Included as part of the PRECAUTIONS section.

Hepatotoxicity

Cases of liver failure, some leading to liver transplant or death, have occurred with the use of Lamisil (terbinafine) Tablets in individuals with and without pre-existing liver disease.

In the majority of liver cases reported in association with Lamisil (terbinafine) use, the patients had serious underlying systemic conditions. The severity of hepatic events and/or their outcome may be worse in patients with active or chronic liver disease. Treatment with Lamisil (terbinafine) Tablets should be discontinued if biochemical or clinical evidence of liver injury develops.

Lamisil (terbinafine) Tablets are not recommended for patients with chronic or active liver disease. Before prescribing Lamisil (terbinafine) Tablets, pre-existing liver disease should be assessed. Hepatotoxicity may occur in patients with and without pre-existing liver disease. Patients prescribed Lamisil (terbinafine) Tablets should be warned to report immediately to their physician any symptoms of persistent nausea, anorexia, fatigue, vomiting, right upper abdominal pain or jaundice, dark urine or pale stools. Patients with these symptoms should discontinue taking oral terbinafine, and the patient's liver function should be immediately evaluated.

Taste Disturbance Including Loss of Taste

Taste disturbance, including taste loss, has 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. Taste disturbance may resolve within several weeks after discontinuation of treatment, but may be prolonged (greater than one year), or may be permanent. If symptoms of a taste disturbance occur, Lamisil (terbinafine) Tablets should be discontinued.

Smell Disturbance Including Loss of Smell

Smell disturbance, including loss of smell, has been reported with the use of Lamisil (terbinafine) Tablets. Smell disturbance may resolve after discontinuation of treatment, but may be prolonged (greater than one year), or may be permanent. If symptoms of a smell disturbance occur, Lamisil (terbinafine) Tablets should be discontinued.

Depressive Symptoms

Depressive symptoms have occurred during postmarketing use of terbinafine. Prescribers should be alert to depressive symptoms, and patients should be instructed to report depressive symptoms to their physician.

Hematologic Effects

Transient decreases in absolute lymphocyte counts (ALC) have been observed in controlled clinical trials. In placebo-controlled trials, 8/465 Lamisil (terbinafine) -treated patients (1.7%) and 3/137 placebo-treated patients (2.2%) had decreases in ALC to below 1000/mm³ on two or more occasions. In patients with known or suspected immunodeficiency, physicians should consider monitoring complete blood counts if treatment continues for more than six weeks. Cases of severe neutropenia have been reported. These were reversible upon discontinuation of Lamisil (terbinafine) , with or without supportive therapy. If clinical signs and symptoms suggestive of secondary infection occur, a complete blood count should be obtained. If the neutrophil count is ≤ 1,000 cells/mm³, Lamisil (terbinafine) should be discontinued and supportive management started.

Skin Reactions

There have been postmarketing reports of serious skin reactions (e.g., Stevens-Johnson Syndrome and toxic epidermal necrolysis). If progressive skin rash occurs, treatment with Lamisil (terbinafine) Tablets should be discontinued.

Lupus Erythematosus

During post-marketing experience, precipitation and exacerbation of cutaneous and systemic lupus erythematosus have been reported in patients taking Lamisil (terbinafine) Tablets. Lamisil (terbinafine) Tablets should be discontinued in patients with clinical signs and symptoms suggestive of lupus erythematosus.

Laboratory Monitoring

Measurement of serum transaminases (ALT and AST) is advised for all patients before taking Lamisil (terbinafine) Tablets.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

In a 28-month oral carcinogenicity study in rats, an increase in the incidence of liver tumors was observed in males at the highest dose tested, 69 mg/kg/day [2x the Maximum Recommended Human Dose (MRHD) based on AUC comparisons of the parent terbinafine]; however, even though dose-limiting toxicity was not achieved at the highest tested dose, higher doses were not tested.

The results of a variety of in vitro (mutations in E. coli and S. typhimurium, DNA repair in rat hepatocytes, mutagenicity in Chinese hamster fibroblasts, chromosome aberration and sister chromatid exchanges in Chinese hamster lung cells), and in vivo (chromosome aberration in Chinese hamsters, micronucleus test in mice) genotoxicity tests gave no evidence of a mutagenic or clastogenic potential.

Oral reproduction studies in rats at doses up to 300 mg/kg/day (approximately 12x the MRHD based on body surface area comparisons, BSA) did not reveal any specific effects on fertility or other reproductive parameters. Intravaginal application of terbinafine hydrochloride at 150 mg/day in pregnant rabbits did not increase the incidence of abortions or premature deliveries nor affect fetal parameters.

Use In Specific Populations

Pregnancy

Pregnancy Category B

There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, and because treatment of onychomycosis can be postponed until after pregnancy is completed, it is recommended that Lamisil (terbinafine) not be initiated during pregnancy.

Oral reproduction studies have been performed in rabbits and rats at doses up to 300 mg/kg/day (12x to 23x the MRHD, in rabbits and rats, respectively, based on BSA) and have revealed no evidence of impaired fertility or harm to the fetus due to terbinafine.

Nursing Mothers

After oral administration, terbinafine is present in breast milk of nursing mothers. The ratio of terbinafine in milk to plasma is 7:1. Treatment with Lamisil (terbinafine) is not recommended in nursing mothers.

 Use

The safety and efficacy of Lamisil (terbinafine) Tablets have not been established in pediatric patients with onychomycosis.

Geriatric Use

Clinical studies of Lamisil (terbinafine) Tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

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