Impact of rifampin on serum amiodarone concentrations in a patient with congenital heart disease.

A 33-year-old woman with congenital heart disease and atrial and ventricular arrhythmias, managed over the long term with an implantable cardioverter defibrillator, epicardial pacing system, and amiodarone, experienced an increase in palpitations and a shock from her defibrillator. Evaluation revealed decreases in amiodarone and desethylamiodarone serum concentrations from previous levels. Rifampin had been added to her therapy 5 weeks earlier. Increases in amiodarone and desethylamiodarone concentrations were observed after an increase in the amiodarone dosage and discontinuation of rifampin. The time course suggested that the addition of rifampin led to reductions in serum concentrations of both the drug and metabolite.

Mycophenolate mofetil: a unique immunosuppressive agent.

The mechanism of action, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of mycophenolate mofetil are reviewed. Mycophenolate mofetil is used to prevent or treat allograft rejection after solid-organ transplantation. A prodrug, mycophenolate mofetil is rapidly hydrolyzed to mycophenolic acid after oral administration. Mycophenolic acid inhibits de novo purine synthesis, resulting in antiproliferative effects on T and B lymphocytes. The absolute bioavailability of mycophenolic acid is 94% for oral administration; the maximum plasma concentration occurs after two hours. Mycophenolic acid undergoes hepatic glucuronidation to an inactive salt that is renally excreted. Clinical trials of mycophenolate mofetil in renal transplant patients suggest that the drug is effective for the prevention of acute rejection and as rescue therapy. Clinical data on mycophenolate mofetil therapy in liver transplant patients are too limited to permit conclusions. Clinical trials of the drug for primary immunosuppression in heart transplant patients have not been conducted, but studies of this agent as rescue therapy suggest efficacy. Mycophenolic acid has proved useful for long-term management of psoriasis. The most common adverse effects of mycophenolate mofetil are gastrointestinal. Nephrotoxicity and overt hepatotoxicity have not been reported, but the drug may be linked to bone marrow suppression and certain malignancies. Mycophenolate mofetil is available as a 250-mg capsule for oral use. The recommended initial dosage is 1 g twice daily. Mycophenolate mofetil appears to be a useful addition to the armamentarium of immunosuppressive drugs, particularly for kidney transplant patients, but more study is needed to clarify its role.

Meta-analysis of the use of low-dose beta-adrenergic blocking therapy in idiopathic or ischemic dilated cardiomyopathy.

We concluded that low-dose beta-adrenergic blocking agents are beneficial in the treatment of patients with ischemic or idiopathic cardiomyopathy. Low-dose beta blockers appear to improve NYHA functional class and LVEF.

Treatment of resistant atrial fibrillation. A meta-analysis comparing amiodarone and flecainide.

BACKGROUND: Chronic atrial fibrillation (AF) is a common arrhythmia with significant morbidity and mortality. Maintenance of normal sinus rhythm (NSR) can be achieved with antiarrhythmic drug therapy. The antiarrhythmic effects of amiodarone hydrochloride and flecainide acetate in patients with resistant chronic AF have been investigated separately in several small studies. This investigation compared amiodarone to flecainide in maintaining NSR in patients with resistant chronic AF. METHODS: Studies using amiodarone or flecainide in the treatment of patients with chronic AF refractory to class I antiarrhythmic drugs or sotalol hydrochloride were identified. The results of six trials of amiodarone (200 to 400 mg/d, 315 patients) and two trials of flecainide (200 to 300 mg/d, 163 patients) were aggregated using meta-analytic techniques. The percentages of patients taking amiodarone or flecainide and remaining in NSR at 3 and 12 months were compared relative to results for quinidine, which were acquired from a meta-analysis of quinidine used as first-line therapy for AF. RESULTS: After 3 and 12 months of treatment with amiodarone, 217 (72.6%) of 299 patients and 64 (59.8%) of 107 patients, respectively, remained in NSR. These percentages were significantly greater (P < .0001) than those for quinidine (70% and 50%, respectively). For flecainide, the percentage of patients remaining in NSR was significantly lower (P < .0001) than for quinidine: 79 (48.5%) and 56 (34%) of 163 patients, respectively. The aggregated percentages of patients requiring withdrawal of amiodarone and flecainide were similar: 9.5% and 8.6%, respectively. Mortality and proarrhythmia could not be assessed. CONCLUSION: This analysis suggests that low-dose amiodarone is more efficacious and equally well tolerated when compared with flecainide in the management of chronic, drug-resistant AF.

Empiric long-term amiodarone prophylaxis following myocardial infarction. A meta-analysis.

BACKGROUND: The prophylactic administration of amiodarone following acute myocardial infarction has been investigated in several small trials. This study combined the results of these small trials in a meta-analysis to determine the effects of prophylactic low-dose amiodarone on mortality following acute myocardial infarction. METHODS: Four prospective, randomized, placebo-controlled trials, which investigated the prophylactic administration of low-dose amiodarone (200 to 400 mg/d) to patients after acute myocardial infarction, were selected from the current literature according to strict inclusion criteria. A total of 1140 patients, 566 in the amiodarone-treated group and 574 in the placebo-treated group, were included in the analysis. Sudden cardiac death, cardiac mortality, and total mortality were the end points of interest. In addition, the effect of impaired left ventricular function (ejection fraction, < 45%) on total mortality was assessed. Data were aggregated by using the Mantel-Haenszel method to obtain final summary statistics for these end points. RESULTS: Patients treated with low-dose amiodarone exhibited a lower incidence of sudden cardia death (3.1%) and total mortality (6.1%) when compared with patients treated with placebo (6.9% and 11.2%, respectively; both P < .01; and 95% confidence interval [CI], 0.011 to 0.065 and 0.013 to 0.082, respectively). There was no significant difference between the amiodarone- and placebo-treated groups with respect to cardiac mortality (2.6% vs 3.7%, respectively; P = .26; and 95% CI, -0.012 to 0.032). For patients with a left ventricular ejection fraction of less than 45%, total mortality was 5.5% in the amiodarone-treated group and 9.4% in the placebo-treated group (P = .30; CI, -0.023 to 0.101). CONCLUSIONS: Although further data from ongoing large, randomized trials are needed, this meta-analysis suggests that the prophylactic administration of low-dose amiodarone to patients following acute myocardial infarction reduces the incidence of both sudden cardiac death and total mortality. The benefits of low-dose amiodarone may be limited to patients with preserved left ventricular function.