Prescription Drug Information: Terbinafine (Page 3 of 3)

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Terbinafine is an allylamine antifungal [see Clinical Pharmacology (12.4)] .

12.2 Pharmacodynamics

The pharmacodynamics of terbinafine tablets is unknown.

12.3 Pharmacokinetics

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 mcg•h/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. In patients with renal impairment (creatinine clearance less than or equal to 50 mL/min) or hepatic cirrhosis, the clearance of terbinafine is decreased by approximately 50% compared to normal volunteers. No effect of gender on the blood levels of terbinafine was detected in clinical trials. No clinically relevant age-dependent changes in steady-state plasma concentrations of terbinafine have been reported.

12.4 Microbiology

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 , terbinafine hydrochloride may be fungicidal. However, the clinical significance of in vitro data is unknown.
Terbinafine has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections:
Trichophyton mentagrophytes
Trichophyton rubrum
The following in vitro data are available, but their clinical significance is unknown. In vitro , terbinafine exhibits satisfactory MIC’s against most strains of the following microorganisms; however, the safety and efficacy of terbinafine in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials:
Candida albicans
Epidermophyton floccosum
Scopulariopsis brevicaulis
Susceptibility Testing

For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility


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 (mutations in E. coli and S. typhimurium , DNA repair in rat hepatocytes, mutagenicity in Chinese hamster fibroblasts, chromosome aberration, and sister chromatid exchanges in Chinese hamster lung cells), and in vivo (chromosome aberration in Chinese hamsters, micronucleus test in mice) genotoxicity tests gave no evidence of a mutagenic or clastogenic potential.

Oral reproduction studies in rats at doses up to 300 mg/kg/day (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.

13.2 Animal Toxicology and/or Pharmacology


A wide range of in vivo studies in mice, rats, dogs, and monkeys, and in vitro studies using rat, monkey, and human hepatocytes suggest that peroxisome proliferation in the liver is a rat-specific finding. However, other effects, including increased liver weights and APTT, occurred in dogs and monkeys at doses giving C ss trough levels of the parent terbinafine 2 to 3 times those seen in humans at the MRHD. In a 52-week oral toxicology study conducted in juvenile maturing dogs, increased heart and liver weights were noted in males and signs of CNS disturbance including 3 cases of single episodes of seizures were noted in females at the highest dose tested, 100 mg/kg/day [19 times (males) and 10 times (females) the MRHD based on AUC comparisons of the parent terbinafine]. No treatment related findings were noted at 30 mg/kg/day [1.6 times (males) and 1.9 times (females) the MRHD based on AUC comparisons of the parent terbinafine] in this study.

14 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 5mm 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%.

16 HOW SUPPLIED/STORAGE AND HANDLING

Terbinafine Tablets USP, 250 mg are supplied as white to off-white, round uncoated, biconvex beveled edge tablets having ‘D’ debossed on one side and ‘74’ on the other side.

NDC: 70518-2941-00

PACKAGING: 30 in 1 BLISTER PACK

Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from light.

Repackaged and Distributed By:

Remedy Repack, Inc.

625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-Approved Medication Guide.

Patients taking terbinafine tablets should receive the following information and instructions:

  • Advise patients to immediately report to their physician or get emergency help if they experience any of the following symptoms: hives, mouth sores, blistering and peeling of skin, swelling of face, lips, tongue, or throat, difficulty swallowing or breathing. Terbinafine tablets treatment should be discontinued.
  • Advise patients to immediately report to their physician any symptoms of persistent nausea, anorexia, fatigue, vomiting, right upper abdominal pain, jaundice, dark urine, or pale stools. Terbinafine tablets treatment should be discontinued.
  • Advise patients to report to their physician any signs of taste disturbance, smell disturbance and/or depressive symptoms, fever, skin eruption, lymph node enlargement, erythema, scaling, loss of pigment, and unusual photosensitivity that can result in a rash. Terbinafine tablets treatment should be discontinued.
  • Advise patients to minimize exposure to natural and artificial sunlight (tanning beds or UVA/B treatment) while using terbinafine tablets.
  • Advise patients that if they forget to take terbinafine tablets, to take their tablets as soon as they remember, unless it is less than 4 hours before the next dose is due.
  • Advise patients to call their physician if they take too many terbinafine tablets.
  • Advise patients to call their physician if they become pregnant during treatment with terbinafine tablets.

Dispense with Medication Guide available at: www.aurobindousa.com/product-medication-guides

Distributed by:
Aurobindo Pharma USA, Inc.
279 Princeton-Hightstown Road
East Windsor, NJ 08520
Manufactured by:
Aurobindo Pharma Limited
Hyderabad-500 038, India
Revised: 04/2019

Repackaged By / Distributed By: RemedyRepack Inc.

