Miconazole

Miconazole is a topical imidazole antifungal used for cutaneous and vulvovaginal candidiasis, dermatophytosis and oropharyngeal candidiasis (oral gel). Systemic absorption from the oral gel is enough to inhibit CYP2C9 and cause a clinically important rise in warfarin effect.

Class. Imidazole antifungal.

Mechanism. Inhibits CYP51 and ergosterol synthesis, with additional direct membrane damage.

Pharmacokinetics. Minimal absorption from skin and vagina. About 25 to 30% of the oral gel dose is absorbed. Hepatic metabolism and strong inhibition of CYP2C9 and CYP3A4.

Skin infection. Cream 2% twice daily for 2 to 4 weeks; continue for 2 weeks after resolution.

Vulvovaginal candidiasis. Pessary 1200 mg as a single dose; or 400 mg nightly for 3 nights; or 200 mg nightly for 7 nights.

Oropharyngeal candidiasis. Oral gel 2%, adults 2.5 mL four times daily after food, held in the mouth before swallowing, continued for 7 days after resolution (at least 2 weeks overall).

Children. Oral gel is dosed by age band with a lower dose, avoided under 4 months and used with care in young children because of choking risk.

Loading dose, maintenance dose and titration. Not applicable. Maximum: oral gel 10 mL daily in adults.

Main alternatives. Clotrimazole or nystatin; fluconazole for oral candidiasis when warfarin interaction is a concern.

Contraindications. Hypersensitivity, concurrent warfarin (oral gel) unless INR monitoring is arranged, and co-prescription of cisapride, pimozide, simvastatin, lovastatin or ergot alkaloids with the oral gel.

Serious adverse effects. Bleeding from potentiated warfarin, allergic reactions, and rarely hepatotoxicity.

Common adverse effects. Local irritation, nausea, taste change and diarrhoea (oral gel).

Interactions. Raises warfarin (INR may double), sulphonylureas, phenytoin, ciclosporin, statins and carbamazepine. Weakens latex.

Common prescribing errors. Prescribing oral gel to patients on warfarin without INR checks, stopping after symptom relief, and giving to infants who may choke.

Special groups. - Pregnancy: topical and vaginal use acceptable in the second and third trimesters; avoid in the first trimester where possible. - Breastfeeding: compatible for topical use; oral gel for the mother is acceptable, not applied to the breast before feeding. - Children: from 4 months for oral gel with care. - Older adults: check warfarin and sulphonylurea interactions. - Kidney impairment: no adjustment. - Liver impairment: caution with oral gel.

Formulations. Cream 2%; oral gel 2%; vaginal pessary or ovule 200 mg, 400 mg and 1200 mg.

Administration. Oral gel after food, held in the mouth, with dentures removed and cleaned.

Baseline. Medication review, especially warfarin, statins and sulphonylureas; INR if on warfarin.

Monitoring. INR within 3 to 5 days in patients on warfarin and after stopping; symptom response at 1 to 2 weeks.

Stopping thresholds. Stop for allergic reaction, INR over the target range with bleeding, or choking in young children.

Referral and escalation. Review for treatment failure, recurrent infection or diagnosis uncertainty.