From the Guidelines
Fluconazole commonly causes side effects including headache, skin rash, gastrointestinal complaints, and insomnia, with adverse effects leading to treatment discontinuation occurring in up to 58% of patients receiving higher weekly doses. The common adverse effects of fluconazole are well-documented, with headache, skin rash, gastrointestinal complaints, and insomnia being the most frequently reported 1. More serious but less common side effects include liver problems, severe skin reactions, and QT prolongation. Rare but serious side effects include severe allergic reactions and Stevens-Johnson syndrome. The medication can interact with other drugs, potentially increasing their effects or toxicity.
Key Side Effects
- Headache
- Skin rash
- Gastrointestinal complaints
- Insomnia
- Liver problems
- Severe skin reactions
- QT prolongation
- Severe allergic reactions
- Stevens-Johnson syndrome Side effects are more common with higher doses and longer treatment durations, as seen in studies where higher doses (300-450 mg per week) and longer treatment duration (9 and 12 months) were associated with higher cure rates but also increased adverse effects 1. Patients should contact their healthcare provider if they experience persistent or severe side effects, especially signs of liver problems or allergic reactions. These side effects occur because fluconazole inhibits fungal cytochrome P450 enzymes but can also affect similar enzymes in humans, disrupting normal metabolism of medications and endogenous compounds. Elderly patients and those with kidney or liver impairment may experience more side effects due to decreased drug clearance, as fluconazole elimination is almost entirely renal, and a dose reduction is needed in patients with creatinine clearance <50 mL/minute 1.
From the FDA Drug Label
Fluconazole is generally well tolerated. In some patients, particularly those with serious underlying diseases such as AIDS and cancer, changes in renal and hematological function test results and hepatic abnormalities have been observed during treatment with fluconazole and comparative agents, but the clinical significance and relationship to treatment is uncertain The most common treatment-related adverse events reported in the patients who received 150 mg single dose fluconazole for vaginitis were headache (13%), nausea (7%), and abdominal pain (6%). The following treatment-related clinical adverse events occurred at an incidence of 1% or greater in 4048 patients receiving fluconazole for 7 or more days in clinical trials: nausea 3.7%, headache 1.9%, skin rash 1.8%, vomiting 1.7%, abdominal pain 1.7%, and diarrhea 1. 5%. Hepato-biliary: In combined clinical trials and marketing experience, there have been rare cases of serious hepatic reactions during treatment with fluconazole. 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.
The side effects of fluconazole include:
- Common adverse events:
- Headache (13% in single dose, 1.9% in multiple doses)
- Nausea (7% in single dose, 3.7% in multiple doses)
- Abdominal pain (6% in single dose, 1.7% in multiple doses)
- Diarrhea (3% in single dose, 1.5% in multiple doses)
- Skin rash (1.8% in multiple doses)
- Vomiting (1.7% in multiple doses)
- Rare but serious adverse events:
- Anaphylaxis (including angioedema, face edema, and pruritus)
- Hepatic reactions (including hepatitis, jaundice, and fulminant hepatic failure)
- QT prolongation and torsade de pointes 2
From the Research
Fluconazole Side Effects
- The most common adverse effects of fluconazole are xerosis, alopecia, and fatigue, as reported in a study of 124 patients receiving long-term fluconazole therapy for coccidioidomycosis 3.
- A significant number of patients (51.6%) experienced adverse effects, and around two-thirds of them required a therapeutic change 3.
- High-dose fluconazole has been associated with increased risk of adverse effects, with patients experiencing adverse effects being prescribed higher total daily fluconazole doses 3.
- Fluconazole can also cause neurologic adverse effects, including paresthesia, dysesthesia, and numbness, although these are relatively rare 4.
- A case report described a patient who developed severe systemic and neurologic symptoms, including polyneuropathy, lower gastrointestinal system bleeding, acute renal insufficiency, thrombotic thrombocytopenic purpura, and confusional state, after taking fluconazole for onychomycosis without a prescription 4.
- Other studies have reported that fluconazole is generally well-tolerated, with few laboratory abnormalities related to the drug 5, 6.
- However, there are concerns about the overuse of fluconazole and the development of fluconazole-resistant Candida albicans strains, which may impact its use as prophylaxis for recurrent vulvovaginal candidiasis 7.