Fluconazole abnormal

Mechanism of Action. Itraconazole works like fluconazole and similar azoles. These drugs disrupt membrane function of the fungal cell by inhibiting the synthesis of key membrane components such as sterols, and by directly damaging other membrane components such as phospholipids. Impaired membrane function leads to metabolic abnormalities and subsequent death of the fungal cell. 

There has been an open, randomized comparison of amphotericin deoxycholate 0.5 mg/kg/day intravenously versus fluconazole 400 mg/day orally for empirical antifungal therapy in neutropenic patients with cancer and fever refractory to broad-spectrum antibiotics (51). Patients with abnormal hepatic or renal function were excluded, as were those with proven or suspected invasive fungal infection. The mean duration of therapy was 8.3 days with amphotericin deoxycholate and 7.9 days... 

Fluconazole is generally well tolerated. The most common adverse effects are nausea and vomiting. Abnormal liver function tests and slight increases in hepatic enzymes have been reported, and there have been anecdotal reports of hepatitis and hepatic failure. Early studies have shown no changes in testosterone concentrations or in the adrenal response to ACTH. Rashes and a few cases of exfoliative skin disorder have been reported (SED-12,681) and have been seen more frequently in patients with AIDS (29). Alopecia has been reported in a few cases with the use of high doses for prolonged periods of time (SEDA-18, 281). Rare instances of anaphylactoid reactions have been reported (SED-12, 681) (30). Rare instances of hypersensitivity reactions have occurred in other individuals (SEDA-16, 293) (SEDA-17,320). Tumor-inducing effects have not been reported. 

In a study using the UK General Practice Research Database to determine rates of drug-induced, rare, serious adverse effects on the liver, kidneys, skin, or blood, occurring within 45 days of completing a prescription or refill in 54 803 users of either fluconazole or itraconazole, three had illnesses for which a fluconazole-induced cause could not be ruled out one with thrombocytopenia, one with neutropenia, and one with an abnormal liver function test just after receiving fluconazole (31). The rates were 2.8/100 000 prescriptions (95% Cl = 0.8, 10) for serious, adverse blood events and 1.4/100 000 prescriptions (95% Cl = 0.25, 8.2) for serious, adverse liver events. These results suggest that fluconazole does not commonly have serious adverse effects on the liver, kidneys, skin, or blood. 

A 68-year-old woman with Candida glabrata isolated from a presacral abscess developed torsade de pointes after 8 days treatment with oral fluconazole 150 mg/day (32). She had no other risk factors for torsade de pointes, including coronary artery disease, cardiomyopathy, congestive heart failure, or electroljde abnormalities. The dysrhythmia resolved when fluconazole was withdrawn, but she continued to have ventricular extra beats and non-sustained ventricular tachycardia for 6 days. 

The efficacy and safety of fluconazole in neonates with Candida fungemia has been evaluated in a multicenter prospective study (65). Fluconazole was safe and effective even in complicated cases, including infants of very low birth weights. Two of 50 neonates developed raised liver enzymes during fluconazole therapy and two others had raised serum creatinine concentrations. In none of them did these abnormalities necessitate discontinuation of antifungal therapy. 

The efficacy, safety, and tolerability of voriconazole and fluconazole have been compared in 391 immunocompromised adults with esophageal candidiasis in a randomized, double-blind, multicenter trial (11). Most of the patients (94%) had AIDS. Following randomization, they took either voriconazole (200 mg bd) or fluconazole (400 mg on day 1 followed by 200 mg od) for a median of 14 or 15 days respectively. Treatment was continued for 7 days after the resolution of aU signs and symptoms but was not allowed to exceed 42 days. The two drugs achieved comparable success rates (98% voriconazole, 95% fluconazole), as assessed by esophagoscopy in the primary efficacy analysis in 256 patients. More patients discontinued voriconazole because of laboratory test abnormalities (3.5 versus 1%) or treatment-related adverse events (2.5 versus 0.5%). The most frequent... 

Placebo-controlled studies In a doubleblind, placebo-controUed, randomized trial in 26 centers in the USA of the use of intravenous fluconazole 800 mg/day for 2 weeks in 249 adults in ICU with a high risk of invasive candidiasis, seven who were given fluconazole and 10 who were given placebo had adverse events resulting in withdrawal of the study drug there were abnormal liver function tests in three and five subjects respectively [55 ]. 

Fig. 9. Scanning electron microscopic finding. No abnormal appearance is seen after exposure for 4 min to fluconazole (1 mg/ml).

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