Atovaquone: a new antipneumocystis agent

The mechanism of action, pharmacokinetics and pharmacodynamics, clinical efficacy, adverse effects, and dosage of atovaquone in the management of mild to moderate Pneumocystis carinii pneumonia (PCP) are reviewed. Atovaquone has a novel mechanism of action that has been hypothesized to result in microbicidal rather than microbistatic activity against Pneumocystis carinii. Absorption of the drug is significantly enhanced by the presence of food, particularly food with a high fat content. In comparative trials, atovaquone was slightly less effective than trimethoprim-sulfamethoxazole and as effective as pentamidine isethionate in treating mild to moderate PCP. Atovaquone is associated with a lower incidence of treatment-limiting adverse reactions than are trimethoprim-sulfamethoxazole and pentamidine isethionate. The most commonly occurring adverse effect in patients receiving atovaquone is rash, and the drug does not appear to cause bone marrow suppression. The FDA-approved dosage regimen for atovaquone in treating mild to moderate PCP is 750 mg (three 250-mg tablets) administered orally three times daily with food for 21 days. Atovaquone may be considered a first-line treatment for patients with the acquired immunodeficiency syndrome who have mild to moderate PCP and have demonstrated an intolerance to trimethoprim-sulfamethoxazole.