Fluconazole
A triazole antifungal taken by mouth or IV, used for thrush, deep Candida infections and cryptococcal meningitis.
Drug card
- Class
- Azole antifungal
- How it works
- Inhibiting the fungal P450 enzyme that makes ergosterol for the cell membrane
- Used for
- Thrush of the vagina, mouth or esophagus
- Candida in the blood and deep organs
- Cryptococcal meningitis
- Known for
- Liver injury, rarely liver failure
- Long QT interval and torsades de pointes
- Its name
- -conazole means an azole antifungal
Study it as a flashcard, and it comes back before you forget it.
Mechanism of action
How does fluconazole work?
Fluconazole selectively inhibits fungal 14α-demethylase. It is water-soluble, over 90% absorbed by mouth, reaches the cerebrospinal fluid at about 80% of plasma levels and is cleared mostly unchanged by the kidneys. It inhibits human CYP2C19 strongly and CYP2C9 and CYP3A4 moderately, and it blocks the cardiac IKr potassium current, which lengthens the QT interval.
Like other azole antifungals: Azoles inhibit lanosterol 14α-demethylase, the fungal cytochrome P450 enzyme that turns lanosterol into ergosterol, the main sterol of fungal membranes. Ergosterol runs short and 14α-methyl sterols build up, so the membrane fails and the fungus stops growing. Imidazoles such as clotrimazole are used mostly on skin and mucosa; triazoles such as fluconazole and itraconazole are taken by mouth or given IV.
Uses
What is fluconazole used for?
- Thrush of the vagina, mouth or esophagus
- Candida in the blood and deep organs
- Cryptococcal meningitis
Side effects
Side effects of fluconazole
- Liver injury, rarely liver failureKnown forSerious
- Long QT interval and torsades de pointesKnown forSerious
- Headache
- Nausea
- Abdominal pain
- Diarrhea
- Rash
- Taste change
- Severe skin reactions such as SJS and TENSerious
- Birth defects with high doses in early pregnancySerious
- SeizuresSerious
- Low white cell count, even agranulocytosisSerious
Known for marks what an exam expects you to know it for.
Watch for
Cautions and what sets it apart
- Raises levels of warfarin, phenytoin, sulfonylureas, ciclosporin and some statins: monitor or adjust.
- Contraindicated with QT-prolonging CYP3A4 substrates such as erythromycin, pimozide and quinidine.
- Lower the dose in kidney disease, since most of the drug leaves unchanged in urine.
- Pregnancy: avoid unless the infection is serious; high first-trimester doses are linked to birth defects.
Good to know: Unlike most azoles it is cleared by the kidney, and it reaches the CSF well, which suits cryptococcal meningitis. It also prevents Candida infection after bone marrow transplant. Candida krusei is resistant.
Remember it
A way to remember it
Azoles jam P450s: the fungus's and ours.
Their target, 14α-demethylase, is a fungal cytochrome P450 enzyme. Azoles also slow human P450 enzymes such as CYP3A4, which is why they raise the levels of so many other drugs.
Written for biofideX
Its name
-conazole means azole antifungal
Fluconazole, itraconazole and voriconazole share it. Clotrimazole, an imidazole antifungal, doesn't, and metronidazole (-nidazole) is not an antifungal.
- Every drug name stem
Its class
Azole antifungals
Other azole antifungals with a card:
Easily mixed up with allylamines, polyene antifungals and benzimidazole anthelmintics.
Sources
Checked against
Written for biofideX in plain words, after checking these references:
For learning pharmacology, not for treatment decisions: no doses are given, and a prescriber, pharmacist or the product's own label is the word on any one patient. Spotted a mistake? Tell us and we'll correct it.
Antifungals and antiparasitics
Fluconazole is one of 14 drugs practiced together here: their classes, how they work, what they treat and what they're known for.
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