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In vitro data suggest that trimetrexate is extensively metabolized by CYP3A4. In vitro animal models have demonstrated that ketoconazole potently inhibits the metabolism of trimetrexate.

Findings of in vitro metabolic studies indicate that verapamil is metabolized by enzymes including CYP3A4. Ketoconazole may increase verapamil serum concentrations. Studies have shown that absorption of ketoconazole is impaired when gastric acid production is decreased. Close monitoring for both plasma concentrations of carbamazepine and reduced ketoconazole efficacy is recommended. La roche sophie administration of ketoconazole with phenytoin may alter the metabolism of one or both of the dermacombin. Concomitant administration of rifampin and rifabutin with ketoconazole tablets reduces the blood concentrations of the latter.

INH (Isoniazid) was also reported to affect ketoconazole concentrations adversely. Concomitant administration of ritonavir with ketoconazole tablets increases was shown to increase the cabbage soup diet soup bioavailability of ketoconazole. Rare cases cabbage soup diet soup a disulfiram-like reaction to alcohol have been cabbage soup diet soup. These experiences have been characterized by flushing, rash, peripheral edema, nausea, and headache.

Symptoms resolved within a few hours. However, no related changes were noted in the QTc on ECG taken at 2, 6, and 24 hours after the coadministration. Also, there were no clinically significant differences in adverse events when loratadine was administered with or without ketoconazole. Serious hepatotoxicity, including cases with a fatal outcome or requiring liver transplantation, has occurred with the use of carprofen ketoconazole.

Serious hepatotoxicity was reported both by patients receiving high cabbage soup diet soup for short treatment durations and by patients receiving low doses for long durations. Cases of hepatitis have been reported in children. At baseline, obtain laboratory tests (such as SGGT, alkaline phosphatase, ALT, AST, total bilirubin (TBL), Prothrombin Time (PT), International Normalization Ratio (INR), and testing for viral hepatitides).

Patients should be advised cabbage soup diet soup alcohol consumption while on treatment. Prompt recognition of liver injury is essential. During the course of treatment, serum ALT should be monitored weekly for the duration of treatment.

If ALT values increase to a level above the upper limit of normal or 30 percent above baseline, or if the patient develops symptoms, ketoconazole treatment should be interrupted and cabbage soup diet soup full set of liver tests should be obtained.

Liver tests should be repeated to ensure normalization of values. Hepatotoxicity has been reported with restarting oral ketoconazole (rechallenge). If it is decided to restart oral ketoconazole, monitor the patient frequently to detect any recurring liver injury from the drug. Ketoconazole can prolong the QT interval. Co-administration of the following drugs with ketoconazole is contraindicated: dofetilide, quinidine, pimozide, and cisapride.

Ketoconazole can cause elevated plasma concentrations of these drugs which may prolong the QT interval, sometimes resulting in life-threatening ventricular dysrhythmias such as torsades de pointes.

This effect is not shared with other azoles.



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