Antifungal azoles ketoconazole

The risk of myopathy appears to be increased by high levels of HMG-CoA reductase inhibitory activity in plasma. Lovastatin is metabolized by the CYP isoform 3A4. Certain drugs, that share this metabolic pathway can raise the plasma levels of lovastatin and may increase the risk of myopathy. These include cyclosporine, itraconazole, ketoconazole and other antifungal azoles, the macrolide antibiotics erythromycin and clarithromycin, HIV protease inhibitors, the antidepressant nefazodone, or large quantities of grapefruit juice (greater than 1 quart daily)... 

Ketoconazole [kee toe KON a zole], a substituted imidazole, is one of a family of azoles useful in treating systemic mycoses. In addition to its antifungal activity, ketoconazole also inhibits gonadal and adrenal steroid synthesis in humans by blocking C17-20 lyase, Up-hydroxylase, and cholesterol side-chain cleavage thus, it suppresses testosterone and cortisol synthesis. 

CARBAMAZEPINE ANTIFUNGALS - ITRACONAZOLE, KETOCONAZOLE, MICONAZOLE, POSACONAZOLE, VORICONAZOLE 1 plasma concentrations of itraconazole and of its active metabolite, ketoconazole, posaconazole and voriconazole, with risk of therapeutic failure, t carbamazepine plasma concentrations These azoles are highly lipophilic, and clearance is heavily dependent upon metabolism by CYP isoenzymes. Carbamazepine is a powerful inducer of CYP3A4 and other CYP isoenzymes (CYP2C18/19, CYP1A2), and the result is very low or undetectable plasma levels. Inhibition of P-gp t bioavailability of carbamazepine Avoid co-administration of posaconazole or voriconazole with carbamazepine. Watch for inadequate therapeutic effects, and t dose of itraconazole. Higher doses of itraconazole may not overcome this interaction. Consider use of the less lipophilic fluconazole, which is less dependent on CYP metabolism. Necessary to monitor carbamazepine levels... 

TOREMIFENE ANTIFUNGALS-AZOLES t plasma concentrations of toremifene Due to inhibition of metabolism of toremifene by the CYP3A4 isoenzymes by ketoconazole Clinical relevance is uncertain. Necessary to monitor for clinical toxicities... 

ANTACIDS ANTIFUNGALS-AZOLES 1 plasma concentration of itraconazole and ketoconazole, with risk of therapeutic failure Itraconazole absorption in capsule form requires an acidic gastric environment, and thus absorption would be 1 Separate administration of agents that 1 gastric acidity by 1-2 hours. However, absorption of itraconazole liquid solution does not require an acidic environment it could be used instead and does not need to be given with food. Fluconazole absorption is not pH-dependent, so this is a suitable alternative... 

Other inhibitors of HZ formation are thought to act similarly to the quinohne family. Binding of the antifungal azole-based drugs (clotrimazole, ketoconazole, and miconazole) to heme is thought to damage parasite cell membranes and cause... 

For details of interactions with individual antifungal azoles, see individual monographs (fluconazole, itraconazole, ketoconazole, miconazole, and voriconazole). 

Azole antifungal agents (ketoconazole. Itraconazole, ketoconazole, and voriconazole concentrations may be... 

Azole antifungals (eg, ketoconazole) are inhibitors of cytochrome P450, especially CYP3A4, the most abundant isozyme form in human liver, which metabolizes a wide range of drugs. All of the other drugs listed are known to be inducers of cytochrome P450 with chronic use. 

Ketoconazole Antifungal azole prototype active systemically inhibits the synthesis of er-... 

The azole antifungal drug ketoconazole was found to inhibit Fe(III)-ascorbate dependent lipid peroxidation using either rat hver microsomes or ox-brain phospholipid hposomes as the substrates (Wiseman et al. 1991). It also inhibited microsomal peroxidation induced by the Fe(III)-ADP/NADPH system. The related azoles, miconazole and clotrimazole, were much weaker inhibitors than ketoconazole. Ketoconazole was approximately equipotent... 

Specific concomitant medications or consumptions (check specific statin package insert for warnings) fibrates (especially gemfibrozil, but other fibrates too), nicotinic acid (rarely), cyclosporine, azole antifungals such as itraconazole and ketoconazole, macrolide antibiotics such as erythromycin and clarithromycin, protease inhibitors used to treat Acquired Immune Deficiency Syndrome, nefazodone (antidepressant), verapamil, amiodarone, large quantities of grapefruit juice (usually more than 1 quart per day), and alcohol abuse (independently predisposes to myopathy)... 

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... 

Azole antifungals (fluconazole, itraconazole, ketoconazole, miconazole)... 

Drugs that may be affected by proton pump inhibitors include azole antifungal agents (eg, itraconazole, ketoconazole), benzodiazepines, cilostazol, clarithromycin, digoxin, phenytoin, salicylates, sulfonylureas, and warfarin. Drugs that may affect proton pump inhibitors include sucralfate and clarithromycin. 

Drugs that may affect cyclosporine include allopurinol, amiodarone, androgens (eg, danazol, methyltestosterone), anticonvulsants (eg, carbamazepine, phenobarbital, phenytoin), azole antifungals (eg, fluconazole, ketoconazole), beta-blockers, bosentan, bromocriptine, calcium channel blockers, colchicine, oral contraceptives, corticosteroids, fluoroquinolones (eg, ciprofloxacin), foscarnet, HMG-CoA reductase inhibitors, imipenem-cilastatin, macrolide antibiotics, methotrexate, metoclopramide, nafcillin, nefazodone, orlistat, potassium-sparing diuretics, probucol, rifamycins (rifampin, rifabutin), serotonin reuptake inhibitors (SSRIs eg, fluoxetine, sertraline),... 

The azole derivatives for systemic administration include the imidazoles ketoconazole and miconazole and the triazoles fluconazole, itraconazole, posaconazole and voriconazole. They are broad spectrum antifungals and have activity against several dermatophytes, Candida, Cryptococcus and other fungi that cause deep-seated infections. 

Cyclosporin is metabolised by the hepatic cytochrome P-450 enzyme system, and enzyme induction by phenobarbital, phenytoin, carbamazepine, or rifampicin will drastically increase the clearance of cyclosporin. Concurrent administration of these drugs has caused rejection of transplanted organs. Conversely, the use of enzyme inhibitors, such as erythromycin or the azole antifungal agents, e.g. ketoconazole, will increase the blood concentrations of cyclosporin leading to an increased risk of toxic side effects. 

Ketoconazole, 1% shampoo, apply every 3-4 days Nizoral A-D Synthetic azole antifungal agent with activity versus Pityrosporum ovale, a fungus that may cause seborrhea and dandruff. Massage over entire scalp for 3 minutes. Rinse thoroughly and repeat application. 

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