Terbinafine (described above) is effective given orally for the treatment of onychomycosis. Recommended oral dosage is 250 mg daily for 6 weeks for fingernail infections and 12 weeks for toenail infections. Patients receiving terbinafine for onychomycosis should be monitored closely with periodic laboratory evaluations for possible hepatic dysfunction. Rare cases of liver failure have occurred with the use of oral terbinafine; therefore, its use is not recommended in patients with chronic or active liver disease.
Griseofulvin, effective orally against dermatophyte infections caused by Epidermophyton, Microsporum, and Trichophyton, is ineffective against Candida and P orbiculare. Griseofulvin’s mechanism of antifungal action is not fully understood, but it is active only against growing cells.
Following oral administration of 1 g of microsize griseofulvin, drug can be detected in the stratum corneum 4–8 hours later. Reducing the particle size of the medication greatly increases drug absorption. Formulations that contain the smallest particle size are labeled “ultramicrosize.” Ultramicrosize griseofulvin achieves bioequivalent plasma levels with half the dose of microsize drug. In addition, solubilizing griseofulvin in polyethylene glycol enhances absorption even further. Microsized griseofulvin is available as 250 mg and 500 mg tablets, and ultramicrosized drug as 125 mg, 165 mg, 250 mg, and 330 mg tablets and as 250 mg capsules.
The usual adult dosage of the microsize form of the drug is 500 mg daily in single or divided doses with meals; occasionally, 1 g/d is indicated in the treatment of recalcitrant infections. The pediatric dosage is 10 mg/kg of body weight daily in single or divided doses with meals. An oral suspension is available for use in children.
Griseofulvin is most effective in treating tinea infections of the scalp and glabrous (nonhairy) skin. In general, infections of the scalp respond to treatment in 4–6 weeks, and infections of glabrous skin will respond in 3–4 weeks. Dermatophyte infections of the nails respond only to prolonged administration. Fingernails may respond to 6 months of therapy, whereas toenails are recalcitrant to treatment and may require 8–18 months of therapy; relapse almost invariably occurs.
Adverse effects seen with griseofulvin therapy include headaches, nausea, vomiting, diarrhea, photosensitivity, peripheral neuritis, and occasionally mental confusion. Griseofulvin is derived from a Penicillium mold, and cross-sensitivity with penicillin may occur. It is contraindicated in patients with porphyria or hepatic failure or those who have had hypersensitivity reactions to it in the past. Its safety in pregnant patients has not been established. Leukopenia and proteinuria have occasionally been reported. Therefore, in patients undergoing prolonged therapy, routine evaluation of the hepatic, renal, and hematopoietic systems is advisable. Coumarin anticoagulant activity may be altered by griseofulvin, and anticoagulant dosage may require adjustment.
ACYCLOVIR, VALACYCLOVIR, PENCICLOVIR, & FAMCICLOVIR
Acyclovir, valacyclovir, penciclovir, and famciclovir are synthetic guanine analogs with inhibitory activity against members of the herpesvirus family, including herpes simplex types 1 and 2. Their mechanism of action, indications, and oral use in the treatment of cutaneous infections are discussed in Chapter 49.