CHF and arrhythmias:

Indications for: RYTHMOL SR

To prolong recurrence of symptomatic atrial fibrillation in patients without structural heart disease.

Clinical Trials:

Rythmol SR has been evaluated in patients with a history of electrocardiographically documented recurrent episodes of symptomatic AF in 2 randomized, double-blind, placebo-controlled trials (RAFT and ERAFT).

RAFT

  • Rythmol SR 225mg twice daily, Rythmol SR 325mg twice daily, Rythmol 425mg twice daily and placebo were compared.
  • Patients with symptomatic, episodic AF; 59% male, mean age 63 years, 91% white, 6% black.
  • Rythmol SR was administered for up to 39 weeks.
  • Compared with placebo, Rythmol SR was shown to significantly prolong the time to first recurrence of symptomatic atrial arrhythmia, predominantly AF from day 1 of randomization (primary endpoint).
  • Hazard ratio compared with placebo: 
    • Rythmol SR 225mg twice daily (n=126): 0.67 (95% CI, 0.49-0.93)
    • Rythmol SR 325mg twice daily (n=135): 0.43 (95% CI, 0.31-0.61)
    • Rythmol SR 425mg twice daily (n=136): 0.35 (95% CI, 0.24-0.51)
  • The antiarrhythmic effect was not influenced by the individual use of calcium channel blockers, beta blockers, or digoxin.

ERAFT

  • Rythmol SR 325mg twice daily, Rythmol SR 425mg twice daily and placebo were compared.
  • 293 patients with documented electrocardiographic evidence of symptomatic paroxysmal AF; 61% male, 100% white, mean age of 61 years.
  • Double-blind treatment phase consisted of a 4-day loading period followed by a 91-day efficacy period.
  • Rythmol SR was shown to prolong the time to the first recurrence of symptomatic atrial arrhythmia from day 5 of randomization (primary endpoint).
  • Both doses were superior to placebo.
  • Antiarrhythmic effect was not influenced by use of calcium channel blockers, beta blockers, or digoxin.

Adult Dosage:

Individualize. Not interchangeable on a mg-to-mg basis with immediate-release form (see full labeling). Swallow whole. Initially 225mg every 12hrs. May increase at 5-day intervals to 325mg every 12hrs; max 425mg every 12hrs. When switching from 150mg three times daily of the immediate-release form, start Rythmol SR at 325mg twice daily. QRS widening, 2nd or 3rd degree AV block, or hepatic impairment: reduce dose.

Children Dosage:

Not established.

RYTHMOL SR Contraindications:

Heart failure. Cardiogenic shock. SA, AV and intraventricular disorders of impulse generation or conduction (eg, sick sinus syndrome, AV block), unless paced. Known Brugada Syndrome. Bradycardia. Marked hypotension. Bronchospastic disorders. Severe obstructive pulmonary disease. Marked electrolyte imbalance.

Boxed Warning:

Mortality.

RYTHMOL SR Warnings/Precautions:

Significant proarrhythmic risk in structural heart disease. Avoid in patients with non-life-threatening ventricular arrhythmias. Monitor ECG, pacemakers before and during therapy. May provoke overt heart failure. Discontinue if ECG changes are suggestive of Brugada Syndrome. Monitor for agranulocytosis. Hepatic or renal dysfunction: monitor. Elderly. Labor & delivery, fetal/neonatal: monitor. Pregnancy. Nursing mothers.

See Also:

RYTHMOL SR Classification:

Class IC antiarrhythmic.

RYTHMOL SR Interactions:

Avoid drugs that may prolong the QT interval (eg, antiarrhythmics, some phenothiazines, tricyclic antidepressants, oral macrolides). Avoid concomitant Class IA and III antiarrhythmics (including quinidine, amiodarone). Potentiates β-blockers, warfarin, digoxin (consider reducing their doses when starting propafenone). Potentiated by CYP2D6 inhibitors (eg, desipramine, paroxetine, ritonavir, sertraline) and CYP3A4 inhibitors (eg, ketoconazole, saquinavir, erythromycin, grapefruit juice); avoid simultaneous use with both. Antagonized by rifampin. May be antagonized by orlistat. Local anesthetics may increase CNS effects.

Adverse Reactions:

Unusual taste, nausea, vomiting, dizziness, constipation, headache, fatigue, 1st degree AV block, intraventricular conduction delay, palpitations, chest pain, dyspnea, anxiety, upper respiratory tract infection, edema, influenza, angina pectoris, atrial flutter, heart failure, bradycardia, blurred vision; new or worsened arrhythmias, conduction disturbances, elevated ANA titers, exacerbation of myasthenia gravis.

Metabolism:

Hepatic (CYP2D6, CYP3A4, CYP1A2).

In over 90% of patients, propafenone is rapidly and extensively metabolized with an elimination half-life from 2 to 10 hours. 

In <10% of patients, metabolism of propafenone is slower because the 5-hydroxymetabolite is not formed or is minimally formed; the estimated propafenone elimination half-life ranges from 10 to 32 hours.

Drug Elimination:

Extensive metabolizers: Elimination half-life from 2 to 10 hours. 

Slow metabolizers: Elimination half-life from 10 to 32 hours.

Generic Drug Availability:

YES

How Supplied:

Tabs—Contact supplier; SR caps—60