Fluconazole (Diflucan) Adverse Reactions
- abdominal pain
- agranulocytosis
- alopecia
- anaphylactoid reactions
- anemia
- angioedema
- diarrhea
- dizziness
- dysgeusia
- dyspepsia
- elevated hepatic enzymes
- eosinophilia
- erythema
- exfoliative dermatitis
- headache
- hepatic failure
- hepatitis
- hypercholesterolemia
- hypertriglyceridemia
- hypokalemia
- jaundice
- leukopenia
- nausea/vomiting
- neutropenia
- pruritus
- QT prolongation
- rash (unspecified)
- renal failure (unspecified)
- seizures
- Stevens-Johnson syndrome
- teratogenesis
- thrombocytopenia
- torsade de pointes
- toxic epidermal necrolysis
Fluconazole (Diflucan) Adverse Reactions
In comparative clinical trials of fluconazole 150 mg single doses for vaginal candidiasis (n = 448), the overall incidence of adverse effects possibly related to fluconazole was 26% compared to 16% for comparative agents (n = 422). The most common treatment-related adverse reactions associated with fluconazole were headache (13%), nausea (7%), and abdominal pain (6%). Other adverse effects reported included diarrhea (3%), dyspepsia (1%), dizziness (1%), and dysgeusia (1%). Most reported adverse effects were mild to moderate in severity. During multiple dose therapy with fluconazole, 16% of patients (n = > 4000) experienced adverse reactions. The most frequently reported (>= 1% of patients) adverse reactions during multi-dose therapy (7 days or more) were nausea/vomiting (3.7%/1.7%), headache (1.9%), skin rash (unspecified) (1.8%), abdominal pain (1.7%), and diarrhea (1.5%). Discontinuation of therapy occurred in 1.5% of patients due to adverse reactions and 1.3% due to laboratory test abnormalities. Clinical adverse reactions were reported more frequently in HIV infected patients (21%) than in non-HIV infected patients (13%); however, the patterns and the proportion of patients discontinuing therapy due to adverse reactions were similar in both groups. Rarely, angioedema and anaphylactoid reactions (including facial edema and pruritus) have been reported with single and multiple dose therapy. In the elderly, post-marketing reports of anemia and acute renal failure (unspecified) were more frequent than in younger patients; however, because these reports were voluntary and the elderly tend to have an increased incidence of anemia and renal failure, a causal relationship to fluconazole therapy was not possible to establish. In children receiving fluconazole in phase II/III clinical trials in the US and Europe (n = 577), the most commonly reported adverse reactions were nausea/vomiting (2%/5%), abdominal pain (3%), and diarrhea (2%); discontinuation of therapy occurred in 2.3% of children due to adverse reactions and 1.4% due to laboratory abnormalities (primarily elevations of transaminases or alkaline phosphatase).
Exfoliative skin disorders, such as Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported rarely in patients taking fluconazole who have concurrent malignancy or AIDS. This exfoliative skin disorder was exhibited by erythema, blisters, exfoliative dermatitis, and exfoliation of mucous membranes. Since patients were often receiving multiple medications, a definite causal relationship has yet to be determined. Patients should be monitored for development of rash while receiving fluconazole. Alopecia has been reported in 33 patients during fluconazole administration. In most cases, the hair loss involved the scalp but in others substantial loss of facial, leg, axillary, pubic, or chest hair occurred. In 3 patients, scalp hair loss required the use of a wig. In almost all patients, the alopecia resolved after discontinuation or reduction in the dose of fluconazole.
Rare cases of hepatotoxicity are noted in combined clinical trials and marketing experience with fluconazole. These hepatic reactions have ranged from mild elevated hepatic enzymes to clinical hepatitis, cholestasis, and fulminant hepatic failure, including fatalities. Elevated hepatic enzymes of > 8 times the upper limit of normal was reported in about 1% of fluconazole patients in clinical trials. Patients with severe underlying disease, predominantly AIDS or malignancies, experienced elevated hepatic enzymes and were receiving multiple concomitant medications, including many known to be hepatotoxic. The incidence of abnormally elevated serum transaminases was greater in patients taking fluconazole with one or more of the following medications: rifampin, phenytoin, isoniazid, valproic acid, or oral sulfonylureas. Cases of fatal hepatic reactions occurred primarily in patients with serious underlying medical conditions (predominantly AIDS or malignancy) and often while taking multiple concomitant medications. Transient hepatic reactions, including hepatitis and jaundice, have occurred in patients with no other identifiable risk factors. In each of these cases, hepatic function returned to baseline after stopping fluconazole. Hypercholesterolemia and hypertriglyceridemia have occurred with fluconazole. Fluconazole has been associated with teratogenesis when used early in a pregnancy at high doses. Fluconazole produces a characteristic pattern of fetal abnormalities including craniofacial, skeletal and cardiac anomalies, similar to Antley-Bixler syndrome when used during the first trimester. These effects may be dose-dependent. The nature of the observed birth defects suggests that the teratogenic effects may occur before the woman is aware she is pregnant. The exact mechanism is not known.
Hypokalemia requiring either potassium supplementation or discontinuation of therapy has been seen occasionally in some patients receiving fluconazole.
Leukopenia, including neutropenia and agranulocytosis, thrombocytopenia and eosinophilia have been reported rarely in patients taking fluconazole.
Seizures have been reported during post-marketing experience with fluconazole.
Some azole antifungals, including fluconazole, have been associated with QT prolongation. During post-marketing surveillance, there have been very rare reports of QT prolongation and torsade de pointes in patients taking fluconazole. These reports included seriously ill patients with multiple confounding risk factors, such as structural cardiac disease, electrolyte imbalances, and concomitant medications that may have been contributory. Fluconazole is not likely to cause torsade de pointes at usual therapeutic dosages.
[ Last revised: 11/3/2004 1:54:00 PM ]
References
. Pappas PG, Kauffman CA, Perfect J et al. Alopecia associated with fluconazole therapy. Ann Intern Med 1995;123:354-7.
. Pursley TJ, Blomquist IK, Abraham J, et al. Fluconazole-induced congenital anomalies in three infants. Clin Inf Dis 1996;22:336-40.
. 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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