Ketoconazole gastrointestinal effects

May cause mild CNS and gastrointestinal effects and i bioavailability of drugs that require acidity for oral absorption (e.g., fluoroquinolones, ketoconazole)... 

The peak plasma level of ketoconazole 400 mg daily was similar to that usually seen with ketoconazole 800 mg alone when saquinavir/ritonavir were given.Moreover, in this study, dose escalation to higher doses of ketoconazole was discontinued after the first patient given ketoconazole 600 mg daily stopped treatment early because of adverse gastrointestinal effects. However, saquinavir alone did not affect ketoconazole pharmacokinetics. ... 

Systemic adverse effects associated with vaginal azoles are less frequent than with oral products. Local discomfort such as burning may occur with the first application. Fifteen percent of patients experience gastrointestinal side effects with orally administered antifungal agents.13 Oral ketoconazole is associated with hepatic toxicity at a rate of 1 in 15,000.14... 

Ketoconazole can be used as palliative treatment for Cushing s syndrome in patients undergoing surgery or receiving pituitary radiation and in those for whom more definitive treatment is still contemplated. Because surgical treatment is not always well tolerated by elderly patients, ketoconazole 200 to 1,000 mg/day can be a valuable alternative for the control of hypercortisolism. Common side effects include pruritus, fiver dysfunction, and gastrointestinal symptoms. 

Ketoconazole (Nizoral) has a broad therapeutic potential for a number of superficial and systemic fungal infections. Ketoconazole dissolves in an acidic media therefore, antacids or histamine2-receptor-blocking agents reduce its effectiveness (Figure 45.3). Ketoconazole can cause gastrointestinal disturbances. 

Interactions. Drugs that lower gastric acidity, e.g. antacids, histamine H2 receptor antagonists, impair the absorption of ketoconazole from the gastrointestinal tract. Like all imidazoles, ketoconazole binds strongly to several cytochrome P450 isoenzymes and thus inhibits the metabolism (and increases effects of) oral anticoagulants, phenytoin and cyclosporin, and increases the risk of cardiac arrhythmias with terfenadine. A disulfiram-like reaction occurs with alcohol. Concurrent use of rifampicin, by enzyme induction of CYP 3A, markedly reduces the plasma concentration of ketoconazole. 

Ketoconazole was the first azole available for oral administration. However, it has been supplanted by newer azoles with fewer adverse effects and more reliable absorption from the gastrointestinal tract. Even after years of use, new adverse effects (often related to high doses and/or newer indications) continue to be reported. 

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