Fluconazole (Diflucan) Contraindications and Precautions
- breast-feeding
- azole antifungals hypersensitivity
- cardiac disease
- elderly
- electrolyte imbalance
- hepatic disease
- pregnancy
- QT prolongation
- renal failure
- renal impairment
- torsade de pointes
Fluconazole (Diflucan) Contraindications and Precautions
Fluconazole should be administered cautiously in patients with potentially proarrhythmic conditions, including patients with a history of torsade de pointes. Some azole antifungals, including fluconazole, have been associated with QT prolongation. During post-marketing surveillance, rare cases of QT prolongation and torsade de pointes have been reported with fluconazole use. These reports have included seriously ill patients with multiple confounding risk factors that may have been contributory, such as structural cardiac disease, electrolyte imbalance, and concomitant medications that could be associated with proarrhythmic conditions. At usual therapeutic dosages, fluconazole is not likely to cause QT prolongation or torsade de pointes.
Fluconazole can be hepatotoxic and should be used with caution in patients with preexisting hepatic disease. The related azole, ketoconazole, also has been associated with hepatotoxicity. Liver-function tests should be monitored. If signs and symptoms of hepatotoxicity develop, fluconazole therapy should be stopped.
Approximately 60-80% of fluconazole is renally excreted (fluconazole_diflucan/#pharma">see Pharmacokinetics). Dose reduction or extension of the dosing interval is indicated in patients with renal impairment or renal failure.
Fluconazole is classified as a FDA pregnancy category C drug. It should be used during pregnancy only when the potential benefits outweigh the risks. There have been reports of infants with severe skeletal abnormalities born to women who used fluconazole while pregnant. Fluconazole may produce a Antley-Bixler-like syndrome when used at high doses for long duration in early pregnancy. The nature of the observed birth defects suggests that the teratogenic effect may occur early in the first trimester. The revised CDC Guidelines for the Prevention of Opportunistic Infections in Patients with HIV recommend that oral azole antifungals, including fluconazole, not be started during pregnancy and that these agents should be discontinued in HIV-positive women who become pregnant. Women receiving fluconazole should take effective birth control.
The manufacturer does not recommend the use of fluconazole in breast-feeding women. Fluconazole is distributed in human breast milk at concentrations similar to those in the plasma. However, conflicting information is available; according to the American Academy of Pediatrics (AAP) no particular problems have been reported in infants of mothers who have taken fluconazole during lactation.
Fluconazole should be used with caution in patients with azole antifungals hypersensitivity. Fluconazole may have a cross sensitivity with other azole derivatives.
The safety of fluconazole has been studied in children ages 1 day to 17 years, however, the efficacy of fluconazole has not been established in infants less than 6 months of age. Several studies have shown fluconazole to be effective in treating oropharyngeal candidiasis in children 6 months to 13 years. Fluconazole has also been shown effective in treating serious systemic fungal infections and for suppression of cryptococcal meningitis; there is no information regarding the efficacy of fluconazole for primary treatment of cryptococcal meningitis in children. Pharmacokinetic studies in children have established dose proportionality between children and adults.
Controlled clinical trials of fluconazole did not include sufficient numbers of elderly patients (>= 65 years of age) to evaluate whether they respond differently from younger patients in each indication. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Since fluconazole is primarily cleared renally and elderly patients are more likely to have decreased renal function, care should be taken to adjust dose based on creatinine clearance. It may also be useful to monitor renal function.
[ Last revised: 11/3/2004 1:54:00 PM ]
References
. Meneghelli UG, Zaterka S, de Paula Castro L, et al. Pantoprazole versus ranitidine in the treatment of duodenal ulcer: a multicenter study in Brazil. Am J Gastroenterol 2000;95:62-6.
. American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776-89.
. The University of Arizona Center for Education and Research on Therapeutics (ArizonaCERT). QT drug lists. Retrieved April 15, 2004. Available on the World Wide Web at http://www.qtdrugs.org.
. Diflucan® (fluconazole) package insert. New York, NY. Pfizer; 2004 Aug.
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