Lamisil (Terbinafine) Interactions
- Amoxapine
- Atomoxetine
- Caffeine
- Carvedilol
- Cimetidine
- Clozapine
- Codeine
- Cyclobenzaprine
- Cyclosporine
- Darifenacin
- Dexfenfluramine
- Dextromethorphan
- Donepezil
- Doxercalciferol
- Encainide
- Fenfluramine
- Flecainide
- Fluoxetine
- Fluphenazine
- Galantamine
- Green Tea
- Guarana
- Haloperidol
- Hydrocodone
- Maprotiline
- Meperidine
- Methadone
- Methamphetamine
- Metoprolol
- Mexiletine
- Oxycodone
- Paroxetine
- Perphenazine
- Propafenone
- Propranolol
- Rifampin
- Risperidone
- Terfenadine
- Theophylline, Aminophylline
- Thioridazine
- Timolol
- Tramadol
- Trazodone
Tricyclic antidepressants
- Venlafaxine
- Warfarin
- Zolpidem
Lamisil (Terbinafine) Interactions
Topical terbinafine formulations are not extensively absorbed and are unlikely to exhibit significant drug interactions.
In vitro studies have shown systemic terbinafine to inhibit hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme. A pharmacokinetic interaction in vivo has been reported between dextromethorphan and terbinafine, but the clinical relevance of the interaction is not known. Other drugs metabolized by CYP2D6 include amoxapine, atomoxetine, certain beta-blockers (e.g., carvedilol, metoprolol, propranolol, and timolol), certain antiarrhythmics (e.g., encainide, flecainide, mexiletine, and propafenone), clozapine, codeine, cyclobenzaprine, fenfluramine, darifenacin, dexfenfluramine, dextromethorphan, donepezil, fluoxetine, galantamine, haloperidol, hydrocodone, maprotiline, meperidine, methadone, methamphetamine, oxycodone, paroxetine, risperidone, some phenothiazines such as fluphenazine, perphenazine, thioridazine (thioridazine is contraindicated with CYP2D6 inhibitors), tramadol, trazodone, tricyclic antidepressants, venlafaxine, or zolpidem. This list is not inclusive of all agents metabolized by CYP2D6. The conversion of codeine to its active metabolite (morphine), may be decreased due to inhibition of CYP2D6. Topical forms of terbinafine do not interact.
The effects of oral terbinafine on the pharmacokinetics of desipramine were evaluated in healthy volunteers characterized as extensive metabolizers. In this study, there was a 2-fold increase in the Cmax and a 5-fold increase in the AUC of desipramine. These effects persisted even after 4 weeks following discontinuation of terbinafine. An interaction has been reported in one patient stabilized on desipramine therapy and then subsequently starting terbinafine therapy; desipramine plasma concentrations increased about 3-fold after terbinafine was started and then decreased after terbinafine was stopped. One case of nortriptyline intoxication secondary to concomitant terbinafine use has been reported. Serum concentrations of nortriptyline were increased greater than 2-fold after addition of terbinafine therapy; concentrations declined after stopping terbinafine and stabilized after 3 weeks. Other tricyclic antidepressants metabolized by cytochrome P450 2D6 (e.g., amitriptyline, clomipramine, doxepin, and imipramine) may have increased levels when given concurrently with terbinafine.
Systemic terbinafine has been found to increase the clearance of cyclosporine by 15%. In 4 patients, addition of terbinafine 250 mg daily to a stable cyclosporine dosage lowered trough cyclosporine concentrations. A stepwise increase in the cyclosporine dosage from 3.6 mg/kg/day to 6.5 mg/kg/day was necessary for 1 patient, and the cyclosporin concentration rose from 93 ng/ml to 173 ng/ml 1 week after terbinafine cessation. As decreased cyclosporine serum concentrations and thus, an increased risk of organ rejection are possible, monitoring of cyclosporine concentrations is recommended during terbinafine use. Monitoring of cyclosporine concentrations is also recommended after terbinafine cessation, as an increase in the serum cyclosporine concentration is possible. Topical forms of terbinafine do not interact.
According to the manufacturer, orally administered terbinafine decreases caffeine clearance by 19%. One study reported that oral terbinafine decreased the elimination of caffeine by 21%. Another study reported that oral terbinafine does not alter the activity of CYP1A2, N-acetyltransferase, or xanthine oxidase, the enzymes responsible for caffeine metabolism. Oral terbinafine is also reported to decrease theophylline clearance by 14%. All studies were performed in healthy volunteers. It is unknown if these interactions would be clinically significant; the exact mechanisms are not known. Patients who receive theophylline or aminophylline concurrently with terbinafine should be monitored for increased or decreased effects of these narrow therapeutic window drugs. During concomitant therapy with terbinafine, it may be prudent to limit or avoid caffeine-containing products such as guarana and beverages including coffee, green tea, other teas, or colas in an effort to minimize caffeine-related side effects.
According to the manufacturer, rifampin doubles terbinafine’s clearance systemically. Studies were performed in normal volunteers. It is unknown if this interaction would be clinically significant; the exact mechanisms are not known. When terbinafine is administered to patients who are prescribed rifampin, patients should be monitored for decreased responses to terbinafine therapy.
According to the manufacturer, cimetidine decreases the clearance of systemic terbinafine by one-third. Studies were performed in normal volunteers. It is unknown if this interaction would be clinically significant; the exact mechanisms are not known.
One case report exists in the literature regarding a patient previously stabilized on warfarin and cimetidine who experienced gastrointestinal bleeding and coagulopathy within one month of initiating oral terbinafine treatment for onychomycosis. Terbinafine may have had an effect on the metabolism of warfarin; the reduction in terbinafine clearance by cimetidine may have contributed to the interaction. According to the manufacturer, single doses of warfarin, when administered in healthy volunteers receiving chronic terbinafine therapy, have not been reported to cause changes in anticoagulation. However, there are spontaneous reports of altered INR or prothrombin time (prolongation or reduction) in patients receiving terbinafine and warfarin concurrently. Topical forms of terbinafine do not interact.
QTc interval prolongation of > 10% occurred in some patients receiving oral terfenadine with oral terbinafine concurrently compared to oral terbinafine alone. The effect of terbinafine on terfenadine serum concentrations is unknown, but terbinafine does not appear to alter the clearance of terfenadine’s metabolite, fexofenadine. The incidence of ECG abnormalities in the combined treatment group was not significantly different than that of the terbinafine treatment group. No clinically significant interactions between terbinafine and either astemizole or terfenadine have been reported in post-marketing surveillance to date. However, patients with pre-existing conduction abnormalities might be more susceptible to QTc interval prolongations. The manufacturer has stated that terfenadine and terbinafine are not known to interact.
Limited in vivo studies of single doses of digoxin given concurrently with chronically administered systemic terbinafine have not noted pharmacokinetic or pharmacodynamic interactions.
In vitro studies suggest that terbinafine may have synergistic activity against fungal species, including Candida sp., when given with other antifungals, including amphotericin B, itraconazole, and fluconazole. Clinical study is needed to elucidate the potential utility of terbinafine combinations with other antifungal agents.
Doxercalciferol is converted in the liver to 1,25-dihydroxyergocalciferol, the major active metabolite, and 1-alpha, 24-dihydroxyvitamin D2, a minor metabolite. Although not specifically studied, cytochrome P450 enzyme inhibitors including terbinafine may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if terbinafine is coadministered with doxercalciferol.
[ Last revised: 8/31/2005 3:00:00 PM ]
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