Ketoconazole, hepatotoxicity

Kathon CG, 31.134 Kava kava liver damage, 27.518 adverse reactions, 28.579 Ketoconazole, hepatotoxicity, 12.229 Ketorolac, risk of adverse reactions, 17.110 Khat, 30.43... 

Hepatotoxicity Hepatotoxicity, primarily of the hepatocellular type, has been associated with ketoconazole, including rare fatalities. Measure liver function before starting treatment and frequently during treatment. Monitor patients receiving ketoconazole concurrently with other potentially hepatotoxic drugs, particularly those patients requiring prolonged therapy or those with a history of liver disease. 

Metyrapone is a competitive inhibitor of 11 beta hydroxylation in the adrenal cortex, and effectively inhibits cortisol production. It is used in low doses, titrated to achieve plasma cortisol levels as close as possible to normal day-time values. Occasionally it is used in higher doses combined with replacement corticosteroid treatment. Its main side effects relate to overdosage and resulting hypoadrenalism, but it can also cause hirsutism and hypertension, due to accumulation of precursor steroids. Ketoconazole is also sometimes used to suppress adrenal steroid production, but its potential for hepatotoxicity limits its... 

Fluconazole (Diflucan) may be better absorbed and is possibly less hepatotoxic than ketoconazole, but it is considerably more expensive, an important consideration given the required length of therapy for most cutaneous fungal diseases. 

Buffering agents that are compounded with didanosine to counteract its degradation by gastric acid may interfere with the absorption of other drugs that require acidity (e.g., indinavir, delavirdine, ketoconazole, fluoroquinolones, tetracyclines, dapsone). An enteric-coated formulation Videx EC) that dissolves in the basic pH of the small intestine is not susceptible to these interactions. Ganciclovir and valganciclovir can increase blood levels of didanosine. The use of zalcitabine with didanosine is not recommended because that combination carries an additive risk of peripheral neuropathy. The combination of didanosine with stavudine increases the risk of pancreatitis, hepatotoxicity, and peripheral neuropa-... 

Itraconazole is usually well tolerated but can be associated with nausea and epigastric distress. Dizziness and headache also have been reported. High doses may cause hypokalemia, hypertension, and edema. Itraconazole, unlike ketoconazole, is not associated with hormonal suppression. Hepatotoxicity occurs in fewer than 5% of cases and is usually manifested by reversible Uver enzyme elevations. 

Ketoconazole has been used for the treatment of patients with Cushing s syndrome due to several causes. Dosages of 200-1200 mg/d have produced a reduction in hormone levels and clinical improvement in some patients. This drug has some hepatotoxicity and should be started at 200 mg/d and slowly increased by 200 mg/d every 2-3 days up to a total daily dose of 1000 mg. 

Warnings Hepatotoxicity, primarily of the hepatocellular type, has been reported Anaphylaxis may occur after the first dose Deaths within 2 weeks of treatment initiation have been reported in patients with prostate cancer the role of ketoconazole in these deaths has not been ascertained, but it is known that ketoconazole can suppress adrenal corticosteroid secretion... 

Echinacea 1. Hepatotoxic drugs, e.g. anabolic steroids 2. amiodarone 3. Methotrexate 4. Ketoconazole Risk of additive hepatotoxicity Use of echinacea for over 8 weeks can cause hepatotoxicity Be aware and use drugs with a potential to cause hypertonicity cautiously, monitoring clinically and biochemically for any early signs of hepatic dysfunction... 

The effect of ketoconazole appears to be mediated by inhibition of adrenal ll-jl-hydroxylase and 17,20-lyase, and in some nnknown way it prevents the expected rise in ACTH secretion in patients with Cnshing s disease (SEDA-12, 228) (SEDA-17, 323). It may, however, canse such a rapid reduction in semm cortisol concentrations that a crisis is precipitated, and patients adrenal fnnction should be carefully monitored. While ketoconazole (400-800 mg/day) may be a good alternative to other adrenal steroid inhibitors, patients shonld be observed for signs of hepatotoxicity. Acnte adrenal crisis occasionally occnrs (8). 

Some antifungal drugs such as ketoconazole (see Chapter 48) inhibit CYPs and thereby block the synthesis of steroid hormones, including testosterone and cortisol. Because they may induce adrenal insufficiency and are associated with hepatotoxicity, these drugs generally are not used to inhibit androgen synthesis, but sometimes are employed in cases of glucocorticoid excess. 

Previously, several studies have demonstrated that endocrine disorders and hepatotoxicity are a big concern with ketoconazole therapy [18, 19 ]. 

Yan JY, Nie XL, Tao QM, Zhan SY, Zhang YD. Ketoconazole associated hepatotoxicity a systematic review and meta-analysis. Biomed Environ Sci July 2013 26(7) 605-10. 

R. J. Rodriguez and D. Acosta, Comparison of ketoconazole- and fluconazole-induced hepatotoxicity in a primary culture system of rat hepatocytes. Toxicology, 1995, 96, 83-92. 

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