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Ketoconazole, the most commonly used imidazole, is an effectiveoral antimycotic drug with a broad spectrum of activity.
When given orally, ketoconazole is absorbed variably and distrib-uted widely. It undergoes extensive liver metabolism and is ex-creted through bile and stool.
Within the fungal cells, ketoconazole interferes with sterol synthe-sis, damaging the cell membrane and increasing its permeability. This leads to a loss of essential intracellular elements and inhibi-tion of cell growth.
Ketoconazole usually produces fungistatic effects, but can also produce fungicidal effects under certain conditions.
Ketoconazole is used to treat topical and systemic infections caused by susceptible fungi, which include dermatophytes and most other fungi.
Ketoconazole may have significant interactions with other drugs.
· Ketoconazole used with drugs that decrease gastric acidity, such as cimetidine, ranitidine, famotidine, nizatidine, antacids, and anticholinergic drugs, may decrease absorption of ketocona-zole and reduce its antimycotic effects. If the patient must take these drugs, delay administration of ketoconazole by at least
· 2 hours.
· Taking ketoconazole with phenytoin may alter metabolism and increase blood levels of both drugs.
· When taken with theophylline, ketoconazole may decrease the serum theophylline level.
· Using ketoconazole with other liver-toxic drugs may increase the risk of liver disease.
· Combined with cyclosporine therapy, ketoconazole may in-crease cyclosporine and serum creatinine levels.
· Ketoconazole increases the effect of oral anticoagulants and can cause hemorrhage.
· Ketoconazole can inhibit the metabolism (and possibly increase levels) of quinidine, sulfonylureas, carbamazepine, and protease inhibitors.
· Ketoconazole shouldn’t be given with rifampin because serum ketoconazole levels may decrease. (See Adverse reactions to keto-conazole.)
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