Terbinafine - Terbinafine tablet

Terbinafine tablets are indicated for the treatment of onychomycosis of the toenail or fingernail due to dermatophytes (tinea unguium).

Prior to initiating treatment, appropriate nail specimens for laboratory testing [potassium hydroxide (KOH) preparation, fungal culture, or nail biopsy] should be obtained to confirm the diagnosis of onychomycosis.

• Prior to administering, evaluate patients for evidence of chronic or active liver disease. (
  
  
  
  
  2.1 Assessment Prior to Initiation

  Before administering terbinafine tablets, evaluate patients for evidence of chronic or active liver disease

  [see Contraindications and Warnings and Precautions ].
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• Fingernail onychomycosis: One tablet, once daily for 6 weeks. (
  
  
  
  2.2 Dosage

  Fingernail onychomycosis: One 250 mg tablet once daily for 6 weeks.

  
  
  

  Toenail onychomycosis: One 250 mg tablet once daily for 12 weeks.

  
  
  

  The optimal clinical effect is seen some months after mycological cure and cessation of treatment. This is related to the period required for outgrowth of healthy nail.
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• Toenail onychomycosis: One tablet, once daily for 12 weeks. (
  
  
  
  2.2 Dosage

  Fingernail onychomycosis: One 250 mg tablet once daily for 6 weeks.

  
  
  

  Toenail onychomycosis: One 250 mg tablet once daily for 12 weeks.

  
  
  

  The optimal clinical effect is seen some months after mycological cure and cessation of treatment. This is related to the period required for outgrowth of healthy nail.
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Terbinafine tablets, USP 250 mg are available for oral administration as white to off-white, round, biconvex tablets with beveled edges, debossed with "CE" on one side, and "45" on other side.

Risk Summary

Available data from postmarketing cases on the use of terbinafine tablets in pregnant women are insufficient to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

In animal reproduction studies, terbinafine did not cause malformations or any harm to the fetus when administered to pregnant rabbits and rats during the period of organogenesis at oral doses up to 12 and 23 times the maximum recommended human dose (MRHD) of 250 mg/day, respectively (see data)

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The background risk of major birth defects and miscarriage for the indicated population is unknown; however, in the U.S. general population, the estimated background risk of major birth defects is 2%-4% and of miscarriage is 15%-20% of clinically recognized pregnancies.

Data

In embryo-fetal development studies in rats and rabbits, pregnant animals received orally (by gavage) doses of terbinafine up to 300 mg/kg/day, during the period of organogenesis. There were no maternal or embryo-fetal effects in either species up to the maximum dose tested. The 300 mg/kg/day dose level in rats and rabbits corresponds to 23 and 12 times the MRHD [based on body surface area (BSA) comparisons], respectively.

In a rat peri-and postnatal development study, terbinafine doses of up to 300 mg/kg/day (12 times the MRHD based on BSA comparisons) given by oral gavage during late pregnancy and lactation (Day 15 of gestation to day 20 post-partum) had no adverse effects on parturition and lactation.

• Liver failure, sometimes leading to liver transplant or death, has occurred with the use of oral terbinafine. Obtain pretreatment serum transaminases. Prior to initiating treatment and periodically during therapy, assess liver function tests. Discontinue terbinafine tablets if liver injury develops. (
  
  
  
  5.1 Hepatotoxicity

  Terbinafine tablets are contraindicated for patients with chronic or active liver disease. Before prescribing terbinafine tablets, 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 terbinafine tablets in individuals with and without preexisting liver disease.

  In the majority of liver cases reported in association with use of terbinafine 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. Periodic monitoring of liver function tests is recommended. Discontinue terbinafine tablets if biochemical or clinical evidence of liver injury develops.

  Warn patients prescribed terbinafine tablets 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 taking oral terbinafine, and immediately evaluate the patient's liver function.
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• 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 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, 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, terbinafine tablets should be discontinued.
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• 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 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 1 year), or may be permanent. If symptoms of a smell disturbance occur, terbinafine tablets should be discontinued.
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• Depressive symptoms have been reported with terbinafine use. Prescribers should be alert to the development of depressive symptoms. (
  
  
  
  5.4 Depressive Symptoms

  Depressive symptoms have occurred during postmarketing use of terbinafine tablets. Prescribers should be alert to the development of depressive symptoms, and patients should be instructed to report depressive symptoms to their physician.
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• Severe neutropenia has been reported. If the neutrophil count is less than or equal to 1,000 cells/mm
  
  
  ³, terbinafine tablets should be discontinued. (
  
  
  
  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 terbinafine tablets (1.7%) and 3/137 subjects receiving placebo (2.2%) had decreases in ALC to below 1,000 /mm³on 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 terbinafine 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

  less than or equal to

  1,000 cells/mm³, terbinafine tablets should be discontinued and supportive management started.
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• 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 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 terbinafine tablets should be discontinued.
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