TERBINAFINE- terbinafine hydrochloride_tablet

Terbinafine is an allylamine antifungal [see Clinical Pharmacology (12. 4) The pharmacodynamics of terbinafine tablets is unknown. Following oral administration, terbinafine is well absorbed (greater than 70%) and the bioavailability of terbinafine tablets as a result of first-pass metabolism is approximately 40%. Peak plasma concentrations of 1 mcg/mL appear within 2 hours after a single 250 mg dose; the AUC is approximately 4. 56 mcgh/mL. An increase in the AUC of terbinafine of less than 20% is observed when terbinafine tablets are administered with food. In plasma, terbinafine is greater than 99% bound to plasma proteins and there are no specific binding sites. At steady-state, in comparison to a single dose, the peak concentration of terbinafine is 25% higher and plasma AUC increases by a factor of 2. 5; the increase in plasma AUC is consistent with an effective half-life of ~36 hours. Terbinafine is distributed to the sebum and skin. A terminal half-life of 200 to 400 hours may represent the slow elimination of terbinafine from tissues such as skin and adipose. Prior to excretion, terbinafine is extensively metabolized by at least 7 CYP isoenzymes with major contributions from CYP2C9, CYP1A2, CYP3A4, CYP2C8, and CYP2C19. No metabolites have been identified that have antifungal activity similar to terbinafine. Approximately 70% of the administered dose is eliminated in the urine. Terbinafine, an allylamine antifungal, inhibits biosynthesis of ergosterol, an essential component of fungal cell membrane, via inhibition of squalene epoxidase enzyme. This results in fungal cell death primarily due to the increased membrane permeability mediated by the accumulation of high concentrations of squalene but not due to ergosterol deficiency. Depending on the concentration of the drug and the fungal species test in vitro in vitro in vitro Trichophyton rubrum in vitro In vitro Epidermophyton floccosum Scopulariopsis brevicaulis.

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

Prior to administering, evaluate patients for evidence of chronic or active liver disease. 1) Fingernail onychomycosis: One 250 mg tablet, once daily for 6 weeks. 2) Toenail onychomycosis: One 250 mg tablet, once daily for 12 weeks. 2) Before administering terbinafine tablets, evaluate patients for evidence of [see Contraindications (4) Warnings and Precautions (5. 1) Fingernail onychomycosis: One 250 mg tablet once daily for 6 weeks.

Common (greater than 2% of patients treated with terbinafine tablets) reported adverse events include headache, diarrhea, rash, dyspepsia, liver enzyme abnormalities, pruritus, taste disturbance, nausea, abdominal pain, and flatulence. 1) 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. Adverse Event Discontinuation Terbinafine Placebo Terbinafine Placebo * Liver enzyme abnormalities greater than or equal to 2 times the upper limit of normal range. Headache 12. 2 0 Gastrointestinal Symptoms: Dermatological Symptoms: Liver Enzyme Abnormalities* 3. 2 0 Taste Disturbance 2. 2 0 Visual Disturbance 1. 9 0 The following adverse events have been identified during post-approval use of terbinafine tablets. 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. [see Warnings and Precautions (5. 5) [see Warnings and Precautions (5. 7) Psychiatric disorders: [see Warnings and Precautions (5. 4) [see Warnings and Precautions (5. 3) ] Eye disorders: [see Warnings and Precautions (5. 1) [see Warnings and Precautions (5.

Terbinafine tablets are contraindicated in patients with: History of allergic reaction to oral terbinafine because of the risk of anaphylaxis [see Adverse Reactions (6. 2) Chronic or [see Warnings and Precautions (5. 1) History of allergic reaction to oral terbinafine because of the risk of anaphylaxis. (4) Chronic or active liver disease.

