Itraconazole is a prescription medication classified as an antifungal agent. It is used for the treatment of fungal infections, including those caused by aspergillus, candida, and cryptococcus. It is available as a capsule, oral solution and injectable solution. The metabolism, or breakdown, of this medication can affect other drugs you may be taking and can cause adverse reactions. Always inform your physician of all the medications you take before starting a new medical therapy.
Metabolism
The cytochrome P450 is a family of enzymes found in high concentrations in the liver, and they are directly involved in the metabolism of drugs. One of these enzymes, cytochrome P450 3A4, is the major site of itraconazole metabolism. The breakdown of the medication produces byproducts, called metabolites. According to the "Drug Information Handbook," hydroxy-itraconazole is a metabolite that appears to have antifungal activity as well.
Increased Effect
Itraconazole inhibits, or blocks, the actions of cytochrome P450 3A4, or CYP 3A4, and may cause an increase in blood levels of medications broken down by this enzyme. Itraconazole is contraindicated with cisapride, dofetilide, lovastatin, midazolam, simvastatin, ergot derivatives, and triazolam. Other medications whose levels may be increased and that should therefore be used with caution include alfentanil, diazepam, buspirone, felodipine, verapamil, digoxin, warfarin and zolpidem. Higher blood levels of these medications may result in an increase in side effects associated with them.
Decreased Effect
Certain medications, such as rifampin, rifabutin, isoniazid, nafcillin, phenobarbital, phenytoin and carbamazepine, induce, or enhance, the actions of CYP 3A4. This results in an increase in the metabolism of itraconazole and a decreased effect of the drug. In turn this may lead to therapeutic failure. "Pharmacotherapy: A Pathophysiologic Approach" explains that an higher dose of the drug may be necessary if the patient is receiving any of these medications.
Prevention and Monitoring
Your physician can recognize if there is a drug interaction between itraconazole and a new medication and adjust your dose accordingly. Be aware of the side effects associated with itraconazole, such as nausea, headache, fatigue and an increase in blood pressure -- and those of all your medications. If you develop side effects that become persistent and bothersome, inform your physician. Patients with pre-existing liver dysfunction and all patients being treated longer than one month with itraconazole should undergo a liver function test to measure liver enzymes. Elevated liver enzymes can indicate liver dysfunction and liver damage. An increase in medication levels may increase the risk of developing elevated liver enzymes; keep your appointments to ensure that you are being monitored properly.
References
- "Drug Information Handbook"; Charles F. Lacy et al.; 2009
- "Pharmacotherapy: A Pathophysiologic Approach"; Joseph T. Dipiro et al.; 2008
Member Comments