Fluconazole (Diflucan)

1. Health Canada Product Monograph — Fluconazole

• Fluconazole treats oropharyngeal and esophageal candidiasis, yeast infections of the mouth, throat, and swallowing tube.
• Fluconazole treats serious systemic candida infections, including infections of the urinary tract, abdominal cavity, and lungs.
• Fluconazole treats cryptococcal meningitis, a serious fungal infection affecting the lining of the brain and spinal cord.
• Fluconazole is used to prevent the recurrence of cryptococcal meningitis in patients with AIDS.
• Fluconazole is used to reduce the risk of candida infections in patients undergoing bone marrow transplantation who are receiving chemotherapy or radiation therapy.

• Fluconazole should not be used during pregnancy except for severe or potentially life-threatening fungal infections, where the benefit to the mother is judged to outweigh the risk to the baby.
• Repeated or high-dose fluconazole use during the first trimester has been associated with an increased risk of miscarriage and a distinctive pattern of birth defects, including skull, facial, and bone abnormalities and heart defects.
• Even low, single doses used during the first trimester have been linked in some studies to an increased risk of miscarriage and birth defects.
• Women who become pregnant while taking fluconazole should notify their doctor immediately.

• Fluconazole passes into breast milk at concentrations similar to those in the mother's blood, so breastfeeding is not recommended while taking this medication.

• Fluconazole is generally well tolerated in patients 65 years of age and older.
• Because older adults are more likely to have reduced kidney function, caution is needed and the dose should be adjusted based on kidney function; monitoring kidney function may be useful.
• In bone marrow transplant patients, a higher rate of treatment discontinuation due to side effects was seen in older patients compared with younger patients.

• Fluconazole is approved for use in children, with dosing based on body weight for the same infections treated in adults.
• Fluconazole has been shown effective for oropharyngeal candidiasis in children 6 months to 13 years of age, and for serious systemic candida and cryptococcal infections in children.
• Effectiveness has not been established in infants younger than 6 months of age, although a small number of infants in this age range have been treated safely.

• Because oral absorption of fluconazole is rapid and nearly complete, the same daily dose is used whether it is given as oral suspension or by intravenous infusion.
• For oropharyngeal candidiasis, the usual adult dose is taken once daily for at least 2 weeks; children receive a weight-based dose for the same duration.
• For esophageal candidiasis, the usual adult dose is taken once daily for at least 3 weeks and for at least 2 weeks after symptoms resolve.
• For serious systemic candida infections, the usual adult dose is taken once daily for at least 4 weeks and for at least 2 weeks after symptoms resolve; a loading dose of twice the daily dose is often given on the first day.
• For cryptococcal meningitis, the usual adult dose is taken once daily for a minimum of 10 weeks; a lower maintenance dose is then used to prevent recurrence in patients with AIDS.
• For prevention of candidiasis during bone marrow transplantation, the usual adult dose is taken once daily, started before the anticipated drop in white blood cell counts and continued for 7 days after counts recover.
• The dose must be reduced in patients with impaired kidney function, based on creatinine clearance, after an initial loading dose; patients on hemodialysis receive their dose after each dialysis session.
• The intravenous infusion should be given at a controlled, limited maximum rate to avoid infusing it too quickly.

If overdose is suspected, seek emergency medical attention immediately or contact your regional Poison Control Centre without delay.

• Reports of fluconazole overdose have included hallucinations and paranoid behaviour.
• Treatment of overdose is mainly supportive, including symptomatic care and gastric lavage if appropriate soon after ingestion.
• A few hours of hemodialysis removes a substantial portion of the drug from the blood, which can be considered in severe cases.
• Activated charcoal may help reduce absorption of drug that has not yet been absorbed.

• Headache may occur.
• Nausea may occur.
• Abdominal pain may occur.
• Diarrhea may occur.
• Vomiting may occur.
• Skin rash may occur.
• Changes in liver enzyme blood tests may occur.
• Dizziness may occur.
• Taste changes may occur.
• When used as a single dose for vaginal yeast infection, headache, nausea, and abdominal pain are the most commonly reported effects.

Serious side effects require immediate discussion with the prescriber or emergency care.

