Atovaquone: A Review with Emphasis on its Role in the Treatment of Pneumocystis Carinii Pneumonia

Abstract

Objective:

To discuss the mechanism of action, in vitro and in vivo activity, pharmacokinetics, clinical trials, adverse effects, drug interactions, and dosage guidelines of atovaquone.

Data Sources:

Pertinent literature published since 1988 was identified via a MEDLINE search. Published proceedings of selected conferences were also used.

Study Selection:

All basic science, microbiologic, and pharmacokinetic articles were evaluated. Since only limited data regarding atovaquone are available in the literature, all clinical trials involving the use of atovaquone in the treatment of Pneumocystis carinii pneumonia were reviewed.

Data Synthesis:

Atovaquone is an antiprotozoal agent that was recently approved for the treatment of mild to moderate P. carinii pneumonia (PCP) in patients who are intolerant of trimethoprim/sulfamethoxazole (TMP/SMX). The exact mechanism of action of atovaquone against P. carinii has not been determined. The drug has in vitro and in vivo activity against P. carinii, Toxoplasma gondii, and Plasmodium species. The bioavailability of oral atovaquone is highly variable. The drug must be administered with food to enhance absorption. In a double-blind comparative trial in AIDS patients with mild to moderate PCP, those who were treated with atovaquone had a significantly higher mortality rate than those treated with TMP/SMX. More patients who received TMP/SMX experienced adverse effects that resulted in discontinuation of therapy.

Conclusions:

Because of concerns of increased mortality in atovaquone recipients, the drug should be reserved for the treatment of mild to moderate PCP in patients who are unable to tolerate TMP/SMX and trimethoprim-dapsone.