Note: This document contains side effect information about fluconazole. Some of the dosage forms listed on this page may not apply to the brand name Diflucan.

In Summary

More frequent side effects include: vomiting. See below for a comprehensive list of adverse effects.

For the Consumer

Applies to fluconazole: oral powder for suspension, oral tablet

Other dosage forms:

• intravenous solution

Along with its needed effects, fluconazole (the active ingredient contained in Diflucan) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking fluconazole:

Rare

• Chills
• clay-colored stools
• cough
• dark urine
• diarrhea
• difficulty with swallowing
• dizziness
• fast heartbeat
• fever
• general feeling of tiredness or weakness
• headache
• hives, itching, or skin rash
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• light-colored stools
• loss of appetite
• nausea
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• stomach pain, continuing
• tightness in the chest
• unpleasant breath odor
• unusual tiredness or weakness
• upper right abdominal or stomach pain
• vomiting
• vomiting of blood
• yellow eyes and skin

Incidence not known

• Black, tarry stools
• blistering, peeling, or loosening of the skin
• chest pain or discomfort
• decreased urine
• dry mouth
• fainting
• hoarseness
• increased thirst
• irregular or slow heart rate
• joint or muscle pain
• loss of bladder control
• lower back or side pain
• mood changes
• muscle pain or cramps
• muscle spasm or jerking of the arms and legs
• numbness or tingling in the hands, feet, or lips
• painful or difficult urination
• pale skin
• red skin lesions, often with a purple center
• red, irritated eyes
• seizures
• sore throat
• sores, ulcers, or white spots in the mouth or on the lips
• sudden loss of consciousness
• swollen glands
• unusual bleeding or bruising

Get emergency help immediately if any of the following symptoms of overdose occur while taking fluconazole:

Symptoms of overdose

• Fearfulness, suspiciousness, or other mental changes
• seeing, hearing, or feeling things that are not there

Some side effects of fluconazole may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common

• Belching
• change in taste or bad, unusual, or unpleasant (after) taste
• heartburn
• indigestion
• stomach discomfort or upset

Incidence not known

• Hair loss or thinning of the hair

For Healthcare Professionals

Applies to fluconazole: intravenous solution, oral powder for reconstitution, oral tablet

General

This drug was generally well tolerated. Changes in renal and hematological function test results and hepatic abnormalities reported during therapy with this and comparative agents in some patients, primarily those with serious underlying diseases (e.g., AIDS, cancer); clinical significance and relationship to therapy unclear.

During clinical trials of single-dose therapy, side effects possibly related to therapy were reported in 26% of patients using this drug and 16% of patients using active comparative agents. The most common side effects reported in patients receiving a single 150 mg dose of this drug for vaginitis were headache, nausea, and abdominal pain. Most side effects were of mild to moderate severity.

During clinical trials of multiple-dose therapy, side effects were reported in 16% of patients. Therapy discontinuation occurred in 1.5% and 1.3% of patients due to adverse clinical events and laboratory test abnormalities, respectively. Clinical side effects were reported more often in HIV-infected patients than in non-HIV-infected patients (21% versus 13%), but the patterns in both groups were similar.

Nervous system

Rare cases of seizures have been reported, but a causal relationship was difficult to establish, since some of these patients had cryptococcal meningitis or severe underlying disease. Nonetheless, at least 1 case of seizure following a 100 mg oral dose has been reported.

Seizures, dizziness, paresthesia, somnolence, tremor, and vertigo have also been reported during postmarketing experience.

Very common (10% or more): Headache (up to 13%)

Uncommon (0.1% to 1%): Seizures, dizziness, paresthesia, somnolence, vertigo, visual field defect, taste perversion, hyperkinesia, hypertonia

Rare (less than 0.1%): Tremor

Frequency not reported: Dysesthesias

Gastrointestinal

Very common (10% or more): Nausea, abdominal pain, diarrhea, vomiting

Common (1% to 10%): Dyspepsia

Uncommon (0.1% to 1%): Constipation, flatulence, loose stools, dry mouth

Frequency not reported: General abdominal discomfort

Dry mouth, dyspepsia, and vomiting have also been reported during postmarketing experience.

