indication

For the treatment of dermatophyte infections of the toenail or fingernail caused by susceptible fungi. Also for the treatment of tinea capitis (scalp ringworm) and tinea corporis (body ringworm) or tinea cruris (jock itch).

pharmacology

Terbinafine is an allylamine antifungal agent and acts by inhibiting squalene epoxidase, thus blocking the biosynthesis of ergosterol, an essential component of fungal cell membranes. In vitro, mammalian squalene monooxygenase (squalene 2,3-epoxidase) is only inhibited at higher (4000 fold) concentrations than is needed for inhibition of the dermatophyte enzyme. Depending on the concentration of the drug and the fungal species test in vitro, Terbinafine may be fungicidal. However, the clinical significance of in vitro data is unknown.

mechanism of action

Terbinafine is hypothesized to act by inhibiting squalene monooxygenase, thus blocking the biosynthesis of ergosterol, an essential component of fungal cell membranes. This inhibition also results in an accumulation of squalene, which is a substrate catalyzed to 2,3-oxydo squalene by squalene monooxygenase. The resultant high concentration of squalene and decreased amount of ergosterol are both thought to contribute to terbinafine's antifungal activity.

biotransformation

Hepatic

absorption

Readily absorbed from gastrointestinal tract.

half life

36 hours

route of elimination

Prior to excretion, terbinafine is extensively metabolized.

drug interactions

Aminophylline: Terbinafine increases the effect and toxicity of theophylline

Amitriptyline: Terbinafine may reduce the metabolism and clearance of Amitryptyline. Consider alternate therapy or monitor for therapeutic/adverse effects of Amytriptyline if Terbinafine is initiated, discontinued or dose changed.

Amoxapine: Terbinafine may reduce the metabolism and clearance of Amoxapine. Consider alternate therapy or monitor for therapeutic/adverse effects of Amoxapine if Terbinafine is initiated, discontinued or dose changed.

Aripiprazole: Terbinafine may reduce the metabolism and clearance of Aripiprazole. Consider alternate therapy or monitor for therapeutic/adverse effects of Aripiprazole if Terbinafine is initiated, discontinued or dose changed.

Atomoxetine: Terbinafine, a CYP2D6 inhibitor, may reduce the metabolism and clearance of Atomoxetine. Consider alternate therapy or monitor for therapeutic/adverse effects of Atomoxetine if Terbinafine is initiated, discontinued or dose changed.

Caffeine: Terbinafine may increase the plasma concentration of Caffeine.

Captopril: Terbinafine may reduce the metabolism and clearance of Captopril. Consider alternate therapy or monitor for therapeutic/adverse effects of Captopril if Terbinafine is initiated, discontinued or dose changed.

Carvedilol: Terbinafine may reduce the metabolism and clearance of Carvedilol. Consider alternate therapy or monitor for therapeutic/adverse effects of Carvedilol if Terbinafine is initiated, discontinued or dose changed.

Chloroquine: Terbinafine may reduce the metabolism and clearance of Chloroquine. Consider alternate therapy or monitor for therapeutic/adverse effects of Chloroquine if Terbinafine is initiated, discontinued or dose changed.

Chlorpromazine: Terbinafine may reduce the metabolism and clearance of Chlorpromazine. Consider alternate therapy or monitor for therapeutic/adverse effects of Chlorpromazine if Terbinafine is initiated, discontinued or dose changed.

Clomipramine: Terbinafine may reduce the metabolism and clearance of Clomipramine. Consider alternate therapy or monitor for therapeutic/adverse effects of Clomipramine if Terbinafine is initiated, discontinued or dose changed.

Codeine: Terbinafine may decrease the efficacy of Codeine by inhibiting active metabolite production. Consider an alternate analgesic or monitor for effectiveness of Codeine.

Cyclosporine: Terbinafine may decrease the plasma concentration and therapeutic effect of cyclosporine.

Desipramine: Terbinafine may increase the effect and toxicity of the tricyclic antidepressant, desipramine, by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of desipramine if terbinafine is initiated, discontinued or dose changed.

Dextromethorphan: Terbinafine may reduce the metabolism and clearance of Dextromethorphan. Consider alternate therapy or monitor for therapeutic/adverse effects of Dextromethorphan if Terbinafine is initiated, discontinued or dose changed.

