Azoles (specifically imidazole)
Fungi: Blastomyces dermatitidis, Candida spp, Coccidioides immitis, Cryptococcus neoformans, Dermatophytes (Trichophyton, Microsporum, Epidermophyton), Histoplasma capsulatum, Malassezia furfur, Naegleria fowleri, Nocardia spp, Paracoccidioides brasiliensis, Sporotrichum schenckii
Bind to the heme moiety of the fungal cytochrome P-450 dependent enzyme lanosterol 14-a-demethlyase. Inhibits 14-a-demethlyase, blocks formation of ergosterol and leads to the buildup of toxic methylated 14-a-sterols. Both effects serve to inhibit cell growth.
Other azoles have shown in murine models to exhibit AUC:MIC ratio as predictive of effect for Candida spp. This may vary by fungal species however.
Absorption: Topical: negligible through intact skin
Time to peak, serum:
Oral, topical: Salivary levels occur within 3 hours after 30 minutes of dissolution time
Vaginal cream: High vaginal levels: 8-24 hours.
Excretion: Feces (as metabolites)
Gastrointestinal: nausea, vomiting
Genitourinary: vaginal/vulvar bleeding
Burning or itching of penis of sexual partner; polyuria; vulvar itching, soreness, edema, discharge.
Cream, topical: 1% (15g, 30g, 45g, 90g)
Cream, vaginal: 1% (45g, 90g), 2% (25g)
Lotion: 1% (30 mL)
Solution, topical: 1% (10 mL, 30 mL)
Tablet, vaginal: 100mg, 200mg, 500mg
Adults and children > 3 years:
Troche: 10 mg troche dissolved 5 times/day for 14 days.
Adults and children > 12 years:
Vaginal cream 1%: Insert 1 applicatorful daily (preferably at bedtime) for 7 – 14 days.
2%: Insert 1 applicatorful daily (preferably at bedtime) for 3 consecutive days.
Vaginal tablets: Insert 100 mg/day for 7 days or 500 mg single dose.
Topical: Apply to affected area twice daily (morning and evening).
Renal failure: No dosing adjustment necessary
Hepatic failure: No dosing adjustment necessary
Precautions: Clotrimazole should not be used for treatment of systemic fungal infection
Clotrimazole is an inhibitor of the cytochrome P450 3A4, 2A6, 2C8/9, and 2E1 isoenzymes. Caution should be exercised and monitoring is suggested when concomitantly administering clotrimazole with drugs that have narrow therapeutic windows and are substrates of aforementioned CYP substrates.
Topical: Category B: No evidence of risk in humans but studies inadequate.
Troches: Category C: Risk unknown. Human studies inadequate.
Consider periodic liver function tests during prolonged oral therapy with clotrimazole lozenges.
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