(for veterinary information only)
BRAND NAMES: ITRAFUNGOL, ONMEL, SPORONOX
The development of oral medications to be used in the treatment of invasive fungal infections has represented an immense medical breakthrough. With oral treatment available, human patients no longer require hospitalization several days per week for intravenous treatment of their disease; a more normal and productive lifestyle is now possible. Further, the toxicity profiles of the newer oral drugs represents vast improvement over those of the injectables.
Ketoconazole was the first such oral antifungal drug but it had room for improvement regarding its side effect potential. There were problems with nausea, liver toxicity, and feminization of male patients. Itraconazole was developed in answer to these concerns. Its potential for side effects is far lower, although its expense, unfortunately, has been problematic.
HOW THIS MEDICATION WORKS
Itraconazole works by inhibiting the fungal enzymes that produce “ergosterol,” an important component of the fungal cell wall. Without adequate ergosterol, the fungal cell becomes weak, leaky and ultimately dies.
Fungal infections for which itraconazole can be used include:
The chief reason for choosing itraconazole over other antifungal agents is to avoid side effects over the long treatment courses that are typically needed for the treatment of fungal disease. While itraconazole users do not commonly experience side effects, it is important to be aware of what to watch for; the main issue of concern being liver toxicity.
Side effects of note are appetite loss, vomiting, and/or diarrhea. If they occur, medication should be discontinued and liver enzymes should be checked. Appetite loss in particularly is felt to be an important sign of toxicity and generally does not occur until itraconazole has been in use for over one month.
If an adverse side effect occurs, it is expected to resolve with discontinuation of the medication. After recovery, itraconazole can usually be restarted at a lower dose.
IF YOU THINK YOUR PET MAY BE HAVING AN ADVERSE DRUG REACTION,
Itraconazole should not be given to patients with known liver disease if possible. In one research publication, an SGPT/ALT enzyme level of 250 IU/L was felt to be the highest tolerable level compatible with itraconazole use. Approximately 5-10% of dogs receiving standard doses of itraconazole will develop liver disease severe enough to warrant discontinuing the medication. Expect periodic evaluation of liver enzymes (blood testing) to be recommended throughout the duration of itraconazole therapy.
Another side effect worth mentioning is "necroulcerative dermatitis" which occurs in 5-10% of dogs receiving itraconazole on the higher end of the recommended dosage spectrum. This reaction leads to a blood vessel inflammation which in turn leads to ulcers in the skin. Discontinuing itraconazole leads to resolution of this condition should it arise.
INTERACTIONS WITH OTHER DRUGS
The use of itraconazole in combination with the antacids famotidine (Pepcid®), ranitidine (Rantac®), or cimetidine (Tagamet®), omeprazole (Prilosec®), or with the antibiotic rifampin will lead itraconazole to be less effective. If itraconazole must be used with these medications, it is recommended that at least 2 hours pass between the antacid administration and the administration of itraconazole.
Serious heart abnormalities have resulted when itraconazole was used with the antihistamine terfenadine (Seldane) or with the intestinal motility modifier cisapride (Propulsid®). These medications should not be used with itraconazole.
The following heart medicines will be stronger in the presence of itraconazole and dosage may need to be reduced: amlodipine, digoxin, warfarin, or quinidine. A similar problem occurs with cyclosporine, an immune suppressant used in immune mediated disease, allergy, or after an organ transplant. In fact, there is a long list of medications that are made stronger (and potentially more toxic) when combined with itraconazole. Other drugs include: glipizide (a treatment for diabetic cats), the benzodiazepine tranquilizers (such as diazepam and alprazolam), buspirone and clomipramine ( anti-anxiety medications), fentanyl (a narcotic pain reliever), and cyclophosphamide (an agent of chemotherapy). Because of this long list of interactions, it is important not to combine any medication with itraconazole without checking with your veterinarian first.
The macrolide antibiotics, such as erythromycin, actually boost itraconazole levels and could increase the potential for itraconazole toxicity.
CONCERNS AND CAUTIONS
ITRACONAZOLE CAPSULES WORK BEST WHEN GIVEN WITH FOOD.
The 100 mg itraconazole capsule is an inconvenient size for most animal patients. For this reason, it is common to have a “compounding pharmacy” make up a prescription as either capsules or flavored liquid in a size that fits the individual patient in question. There is one important caveat regarding going through a compounding pharmacy for itraconazole and this regards the materials the pharmacy uses to make up formulations. Compounded itraconazole can be made up from the prescription product (either brand name or generic) or it can be made up from itraconazole available in bulk (which is usually much less costly). The bulk substance is not recommended as it is not as stable as the prescription capsules nor is it absorbed into the patient's body as effectively. The capsules (but not the bulk powder) utilize special itraconazole-coated beads which are responsible for proper uptake of the drug. The compounding pharmacy must keep the beads intact in making their formulations.
There is an oral liquid version of Sporonox® available in the U.S. however it is of a relatively low concentration which means the dosing volumes needed even for a small cat would be somewhat inconveniently large. More recently (November 2016), a new oral liquid product called "Itrafungol" has been approved for feline use in the U.S. Its introduction will hopefully alleviate some of the issues that have been problematic with compounding.
Itraconazole is able to penetrate most body tissues and thus fight fungal infections in most organs. It cannot penetrate, however, the blood/brain barrier and thus is useless in central nervous system fungal infections. In such a situation, another closely related medication (fluconazole) would be helpful.
FUNGAL INFECTIONS AS A GENERAL RULE ARE VERY RESISTANT
Itraconazole is dangerous if given in pregnancy. If a pet is pregnant, itraconazole should be avoided unless the fungal infection in question is potentially life-threatening.
Itraconazole should also be avoided in lactation as it will be delivered via milk to any nursing young.
It is important to give itraconazole with food for best absorption into the body.
Itraconazole can reduce the strength of the heart's contractions to an extent that would not be significant in the absence of heart disease. This could, however, be a problem in a patient with reduced heart function.
Page last updated: 1/9/2019