Itraconazole
A triazole antifungal taken by mouth for aspergillosis, histoplasmosis, blastomycosis and fungal nail infections.
Drug card
- Class
- Azole antifungal
- How it works
- Inhibiting the fungal P450 enzyme that makes ergosterol for the cell membrane
- Used for
- Aspergillosis when amphotericin B fails or is not tolerated
- Histoplasmosis and blastomycosis
- Fungal nail infection (onychomycosis)
- Mouth and esophageal thrush (oral solution)
- Known for
- Heart failure
- Liver injury, rarely fatal liver failure
- 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 itraconazole work?
Itraconazole is a triazole that blocks the fungal P450-dependent synthesis of ergosterol. Capsules are best absorbed straight after a full meal and poorly when stomach acid is low. Itraconazole and its hydroxy metabolite strongly inhibit CYP3A4 and also inhibit P-glycoprotein, and the drug has a negative inotropic effect, weakening heart muscle contraction.
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 itraconazole used for?
- Aspergillosis when amphotericin B fails or is not tolerated
- Histoplasmosis and blastomycosis
- Fungal nail infection (onychomycosis)
- Mouth and esophageal thrush (oral solution)
Side effects
Side effects of itraconazole
- Heart failureKnown forSerious
- Liver injury, rarely fatal liver failureKnown forSerious
- Nausea
- Rash
- Leg swelling (edema)
- High blood pressure (pseudoaldosteronism)
- Low potassium (hypokalemia)
- Peripheral neuropathySerious
- Hearing loss, sometimes permanentSerious
- Long QT and torsades with interacting drugsSerious
- Severe skin reactions such as SJS and TENSerious
- Breast enlargement in men (gynecomastia)
Known for marks what an exam expects you to know it for.
Watch for
Cautions and what sets it apart
- Strong CYP3A4 inhibitor: many drugs are contraindicated with it, such as simvastatin, oral midazolam, pimozide and quinidine.
- Do not use for nail infections in people with heart failure or reduced ventricular function.
- Take capsules after a full meal; acid-lowering drugs such as PPIs reduce their absorption.
- Monitor liver function and stop at signs of liver injury.
Good to know: The 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.
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
Itraconazole 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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