Ketoconazole Disease Interactions

Serious hepatotoxicity including cases with a fatal outcome or requiring liver transplant have been reported. Some patients had no obvious risk factors for liver disease. Liver function tests should be performed prior to initiation of therapy and regularly during treatment in patients receiving prolonged therapy with ketoconazole, particularly those with a current or past history of liver disease. Therapy should be withdrawn if persistent elevations or worsening of liver enzyme levels occur, or if the abnormalities are accompanied by symptoms of possible liver injury. Since ketoconazole is primarily metabolized by the liver, empirically reducing the dosage may also be appropriate in patients with existing liver disease. The use of oral ketoconazole tablets is contraindicated in patients with acute or chronic liver disease.

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Some azole antifungals have been associated with prolongation of the QT interval on the ECG. Rare cases of QT prolongation and torsade de pointes have been reported during postmarketing experience; such reports usually involved seriously ill patients with multiple confounding risk factors, such as structural heart disease, electrolyte abnormalities, and concomitant medications. These drugs should be administered with caution to patients with potentially proarrhythmic conditions, such as congenital/acquired QT prolongation, cardiomyopathy (especially when heart failure is present), sinus bradycardia, and existing symptomatic arrhythmias. Concomitant use with other medications that have potential to increase the risk of cardiotoxicity should be avoided.

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Nizoral (brand of ketoconazole) tablets require acidity for proper dissolution and absorption. Therefore, the drug may not be effective in patients with achlorhydria. Taking the medication with an acidic beverage such as orange or cranberry juice may help, but an alternative antifungal agent should be considered.

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Ketoconazole tablets decrease adrenal corticosteroid secretion at doses of 400 mg and higher. Adrenal function should be monitored in patients with adrenal insufficiency or with borderline adrenal function and in patients with prolonged periods of stress due to major surgery, intensive care, etc.

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