CLINICAL-EXPERIENCE WITH ATOVAQUONE - A NEW DRUG FOR TREATING PNEUMOCYSTIS-CARINII PNEUMONIA

Atovaquone is a new hydroxynapthoquinone antiprotozoal agent active ag ainst Pneumocystis carinii in vitro and in animal models. The authors report an experience using atovaquone to treat 25 patients with mild t o moderate P. carinii pneumonia. Eligible patients were treated for 21 days with 750 mg of atovaquone orally three times daily. Prednisone w as added when the P(A-a)O-2 gradient was between 35-45 mm Hg. Patients were treated under three treatment protocols. Patients in Group 1 par ticipated in one of two randomized comparative drug trials, designed f or patients with and without sulfonamide intolerance. Six of seven pat ients successfully completed treatment, and one patient discontinued t reatment because of an adverse reaction (>5 times baseline increase in transaminase level). Patients in Group 2 were treated with atovaquone for mild to moderate P. carinii pneumonia under a treatment Investiga tional New Drug protocol because of prior sulfonamide reactions. Fifte en of these 18 patients successfully completed treatment; one died fro m other complications during treatment and two discontinued treatment for adverse reactions (>5 times baseline increase in transaminase leve ls, and a diffuse rash). Serum transaminase levels returned to normal at the end of treatment in all patients with elevated levels. All pati ents demonstrated clinical resolution of their pneumonia and improveme nt of pretreatment hypoxemia (Group 1: pretreatment PaO2 = 82 +/- 14 m m Hg, posttreatment PaO2 = 92 +/- 9 mm Hg). Overall, 21 (84%) of 25 pa tients successfully finished therapy without significant adverse react ions. Atovaquone appears to be an effective and well-tolerated oral tr eatment for mild to moderate P. carinii pneumonia. The main toxicities appear to be a reversible serum transaminase rise and a nondesquamati ng rash. Currently, atovaquone should be considered as an alternative therapy for intolerant patients or as salvage therapy.