pafenone therapy and upon discontinuation of therapy, the white count usually normalized by 14 days. Unexplained fever or decrease in white cell count, particularly during the initial 3 months of therapy, warrant consideration of possible agranulocytosis or granulocytopenia. Instruct patients to report promptly any signs of infection such as fever, sore throat, or chills.
5.8 Use in Patients with Hepatic Dysfunction
Propafenone is highly metabolized by the liver. Severe liver dysfunction increases the bioavailability of propafenone to approximately 70% compared to 3-40% in patients with normal liver function when given RYTHMOL immediate-release tablets. In 8 patients with moderate to severe liver disease administered RYTHMOL immediate-release tablets, the mean half-life was approximately 9 hours. No studies have compared bioavailability of propafenone from RYTHMOL SR in patients with normal and impaired hepatic function. Increased bioavailability of propafenone in these patients may result in excessive accumulation. Carefully monitor patients with impaired hepatic function for excessive pharmacological effects [see Overdosage (10)].
5.9 Use in Patients with Renal Dysfunction
Approximately 50% of propafenone metabolites are excreted in the urine following administration of RYTHMOL immediate release-tablets. No studies have been performed to assess the percentage of metabolites eliminated in the urine following the administration of RYTHMOL SR capsules.
In patients with impaired renal function monitor for signs of overdosage [see Overdosage (10)].
5.10 Use in Patients with Myasthenia Gravis
Exacerbation of myasthenia gravis has been reported during propafenone therapy.
5.11 Elevated ANA Titers
Positive ANA titers have been reported in patients receiving propafenone. They have been reversible upon cessation of treatment and may disappear even in the face of continued propafenone therapy. These laboratory findings were usually not associated with clinical symptoms, but there is one published case of drug-induced lupus erythematosis (positive rechallenge); it resolved completely upon discontinuation of therapy. Carefully eva luate patients who develop an abnormal ANA test and if persistent or worsening elevation of ANA titers is detected, consider discontinuing therapy.
5.12 Impaired Spermatogenesis
Reversible disorders of spermatogenesis have been demonstrated in monkeys, dogs and rabbits after high dose intravenous administration of propafenone. eva luation of the effects of short-term RYTHMOL administration on spermatogenesis in 11 normal subjects suggested that propafenone produced a reversible, short-term drop (within normal range) in sperm count.
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data described below reflect exposure to RYTHMOL SR 225 mg twice daily in 126 patients, to RYTHMOL SR 325 mg twice daily in 135 patients, to RYTHMOL SR 425 mg twice daily in 136 patients, and to placebo in 126 patients for up to 39 weeks (mean 20 weeks) in a placebo-controlled trial (RAFT) conducted in the US. The most commonly reported adverse events with propafenone (>5% and greater than placebo) excluding those not reasonabl |
