Consumer medicine information

APO-Terbinafine

Terbinafine

BRAND INFORMATION

Brand name

APO-Terbinafine

Active ingredient

Terbinafine

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using APO-Terbinafine.

What is in this leaflet

This leaflet answers some common questions about this medicine. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking this medicine against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What this medicine is used for

Terbinafine is used to treat:

  • fungal infections of the finger nails and toe nails
  • tinea (ringworm) infections of the groin and body
  • tinea infections of the feet, commonly called "athlete's foot"

These infections are caused by a group of fungi called dermatophytes.

Terbinafine works by killing dermatophytes.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed this medicine for another reason.

It is available only with a doctor's prescription.

There is no evidence that this medicine is addictive.

This medicine should not be used in children.

Before you take this medicine

When you must not take it

Do not take this medicine if you have an allergy to:

  • any medicine containing terbinafine
  • any of the ingredients listed at the end of this leaflet

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin

Do not take this medicine if you have or have had a problem with your liver. This medicine is not recommended if you currently have a liver problem because it may make the problem worse. If you had a liver problem in the past and your liver is functioning normally now, your doctor may prescribe this medicine, but may want to check your liver function before and during treatment. Your doctor might take blood tests to monitor your liver function. In case of abnormal test results, he or she may ask you to stop taking this medicine.

Do not take this medicine if you have or have had a problem with your kidneys.

Do not take this medicine if you are pregnant. Do not take this medicine whilst pregnant until you and your doctor have discussed the risks and benefits involved.

Do not breastfeed if you are taking this medicine. This medicine passes into breast milk. Do not take this medicine whilst breastfeeding as there is a possibility that your baby could be affected.

Do not take this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start taking this medicine, talk to your doctor.

Before you start to take it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

  • problems with your liver
  • problems with your kidney
  • skin problems (e.g. psoriasis or lupus erythematosus)
  • blood disorders, or experience weakness, unusual bleeding, bruising or frequent infections

Tell your doctor if you are pregnant or plan to become pregnant or are breastfeeding. Your doctor can discuss with you the risks and benefits involved.

Tell your doctor if you have skin problems such as rash, red skin, blistering of the lips, eyes or mouth, skin peeling, fever (possible signs of serious skin reactions), or rash due to high level of a specific type of white blood cells (eosinophilia).

Tell your doctor if you have or have had thickened patches of red/ silver skin (psoriasis), or facial rash, joint pain, muscle disorder or fever (cutaneous and systemic lupus erythematosus).

If you have not told your doctor about any of the above, tell them before you start taking this medicine.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interact with terbinafine. These include:

  • some medicines used to treat depression and other mental disorders, including obsessive-compulsive disorders and panic attacks e.g. tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and monoamine oxidase inhibitors (MAOIs).
  • some medicines for Parkinson's disease
  • some medicines used to treat an irregular heartbeat, heart problems, high blood pressure and migraines (e.g. metoprolol)
  • some medicines used to treat stomach ulcers (e.g. cimetidine)
  • certain antibiotics (e.g. rifampicin)
  • dextromethorphan, a cough suppressant
  • caffeine
  • cyclosporin, used to help prevent organ transplant rejection, or to treat certain problems with the immune system
  • fluconazole, to treat fungal infections
  • oral contraceptives (birth control pills) - you may have problems, such as bleeding between periods, while you are taking terbinafine
  • warfarin, used to prevent blood clots.

These medicines may be affected by terbinafine or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

Other medicines not listed above may also interact with terbinafine.

How to take this medicine

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

If you do not understand the directions, ask your doctor or pharmacist for help.

How much to take

Your doctor will tell you how much of this medicine you should take. This will depend on your condition and whether you are taking any other medicines.

The usual dose of terbinafine is one tablet (250 mg) taken once each day.

How to take it

Swallow the tablet with a full glass of water.

If you find that terbinafine upsets your stomach, try taking it immediately after a light meal.

When to take it

Take your medicine at about the same time each day. Taking it at the same time each day will have the best effect. It will also help you remember when to take it.

How long to take it for

Continue taking your medicine for as long as your doctor tells you. Do not take it for longer than this.

If you forget to take it

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Otherwise, take it as soon as you remember, and then go back to taking your medicine as you would normally.

Do not take a double dose to make up for the dose that you missed. This may increase the chance of you experiencing side effects.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering to take your medicine, ask your pharmacist for some hints.

If you take too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone 13 11 26) for advice or go to Accident and Emergency at the nearest hospital, if you think that you or anyone else may have taken too much of this medicine. Do this even if there are no signs of discomfort or poisoning.

You may need urgent medical attention.

While you are taking this medicine

Things you must do

Make sure you are taking your tablet every day and continue taking it until your doctor tells you to stop. This will ensure that all of the infection is gone and will lessen the chance of the infection coming back once you stop taking this medicine.

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking this medicine.

Tell any other doctors, dentists, and pharmacists who treat you that you are taking this medicine.

If you are going to have surgery, tell the surgeon or anaesthetist that you are taking this medicine. It may affect other medicines used during surgery.

