Clinical Studies Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The most frequently reported adverse events observed in the three US/Canadian placebo-controlled trials are listed in the table below. The adverse events reported encompass gastrointestinal symptoms (including diarrhea, dyspepsia, and abdominal pain), liver test abnormalities, rashes, urticaria, pruritus, and taste disturbances. Changes in the ocular lens and retina have been reported following the use of Lamisil (terbinafine) Tablets in controlled trials. The clinical significance of these changes is unknown. In general, the adverse events were mild, transient, and did not lead to discontinuation from study participation.

Postmarketing Experience

The following adverse events have been identified during post-approval use of Lamisil (terbinafine) . Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Adverse events, based on worldwide experience with Lamisil (terbinafine) Tablets use, include: idiosyncratic and symptomatic hepatic injury and more rarely, cases of liver failure, some leading to death or liver transplant, serious skin reactions (e.g., Stevens-Johnson Syndrome and toxic epidermal necrolysis), severe neutropenia, thrombocytopenia, agranulocytosis, pancytopenia, anemia, angioedema, and allergic reactions (including anaphylaxis) [see WARNINGS AND PRECAUTIONS].

Psoriasiform eruptions or exacerbation of psoriasis, acute generalized exanthematous pustulosis and precipitation and exacerbation of cutaneous and systemic lupus erythematosus have been reported in patients taking Lamisil [see WARNINGS AND PRECAUTIONS].

Cases of taste disturbance, including taste loss, have been reported with the use of Lamisil (terbinafine) Tablets. It can be severe enough to result in decreased food intake, weight loss, and depressive symptoms [see WARNINGS AND PRECAUTIONS]. Depressive symptoms independent of taste disturbance have been reported with use of Lamisil (terbinafine) Tablets. In some cases, depressive symptoms have been reported to subside with discontinuance of therapy and to recur with reinstitution of therapy [see WARNINGS AND PRECAUTIONS]. Cases of smell disturbance, including smell loss, have been reported with the use of Lamisil Tablets [see WARNINGS AND PRECAUTIONS].

Other adverse reactions which have been reported include malaise, fatigue, vomiting, arthralgia, myalgia, rhabdomyolysis, reduced visual acuity, visual field defect, hair loss, serum sickness-like reaction, vasculitis, pancreatitis, influenza-like illness, pyrexia, and increased blood creatine phosphokinase.

Altered prothrombin time (prolongation and reduction) in patients concomitantly treated with warfarin has been reported.

Read the Lamisil (terbinafine) Side Effects Center for a complete guide to possible side effects »

Drug-Drug Interactions

In vivo studies have shown that terbinafine is an inhibitor of the CYP450 2D6 isozyme. Drugs predominantly metabolized by the CYP450 2D6 isozyme include the following drug classes: tricyclic antidepressants, selective serotonin reuptake inhibitors, beta-blockers, antiarrhythmics class 1C (e.g., flecainide and propafenone) and monoamine oxidase inhibitors Type B. Coadministration of Lamisil (terbinafine) should be done with careful monitoring and may require a reduction in dose of the 2D6-metabolized drug. In a study to assess the effects of terbinafine on desipramine in healthy volunteers characterized as normal metabolizers, the administration of terbinafine resulted in a 2-fold increase in Cmax and a 5-fold increase in AUC. In this study, these effects were shown to persist at the last observation at 4 weeks after discontinuation of Lamisil (terbinafine) Tablets. In studies in healthy subjects characterized as extensive metabolizers of dextromethorphan, terbinafine increases the dextromethorphan/dextrorphan metabolite ratio in urine by 16- to 97-fold on average. In vitro studies with human liver microsomes showed that terbinafine does not inhibit the metabolism of tolbutamide, ethinylestradiol, ethoxycoumarin, cyclosporine, cisapride and fluvastatin. In vivo drug-drug interaction studies conducted in healthy volunteer subjects showed that terbinafine does not affect the clearance of antipyrine or digoxin. Terbinafine decreases the clearance of caffeine by 19%. Terbinafine increases the clearance of cyclosporine by 15%.

The influence of terbinafine on the pharmacokinetics of fluconazole, trimethoprim, sulfamethoxazole, zidovudine or theophylline was not considered to be clinically significant. Co-administration of a single dose of fluconazole (100mg) with a single dose of terbinafine resulted in a 52% and 69% increase in terbinafine Cmax and AUC, respectively. Fluconazole is an inhibitor of CYP2C9 and CYP3A enzymes. Based on this finding, it is likely that other inhibitors of both CYP2C9 and CYP3A4 (e.g., ketoconazole, amiodarone) may also lead to a substantial increase in the systemic exposure (Cmax and AUC) of terbinafine.

There have been spontaneous reports of increase or decrease in prothrombin times in patients concomitantly taking oral terbinafine and warfarin, however, a causal relationship between Lamisil (terbinafine) Tablets and these changes has not been established.

Terbinafine clearance is increased 100% by rifampin, a CYP450 enzyme inducer, and decreased 33% by cimetidine, a CYP450 enzyme inhibitor. Terbinafine clearance is unaffected by cyclosporine.

There is no information available from adequate drug-drug interaction studies with the following classes of drugs: oral contraceptives, hormone replacement therapies, hypoglycemics, phenytoins, thiazide diuretics, and calcium channel blockers.

Food Interactions

An evaluation of the effect of food on Lamisil (terbinafine) Tablets was conducted. An increase of less than 20% of the AUC (i.e. area under the curve) of terbinafine was observed when Lamisil (terbinafine) Tablets were administered with food. Lamisil (terbinafine) Tablets can be taken with or without food.

Last reviewed on RxList: 5/19/2011
This monograph has been modified to include the generic and brand name in many instances.