Clotrimazole

Clotrimazole is a topical imidazole antifungal used for vulvovaginal and cutaneous candidiasis, dermatophytosis, pityriasis versicolor and oropharyngeal candidiasis (lozenge). Systemic absorption is minimal, and the usual problems are local irritation and weakened latex.

Class. Imidazole antifungal.

Mechanism. Inhibits CYP51 and ergosterol synthesis; at high concentrations directly damages the membrane.

Pharmacokinetics. Minimal absorption from skin and vagina. The lozenge dissolves slowly in the mouth, giving local salivary levels; the swallowed portion is absorbed and metabolised in the liver.

Vulvovaginal candidiasis. - Pessary 500 mg: single dose at night. - Pessary 200 mg: nightly for 3 nights. Pessary 100 mg: nightly for 6 nights. - Cream 1%: applied to the vulva and surrounding skin 2 to 3 times daily.

Skin infection (tinea, cutaneous candidiasis, pityriasis versicolor). Cream 1% twice daily for 2 to 4 weeks; continue for 1 to 2 weeks after clearance.

Oropharyngeal candidiasis (lozenge 10 mg). One lozenge dissolved slowly in the mouth 5 times daily for 14 days (age 3 years and over).

Loading dose, maintenance dose and titration. Not applicable. Maximum: lozenge 5 a day.

Main alternatives. Oral fluconazole (not in pregnancy for repeated doses), miconazole oral gel, nystatin.

Contraindications. Hypersensitivity to imidazoles.

Serious adverse effects. Allergic contact dermatitis and, rarely, anaphylaxis. Lozenge: raised liver enzymes and hepatotoxicity.

Common adverse effects. Local burning, itching, erythema and vaginal irritation; lozenge: nausea, vomiting and taste change.

Interactions. Topical: negligible. Lozenge: CYP3A4 inhibition may raise tacrolimus and sirolimus levels. Oil-based creams and pessaries weaken latex condoms and diaphragms.

Common prescribing errors. Stopping once symptoms ease, using lozenges in children under 3 years, and not warning about latex.

Special groups. - Pregnancy: vaginal pessaries are acceptable, using a 6 to 7 night course; insert by hand if an applicator is a concern. - Breastfeeding: compatible. - Children: topical cream from infancy; lozenges from 3 years. - Older adults: usual doses. - Kidney impairment: no adjustment. - Liver impairment: caution with lozenges.

Formulations. Cream 1%; vaginal pessaries 100 mg, 200 mg and 500 mg; lozenge 10 mg.

Administration. Insert pessaries high in the vagina at night; apply cream thinly. Lozenges must dissolve slowly and not be chewed or swallowed.

Baseline. Confirm the diagnosis; liver tests if the lozenge is used with liver disease.

Monitoring. Symptom resolution at 1 to 2 weeks; liver tests with prolonged lozenge use.

Stopping thresholds. Stop for allergic reaction or marked irritation.

Referral and escalation. Review for treatment failure, recurrent infection (4 or more episodes in a year) or diagnosis uncertainty.