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.

• FluconazoleUnlike 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.
• ItraconazoleThe azole most linked to heart failure, from its negative inotropic effect. Capsules and oral solution are not interchangeable: the solution gives higher levels and is the form proven for thrush.
• ClotrimazoleMostly a local drug, used on the skin and in the vagina and mouth; unlike fluconazole or itraconazole, it is not given to treat infections deep in the body.

• Thrush (Candida) of the vagina, mouth and skin
• Cryptococcal meningitis
• Deep fungal infections such as histoplasmosis
• Aspergillosis
• Ringworm and athlete's foot
• Fungal nail infection

• Liver injury, rarely liver failureKnown forSerious
• Long QT interval and torsades de pointesKnown forSerious
• Nausea and vomiting
• Abdominal pain
• Headache
• Rash
• Heart failure (itraconazole)Serious
• Severe skin reactions such as SJS and TENSerious
• Low potassium (hypokalemia)
• Adrenal insufficiencySerious

What the class has in common. Each drug's card has its own, and Known for marks what an exam expects you to know.

• They inhibit human CYP3A4 and other P450s, raising levels of many drugs: warfarin, some statins, ciclosporin, QT-prolonging drugs.
• Check liver function on long courses and stop at signs of liver injury.
• Itraconazole is not used for nail infections in people with heart failure.
• Pregnancy: avoid systemic azoles unless the infection is serious; high-dose fluconazole is linked to birth defects.

Written for biofideX in plain words, after checking these references:

• Fluconazole tablets: label (DailyMed)
• Itraconazole capsules: label (DailyMed)
• Fluconazole (NCI Thesaurus)
• Clotrimazole (NCI Thesaurus)
• Clotrimazole (NHS)

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.