Itraconazole

Itraconazole is a broader-spectrum azole than fluconazole that could probably have a bigger place in antifungal pharmacotherapy today if it were not for pharmacokinetic issues that have hampered its greater use. It has activity against  Aspergillus and other mould species and was once commonly used as a step-down therapy in aspergillosis, but this use has declined since voriconazole became available.

Spectrum

Good: Candida albicans, Candida tropicalis, Candida parapsilosis, Candida lusitaniae, Crypto-coccus neoformans, Aspergillus  species, many dimorphic fungi

Moderate:  Candida glabrata and  Candida krusei  (can be susceptible dose-dependent, or resistant)

Poor: Zygomycetes, many other moulds

Adverse Effects

Itraconazole’s adverse effect profile causes more concerns than that of fluconazole. In addition to causing hepatotoxicity, itraconazole is a negative ionotrope and is contraindicated in patients with heart failure. The oral solution is associated with diarrhea. It is also a stronger inhibitor of cytochrome P450 enzymes and has a long list of drug interactions. QTc prolongation can also occur.

Important Facts

• Itraconazole comes in two different formulations with different bioavailabilities and require-ments. The capsules have lower bioavailability than the solution and are less preferred for systemic fungal infections.

• The oral formulations of itraconazole have different instructions with regard to taking them with meals. Capsules should always be taken with a full meal, whereas the solution should be taken on an empty stomach. Absorption can also be lowered by agents that decrease gastric acidity, such as proton-pump inhibitors; try having your patients take their itraconazole with a soda.

• Because itraconazole absorption is so erratic and unpredictable, concentrations are often monitored. Consider checking a trough concentration on your patient if he or she is taking it for a serious fungal infection and/or for a long time.

• Itraconazole was once available in an IV formulation, but this has been discontinued by the manufacturer. Ignore older references that sug-gest using it.

What It’s Good For

Itraconazole remains a drug of choice for some dimorphic fungal infections, like histoplasmosis. It once had a larger role in the management and prophylaxis of aspergillosis and other mould infections,  but it has been largely replaced by voriconazole.

Don’t Forget!

Watch for those drug interactions, and be sure to counsel your patients on how to take their itraconazole formulation.

References

Gallagher ,J.C. and MacDougall ,c. (2012). Antibiotics Simplified. Second Edition. Jones & Bartlett Learning, LLC.