Miconazole

Indications

Miconazole (Monistat) is a broad-spectrum imidazole antifungal agent used in the topical treatment of cutaneous dermatophyte infections and mucous membrane Candida infections, such as vaginitis. Minimal absorption occurs from skin or mucous membrane surfaces. Local irritation to skin and mucous membranes can occur with topical use; headaches, urticaria, and abdominal cramping have been reported with treatment for vaginitis.

Therapeutic Function

Antifungal

Synthesis

Miconazole, 1-[2,4-dichloro-β-[(2,4-dichlorobenzyl)oxy]phenethyl]-imidazole (35.2.7), like ketoconazol, is synthesized from 2,4-dichlorophenacylbromide, which is reacted with imidazole to make 1-(2,4-dichlorobenzoylmethyl)-imidazole[2,4-dichloro-ω-(1-imidazolyl)-acetophenone] (35.2.5). Reducing the carbonyl group in this molecule with sodium borohydride gives 1-(2,4-dichlorophenyl)-3-(1-imidazolyl)-ethanol (35.2.6), and the hydroxyl group is alkylated by 2,4-dichlorobenzylbromide using a powerful base such as sodium hydride to make miconazole (35.2.7).

Veterinary Drugs and Treatments

Miconazole is a broad spectrum imidazole antifungal agent with some antibacterial activity. Miconazole will penetrate the intact corneal epithelium. Topical miconazole therapy has been a favorite first choice agent for treatment of fungal keratitis in the horse by veterinary ophthalmologists for several years. Miconazole may be delivered by subconjunctival route, but with some local irritation, and topical use is the most commonly employed treatment method.

Drug interactions

Potentially hazardous interactions with other drugs Anticoagulants: effect of coumarins enhanced. Antidepressants: avoid concomitant use with reboxetine. Antidiabetics: enhances hypoglycaemic effect of gliclazide and glipizide; concentration of sulphonylureas increased. Antiepileptics: effect of fosphenytoin and phenytoin enhanced; possibly increased carbamazepine concentration. Antihistamines: avoid with mizolastine, risk of ventricular arrhythmias. Antimalarials: avoid with piperaquine with artenimol and artemether with lumefantrine. Antipsychotics: increased risk of ventricular arrhythmias with pimozide - avoid; possibly increased concentration of quetiapine - avoid. Antivirals: concentration of saquinavir possibly increased. Ciclosporin: possibly increased ciclosporin concentration. Ergot alkaloids: increased risk of ergotism with ergotamine and methysergide - avoid. Sirolimus: concentration increased by miconazole. Statins: possibly increased risk of myopathy with atorvastatin and simvastatin - avoid with simvastatin. Tacrolimus: possibly increased tacrolimus concentration

Metabolism

Miconazole is metabolised in the liver to inactive metabolites; 10-20% of an oral dose is excreted in the urine as metabolites. About 50% of an oral dose may be excreted mainly unchanged in the faeces