Safety and tolerance of high dose fluconazole in disseminated coccidioidomycosis

Singh, S. S.;Caldwell, J. W.;Johnson, R. H.;Einstein, H. E.;Williams, P. L.


Fluconazole, a significant advance in treating disseminated coccidioidomycoses (DC), is frequently required in doses > 400 mg. We retrospectively evaluated 70 consecutive patients receiving fluconazole (F) for adverse effects (AE's). All patients had DC. The mean age of the 47 males and 23 females was 33 years. Fifty-five (percent) had meningitis and fifteen (19 percent) had other sites of dissemination. All patients received F in doses ranging hom 400 mg to 1200 mg/day. Twenty three (32 percent) received 400 mg only, while 47 (68 percent) required higher doses. Adverse events were more common with higher doses. Fifty percent of 57 patients receiving daily F 400 mg had at least one AE, as compared to 60 percent of 47 on greater than or equal to 800 mg. Multiple AE's occurred in 16 percent when receiving 400 mg as compared to 34 percent when doses were greater than or equal to 800 mg (p = 0.05). AE's in order of frequency were: nausea/vomiting (27 percent), weightless (23 percent), arthralgias (16 percent), alopecia (14 percent), skin reactions (14 percent), increased alkaline phosphatase (11 percent), abdominal pain (5.7 percent), and increased transaminases (5 percent). Mean serum levels ranged from 18mcg/ml for skin reactions to 26mcg/ml for alkaline phosphatase elevations. Dose limiting reactions (7 nausea/vomiting, 3 increased transaminases, 5 other) occurred in 15 patients (21 percent). Seventy-five percent of the time, patients had stable or improving disease symptoms at the time AE's were noted. One patient with fatty liver was removed from therapy.Adverse reactions to F are dose related and significantly higher when doses equal or exceed 800 mg in DC. Nausea and vomiting, weight loss, alopecia, and arthralgias are more common than previously appreciated. Nausea/vomiting and liver-function abnormalities can be temporarily dose limiting. Tolerance to AE's improves over time.

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Full conference title: 

Coccidioidomycosis - Centennial Conference
    • Coccidioidomycosis