Side Effects and Drug Interactions

Common side effects of oral azole drugs (ketoconazole, fluconazole and itraconazole) are nausea, vomiting and belly pain. Others include headaches, dizziness, drowsiness, fever, diarrhea, rash and changes in the sense of taste. The most serious problem is liver toxicity, but this is rare and usually reverses after treatment when the drug is stopped. Nevertheless, liver function should be monitored closely, particularly with ketoconazole.

Intravenous amphotericin B may pose serious side effects, including kidney toxicity. The most common side effects are fever, shaking, chills, altered blood pressure, nausea, vomiting and headache. These reactions are usually severe after the first few doses and lessen with subsequent treatment. Liposomal versions of the drug (like Abelcet) are generally less toxic and as effective than its earlier formula. Intravenous amphotericin B should only be used in cases where there is a direct threat to life or all other treatments have failed.

Oral azole drugs have similar drug interactions:

• Anyone taking the antihistamines terfenadine (Seldane) or astemizole (Hismanal) or the anti-reflux drug cisapride (Propulsid) SHOULD NOT take ketoconazole or itraconazole and should probably avoid fluconazole. These drugs can interact to cause serious heart problems.
• Azole drugs should not be taken with the sedatives triazolam (Halcion) or midazolam (Versed) as this could lead to dangerous levels of sedation.
• When taken with warfarin (Coumadin), azoles can make the blood clot more slowly, so clotting time should be monitored.
• Taking azoles with oral hypoglycemic drugs may result in severe low blood sugar (hypoglycemia), so blood glucose levels should be checked carefully.

Amphotericin B has several drug interactions:

• Risk of kidney damage increases when amphotericin B is used with pentamidine (Nebupent), cidofovir (Vistide), adefovir (Preveon), cyclosporine (Neoral) or foscarnet (Foscavir).
• Taking amphotericin B with AZT (Retrovir), flucytosine (Ancobon)or ganciclovir (Cytovene)may result in increased bone marrow damage.

Other drug interactions may occur. More details can be found in Project Inform's Drug Interactions Chart and from your pharmacist.