Continuous-infusion flumazenil in the management of chlordiazepoxide toxicity.

Flumazenil is indicated for reversal of sedation from benzodiazepines administered during therapeutic or diagnostic procedures and during induction or maintenance of general anesthesia, as well as for benzodiazepine overdose. Bolus doses of flumazenil are usually adequate to achieve reversal; however, when medical conditions may lead to a prolonged half-life of the benzodiazepine involved, continuous infusion may be warranted. A 67-year-old man with chlordiazepoxide toxicity required a 9-day infusion of flumazenil to prevent resedation and respiratory insufficiency; he initially was admitted to the hospital for alcohol detoxification. Concomitant medical conditions and the metabolism characteristics of each benzodiazepine must dictate the agent of choice. When measures are required to ensure adequate recovery of a patient's respiratory function and mental awareness, such as in patients with benzodiazepine toxicity, consideration of continuous-infusion flumazenil is warranted.

Rhabdomyolysis after concomitant use of cyclosporine, simvastatin, gemfibrozil, and itraconazole.

OBJECTIVE: To report a case of rhabdomyolysis in a patient receiving cyclosporine, simvastatin, gemfibrozil, and itraconazole. CASE REPORT: Rhabdomyolysis occurring in transplant patients receiving both cyclosporine and the hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor lovastatin has been well documented. The exact mechanism by which this interaction leads to rhabdomyolysis is unknown. Experience with newer agents of the statin drug class in transplant patients is limited. Since the interaction between cyclosporine and HMG-CoA reductase inhibitors involves the CYP3A4 enzyme system, the possibility of amplifying this interaction exists when other drugs affecting the same enzyme system are coprescribed. We describe a case in which a heart transplant recipient stable on a drug regimen that included cyclosporine, simvastatin, and gemfibrozil developed rhabdomyolysis after initiation of the antifungal agent itraconazole. DISCUSSION: Drug-drug interactions due to shared metabolism via the CYP3A4 pathway can result in significant adverse outcomes. This article discusses concurrent use of an HMG-CoA reductase inhibitor with other drugs that inhibit the CYP3A4 isoenzyme, leading to a case of possible fatal rhabdomyolysis. CONCLUSIONS: Clinicians must be aware of drugs metabolized via cytochrome P450 isoenzymes and identify those requiring risk-versus-benefit analysis before prescribing. Patients need to be educated as to signs and symptoms requiring immediate physician intervention.