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 terbinafine tablets not be initiated during pregnancy. Oral reproduction studies have been performed in rabbits and rats at doses up to 300 mg/kg/day [12 times to 23 times 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. 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 terbinafine tablets is not recommended in women who are nursing. The safety and efficacy of terbinafine tablets have not been established in pediatric patients with onychomycosis. Clinical studies of terbinafine 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. In patients with renal impairment (creatinine clearance less than or equal to 50 mL/min), the use of terbinafine tablets has not been adequately studied. Terbinafine tablets are contraindicated for patients with chronic or active liver disease [see Contraindications (4) Warnings and Precautions (5.

Terbinafine is an inhibitor of CYP450 2D6 isozyme and has an effect on metabolism of desipramine. Drug interactions have also been noted with cimetidine, fluconazole, cyclosporine, rifampin, and caffeine. 1) In vivo max In vivo max max An evaluation of the effect of food on terbinafine tablets was conducted. An increase of less than 20% of the AUC of terbinafine was observed when terbinafine tablets were administered with food. Terbinafine tablets can be taken with or without food.

OVERDOSAGE
Clinical experience regarding overdose with oral terbinafine is limited. Doses up to 5 grams (20 times the therapeutic daily dose) have been taken without inducing serious adverse reactions. The symptoms of overdose included nausea, vomiting, abdominal pain, dizziness, rash, frequent urination, and headache.
NONCLINICAL TOXICOLOGY
In a 28-month oral carcinogenicity study in rats, an increase in the incidence of liver tumors was observed in males at the highest dose tested, 69 mg/kg/day (2 times the MRHD based on AUC comparisons of the parent terbinafine); however, even though dose-limiting toxicity was not achieved at the highest tested dose, higher doses were not tested. The results of a variety of in vitro E. typhimurium in vivo Oral reproduction studies in rats at doses up to 300 mg/kg/day (approximately 12 times the MRHD based on BSA comparisons) did not reveal any specific effects on fertility or other reproductive parameters. Intravaginal application of terbinafine hydrochloride at 150 mg/day in pregnant rabbits did not increase the incidence of abortions or premature deliveries nor affect fetal parameters. A wide range of in vivo in vitro ss.
CLINICAL STUDIES
The efficacy of terbinafine tablets in the treatment of onychomycosis is illustrated by the response of subjects with toenail and/or fingernail infections who participated in 3 U.S./Canadian placebo-controlled clinical trials. Results of the first toenail trial, as assessed at week 48 (12 weeks of treatment with 36 weeks follow-up after completion of therapy), demonstrated mycological cure, defined as simultaneous occurrence of negative KOH plus negative culture, in 70% of subjects. Fifty-nine percent (59%) of subjects experienced effective treatment (mycological cure plus 0% nail involvement or greater than 5 mm of new unaffected nail growth); 38% of subjects demonstrated mycological cure plus clinical cure (0% nail involvement). In a second toenail trial of dermatophytic onychomycosis, in which nondermatophytes were also cultured, similar efficacy against the dermatophytes was demonstrated. The pathogenic role of the nondermatophytes cultured in the presence of dermatophytic onychomycosis has not been established. The clinical significance of this association is unknown. Results of the fingernail trial, as assessed at week 24 (6 weeks of treatment with 18 weeks follow-up after completion of therapy), demonstrated mycological cure in 79% of subjects, effective treatment in 75% of the subjects, and mycological cure plus clinical cure in 59% of the subjects. The mean time to overall success was approximately 10 months for the first toenail trial and 4 months for the fingernail trial. In the first toenail trial, for subjects evaluated at least 6 months after achieving clinical cure and at least 1 year after completing therapy with terbinafine tablets, the clinical relapse rate was approximately 15%.
Medication Guide