Doxepin: Terbinafine may reduce the metabolism and clearance of Doxepin. Consider alternate therapy or monitor for therapeutic/adverse effects of Amytriptyline if Doxepin is initiated, discontinued or dose changed.

Doxorubicin: Terbinafine may reduce the metabolism and clearance of Doxorubicin. Consider alternate therapy or monitor for therapeutic/adverse effects of Doxorubicin if Terbinafine is initiated, discontinued or dose changed.

Duloxetine: Terbinafine may reduce the metabolism and clearance of Duloxetine. Consider alternate therapy or monitor for therapeutic/adverse effects of Duloxetine if Terbinafine is initiated, discontinued or dose changed.

Dyphylline: Terbinafine increases the effect and toxicity of theophylline

Flecainide: Terbinafine may reduce the metabolism and clearance of Flecainide. Consider alternate therapy or monitor for therapeutic/adverse effects of Flecainide if Terbinafine is initiated, discontinued or dose changed.

Fluoxetine: Terbinafine may reduce the metabolism and clearance of Fluoxetine. Consider alternate therapy or monitor for therapeutic/adverse effects of Fluoxetine if Terbinafine is initiated, discontinued or dose changed.

Fluphenazine: Terbinafine may reduce the metabolism and clearance of Fluphenazine. Consider alternate therapy or monitor for therapeutic/adverse effects of Fluphenazine if Terbinafine is initiated, discontinued or dose changed.

Fluvoxamine: Terbinafine may reduce the metabolism and clearance of Fluvoxamine. Consider alternate therapy or monitor for therapeutic/adverse effects of Fluvoxamine if Terbinafine is initiated, discontinued or dose changed.

Haloperidol: Terbinafine may reduce the metabolism and clearance of Haloperidol. Consider alternate therapy or monitor for therapeutic/adverse effects of Haloperidol if Terbinafine is initiated, discontinued or dose changed.

Imipramine: Terbinafine may increase the effect and toxicity of the tricyclic antidepressant, imipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of imipramine if terbinafine is initiated, discontinued or dose changed.

Lidocaine: Terbinafine may reduce the metabolism and clearance of Lidocaine. Consider alternate therapy or monitor for therapeutic/adverse effects of Lidocaine if Terbinafine is initiated, discontinued or dose changed.

Lomustine: Terbinafine may reduce the metabolism and clearance of Lomustine. Consider alternate therapy or monitor for therapeutic/adverse effects of Lomustine if Terbinafine is initiated, discontinued or dose changed.

Maprotiline: Terbinafine may reduce the metabolism and clearance of Maprotiline. Consider alternate therapy or monitor for therapeutic/adverse effects of Maprotiline if Terbinafine is initiated, discontinued or dose changed.

Methamphetamine: Terbinafine may reduce the metabolism and clearance of Methamphetamine. Consider alternate therapy or monitor for therapeutic/adverse effects of Methamphetamine if Terbinafine is initiated, discontinued or dose changed.

Metoprolol: Terbinafine may reduce the metabolism and clearance of Metoprolol. Consider alternate therapy or monitor for therapeutic/adverse effects of Metoprolol if Terbinafine is initiated, discontinued or dose changed.

Mexiletine: Terbinafine may reduce the metabolism and clearance of Mexiletine. Consider alternate therapy or monitor for therapeutic/adverse effects of Mexiletine if Terbinafine is initiated, discontinued or dose changed.

Mirtazapine: Terbinafine may reduce the metabolism and clearance of Mirtazapine. Consider alternate therapy or monitor for therapeutic/adverse effects of Mirtazapine if Terbinafine is initiated, discontinued or dose changed.

Moclobemide: Terbinafine may reduce the metabolism and clearance of Moclobemide. Consider alternate therapy or monitor for therapeutic/adverse effects of Moclobemide if Terbinafine is initiated, discontinued or dose changed.

Nefazodone: Terbinafine may reduce the metabolism and clearance of Nefazodone. Consider alternate therapy or monitor for therapeutic/adverse effects of Nefazodone if Terbinafine is initiated, discontinued or dose changed.

Nortriptyline: Terbinafine may increase the effect and toxicity of the tricyclic antidepressant, nortriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if terbinafine is initiated, discontinued or dose changed.

Oxtriphylline: Terbinafine increases the effect and toxicity of theophylline

Paroxetine: Terbinafine may reduce the metabolism and clearance of Paroxetine. Consider alternate therapy or monitor for therapeutic/adverse effects of Paroxetine if Terbinafine is initiated, discontinued or dose changed.

