Apo-Fluconazole Special Precautions

General: The convenience of the single oral dose fluconazole regimen for the treatment of vaginal yeast infections should be weighed against the acceptability of a higher incidence of drug related adverse events with fluconazole (26%) versus intravaginal agents (16%) in comparative clinical studies where no difference in efficacy was demonstrated (see ADVERSE REACTIONS).
Fluconazole administered in combination with ethinyl estradiol- and levonorgestrel containing oral contraceptives produced an overall mean increase in ethinyl estradiol and levonorgestrel levels; however, in some patients there were decreases up to 47% and 33% of ethinyl estradiol and levonorgestrel levels, respectively (see INTERACTIONS). The data presently available indicate that the decreases in some individual ethinyl estradiol and levonorgestrel AUC values with fluconazole treatment may be the result of random variation. While there is evidence that fluconazole can inhibit the metabolism of ethinyl estradiol and levonorgestrel, there is no evidence that fluconazole is a net inducer of ethinyl estradiol or levonorgestrel metabolism. The clinical significance of these effects is presently unknown.
Use in Women of Child-Bearing Potential: Since the teratologic effects of fluconazole in humans are unknown, women taking fluconazole for vaginal candidiasis should consider using adequate contraception (see USE IN PREGNANCY as follows).
There have been reports of multiple congenital abnormalities in infants whose mothers were treated with high dose (400 to 800 mg/day) fluconazole therapy for coccidioidomycosis (an unapproved indication). Exposure to fluconazole began during the first trimester in all cases and continued for 3 months or longer. Since there are no adequate studies in pregnant women to assess the potential for fetal risk, fluconazole should not be used in pregnant women unless the potential benefit outweighs the potential risk to the fetus.
Use in Pregnancy: There are no adequate and well-controlled studies in pregnant women. There have been reports of multiple congenital abnormalities in infants whose mothers were treated with high dose (400 to 800mg/day) fluconazole therapy for coccidioidomycosis (an unapproved indication). Exposure to fluconazole began during the first trimester in all cases and continued for 3 months or longer. There have been reports of spontaneous abortion and congenital abnormalities in infants whose mothers were treated with 150 mg of fluconazole as a single or repeated dose in the first trimester. Fluconazole should not be used in pregnant women unless the potential benefit outweighs the potential risk to the fetus.
Fluconazole was administered orally to pregnant rabbits during organogenesis in two studies, at 5, 10 and 20 mg/kg and at 5, 25 and 75 mg/kg respectively. Maternal weight gain was impaired at all dose levels, and abortions occurred at 75 mg/kg (approximately 9.4x the maximum recommended human dose); no adverse fetal effects were detected. In several studies in which pregnant rats were treated orally with fluconazole during organogenesis, maternal weight gain was impaired and placental weights were increased at 25 mg/kg. There were no fetal effects at 5 or 10 mg/kg; increases in fetal anatomical variants (supernumerary ribs, renal pelvis dilation) and delays in ossification were observed at 25 and 50 mg/kg and higher doses. At doses ranging from 80 to 320 mg/kg (approximately 10 to 40x the maximum recommended human dose) embryo lethality in rats was increased and fetal abnormalities included wavy ribs, cleft palate and abnormal craniofacial ossification. These effects are consistent with the inhibition of estrogen synthesis in rats and may be a result of known effects of lowered estrogen on pregnancy, organogenesis and parturition.
Use in Lactation: Fluconazole is secreted in human breast milk at concentrations similar to plasma, hence its use in nursing mothers is not recommended.
Use in Children and Adolescents: The safety and effectiveness of fluconazole 150mg capsules in the treatment of vaginal candidiasis in patients under 18 years of age have not been established.