Mr. Middleton is an instructor of pharmacology at Kellogg Community College in Battle Creek, Mich.
Terbinafine HCl Tablets
Terbinafine hydrochloride (HCl) is thought to disrupt the integrity of fungal cell membranes by reducing membrane levels of ergosterol. Although the drug is indicated for onychomycosis, this ability to disrupt fungal membranes extends to other species, including causes of tinea capitis, tinea corporis, and tinea pedis. Terbinafine is available generically as 250-mg tablets from Apotex Corp and Teva Pharmaceuticals Ltd.
Due to significant first-pass metabolism, bioavailability of terbinafine is only 40%. Although the drug is extensively metabolized, clearance is quickly reduced to 50% among patients with renal or hepatic impairment. In addition, hepatic inhibition of CYP 2D6 from terbinafine results in elevated levels of dextromethorphan, tricyclic antidepressants, selective serotonin reuptake inhibitors, and ?-blockers. Other drug interactions involve aripiprazole, carvedilol, codeine, desipramine, haloperidol, imipramine, methadone, mirtazapine, and thioridazine.
At its most extreme, hepatic disruption from treatment by this antifungal has resulted in death or the need for liver transplantation. Generally, these situations are linked to a previously undiagnosed, underlying hepatic pathology.
The success of terbinafine derives from its ability to distribute in high concentrations into the hair and nail matrix beds, and to remain in these tissues for several weeks to months after discontinuation of the drug. Adult dosing for onychomycosis is an oral daily dose of 250 mg, running 6 weeks for fingernails and 12 weeks for toenails. The use of unapproved "pulse" dosing with 500 mg daily for the first week of the month has variable success.
To prevent unnecessary interactions or hepatic damage, the nail specimen should be cultured to determine the nature of the suspected infection. As the prolonged treatment necessary for dermatologic infections would suggest, reactions such as Stevens Johnson syndrome or toxic epidermal necrolysis are possible, yet rare.