RYTHMOL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for RYTHMOL (RYTHMOL).
Class Ic antiarrhythmic agent; inhibits sodium channels with slow recovery kinetics, slowing conduction velocity; prolongs PR and QRS intervals.
| Metabolism | Extensive hepatic metabolism via CYP2D6 and CYP3A4; two polymorphic phenotypes (extensive and poor metabolizers); active metabolites (5-hydroxypropafenone and N-depropylpropafenone). |
| Excretion | Primarily hepatic metabolism; less than 1% excreted unchanged in urine. Approximately 48% of metabolites excreted in urine and 36% in feces. |
| Half-life | Terminal elimination half-life is 10 to 32 hours (mean 20 hours). Clinically, steady-state is achieved in 4-5 days. Half-life increases in hepatic impairment. |
| Protein binding | Approximately 95% bound, primarily to alpha-1-acid glycoprotein (AAG). Binding is saturable and concentration-dependent within therapeutic range. |
| Volume of Distribution | Vd is 2.5-3.0 L/kg. Indicates extensive tissue distribution, with high affinity for myocardium. |
| Bioavailability | Oral bioavailability is 65-100% (mean 85%). Food increases bioavailability by 15%. |
| Onset of Action | Oral: 2.5 to 3 hours (antiarrhythmic effect); peak effect at 4-6 hours. IV (not available in US): within minutes. |
| Duration of Action | Oral: 8-12 hours (dose-dependent). Clinical dosing interval is every 8 hours. Duration may be prolonged in hepatic impairment. |
Propafenone 150-300 mg orally every 8 hours; maximum 900 mg/day.
| Dosage form | TABLET |
| Renal impairment | CrCl <30 mL/min: reduce dose by 50% and monitor; CrCl <10 mL/min: contraindicated. |
| Liver impairment | Child-Pugh class B: reduce dose by 50%; Child-Pugh class C: contraindicated. |
| Pediatric use | Not recommended for pediatric use; safety and efficacy not established. |
| Geriatric use | Start at lower end of dosing range (150 mg every 8 hours) with careful monitoring due to increased risk of proarrhythmia and renal impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for RYTHMOL (RYTHMOL).
| Breastfeeding | Propafenone is excreted into human milk; M/P ratio approximately 0.4. Limited data suggest low infant exposure. Use with caution, monitor infant for adverse effects (bradycardia, feeding difficulties). |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: limited human data; animal studies show fetal toxicity. Second and third trimesters: risk of fetal bradycardia, arrhythmias, and reduced uteroplacental blood flow. May cause fetal growth restriction. Avoid use unless benefit outweighs risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
In the Cardiac Arrhythmia Suppression Trial (CAST), non-life-threatening ventricular arrhythmias treated with encainide or flecainide showed increased mortality; propafenone is structurally similar and carries similar risk. Use only for life-threatening arrhythmias.
| Serious Effects |
Hypersensitivity to propafenone; preexisting second- or third-degree AV block; sick sinus syndrome (unless paced); cardiogenic shock; uncorrected electrolyte imbalances; bronchospastic disorders; severe hypotension; concurrent use with ritonavir
| Precautions | Proarrhythmic effects (increase in ventricular arrhythmias); negative inotropic effects (may worsen heart failure); conduction disturbances; avoid in preexisting sinus node dysfunction; monitor ECG, liver and renal function; dose adjustment in hepatic impairment. |
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| Monitor maternal ECG, heart rate, blood pressure, and serum drug levels. Fetal monitoring includes heart rate and growth ultrasound. Assess for signs of proarrhythmia or heart block in both mother and fetus. |
| Fertility Effects | No specific human data; animal studies show no significant impairment of fertility. Theoretical risk due to hemodynamic changes. |