The recommended dosage for topical preparations of nystatin in treating paronychial and intertriginous candidiasis is application two or three times a day. Oral candidiasis (thrush) is treated by holding 5 mL (infants, 2 mL) of nystatin oral suspension in the mouth for several minutes four times daily before swallowing.
An alternative therapy for thrush is to retain a vaginal tablet in the mouth until dissolved four times daily. Recurrent or recalcitrant perianal, vaginal, vulvar, and diaper area candidiasis may respond to oral nystatin, 0.5–1 million units in adults (100,000 units in children) four times daily, in addition to local therapy. Vulvovaginal candidiasis may be treated by insertion of 1 vaginal tablet twice daily for 14 days, then nightly for an additional 14–21 days.
Amphotericin B (Fungizone) is available for topical use in cream and lotion form. The recommended dosage in the treatment of paronychial and intertriginous candidiasis is application two to four times daily to the affected area.
Adverse effects associated with oral administration of nystatin include mild nausea, diarrhea, and occasional vomiting. Topical application is nonirritating, and allergic contact hypersensitivity is exceedingly uncommon. Topical amphotericin B is well tolerated and only occasionally locally irritating. The drug may cause a temporary yellow staining of the skin, especially when the cream vehicle is used.
Azole derivatives currently available for oral treatment of candida and dermatophyte infections include fluconazole (Diflucan) and itraconazole (Sporanox). As discussed in Chapter 48, imidazole derivatives act by affecting the permeability of the cell membrane of sensitive cells through alterations of the biosynthesis of lipids, especially sterols, in the fungal cell.
Fluconazole and itraconazole are effective in the therapy of cutaneous infections caused by Epidermophyton, Microsporum, and Trichophyton species as well as Candida. Tinea versicolor is responsive to short courses of oral azoles.
Fluconazole is well absorbed following oral administration, with a plasma half-life of 30 hours. In view of this long half-life, daily doses of 100 mg are sufficient to treat mucocutaneous candidiasis; alternate-day doses are sufficient for dermatophyte infections. The plasma half-life of itraconazole is similar to that of fluconazole, and detectable therapeutic concentrations remain in the stratum corneum for up to 28 days following termination of therapy. Itraconazole is effective for the treatment of onychomycosis in a dosage of 200 mg daily taken with food to ensure maximum absorption for 3 consecutive months. Recent reports of heart failure in patients receiving itraconazole for onychomycosis have resulted in recommendations that it not be given for treatment of onychomycosis in patients with ventricular dysfunction. Additionally, routine evaluation of hepatic function is recommended for patients receiving itraconazole for onychomycosis.
Administration of oral azoles with midazolam or triazolam has resulted in elevated plasma concentrations and may potentiate and prolong hypnotic and sedative effects of these agents. Administration with HMG-CoA reductase inhibitors has been shown to cause a significant risk of rhabdomyolysis. Therefore, administration of the oral azoles with midazolam, triazolam, or HMG-CoA inhibitors is contraindicated.