PEM report number 3. Fluconazole

Abstract

AbstractThree groups of patients who were prescribed the oral anti‐fungal drug fluconazole between September 1988 and January 1989 were studied by Prescription‐Event Monitoring (PEM). The largest group of 13,440 patients, including 560 men, had been treated with a single 150 mg capsule. A smaller group of 798, including 55 men, had received more than one 150 mg capsule and a third small group of 777 patients, including 261 men, had received a course of treatment with 50 mg capsules. The first group was studied between February and June 1989 and the second and third groups in January 1990.In the two groups who had received single or multiple doses of 150 mg, the mean age of women was 34 and 35 years respectively and of men in both groups, 41 years. In the small group receiving 50 mg capsules the patients were considerably older, the males averaging 49 years and the females 46 years. While an overwhelming majority of females were treated for vaginal candidiasis, a significant number of men in the 150 mg groups and almost half the men in the 50 mg group had been treated for oral candidiasis. It was believed that a considerable number of men had been treated prophylactically while their partners were receiving treatment for vaginal candidiasis.General practitioners reported that the single 150 mg capsule had been effective in 85%. As expected, there were many cases of re‐infection or recurrences during the three‐month period of observation.The pattern of events was compared with data obtained from PEM studies of itraconazole and 31 other drugs. Upper respiratory tract and genito‐urinary infections were reported more frequently than with other drugs but the relationship was with the disease being treated rather than with the drug itself.There were four cases of angioneurotic oedema, only two of which were considered to have been possibly related to the use of fluconazole. There were also four reports of liver dysfunction, none of which was considered to be drug related.Although pregnancy is a contra‐indication, a total of 289 were reported. Thirty‐nine had terminated in spontaneous abortion and 38 were terminated therapeutically. Among women who used fluconazole prior to conception there were six abnormal pregnancies including four live births, one stillborn foetus with trisomy‐18 (Edwards' syndrome) and one anencephalic foetus. One mother had used fluconazole a week before conception. The baby had three short fingers on one hand. No abnormalities occurred in babies exposed during their mother's pregnancy.One hundred and twenty‐five deaths were investigated. Eighty of the deaths were due to cancer, 26 to neurological, cardiac or respiratory disease and seven to AIDS. Other or undetermined causes accounted for a further 12 deaths. No death was attributed to treatment.The overall conclusion reached after this study of more than 15,000 patients was that, while many events that had been recorded were attributable to the candidial infection, fluconazole was virtually free from recognizable side‐effects.