WARNINGS AND PRECAUTIONS
Hepatotoxicity
Cases of liver failure, some leading to liver transplant or death, have occurred with the use of Lamisil Tablets in individuals with and without preexisting liver disease.
In the majority of liver cases reported in association with use of Lamisil Tablets, 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 Tablets should be discontinued if biochemical or clinical evidence of liver injury develops.
Lamisil Tablets are not recommended for patients with chronic or active liver disease. Before prescribing Lamisil Tablets, liver function tests should be performed since hepatotoxicity may occur in patients with and without pre-existing liver disease. Periodic monitoring of liver function tests is recommended. Lamisil should be immediately discontinued in case of elevation of liver function tests. Patients prescribed Lamisil 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 Tablets. It can be severe enough to result in decreased food intake, weight loss, anxiety, and depressive symptoms. Taste disturbance may resolve within several weeks after discontinuation of treatment, but may be prolonged (greater than 1 year), or may be permanent. If symptoms of a taste disturbance occur, Lamisil Tablets should be discontinued.
Smell Disturbance Including Loss of Smell
Smell disturbance, including loss of smell, has been reported with the use of Lamisil Tablets. Smell disturbance may resolve after discontinuation of treatment, but may be prolonged (greater than 1 year), or may be permanent. If symptoms of a smell disturbance occur, Lamisil Tablets should be discontinued.
Depressive Symptoms
Depressive symptoms have occurred during postmarketing use of Lamisil Tablets. Prescribers should be alert to the development of depressive symptoms, and patients should be instructed to report depressive symptoms to their physician.
Hematologic Effects
Transient decreases in absolute lymphocyte counts (ALCs) have been observed in controlled clinical trials. In placebo-controlled trials, 8/465 subjects receiving Lamisil Tablets (1.7%) and 3/137 subjects receiving placebo (2.2%) had decreases in ALC to below 1000/mm3 on 2 or more occasions. In patients with known or suspected immunodeficiency, physicians should consider monitoring complete blood counts if treatment continues for more than 6 weeks. Cases of severe neutropenia have been reported. These were reversible upon discontinuation of Lamisil Tablets, 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 ≤1000 cells/mm3, Lamisil Tablets should be discontinued and supportive management started.
Serious Skin/Hypersensitivity Reactions
There have been postmarketing reports of serious skin/hypersensitivity reactions [e.g., Stevens-Johnson Syndrome, toxic epidermal necrolysis, erythema multiforme, exfoliative dermatitis, bullous dermatitis, and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome]. Manifestations of DRESS syndrome may include cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia, and one or more organ complications such as hepatitis, pneumonitis, nephritis, myocarditis, and pericarditis. If progressive skin rash or signs/symptoms of the above drug reactions occur, treatment with Lamisil Tablets should be discontinued.
Lupus Erythematosus
During postmarketing experience, precipitation and exacerbation of cutaneous and systemic lupus erythematosus have been reported in patients taking Lamisil Tablets. Lamisil 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 Tablets.
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 Tablets 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 maximum recommended human dose (MRHD), in rabbits and rats, respectively, based on body surface area (BSA) comparisons] 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 Tablets is not recommended in women who are nursing.
Pediatric Use
The safety and efficacy of Lamisil Tablets have not been established in pediatric patients with onychomycosis.
Geriatric Use
Clinical studies of Lamisil Tablets did not include sufficient numbers of subjects aged 65 years 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.
Renal Impairment
In patients with renal impairment (creatinine clearance less than or equal to 50 mL/min) the use of Lamisil Tablets has not been adequately studied.
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