Itraconazole

Itraconazole is a triazole antifungal with a broad spectrum of activity that is used for various fungal infections. In vulvovaginal candidiasis, it is used when fluconazole or clotrimazole is not sufficiently effective, particularly in infections with non-albicans Candida species (e.g., C. glabrata, C. krusei).

Itraconazole is marketed under the brand name Sempera® and as a generic. It is also approved for fungal skin infections, nail fungus, and systemic mycoses.

Mechanism of action:

• Inhibits 14-alpha-demethylase (CYP51)
• Blocks ergosterol synthesis in the fungal cell membrane
• Ergosterol is an essential component of the fungal cell membrane
• The cell membrane becomes unstable → the fungal cell dies

Broader spectrum than fluconazole:

• Candida albicans and non-albicans species
• Aspergillus
• Dermatophytes
• Also effective against some fluconazole-resistant strains

Pharmacokinetics:

• Lipophilic → good tissue penetration
• Long half-life → the effect persists after discontinuation
• Absorption strongly dependent on stomach acid and food

Itraconazole is suitable for:

• Vulvovaginal candidiasis that does not respond to fluconazole
• Infections with non-albicans Candida species
• Recurrent candidiasis (suppressive therapy)
• Fungal skin and nail infections
• Systemic mycoses

Not suitable:

• Pregnancy (teratogenic in animal studies)
• Heart failure
• Severe hepatic insufficiency
• Concomitant use of certain medications (CYP3A4 interactions)

Vulvovaginal candidiasis:

• 200 mg twice daily for 1 day (short-term therapy)
• Or 200 mg once daily for 3 days

Recurrent candidiasis (suppression):

• 200 mg once daily for the first 3 days of menstruation, over a period of 6 months

Available strengths:

• 100 mg capsules

Important:

• Take the capsules with a full meal (absorption!)
• In achlorhydric gastric conditions (proton pump inhibitors): absorption greatly reduced

How to take:

• Take immediately after a complete meal
• Swallow the capsules whole
• Take with sufficient fluid (1 glass of water)
• In achlorhydria or if you take medicines that reduce stomach acid (e.g. H2 antagonists, proton pump inhibitors): take with a non-diet cola drink

Important notes:

• Absorption is highly dependent on food
• PPIs (omeprazole, etc.) significantly reduce absorption
• Check liver function before and during therapy
• Reliable contraception during therapy and until the first menstrual period after the end of therapy (women)

Itraconazole must not be taken in cases of:

• Hypersensitivity to itraconazole
• Pregnancy
• Heart failure (NYHA III–IV)
• Concomitant use of: terfenadine, astemizole, cisapride, simvastatin, lovastatin, midazolam (oral), triazolam, pimozide, quinidine, dofetilide, ergotamine

Use with caution in:

• Liver disease (hepatotoxic!)
• Impaired kidney function
• Achlorhydria/PPI therapy (reduced absorption)
• QT prolongation
• Breastfeeding (itraconazole passes into breast milk, if in doubt do not breastfeed)

Common (1–10%):

• Nausea, abdominal pain
• Headache
• Elevated liver enzymes
• Skin rash

Uncommon (0.1–1%):

• Diarrhea, constipation
• Dizziness
• Menstrual cycle disorders
• Edema

Rare but serious:

• Hepatotoxicity (ranging from liver inflammation to liver failure)
• Heart failure
• Peripheral neuropathy
• Stevens-Johnson syndrome

Note: For therapy lasting more than 1 month or in the presence of risk factors: regular monitoring of liver function.