Miconazole Phenytoin

Miconazole Phenytoin Zonisamide Risk of toxicity of the object drugs Inhibition of metabolism of the object drugs... 

Drugs that may affect repaglinide include CYP 450 inhibitors (eg, clarithromycin, erythromycin, ketoconazole, miconazole), CYP 450 inducers (eg, barbiturates, carbamazepine, rifampin), beta blockers, calcium channel blockers, chloramphenicol, corticosteroids, coumarins, estrogens, gemfibrozil, isoniazid, itraconazole, levonorgestrel and ethinyl estradiol, MAOIs, nicotinic acid, NSAIDs, oral contraceptives, phenothiazines, phenytoin, probenecid, salicylates, simvastatin, sulfonamides, sympathomimetics, thiazides and other diuretics, and thyroid products. 

Drugs that may interact with miconazole include amphotericin B, astemizole, cisapride, oral anticoagulants, phenytoin, and terfenadine. 

Thiazides and other diuretics Corticosteroids Phenothiazines Thyroid products Estrogens Oral contraceptives Phenytoin Nicotinic acid Sympathomimetics Calcium channel blockers Isoniazid Miconazole... 

A4 Acetaminophen, alfentanil, amiodarone, astemizole, cocaine, cortisol, cyclosporine, dapsone, diazepam, dihydroergotamine, dihydropyridines, diltiazem, ethinyl estradiol, gestodene, indinavir, lidocaine, lovastatin, macrolides, methadone, miconazole, midazolam, mifepristone (RU 486), paclitaxel, progesterone, quinidine, rapamycin, ritonavir, saquinavir, spironolactone, sulfamethoxazole, sufentanil, tacrolimus, tamoxifen, terfenadine, testosterone, tetrahydro-cannabinol, triazolam, troleandomycin, verapamil Barbiturates, carbamazepine, macrolides, glucocorticoids, pioglitazone, phenytoin, rifampin Erythromycin, 613-hydroxy cortisol... 

ITRACONAZOLE, KETOCONAZOLE, MICONAZOLE, POSACONAZOLE, VORICONAZOLE CARBAMAZEPINE, PHENYTOIN L plasma concentrations of itraconazole and of its active metabolite, ketoconazole, posaconazole and voriconazole, with risk of therapeutic failure, t phenytoin levels, but clinical significance uncertain. Carbamazepine plasma concentrations are also t These azoles are highly lipophilic, and clearance is heavily dependent upon metabolism by CYP isoenzymes. Phenytoin and carbamazepine are powerful inducers of CYP3A4 and other CYP isoenzymes (CYP2C18/19, CYP1A2) the result is veiy low or undetectable plasma levels. Phenytoin extensively 1AUC of itraconazole by more than 90%. 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 the use of less lipophilic fluconazole, which is less dependent on CYP metabolism. Necessaiy to monitor phenytoin and carbamazepine levels... 

Rolan PE, Somogyi AA, Drew MJ, Cobain WG, South D, Bochner F. Phenytoin intoxication during treatment with parenteral miconazole. BMJ (Clin Res Ed) 1983 287(6407) 1760. 

Rapid injection of nndilnted miconazole may produce transient tachycardia or arrhythmia. Miconazole and amphotericin B are antagonistic both in vitro and in vivo. The antifnngal activity of the two drngs, when nsed in combination, is less than that of either drng nsed alone. Miconazole enhances the effectiveness of anticoagnlants and increases the sernm level of phenytoin. It has caused rash, pruritis, and phlebitis at the site of infnsion. A transient decrease in hematocrit has been noted. 

A man with epilepsy, well controlled with phenytoin, developed symptoms of phenytoin toxicity within one day of starting intravenous miconazole 500 mg every 8 hours and flucytosine. After one week of eoneurrent treatment his serum phenytoin levels had risen by 50%, from 29 to 43 mierograms/mL. He had some symptoms of very mild phenytoin tox-ieity before the antifungal treatment was started. Another patient develop symptoms of toxicity (nystagmus, ataxia) within 5 days of starting to take oral miconazole 500 mg daily. His serum phenytoin level rose to 40.8 micrograms/mL. After discontinuation of the miconazole the same dose of phenytoin resulted in a level of 14.5 micrograms/mL. ... 

Evidence for increased phenytoin levels with miconazole is limited, even so it would be prudent to monitor serum phenytoin levels, including when the oral gel is used at a dose of 5 to 10 mL four times daily (15 mg/kg per day). ... 

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