• Rare but serious liver problems, including hepatitis, liver failure, and, very rarely, fatal liver injury, have been reported, mainly in patients with serious underlying illness taking multiple medications.
• Serious skin reactions, including exfoliative skin conditions, Stevens-Johnson syndrome, toxic epidermal necrolysis, and DRESS syndrome, have rarely been reported and can be fatal in patients with serious underlying illness.
• Fluconazole can prolong the heart's QT interval and, rarely, has been associated with a dangerous heart rhythm called torsade de pointes.
• Severe allergic reactions, including anaphylaxis and swelling of the face or throat, have rarely been reported.
• Adrenal gland problems (adrenal insufficiency) have been reported rarely.
• Blood disorders, including low white blood cell counts and, rarely, agranulocytosis, and low platelet counts, have been reported.
• Seizures have been reported rarely.
• Seek urgent medical attention for yellowing of the skin or eyes, severe skin rash or blistering, a fast or irregular heartbeat, fainting, or signs of a severe allergic reaction.

• Use with caution in patients with pre-existing liver disease; liver function should be monitored, and the drug stopped if signs of liver injury develop.
• Use with caution in patients with a history of heart rhythm problems, structural heart disease, or slow heart rate, or in those taking other medications that can prolong the QT interval.
• Use with caution in patients with electrolyte imbalances, such as low potassium or magnesium, which can increase the risk of heart rhythm problems.
• Use with caution in patients with impaired kidney function, with dosage adjusted based on kidney function.
• Use with caution in patients taking multiple other medications, given fluconazole's potential for drug interactions.
• Use with caution in patients with HIV/AIDS or other serious underlying illness, who appear to have a higher rate of side effects.

• Contraindicated in patients with known hypersensitivity to fluconazole, other azole antifungals, or any ingredient in the formulation.
• Contraindicated in combination with pimozide, due to the risk of dangerous heart rhythm problems.
• Contraindicated in combination with quinidine, due to the risk of dangerous heart rhythm problems.
• Contraindicated in combination with erythromycin, due to the increased risk of serious heart rhythm problems and sudden death.

• Fluconazole is a moderate inhibitor of certain liver enzymes (CYP2C9 and CYP3A4) and a strong inhibitor of another (CYP2C19), so it can raise blood levels of many other medications; this effect can persist for several days after stopping fluconazole.
• Combining fluconazole with warfarin or other coumarin-type blood thinners can increase bleeding risk and prolong clotting time; monitoring is recommended.
• Combining fluconazole with certain statins, such as atorvastatin or simvastatin, increases the risk of muscle damage (myopathy and rhabdomyolysis).
• Combining fluconazole with cyclosporine can significantly raise cyclosporine levels, requiring monitoring and possible dose adjustment.
• Combining fluconazole with phenytoin can raise phenytoin levels.
• Combining fluconazole with rifampin can lower fluconazole levels, which may require a higher fluconazole dose.
• Combining fluconazole with oral diabetes medications called sulfonylureas can increase the blood-sugar-lowering effect and the risk of low blood sugar.
• Combining fluconazole with certain short-acting benzodiazepines, such as midazolam or triazolam, can increase their sedative effect.
• Combining fluconazole with carbamazepine can raise carbamazepine levels and increase the risk of toxicity.
• Combining fluconazole with amiodarone or other drugs that prolong the QT interval can increase the risk of dangerous heart rhythm problems.
• Combining fluconazole with certain opioid pain medicines, such as fentanyl or methadone, can increase their blood levels and the risk of breathing problems.
• Combining fluconazole with ibuprofen or other NSAIDs metabolized in a similar way can raise their blood levels.
• Combining fluconazole with losartan can reduce its blood-pressure-lowering effect.

• Fluconazole can be taken with or without food; absorption is not significantly affected by food.

• Fluconazole oral suspension can be taken at any time of day, with or without food, and should be shaken well before each use.
• The intravenous form is given by a healthcare professional at a controlled infusion rate and is not affected by meal timing.

• Store fluconazole powder for oral suspension at room temperature (15-30°C) before mixing; after mixing with water, store the suspension between 5-30°C, protected from freezing, shake well before each use, and discard any unused portion after 14 days.
• Store fluconazole solution for intravenous infusion at room temperature (15-30°C) and do not freeze.

• Fluconazole is an effective antifungal medication, but the length of treatment can be several weeks depending on the type of infection being treated.
• Fluconazole has many potential drug interactions; tell your pharmacist or doctor about all other medications you take.
• Report yellowing of the skin or eyes, severe rash, or an irregular heartbeat to a healthcare professional right away.