tatistically significant increase was observed in median AST (SGOT) levels from a baseline value of 30 IU/L to 41 IU/L in one trial and 34 IU/L to 66 IU/L in the other. The overall rate of serum transaminase elevations of more than 8 times the upper limit of normal was approximately 1% in fluconazole-treated patients in clinical trials. These elevations occurred in patients with severe underlying disease, predominantly AIDS or malignancies, most of whom were receiving multiple concomitant medications, including many known to be hepatotoxic. The incidence of abnormally elevated serum transaminases was greater in patients taking DIFLUCAN concomitantly with one or more of the following medications: rifampin, phenytoin, isoniazid, valproic acid, or oral sulfonylurea hypoglycemic agents.
Post-Marketing Experience
In addition, the following adverse events have occurred during post-marketing experience.
Immunologic: In rare cases, anaphylaxis (including angioedema, face edema and pruritus) has been reported.
Body as a Whole: Asthenia, fatigue, fever, malaise.
Cardiovascular: QT prolongation, torsade de pointes. (See PRECAUTIONS.)
Central Nervous System: Seizures, dizziness.
Hematopoietic and Lymphatic: Leukopenia, including neutropenia and agranulocytosis, thrombocytopenia.
Metabolic: Hypercholesterolemia, hypertriglyceridemia, hypokalemia.
Gastrointestinal: Cholestasis, dry mouth, hepatocellular damage, dyspepsia, vomiting.
Other Senses: Taste perversion.
Musculoskeletal System: myalgia.
Nervous System: Insomnia, paresthesia, somnolence, tremor, vertigo.
Skin and Appendages: Acute generalized exanthematous-pustulosis, drug eruption, increased sweating, exfoliative skin disorders including Stevens-Johnson syndrome and toxic epidermal necrolysis (see WARNINGS), alopecia.
Adverse Reactions in Children
The pattern and incidence of adverse events and laboratory abnormalities recorded during pediatric clinical trials are comparable to those seen in adults.
In Phase II/III clinical trials conducted in the United States and in Europe, 577 pediatric patients, ages 1 day to 17 years were treated with DIFLUCAN at doses up to 15 mg/kg/day for up to 1,616 days. Thirteen percent of children experienced treatment-related adverse events. The most commonly reported events were vomiting (5%), abdominal pain (3%), nausea (2%), and diarrhea (2%). Treatment was discontinued in 2.3% of patients due to adverse clinical events and in 1.4% of patients due to laboratory test abnormalities. The majority of treatment-related laboratory abnormalities were elevations of transaminases or alkaline phosphatase.
Percentage of Patients With Treatment-Related Side Effects Fluconazole
(N=577) Comparative Agents
(N=451)
With any side effect 13.0 9.3
Vomiting 5.4 5.1
Abdominal pain 2.8 1.6
Nausea 2.3 1.6
Diarrhea 2.1 2.2
OVERDOSAGE
There have been reports of overdose with fluconazole accompanied by hallucination and paranoid behavior.
In the event of overdose, symptomatic treatment (with supportive measures and gastric lavage if clinically indicated) should be instituted.
Fluconazole is largely excreted in urine. A three-hour hemodialysis session decreases plasma levels by approximately 50%.
In mice and rats receiving very high doses of fluconazole, clinical effec
