warnings and cautions
5 WARNINGS AND PRECAUTIONS • Liver failure, sometimes leading to liver transplant or death, has occurred with the use of oral terbinafine. Obtain pretreatment serum transaminases. Discontinue terbinafine hydrochloride tablets if liver injury develops. (5.1, 5.8) • Taste disturbance, including taste loss, has been reported with the use of terbinafine hydrochloride tablets. Taste disturbance can be severe, may be prolonged, or may be permanent. Discontinue terbinafine hydrochloride tablets if taste disturbance occurs. (5.2) • Smell disturbance, including loss of smell, has been reported with the use of terbinafine hydrochloride tablets. Smell disturbance may be prolonged, or may be permanent. Discontinue terbinafine hydrochloride tablets if smell disturbance occurs. (5.3) • Depressive symptoms have been reported with terbinafine use. Prescribers should be alert to development of depressive symptoms. (5.4) • Severe neutropenia has been reported. If the neutrophil count is ≤ 1,000 cells/mm 3 , terbinafine hydrochloride tablets should be discontinued. (5.5) • Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported with oral terbinafine use. If progressive skin rash occurs, treatment with terbinafine hydrochloride tablets should be discontinued. (5.6) 5.1 Hepatotoxicity Cases of liver failure, some leading to liver transplant or death, have occurred with the use of terbinafine HCl tablets in individuals with and without pre-existing liver disease. In the majority of liver cases reported in association with terbinafine HCl 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 terbinafine HCl tablets should be discontinued if biochemical or clinical evidence of liver injury develops. Terbinafine HCl tablets are not recommended for patients with chronic or active liver disease. Before prescribing terbinafine HCl tablets, pre-existing liver disease should be assessed. Hepatotoxicity may occur in patients with and without pre-existing liver disease. Patients prescribed terbinafine HCl 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. 5.2 Taste Disturbance Including Loss of Taste Taste disturbance, including taste loss, has been reported with the use of terbinafine HCl 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, terbinafine HCl tablets should be discontinued. 5.3 Smell Disturbance Including Loss of Smell Smell disturbance, including loss of smell, has been reported with the use of terbinafine HCl 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, terbinafine HCl tablets should be discontinued. 5.4 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. 5.5 Hematologic Effects Transient decreases in absolute lymphocyte counts (ALC) have been observed in controlled clinical trials. In placebo-controlled trials, 8/465 terbinafine HCl-treated patients (1.7%) and 3/137 placebo-treated patients (2.2%) had decreases in ALC to below 1000/mm 3 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 terbinafine HCl, 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/mm 3 , terbinafine HCl should be discontinued and supportive management started. 5.6 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 terbinafine HCl tablets should be discontinued. 5.7 Lupus Erythematosus During post-marketing experience, precipitation and exacerbation of cutaneous and systemic lupus erythematosus have been reported in patients taking terbinafine HCl tablets. Terbinafine HCl tablets should be discontinued in patients with clinical signs and symptoms suggestive of lupus erythematosus. 5.8 Laboratory Monitoring Measurement of serum transaminases (ALT and AST) is advised for all patients before taking terbinafine HCl tablets.