warnings and cautions
5 WARNINGS AND PRECAUTIONS Liver failure, sometimes leading to death or liver transplant, has occurred with the use of oral terbinafine. Prior to initiating treatment and periodically during therapy, assess liver function tests. Discontinue LAMISIL Oral Granules if liver injury develops. ( 5.1 ) Taste disturbance, including taste loss, has been reported with oral terbinafine use. Taste disturbance can be severe, may be prolonged, or may be permanent. Discontinue LAMISIL Oral Granules if taste disturbance occurs. ( 5.2 ) Smell disturbance, including loss of smell, has been reported with the use of oral terbinafine. Smell disturbance may be prolonged or may be permanent. Discontinue LAMISIL Oral Granules if smell disturbance occurs. ( 5.3 ) Depressive symptoms have been reported with oral terbinafine use. Prescribers should be alert to the development of depressive symptoms. ( 5.4 ) Severe neutropenia has been reported. If the neutrophil count is less than or equal to 1000 cells/mm3, LAMISIL Oral Granules should be discontinued. ( 5.5 ) Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, exfoliative dermatitis, bullous dermatitis, and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome have been reported with oral terbinafine use. If signs or symptoms of drug reaction occur, discontinue LAMISIL Oral Granules. ( 5.6 ) 5.1 Hepatotoxicity LAMISIL Oral Granules are contraindicated for patients with chronic or active liver disease. Before prescribing LAMISIL Oral Granules, perform liver function tests because hepatotoxicity may occur in patients with and without preexisting liver disease. Cases of liver failure, some leading to liver transplant or death, have occurred with the use of oral terbinafine during postmarketing experience in individuals with and without preexisting liver disease. In the majority of liver cases reported in association with oral 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. Periodic monitoring of liver function tests is recommended. Discontinue LAMISIL Oral Granules if biochemical or clinical evidence of liver injury develops. Warn patients prescribed LAMISIL Oral Granules and/or their caregivers to report immediately to their healthcare providers any symptoms or signs of persistent nausea, anorexia, fatigue, vomiting, right upper abdominal pain or jaundice, dark urine, or pale stools. Advise patients with these symptoms to discontinue LAMISIL Oral Granules, and immediately evaluate the patient’s liver function. 5.2 Taste Disturbance Including Loss of Taste Taste disturbance, including taste loss, has been reported with the use of oral terbinafine. 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 Oral Granules should be discontinued. 5.3 Smell Disturbance Including Loss of Smell Smell disturbance, including loss of smell, has been reported with the use of oral terbinafine. 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 Oral Granules should be discontinued. 5.4 Depressive Symptoms Depressive symptoms have occurred during postmarketing use of oral terbinafine. Prescribers should be alert to the development of depressive symptoms, and patients should be instructed to report depressive symptoms to their physician. 5.5 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/mm 3 on 2 or more occasions. In patients with known or suspected immunodeficiency, physicians should consider monitoring complete blood counts (CBCs) if treatment continues for more than 6 weeks. Cases of severe neutropenia have been reported. These were reversible upon discontinuation of oral terbinafine, with or without supportive therapy. If clinical signs and symptoms suggestive of secondary infection occur, a CBC should be obtained. If the neutrophil count is less than or equal to 1000 cells/mm 3 , LAMISIL Oral Granules should be discontinued and supportive management started. 5.6 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] with oral terbinafine. 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 Oral Granules should be discontinued. 5.7 Lupus Erythematosus During postmarketing experience, precipitation and exacerbation of cutaneous and systemic lupus erythematosus have been reported in patients taking oral terbinafine. Therapy should be discontinued in patients with clinical signs and symptoms suggestive of lupus erythematosus. 5.8 Thrombotic Microangiopathy Cases of thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, some fatal, have been reported with terbinafine. Discontinue terbinafine if clinical symptoms and laboratory findings consistent with TMA occur. The findings of unexplained thrombocytopenia and anemia should prompt further evaluation and consideration of diagnosis of TMA.