FDA label 492037eb-718a-41cd-e054-00144ff8d46c

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 tablets if liver injury develops. ( 5.1 , 5.8 ) Taste disturbance, including taste loss, has been reported with the use of terbinafine tablets. Taste disturbance can be severe, may be prolonged, or may be permanent. Discontinue terbinafine tablets if taste disturbance occurs. ( 5.2 ) Smell disturbance, including loss of smell, has been reported with the use of terbinafine tablets. Smell disturbance may be prolonged, or may be permanent. Discontinue terbinafine 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/mm3, terbinafine tablets 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, treatment with terbinafine 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 tablets in individuals with and without preexisting liver disease. In the majority of liver cases reported in association with 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 terbinafine tablets should be discontinued if biochemical or clinical evidence of liver injury develops. Terbinafine tablets are not recommended for patients with chronic or active liver disease. Before prescribing terbinafine 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. Terbinafine tablets should be immediately discontinued in case of elevation of liver function tests. Patients prescribed 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. 5.2 Taste Disturbance Including Loss of Taste Taste disturbance, including taste loss, has been reported with the use of 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, terbinafine 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 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 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 (ALCs) have been observed in controlled clinical trials. In placebo-controlled trials, 8/465 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 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/mm 3 , terbinafine 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]. 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 reactions occur, treatment with terbinafine 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 tablets. Terbinafine 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 tablets.

6 ADVERSE REACTIONS Common (> 2% in patients treated with terbinafine tablets) reported adverse events include headache, diarrhea, rash, dyspepsia, liver enzyme abnormalities, pruritus, taste disturbance, nausea, abdominal pain, and flatulence. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Camber Pharmaceuticals, Inc at 1-866-495-8330 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials 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 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. Adverse Event/ Discontinuation 6.2 Postmarketing Experience The following adverse events have been identified during post-approval use of 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. Blood and lymphatic system disorders: Pancytopenia, agranulocytosis, severe neutropenia, thrombocytopenia, anemia [see Warnings and Precautions ( 5.5 ) ] Immune system disorders: Serious hypersensitivity reactions e.g., angioedema and allergic reactions (including anaphylaxis), precipitation and exacerbation of cutaneous and systemic lupus erythematosus [see Warnings and Precautions ( 5.7 ) ], serum sickness-like reaction Psychiatric disorders: Depressive symptoms independent of taste disturbance have been reported with use of 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 ( 5.4 ) ] Nervous system disorders: Cases of taste disturbance, including taste loss, have been reported with the use of terbinafine tablets. It can be severe enough to result in decreased food intake, weight loss, and depressive symptoms. Cases of smell disturbance, including smell loss, have been reported with the use of terbinafine tablets [see Warnings and Precautions ( 5.2 and 5.3 ) ] Eye disorders: Visual field defects, reduced visual acuity Ear and labyrinth disorders: Hearing impairment, vertigo, tinnitus Vascular disorders: Vasculitis Gastrointestinal disorders: Pancreatitis, vomiting Hepatobiliary disorders: Cases of liver failure some leading to liver transplant or death [see Warnings and Precautions ( 5.1 ) ], idiosyncratic and symptomatic hepatic injury Skin and subcutaneous tissue disorders: Serious skin reactions [e.g., Stevens - Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome] [see Warnings and Precautions ( 5.6 )], acute generalized exanthematous pustulosis, psoriasiform eruptions or exacerbation of psoriasis, photosensitivity reactions, hair loss Musculoskeletal and connective tissue disorders: Rhabdomyolysis, arthralgia, myalgia General disorders and administration site conditions: Malaise, fatigue, influenza-like illness, pyrexia Investigations: Altered prothrombin time (prolongation and reduction) in patients concomitantly treated with warfarin and increased blood creatine phosphokinase have been reported.