Terbinafine Tablets, USP [Terbinafine (ter BIN na feen)] terbinafine tablets? Terbinafine tablets may cause serious side effects, including: Liver problems that can lead to the need for a liver transplant or death nausea poor appetite tiredness vomiting upper right stomach-area (abdomen) pain yellowing of your skin or eyes (jaundice) dark (tea-colored) urine pale or light colored stools Your doctor should do a blood test to check you for liver problems before you start treatment with terbinafine tablets. Your doctor may also check you for liver problems during treatment, and tell you to stop taking terbinafine tablets if you develop liver problems. What are terbinafine tablets? Terbinafine tablets are a prescription medicine used to treat fungal infections of the fingernails and toenails (onychomycosis). Your doctor should do tests to check you for fungal infection of your nails before you start terbinafine tablets. It is not known if terbinafine tablets, are safe and effective in children for the treatment of onychomycosis. Who should not take terbinafine tablets? Do not take terbinafine tablets if you have had a severe allergic reaction to terbinafine hydrochloride when taken by mouth. have had liver disease for a long time (chronic) or have active liver disease. What should I tell my doctor before taking terbinafine tablets? Before taking terbinafine tablets, tell your doctor about all of your medical conditions, including if you: have or had liver problems have a weakened immune system (immunocompromised) have lupus (an autoimmune disease) are pregnant or plan to become pregnant. It is not known if terbinafine tablets will harm your unborn baby. You should not start taking terbinafine tablets during pregnancy. are breastfeeding or plan to breastfeed. Terbinafine hydrochloride passes into your breast milk and may harm your baby. You should not breastfeed while taking terbinafine tablets. Talk to your doctor about the best way to feed your baby if you take terbinafine tablets. Tell your doctor about all the medicines you take, How should I take terbinafine tablets? Take terbinafine tablets exactly as your doctor tells you to take them. Terbinafine hydrochloride comes as a tablet that you take by mouth. Terbinafine tablets are usually taken: 1 time each day for 6 weeks to treat fungal infections of your fingernail, or 1 time each day for 12 weeks to treat fungal infections of your toenail Terbinafine tablets can be taken with or without food. If you miss a dose of terbinafine tablets, take it as soon as you remember. If it is less than 4 hours before your next dose, skip the missed dose. Just take the next dose at your regular time. If you take too many terbinafine tablets, call your doctor. You may have the following symptoms: nausea stomach-area (abdomen) pain rash headache vomiting dizziness frequent urination What should I avoid while taking terbinafine tablets? Avoid sunlight. Terbinafine tablets can make your skin sensitive to the sun and the light from sunlamps and tanning beds. You can get a severe sunburn. Use sunscreen and wear a hat and clothes that cover your skin if you have to be in sunlight. Talk to your doctor if you get sunburn. What are the possible side effects of terbinafine tablets? Terbinafine tablets may cause serious side effects, including: See “What is the most important information I should know about terbinafine tablets?” Change in your sense of taste or loss of taste change in your sense of taste or loss of taste poor appetite change in your mood or depressive symptoms weight loss anxiousness See the list of depressive symptoms below. Change in your sense of smell or loss of smell Depressive symptoms. Tell your doctor right away if you develop any of these signs or symptoms: feel sad or worthless change in sleep pattern loss of energy or interest in daily activities restlessness mood changes Low white blood cell count. Serious skin or allergic reactions, which may include problems with some of your body organs. Tell your doctor right away or get emergency medical skin rash hives sores in your mouth, or your skin blisters and peels swelling of your face, eyes, lips, tongue or throat trouble swallowing or breathing fever swollen lymph glands Also tell your doctor about any new symptoms, such as cough, chest pain, fast heartbeat, or blood in your urine. New or worsening lupus. a skin rash that gets worse (progresses), is scaly, red, shows scarring, or loss of skin color unusual sensitivity to the sun that can cause a rash The most common side effects of terbinafine tablets include: headache diarrhea rash upset stomach abnormal liver function tests itching nausea stomach-area (abdomen) pain gas These are not all of the possible side effects of terbinafine tablets. terbinafine tablets? Store terbinafine tablets at 20° to 25°C (68° to 77°F). Keep terbinafine tablets in a tightly closed container and keep out of the light. Keep terbinafine tablets and all medicines out of the reach of children. terbinafine tablets. terbinafine tablets? www.aurobindousa.com/product-medication-guides Aurobindo Pharma USA, Inc. Aurobindo Pharma Limited

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