James C. Garrelts

Clofazimine: A Review of its Use in Leprosy and Mycobacterium Avium Complex Infection

This article reviews the chemistry, pharmacology, spectrum of activity, pharmacokinetics, clinical efficacy in leprosy and Mycobacterium avium complex (MAC) infection, adverse effects, drug interactions, and special considerations of clofazimine. The drug is active in vivo against M. leprae and in vitro against MAC. In addition, it possesses antiinflammatory and immunosuppressive properties. Clinical studies support the efficacy of clofazimine as a part of multidrug therapy in treating leprosy. It also appears to reduce the incidence and severity of erythema nodosum leprosum reactions that often occur during the treatment of leprosy. Efficacy in treating MAC infection in patients with AIDS is not well documented, despite the use of clofazimine in combination with other agents. A few patients have responded symptomatically and by clearing their mycobacteremia, although there is no evidence that mortality is reduced. Clofazimine is well tolerated, at least when doses ≤100 mg/d are used. Adverse reactions include discoloration of the skin, self-limiting gastrointestinal intolerance, severe and life-threatening abdominal pain and organ damage due to clofazimine crystal deposition, and asymptomatic discoloration of the eye. Clofazimine should be considered for formulary inclusion.

The Pharmacokinetics, Safety, and Tolerance of Cefepime Administered as an Intravenous Bolus or as a Rapid Infusion

OBJECTIVE: To evaluate the pharmacokinetics, safety, and tolerability of cefepime administered as an intravenous bolus and short infusion. METHODS: A single-dose, pharmacokinetic study was conducted on 16 healthy men. Fifty milliliters of a 40 mg/mL solution of cefepime was administered by continuous infusion in intervals of three, five, 10, or 15 minutes. Blood was sampled three minutes through 12 hours after the end of the infusion. Analysis of cefepime was performed by reverse-phase HPLC with ultraviolet detection. Cefepime plasma concentrations versus time were evaluated by noncompartmental methods. History and physical examinations were conducted within two weeks of the start of the study, 24 hours before dosing, and at the end of the study. Assessments for adverse events were made throughout the study. RESULTS: Maximum concentration (Cmax) increased with decreasing time of infusion and was similar to reference values of Cmax. Pharmacokinetic characteristics of cefepime were not affected by the time of infusion and were on average: mean residence time was 2.3 hours, half-life 1.9 hours, the AUC extrapolated to infinity 239 μg•h/mL, total body clearance 142 mL/min, and steady-state volume of distribution 19 L. No serious adverse events, local tolerance at injection site, or significant laboratory abnormalities were noted. CONCLUSIONS: Cefepime 2 g was safely administered to healthy subjects as a rapid, single bolus, and its key pharmacokinetic parameters were consistent with those from longer infusions and other studies.

Alternative Drug Therapies for Mania: A Literature Review:

This article reviews the agents used to treat manic patients. It has been suggested that up to 20 percent of all manic patients are refractory to lithium. We reviewed studies suggesting that drugs affecting the serotoninergic, adrenergic, dopaminergic, and opioid neurotransmission systems, as well as anticonvulsants and others, are possible alternative treatments. Despite the large number of agents used, few large controlled studies carefully examine these interventions. Clinical assessments using specific manic rating scales are lacking in most studies. Among the successful alternative treatments reported, carbamazepine has received the most intensive research. Other suggested therapeutic agents, such as levothyroxine and clorgyline, require additional research to verify their effectiveness. From these pharmacological approaches and an understanding of the pathophysiology of mania, future therapeutic interventions can be formulated.

Venous Thromboembolism Prevention in Acutely Ill Nonsurgical Patients

OBJECTIVE To review recent advances in the prevention of venous thromboembolism (VTE) in acutely ill nonsurgical inpatients. DATA SOURCES A MEDLINE search (1966–March 2005) was done to identify relevant articles relating to prevention of VTE in acutely ill nonsurgical inpatients. STUDY SELECTION AND DATA EXTRACTION Four major prophylaxis trials, one registry, one guideline, and supporting articles representative of the subject matter from the last few years were included. DATA SYNTHESIS Enoxaparin, dalteparin, fondaparinux, and unfractionated heparin 5000 units every 8 hours are effective in reducing the risk of VTE in acutely ill medical patients, but such prophylaxis is currently underused. Barriers to be overcome include recognition of the importance of VTE in this population, definition of the optimal strategy to assess risks, optimal timing of the risk assessment, optimal prophylactic regimen for a given level of risk or disease state, and optimal duration of prophylaxis. We recommend that acutely ill medical inpatients should be risk-stratified early in their hospitalization. At this time, the specific risk-assessment protocol should be derived from the trial(s) of the available formulary agent(s). Decisions about providing prophylaxis must also be made considering anticoagulant contraindications and renal function. Mechanical methods of prophylaxis should be considered as monotherapy only if an anticoagulant contraindication exists. The optimal duration of prophylaxis is not known, but 14 days was used in recent studies. CONCLUSIONS Prophylaxis of VTE in acutely ill medical inpatients is underused. Data provide some guidance for increasing awareness and optimizing patient care.