Perphenazine: Terbinafine may reduce the metabolism and clearance of Perphenazine. Consider alternate therapy or monitor for therapeutic/adverse effects of Perphenazine if Terbinafine is initiated, discontinued or dose changed.

Pipotiazine: Terbinafine may reduce the metabolism and clearance of Pipotiazine. Consider alternate therapy or monitor for therapeutic/adverse effects of Pipotiazine if Terbinafine is initiated, discontinued or dose changed.

Procainamide: Terbinafine may reduce the metabolism and clearance of Procainamide. Consider alternate therapy or monitor for therapeutic/adverse effects of Procainamide if Terbinafine is initiated, discontinued or dose changed.

Promethazine: Terbinafine may reduce the metabolism and clearance of Promethazine. Consider alternate therapy or monitor for therapeutic/adverse effects of Promethazine if Terbinafine is initiated, discontinued or dose changed.

Propafenone: Terbinafine may reduce the metabolism and clearance of Propafenone. Consider alternate therapy or monitor for therapeutic/adverse effects of Propafenone if Terbinafine is initiated, discontinued or dose changed.

Propranolol: Terbinafine may reduce the metabolism and clearance of Propranolol. Consider alternate therapy or monitor for therapeutic/adverse effects of Propranolol if Terbinafine is initiated, discontinued or dose changed.

Protriptyline: Terbinafine may reduce the metabolism and clearance of Protriptyline. Consider alternate therapy or monitor for therapeutic/adverse effects of Protriptyline if Terbinafine is initiated, discontinued or dose changed.

Rifabutin: Rifabutin may increase the metabolism and clearance of Terbinafine. To avoid Terbinafine treatment failure, co-administration should be avoided.

Rifampin: Rifampin may increase the metabolism and clearance of Terbinafine. Co-administration may result in Terbinafine treatment failure.

Rifapentine: Rifapentine may increase the metabolism and clearance of Terbinafine. To avoid Terbinafine treatment failure, co-administration should be avoided.

Risperidone: Terbinafine may reduce the metabolism and clearance of Risperidone. Consider alternate therapy or monitor for therapeutic/adverse effects of Risperidone if Terbinafine is initiated, discontinued or dose changed.

Sertraline: Terbinafine may reduce the metabolism and clearance of Sertraline. Consider alternate therapy or monitor for therapeutic/adverse effects of Sertraline if Terbinafine is initiated, discontinued or dose changed.

Tamoxifen: Terbinafine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Concomitant therapy should be avoided.

Tamsulosin: Terbinafine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Consider alternate therapy or monitor for changes in therapeutic/adverse effects of Tamsulosin if Terbinafine is initiated, discontinued, or dose changed.

Tetrabenazine: Terbinafine may reduce the metabolism and clearance of Tetrabenazine. Consider alternate therapy or monitor for therapeutic/adverse effects of Tetrabenazine if Terbinafine is initiated, discontinued or dose changed.

Theophylline: Terbinafine increases the effect and toxicity of theophylline

Thioridazine: Terbinafine may increase serum concentrations of Thioridazine. Concomitant therapy is contraindicated.

Timolol: Terbinafine may reduce the metabolism and clearance of Timolol. Consider alternate therapy or monitor for therapeutic/adverse effects of Amytriptyline if Timolol is initiated, discontinued or dose changed.

Tolterodine: Terbinafine may reduce the metabolism and clearance of Tolterodine. Consider alternate therapy or monitor for therapeutic/adverse effects of Tolterodine if Terbinafine is initiated, discontinued or dose changed.

Tramadol: Terbinafine may decrease the effect of Tramadol by decreasing active metabolite production.

Trimipramine: Terbinafine may decrease the metabolism and clearance of Trimipramine. Consider alternate therapy or monitor for changes in Trimipramine efficacy and toxicity if Terbinafine is initiated, discontinued or dose changed. Alteration in Trimipramine dose may be required.

Venlafaxine: Terbinafine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Terbinafine is initiated, discontinued, or dose changed.

Zuclopenthixol: Terbinafine, a strong CYP2D6 inhibitor, may increase the serum concentration of zuclopenthixol by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zuclopenthixol if terbinafine is initiated, discontinued or dose changed.