If you become pregnant or start to breastfeed while taking this medicine, tell your doctor immediately.

If you are about to have any blood tests, tell your doctor that you are taking this medicine. It may interfere with the results of some tests.

Keep all your doctor's appointments so that your progress can be checked. Your doctor may do some tests from time to time to make sure the medicine is working and to prevent unwanted side effects.

Any side effects on your liver, kidneys or blood can be detected by blood tests.

Things you must not do

Do not take this medicine to treat any other complaints unless your doctor tells you to.

Do not give your medicine to anyone else, even if they have the same condition as you.

Do not stop taking your medicine or lower the dosage without checking with your doctor.

Things to be careful of

Be careful driving or operating machinery or doing jobs that require you to be alert while you are taking terbinafine until you know how it affects you. This medicine may cause dizziness, light headedness, tiredness, and drowsiness in some people. If you have any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous.

Be careful to keep the infected areas dry and cool and change clothing that is in direct contact with the infected areas every day. This will help to clear up the infection and make sure it does not return.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking this medicine.

All medicines have side effects. Sometimes they are serious but most of the time they are not.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following:

  • nausea (feeling sick) or vomiting
  • upset stomach (heartburn, cramps, wind, belching)
  • loss of appetite
  • diarrhoea
  • aching joints or muscles
  • headache
  • dizziness or light headedness
  • tiredness, sleepiness
  • loss of or change in sense of taste, which usually returns to normal within several weeks of stopping terbinafine
  • other skin problems
  • psoriasis (thickened patches of red skin, often with silvery scales)
  • hair loss
  • tingling or numbness
  • decreased physical sensitivity
  • change in your vision or the appearance of your eye
  • smell disorders or loss of smell
  • anxiety (with symptoms such as sleep disturbances, fatigue, loss of energy or diminished ability to think or concentrate) and depressive symptoms (e.g. depressed mood)
  • decreased hearing, impaired hearing and/or perception of noises in the absence of sound (e.g. hissing or ringing) in ears

If any of the following happen, tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

  • chest pain
  • signs of a possible serious liver problem such as persistent nausea, loss of appetite, unusual tiredness, vomiting, pain in the upper right abdomen, yellowing of the skin and/or eyes, dark urine or pale bowel motions
  • signs of a serious skin reaction such as painful red areas, large blisters, peeling of layers of skin, bleeding in the lips, eyes, mouth, nose or genitals – these signs may be accompanied by fever and chills, aching muscles and feeling generally unwell
  • signs of a possible blood problem such as constant "flu-like" symptoms (fever, sore throat, mouth ulcers, chills, swollen glands, lack of energy) or unusual bleeding or bruising
  • any other signs of infection, apart from the fungal infection you are being treated for
  • possible signs of diseases that affect certain types of blood cells – unusual bleeding or bruising
  • possible signs of a disease that affects the level of red blood cells including abnormal pale skin, mucosal lining or nail beds, unusual tiredness or weakness or breathlessness on exertion
  • possible signs of blood vessel inflammation – rash, fever, itching, tiredness or if you notice appearance of purplish-red spots under the skin surface
  • possible signs of pancreas inflammation – severe upper stomach pain with radiation to the back
  • possible signs of muscle necrosis – unexplained muscle weakness and pain or dark (red-brown) urine
  • symptoms of an allergic reaction including cough, shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue, throat or other parts of the body; rash, itching or hives on the skin

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation. These side effects are very rare.

Tell your doctor or pharmacist if you notice anything that is making you feel unwell.

Other side effects not listed above may occur in some patients.

Some of these side effects can only be found when your doctor does tests from time to time to check your progress.

Storage and Disposal

Storage

Keep your medicine in its original packaging until it is time to take it. If you take your medicine out of its original packaging, it may not keep well.

Keep your medicine in a cool dry place where the temperature will stay below 25°C. Protect from light.

Do not store your medicine or any other medicine, in the bathroom or near a sink. Do not leave it on a window sill or in the car. Heat and dampness can destroy some medicines.

Keep this medicine where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product description

What APO-Terbinafine Tablet looks like

250mg Tablet: white, round, uncoated biconvex tablets with bevelled edges engraved with "APO" on one side and "TER" over "250" and scored through the centre of the other. AUST R 100025.

Available in packs of 42 tablets.

Ingredients

Each tablet contains 250 mg of terbinafine (as hydrochloride) as the active ingredient.

It also contains the following inactive ingredients:

  • methylcellulose
  • croscarmellose sodium
  • magnesium stearate
  • colloidal anhydrous silica

This medicine is does not contain gluten, lactose, sucrose, tartrazine and other azo dyes.

Sponsor

Apotex Pty Ltd
16 Giffnock Avenue
Macquarie Park NSW 2113
AustraliaTel: (02) 8877 8333
Web: www1.apotex.com/au

This leaflet was last updated in:
September 2019.

