RYTHMOL SR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for RYTHMOL SR (RYTHMOL SR).
Class Ic antiarrhythmic agent; sodium channel blocker with slow dissociation kinetics, prolonging atrial and ventricular refractoriness via use-dependent blockade of fast inward sodium channels.
| Metabolism | Extensive hepatic metabolism via CYP2D6 (major), CYP3A4, and CYP1A2; genetic polymorphism (CYP2D6 poor metabolizers) leads to increased exposure. |
| Excretion | Renal (approximately 48% as unchanged drug and metabolites), fecal (approximately 35%), biliary (minor). |
| Half-life | Terminal elimination half-life is 10-17 hours (mean ~13 hours) in adults with normal renal function; prolonged in renal impairment or hepatic dysfunction. |
| Protein binding | 75-95% bound to alpha1-acid glycoprotein (AAG) and albumin; binding is saturable and concentration-dependent. |
| Volume of Distribution | 2-4 L/kg; extensive tissue distribution (e.g., lung, liver, heart). |
| Bioavailability | Oral: 70-90% (sustained-release); ranges from 30-90% due to first-pass metabolism. |
| Onset of Action | Oral: 0.5-2 hours (time to peak antiarrhythmic effect). |
| Duration of Action | Approximately 8-12 hours with sustained-release formulation; clinical effect persists beyond serum levels due to active metabolites. |
325 mg orally every 12 hours; maximum dose 425 mg every 12 hours.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | CrCl 30-60 mL/min: 100% dose; CrCl <30 mL/min: 50-75% dose. |
| Liver impairment | Child-Pugh class A: no adjustment; Child-Pugh class B: 50-75% dose; Child-Pugh class C: contraindicated. |
| Pediatric use | Age ≤50 kg: 5-10 mg/kg/dose orally every 8-12 hours; age >50 kg: 150-300 mg/m²/dose orally every 8-12 hours. |
| Geriatric use | Start at lower end of dosing range (e.g., 150 mg twice daily) due to decreased renal function and increased sensitivity to proarrhythmic effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for RYTHMOL SR (RYTHMOL SR).
| Breastfeeding | Excreted in breast milk; M/P ratio not reported. Potential for infant bradycardia and hypotension. Use with caution, monitor infant for signs of beta-blockade. |
| Teratogenic Risk | Category C. First trimester: animal studies show fetal toxicity; no adequate human studies. Second and third trimesters: risk of fetal bradycardia, arrhythmias, and reduced uterine blood flow due to beta-blockade. Use only if benefit outweighs risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
In the Cardiac Arrhythmia Suppression Trial (CAST), patients with asymptomatic non-life-threatening ventricular arrhythmias who had a recent myocardial infarction had an increased mortality rate when treated with encainide or flecainide (Class Ic drugs). RYTHMOL SR is contraindicated in patients with structural heart disease, coronary artery disease, or recent MI due to increased risk of proarrhythmia and death.
| Serious Effects |
Uncontrolled congestive heart failure; cardiogenic shock; sick sinus syndrome; second- or third-degree AV block (unless pacemaker); bradycardia; hypotension; electrolyte disturbances; known hypersensitivity to propafenone; recent MI or structural heart disease (per CAST trial); concurrent use of ritonavir or other strong CYP2D6/3A4 inhibitors.
| Precautions | Proarrhythmic effects (worsening arrhythmias, new ventricular tachycardia/fibrillation); negative inotropic effects (may precipitate or worsen heart failure); conduction abnormalities (bradycardia, heart block); caution with hepatic/renal impairment; monitor ECG and plasma levels; avoid in structural heart disease. |
Loading safety data…
| Maternal: heart rate, blood pressure, ECG, serum levels (if toxicity suspected). Fetal: heart rate monitoring, ultrasound for growth and amniotic fluid. Neonatal: monitor for bradycardia, hypoglycemia, respiratory depression for 48-72 hours. |
| Fertility Effects | No human studies. Animal studies show no impairment of fertility. Beta-blockers may affect spermatogenesis in males, clinical significance unknown. |