), cardiac conduction disturbances, AV block (1st & 2nd degree), palpitations, congestive heart failure, angina, bradycardia headache, blurred vision, loss of balance, dyspnea, anxiety, constipation, diarrhea, nausea/vomiting, anorexia, abdominal pain, dyspepsia, flatulence
3) uncommon (< 1%)
- new or worsening arrhythmias (pro-arrhythmic effect), abnormal speech, visual disturbance, nightmares, paresthesias, leukopenia, thrombocytopenia, agranulocytosis, bundle branch block
4) cardiac
- exacerbation of ventricular arrhythmia
- prolongation of PR & QRS intervals
- negative inotropic effects
5) other
- bronchospasm
Drug interactions:
1) propafenone increases serum levels of:
a) beta-adrenergic antagonists
b) digoxin
c) warfarin
2) quinidine, cimetidine & beta blockers increase propafenone levels in extensive metabolizers
3) cyclosporine: increased serum levels & decreased renal function
4) rifampin decreases propafenone serum levels
5) propafenone inhibits cyt P450 2D6
a) inhibits its own metabolism
b) may increase levels of drugs metabolized by cyt P450 2D6
6) any drug that inhibits cyt P450 2D6 may increase levels of propafenone
Mechanism of action:
1) both type Ic antiarrhythmic & beta-adrenergic antagonist effects
2) suppresses complex non-sustained ventricular ectopy
3) slows atrial & ventricular conduction velocity without prolonging repolarization
4) non-selective beta-blocker
5) negative inotropic effects
Interactions
drug interactions
drug adverse effects of antiarrhythmic agent, Group IC
Related
cytochrome P450 2D6 (cytochrome P450 2D, cytochrome P450 DB1, debrisoquine-4-hydroxylase, CYP2D6)
General
antiarrhythmic agent, Group IC
Properties
MISC-INFO: elimination route LIVER
KIDNEY
therapeutic-range 0.2-1.5 UG/ML
pregnancy-category C
safety in lactation ?
Database Correlations
PUBCHEM correlations
References
- The Pharmacological Basis of Therapeutics, 9th ed.
Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- Harrison's Principles of Internal Medicine, 13th ed.
Isselbacher et al (ed), Companion Handbook, McGraw
Hill, NY, 1994.
- Manual of Medical Therapeutics, 28th ed, Ewald &
McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 158
- Drug Information & Medication Formulary, Veterans Affairs,
Central California Health Care System, 1st ed., Ravnan et al
eds, 1998 - not on National VA formulary
- Kaiser Permanente Northern California Regional Drug
Formulary, 1998
- Medical Knowledge Self Assessment Program (MKSAP) 11, American
College of Physicians, Philadelphia 1998
- Prescriber's Letter 13(3): 2006
Cytochrome P450 drug interactions
Detail-Document#: 220233
(subscription needed) http://www.prescribersletter.com