<s>[INST] context: Ketoconazole (KTZ): It is the first orally effective broad-spectrum antifungal drug, useful in both dermatophytosis and deep myc osis. The oral absorption of KTZ is facilitated by gastric acidity because it is more soluble at lower pH. Hepatic metabolism is extensive; metabolites are excreted in urine and faeces. Elimination of KTZ is dose dependent: tlh varies from llh to 6 hours. Penetration in CSF is poor: not effective in fungal men ingitis. However, therapeutic concentrations are attained in the skin and vaginal fluid. Adverse effects Ketoconazole is much less toxic than AMB, but more side effects occur than with itraconazole or fluconazole, that have largely replaced it for systemic use. The most common side effects are nausea and vomiting; can be reduced by giving the drug with meals. Others are-loss of appetite, headache, paresthesia, rashes and hair loss. Ketoconazole decreases androgen production from testes, and it displaces testosterone from protein binding sites. Gynaecomastia, loss of hair and libido, and oligozoospermia may be themanifestations. Menstrual irregularities occur in some women due to suppression of estradiol synthesis. A dose-dependent decrease in serum hydro coisone due to synthesis inhibition has also been noticed, but without any clinical manifestations in normal individuals. Mild and asymptomatic elevation of serum transaminases occurs in -5% patients, but serious hepatotoxicity is infrequent. It is contraindicated in pregnant and nursing women. ESSENTIALS OF MEDICAL PHARMACOLOGY K.D.TRIPATHI SIXTH EDITION PAGE NO:762,763 [/INST] question: Most serious adverse effect of ketoconazole is: | options: A: Adrenal insufficiency B: Pellagra like skin lesion C: Liver injury D: Prostate cancer | answer: A </s>