Anti-Fungals For The Treatment Of Candida
The most important drug interactions seen with azole antifungals typically arise from inhibition of CYP 3A4, which plays a critical role in the metabolism of a broad array of drug therapies used for cardiovascular disease, ENDOCRINE DISORDERS including hyperglycemia, anaesthesia, psychiatric disorders, epilepsy, cancer chemotherapy, and treatment of infectious diseases.
A general description of the more common and important drug interactions is summarized below.
Note ALL the `azoles’ work principally by inhibition of cytochrome P450
They are all potentially cause hepatotoxicity (Liver damage)
All are also ANTIANDROGENS & ANTICORTISOL (ketoconazole being the strongest)
Ketoconazole is an ANTI-ANDROGEN & ANTI-CORTISOL
Tablets have been demonstrated to lower serum testosterone. Once therapy with NIZORAL Tablets has been discontinued, serum testosterone levels return to baseline values. Testosterone levels are impaired with doses of 800 mg per day and abolished by 1600 mg per day. NIZORAL Tablets also decrease ACTH induced corticosteroid serum levels at similar high doses. The recommended dose of 200 mg 400 mg daily should be followed closely.
Medications to control excessive production of cortisol include ketoconazole (Nizoral), mitotane (Lysodren) and metyrapone (Metopirone).
Role of ketoconazole treatment in urinary-free cortisol-to-cortisone and tetrahydrocortisol-to-tetrahydrocortisone ratios in nonectopic Cushing’s syndrome.
Note: also contains Fluoride
Reversible acute adrenal insufficiency caused by fluconazole in a critically ill patient
Ketoconazole may inhibit cortisol synthesis, particularly in patients receiving relatively high daily dosages or divided daily dosing of the drug. The adrenocortical response to corticotropin (ACTH) may be at least transiently diminished and a reduction in urinary free and serum cortisol concentrations may occur during therapy with the drug; however, adrenocortical insufficiency has been reported only rarely.
In clinical trials in Europe in patients receiving high-dose (ie, 1.2 g daily) ketoconazole therapy for metastatic prostatic carcinoma, death occurred within 2 weeks after initiating therapy with the drug in 3% of patients. Although these deaths could not be attributed definitely to the drug, in part because of the serious nature of the underlying disease, the possibility exists that ketoconazole-induced adrenocortical insufficiency may have been a contributing factor in some patients. When adrenocortical hypofunction does occur in patients receiving ketoconazole, the condition generally is reversible following discontinuance of the drug but rarely may be persistent.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 521] **PEER REVIEWED**.