Atovaquone. A review of its pharmacological properties and therapeutic efficacy in opportunistic infections

Abstract

Atovaquone has been investigated as an alternative agent for oral use in the treatment of both mild to moderate Pneumocystis carinii pneumonia (PCP) and toxoplasmosis, opportunistic infections commonly experienced by patients with AIDS. In patients with mild to moderate PCP, a dosage of 750mg 3 times daily (administered in tablet form) has similar overall therapeutic efficacy (defined as clinical response without a treatment-limiting adverse event) to the conventional therapies oral cotrimoxazole (trimethoprim-sulfamethoxazole) and intravenous pentamidine, respectively. Response rates to atovaquone are lower than those achieved with cotrimoxazole, but atovaquone has superior tolerability. Atovaquone recipients experienced significantly fewer treatment-limiting adverse effects than patients treated with cotrimoxazole (7 vs 20%) or pentamidine (4 vs 36%). Mortality rates were higher among atovaquone-treated patients than in cotrimoxazole recipients (7 vs 0.6%) 4 weeks after completion of therapy in a large comparative trial, although most deaths were caused by bacterial infections. However, a similar rate of mortality was reported for atovaquone- and pentamidine-treated patients (16 vs 17% 8 weeks after discontinuation of therapy) in another study. In predominantly small numbers of patients with toxoplasmosis, of whom most were unresponsive to conventional agents, atovaquone 750mg 4 times daily (administered as tablets) produced a complete or partial radiological response rate of 37 to 87.5% 52% of patients achieved a complete or partial clinical response after 6 weeks of treatment in the largest trial (n = 87), although the incidence of toxoplasmosis-related death was 24% 18 weeks after therapy was initiated. Thus, atovaquone will be a useful option for the treatment of patients with mild to moderate PCP who are intolerant or unresponsive to cotrimoxazole, especially if the increased plasma drug concentrations observed with the suspension further improve response rates. Atovaquone should also be considered a promising agent for the treatment of toxoplasmosis.