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Fluconazole (Diflucan) is a synthetic triazole antifungal agent for either intravenous or oral administration. It is indicated for treatment of fungal infections caused by Candida albicans and meningitis caused by Cryptococcus neoformans.
Fluconazole is <10% protein bound and has a volume of distribution (averaging 0.9 L/kg) indicating that it distributes into tissues.
Fluconazole is cleared predominantly by the kidney. Ninety plus percent of administered fluconazole is excreted in the urine as parent drug. The apparent elimination half-life is approximately 30 hours (range 20-50 hours). Compromised renal function significantly decreases the rate of elimination and causes fluconazole to accumulate. Distribution and elimination are similar in adults, children as young as age 2 months, and in geriatric patients.(1)
Fluconazole does not undergo extensive hepatic metabolism. However, fluconazole is a potent inhibitor of CYP2C9, which affects drugs metabolized by this system such as benzodiazepines, cyclosporine, statins, phenytoin, sirolimus, tacrolimus, and warfarin.
Fluconazole is generally well tolerated, but toxicity can occur at high serum concentration. Hepatic toxicity has been observed in renally impaired patients treated with fluconazole. Anaphylaxis, seizures, toxic epidermal necrosis, vomiting, and diarrhea also may occur.
Monitoring fluconazole therapy to guide dose adjustment and ensure adequate coverage while avoiding high concentrations associated with toxicity, especially in patients who have severely compromised renal function, for those who are undergoing dialysis, or for those where absorption may be impacted
Routine drug monitoring is not indicated in most patients
Serum concentration of fluconazole correlates with dose (typically 0.1-0.6 gm administered every 24 hours):
-A 0.2 gm dose produces a peak serum concentration (within 30-60 minutes of infusion) of 4.0 to 8.0 mcg/mL in adults
-A 0.4 gm dose produces a peak serum concentration of 8.0 to 16 mcg/mL
Optimal peak serum concentrations vary according to indication. Peak serum concentrations <4.0 mcg/mL are likely to be ineffective, while peak concentrations >20 mcg/mL are unlikely to provide increased efficacy and may predispose the patient to toxicity.
Naltrexone and naproxen interfere with fluconazole, causing an artifactual increase in the fluconazole concentration. Pentoxifylline and hydrocodone interfere with the internal standard peak, causing an artifactual decrease in the fluconazole concentration. Physiologic serum concentrations of naltrexone and hydrocodone are not likely to interfere. Naproxen and pentoxifylline are significant interferences.
Liu Y, Xu C, Yan R, Lim C, et al: Sensitive and specific LC-MS/MS method for the simultaneous measurements of viramidine and ribavirin in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci 2006 Feb 17;832(1):17-23