Hepatic

Fatal hepatic reactions have occurred primarily in patients with serious underlying medical conditions (primarily AIDS or malignancy) and often taking multiple concomitant medications. One reported patient with AIDS experienced acute hepatic necrosis and hepatic failure about 3 weeks after starting this drug.

Transient hepatic reactions have been reported in patients with no other identifiable risk factors. Liver function returned to baseline after stopping this drug.

Serum transaminase elevations (greater than 8 times the upper limit of normal [8 x ULN]; about 1%) and statistically significant increases in AST have been reported. Serum transaminase elevations have been reported primarily in patients with serious underlying medical conditions (primarily AIDS or malignancy) and often taking multiple concomitant medications, including agents known to be hepatotoxic.

Transaminase elevations greater than 2 to 3 x ULN have also been reported.

Cholestasis, hepatocellular damage, and hepatocellular necrosis have also been reported during postmarketing experience.

Very common (10% or more): Increased ALT, increased AST

Uncommon (0.1% to 1%): Serum transaminase elevations, cholestasis, jaundice, increased bilirubin

Rare (less than 0.1%): Serious hepatic reactions, hepatic toxicity (including fatalities), hepatic failure, hepatocellular necrosis, hepatitis, hepatocellular damage

Frequency not reported: Hepatic reactions (ranging from mild transient transaminase elevations to clinical hepatitis, fulminant hepatic failure [including fatalities]), transient hepatic reactions (including hepatitis, jaundice), elevated liver function tests (transient and asymptomatic), cholestatic jaundice, fatal hepatic necrosis, increased plasma levels of hepatic enzymes

Dermatologic

Reversible alopecia has been associated with long-term (2 months or longer) therapy.

In patients with serious underlying diseases (primarily AIDS and malignancy), exfoliative skin disorders have resulted in a fatal outcome.

Acute generalized exanthematous pustulosis, drug eruption, increased sweating, exfoliative skin disorders (including Stevens-Johnson syndrome, toxic epidermal necrolysis), and alopecia have also been reported during postmarketing experience.

Very common (10% or more): Rash

Common (1% to 10%): Maculopapular erythema

Uncommon (0.1% to 1%): Pruritus, genital pruritus, erythematous rash, dry skin, abnormal skin odor, urticaria, herpes simplex, drug eruption, increased sweating

Rare (less than 0.1%): Angioedema, exfoliative skin disorders (including Stevens-Johnson syndrome, toxic epidermal necrolysis), alopecia, acute generalized exanthematous pustulosis, exfoliative dermatitis

Frequency not reported: Reversible alopecia, exfoliative skin disorders (including fatalities)

Metabolic

Very common (10% or more): Increased blood alkaline phosphatase

Uncommon (0.1% to 1%): Hypokalemia, anorexia, decreased appetite

Rare (less than 0.1%): Hypercholesterolemia, hypertriglyceridemia

Hypercholesterolemia, hypertriglyceridemia, and hypokalemia have also been reported during postmarketing experience.

Hypersensitivity

Rare cases of exfoliative dermatitis and ulcerative eruptions consistent with Stevens-Johnson syndrome have been reported in association with hypersensitivity reactions.

A 52-year-old female experienced a fixed drug eruption (FDE) when administered a single 400 mg oral dose for extensive pityriasis versicolor. Within 12 hours, she noticed 3 oval, painful, eroded, pigmented patches over her trunk with diameters of 3 to 4 cm and erythematous halos. A clinical diagnosis of FDE due to drug therapy was made. The FDE was confirmed when the patient was rechallenged with a 25 mg oral dose.

Rare (less than 0.1%): Anaphylactic reaction, anaphylaxis

Frequency not reported: Hypersensitivity reactions (including generalized edema, stridor, hypotension, exfoliative dermatitis, ulcerative eruptions), fixed drug eruption

Postmarketing reports: Anaphylaxis (including angioedema, face edema, pruritus)

Cardiovascular

Most reports of QT interval prolongation and torsades de pointes involved seriously ill patients with multiple confounding risk factors, such as structural heart disease, electrolyte abnormalities, and concomitant medications that may have been contributory.

