These cases of harm, however, were only in women who took large doses for most of the first trimester.Fluconazole is secreted in human milk at concentrations similar to plasma. Therefore, the use of
fluconazole in lactating mothers is not recommended.Fluconazole therapy has been associated with QT interval prolongation, which may lead to serious cardiac arrhythmias. Thus, it is used with caution in patients with risk factors for prolonged QT interval, such as electrolyte imbalance or use of other drugs that may prolong the QT interval (particularly cisapride and pimozide).Fluconazole has also rarely been associated with severe or lethal hepatotoxicity, so liver function tests are usually performed regularly during prolonged fluconazole therapy. In addition, it is used with caution in patients with pre-existing liver disease.Some people are allergic to azoles, so those allergic to other azole drugs might be allergic to fluconazole. That is, some azole drugs have adverse side-effects. Some azole drugs may disrupt estrogen production in pregnancy, affecting pregnancy outcome. Fluconazole taken at low doses is in FDA pregnancy category C. However, high doses have been associated with a rare and distinct set of birth defects in infants. If taken at these doses, the pregnancy category is changed from category C to category D. Pregnancy category D means there is positive evidence of human fetal risk based on human data. In some cases, the potential benefits from use of the drug in pregnant women with serious or life-threatening conditions may be acceptable despite its risks.
While the imidazole antifungals are mainly used topically, fluconazole and certain other triazole antifungals are preferred when systemic treatment is required because of their improved safety and predictable absorption when administered orally.Fluconazoles spectrum of activity includes most Candida species (but not Candida krusei or Candida glabrata), Cryptococcus neoformans, some dimorphic fungi, and dermatophytes, among others. Common uses include:
The treatment of non-systemic Candida infections of the vagina ("yeast infections"), throat, and mouth. Certain systemic Candida infections in people with healthy immune systems, including infections of the bloodstream, kidney, or joints. Other antifungals are usually preferred when the infection is in the heart or central nervous system, and for the treatment of active infections in people with weak immune systems. The prevention of Candida infections in people with weak immune systems, such as those neutropenic due to cancer chemotherapy, those with advanced HIV infections, transplant patients, and premature infants. As a second-line agent for the treatment of cryptococcal meningoencephalitis, a fungal infection of the central nervous system. Resistance
Fungal resistance to drugs in the azole class tends to occur gradually over the course of prolonged drug therapy, resulting in clinical failure in immunocompromised patients (e.g., patients with advanced HIV receiving treatment for thrush or esophageal Candida infection).In C. albicans, resistance occurs by way of mutations in the ERG11 gene, which codes for 14α-demethylase. These mutations prevent the azole drug from binding, while still allowing binding of the enzymes natural substrate, lanosterol. Development of resistance to one azole in this way will confer resistance to all drugs in the class.