625 Kolter Drive, Indiana, PA 15701

(724) 465-8762

Medication Guide

Terbinafine Tablets, USP
[Terbinafine (ter BIN na feen)]

What is the most important information I should know about terbinafine tablets?

Terbinafine tablets may cause serious side effects, including:

  • Liver problems that can lead to the need for a liver transplant or death. This can happen in people who have liver problems and in people who have never had liver problems. Tell your doctor right away if you get any of these symptoms of liver problems:
  • 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 may harm your unborn baby.

Tell your doctor right away if you become pregnant during treatment with terbinafine tablets.

  • are breastfeeding or plan to breastfeed. Terbinafine hydrochloride passes into your breast milk and may harm your baby. 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, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Terbinafine tablets may affect the way other medicines work and other medicines may affect how terbinafine tablets work.

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
  • vomiting
  • stomach-area (abdomen) pain
  • dizziness
  • rash
  • frequent urination
  • headache

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 is common with terbinafine tablets, but can also be severe. This may improve within several weeks after you stop taking terbinafine tablets, but may last for a long time or may become permanent. Tell your doctor if you develop any of the following:
    • 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 may happen with terbinafine tablets. This may improve after you stop taking terbinafine tablets, but may last for a long time or may become permanent. Tell your doctor if you have a 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. Terbinafine tablets may decrease your white blood cell count, especially neutrophils. You may have a higher risk of getting an infection when your white blood cell count is low.
  • Serious skin or allergic reactions, which may include problems with some of your body organs. Tell your doctor right away or get emergency medical help if you get any of these symptoms:
    • 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. Stop taking terbinafine tablets and tell your doctor if you get any of the following:
    • 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

  • Blood clotting problems. When taking terbinafine tablets, you may develop a blood clotting problem, that can sometimes cause death. Tell your doctor, if you get any unexplained bleeding or bruising.

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.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store 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.

General information about the safe and effective use of terbinafine tablets.

Medicines are sometimes prescribed for purposes other than those listed in Medication Guide. Do not use terbinafine tablets for a condition for which it was not prescribed. Do not give terbinafine tablets to other people, even if they have the same symptoms that you have. They may harm them. You can ask your pharmacist or doctor for information about terbinafine tablets that is written for health professionals.

What are the ingredients in terbinafine tablets?

Active ingredient: Terbinafine hydrochloride
Inactive ingredients: Microcrystalline cellulose, sodium starch glycolate, colloidal silicon dioxide, hypromellose, and magnesium stearate.
This Medication Guide has been approved by the U.S. Food and Drug Administration

Dispense with Medication Guide available at: www.aurobindousa.com/product-medication-guides

Distributed by:
Aurobindo Pharma USA, Inc.
279 Princeton-Hightstown Road
East Windsor, NJ 08520
Manufactured by:
Aurobindo Pharma Limited
Hyderabad-500 038, India Revised: 04/2019

Repackaged By / Distributed By: RemedyRepack Inc.

625 Kolter Drive, Indiana, PA 15701

(724) 465-8762

DRUG: Terbinafine

GENERIC: Terbinafine Hydrochloride

DOSAGE: TABLET

ADMINSTRATION: ORAL

NDC: 70518-2941-0

COLOR: white

SHAPE: ROUND

SCORE: No score

SIZE: 11 mm

IMPRINT: D;74

PACKAGING: 30 in 1 BLISTER PACK

ACTIVE INGREDIENT(S):

  • TERBINAFINE HYDROCHLORIDE 250mg in 1

INACTIVE INGREDIENT(S):

  • MICROCRYSTALLINE CELLULOSE
  • SODIUM STARCH GLYCOLATE TYPE A POTATO
  • SILICON DIOXIDE
  • HYPROMELLOSE 2910 (5 MPA.S)
  • MAGNESIUM STEARATE
Remedy_Label
(click image for full-size original)
TERBINAFINE terbinafine hydrochloride tablet
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:70518-2941(NDC:65862-079)
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
TERBINAFINE HYDROCHLORIDE (TERBINAFINE) TERBINAFINE 250 mg
Inactive Ingredients
Ingredient Name Strength
MICROCRYSTALLINE CELLULOSE
SODIUM STARCH GLYCOLATE TYPE A POTATO
SILICON DIOXIDE
HYPROMELLOSE 2910 (5 MPA.S)
MAGNESIUM STEARATE
Product Characteristics
Color white (White to Off-white) Score no score
Shape ROUND (Biconvex Beveled Edge) Size 11mm
Flavor Imprint Code D;74
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:70518-2941-0 30 TABLET in 1 BLISTER PACK None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA078297 11/13/2020
Labeler — REMEDYREPACK INC. (829572556)

Revised: 11/2020 REMEDYREPACK INC.

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