An 11-year-old male with neurofibromatosis-1 presented to the hospital in septic shock secondary to a perforated gastric volvulus. After initial stabilization, the patient underwent total gastrectomy and multiple peritoneal lavages. Culture of peritoneal fluid showed infection with Candida albicans. Therapy was started with fluconazole (the active ingredient contained in Diflucan) 150 mg IV every 12 hours. After starting this drug, the patient developed QT prolongation and complex ventricular arrhythmia. The drug was discontinued. Over the subsequent 36-hours, the patient remained in sinus rhythm except for one brief run of ventricular bigeminy. An ECG recorded 5 months after admission (and about 4 months after cessation of all QT-prolonging medications) showed sinus rhythm with normal heart rate and corrected QT interval.

QT prolongation and torsade de pointes have also been reported during postmarketing experience.

Rare (less than 0.1%): QT prolongation, torsade de pointes

Frequency not reported: Prolongation of the QT interval on the ECG, palpitations, complex ventricular arrhythmia

Hematologic

Anemia, eosinophilia, leukopenia, neutropenia, and thrombocytopenia have been reported, often in patients with severe deep fungal infections or underlying disease.

Spontaneous reports of anemia were more frequent in patients 65 years of age or older than in those between 12 and 65 years of age; however, there is a natural increase in the incidence of anemia in the elderly. A causal relationship to drug exposure could not be determined.

Anemia, leukopenia, neutropenia, agranulocytosis, and thrombocytopenia have also been reported during postmarketing experience.

Uncommon (0.1% to 1%): Anemia

Rare (less than 0.1%): Leukopenia, neutropenia, agranulocytosis, thrombocytopenia

Frequency not reported: Eosinophilia

Other

Uncommon (0.1% to 1%): Thirst, fatigue, malaise, pain, rigors, asthenia, fever, flushing, hot flushes

Rare (less than 0.1%): Face edema

Frequency not reported: Infection due to resistant microorganisms

Fever, asthenia, fatigue, and malaise have also been reported during postmarketing experience.

Musculoskeletal

Uncommon (0.1% to 1%): Back pain, myalgia

Frequency not reported: Joint pain, finger stiffness

Myalgia has also been reported during postmarketing experience.

Psychiatric

Uncommon (0.1% to 1%): Insomnia, nervousness

Insomnia has also been reported during postmarketing experience.

Renal

Uncommon (0.1% to 1%): Polyuria, renal pain, changes in renal function tests

Frequency not reported: Membranous nephropathy

Postmarketing reports: Acute renal failure

A 58-year-old female with a history of hypertension and cervical cancer experienced membranous nephropathy coincident with this drug. The patient presented with increasing generalized edema accompanied by nausea and indigestion for 3 weeks. Clinical findings showed the patient had stage I membranous nephropathy. At initial presentation, the patient's medication history included amlodipine, hydrochlorothiazide, metoclopramide, and levosulpiride. She did not admit to taking fluconazole. Five months after the initial presentation, the patient returned with reports of increasing pedal edema. At that point, the patient admitted to taking this drug once a week for tinea pedis. The patient went into complete remission when the drug was stopped.

Spontaneous reports of acute renal failure were more frequent in patients 65 years of age or older than in those between 12 and 65 years of age; however, there is a natural increase in the incidence of renal failure in the elderly. A causal relationship to drug exposure could not be determined.

Genitourinary

Uncommon (0.1% to 1%): Intermenstrual bleeding, dysmenorrhea, leukorrhea, menorrhagia, uterine spasm, vaginal disorders, female sexual dysfunction

Respiratory

Uncommon (0.1% to 1%): Pharyngitis

Frequency not reported: Respiratory disorders

Ocular

Uncommon (0.1% to 1%): Abnormal vision