Published by MIMS December 2019

BRAND INFORMATION

Brand name

APO-Terbinafine

Active ingredient

Terbinafine

Schedule

S4

 

1 Name of Medicine

Terbinafine (as hydrochloride).

6.7 Physicochemical Properties

Terbinafine hydrochloride is a white to off-white, finely crystalline powder. It is soluble in isopropyl alcohol (> 70 mg/mL at 25°C) and ethanol (> 70 mg/mL at 25°C), and slightly soluble in water (6.3 mg/mL at 25°C).
Chemical name: (E)-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-1- naphthalenemethanamine hydrochloride.
Molecular Formula: C21H26ClN.
Molecular Weight: Terbinafine base: 291.44. Terbinafine Hydrochloride: 327.90.

Chemical structure.


CAS number.

78628-80-5.

2 Qualitative and Quantitative Composition

Each tablet contains 250 mg terbinafine (as hydrochloride) as the active ingredient.
For the full list of excipients see Section 6.1 List of Excipients.

3 Pharmaceutical Form

White, round, uncoated biconvex tablets with bevelled edges engraved with "APO" on one side and "TER" over "250" and scored through the centre of the other.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Oral antifungal agent, ATC Code: D01BA02.
Terbinafine is an allylamine with antifungal activity mainly against dermatophytes, including Trichophyton (e.g. T. rubrum, T. mentagrophytes, T. verrucosum, T. violaceum), Microsporum canis, and Epidermophyton floccosum.

Mechanism of action.

Terbinafine interferes specifically with fungal sterol biosynthesis at an early step. This leads to a deficiency in ergosterol and to an intracellular accumulation of squalene, resulting in fungal cell death. Terbinafine acts by inhibition of squalene epoxidase in the fungal cell membrane. The enzyme squalene epoxidase is not linked to the cytochrome P450 system. When administered orally, the drug concentrates in skin and nails at levels associated with antifungal activity.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Following oral administration, terbinafine is well absorbed (> 70%).
A single oral dose of 250 mg terbinafine results in peak plasma concentrations of 0.97 microgram/mL within 2 hours of administration. The absorption half-life is 0.8 hours and the distribution half-life is 4.6 hours.
An increase in the AUC of terbinafine of less than 20% is observed when terbinafine is administrated with food. 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.

Distribution.

Terbinafine binds strongly to plasma proteins (99%). It concentrates in the lipophilic stratum corneum. Terbinafine is also secreted in sebum, thus achieving high concentrations in hair follicles, hair and sebum-rich skins. There is also evidence from animal studies that terbinafine is distributed into the nail plate in the first few weeks after commencing therapy. Animal studies also indicate that terbinafine accumulates in all lipophilic tissues including the retinal and choroid tissues. In studies conducted so far, no ophthalmological abnormalities attributable to terbinafine have been reported in humans.

Metabolism.

Terbinafine is extensively metabolised in the body. Biotransformation results in metabolites with no antifungal activity.

Excretion.

Terbinafine and its metabolites are excreted predominantly in the urine. The elimination half-life is 17 hours. There is no evidence of accumulation in individuals with normal hepatic and renal function. No age dependent changes in pharmacokinetics have been observed. In patients with renal impairment (creatinine clearance ≤ 50 mL/min) or with pre-existing liver disease, the clearance of terbinafine is decreased by approximately 50% compared to normal volunteers.
When administered orally, the drug concentrates in skin and nails at levels associated with antifungal activity.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

In a 2 year rat carcinogenicity study, small but significant increases in hepatocellular carcinomas, adenomas and combined tumours were seen in males at a dietary dose of 69 mg/kg per day. No increase in hepatic tumours was seen in female rats at a dietary dose of 97 mg/kg per day.

4 Clinical Particulars

4.1 Therapeutic Indications

Terbinafine is indicated for:
Treatment in adults of ringworm (tinea corporis, tinea cruris and tinea pedis) due to infection caused by dermatophytes such as Trichophyton (e.g. T. rubrum, T. mentagrophytes, T. verrucosum, T. violaceum), Microsporum canis and Epidermophyton floccosum, where oral therapy is considered appropriate owing to the site, severity or extent of the infection and the infection is not responsive to topical therapy;
Onychomycosis in adults (fungal infection of the nail) caused by dermatophyte fungi.

4.3 Contraindications

Hypersensitivity to terbinafine or any of the excipients in the formulation (see Section 6.1 List of Excipients).
Severe, chronic, or active hepatic disease (see Section 4.4 Special Warnings and Precautions for Use).

4.4 Special Warnings and Precautions for Use

Use in hepatic impairment.

Terbinafine is contraindicated for patients with chronic or active hepatic disease. Before prescribing terbinafine tablets, liver function tests should be performed since hepatotoxicity may occur in patients with and without pre-existing liver disease. Therefore periodic monitoring (after 4-6 weeks of treatment) of liver function tests is recommended. Terbinafine should be immediately discontinued in case of elevation of liver function tests. Very rare cases of liver failure, some leading to death or liver transplant, have been reported with the use of terbinafine. In the majority of liver failure cases, the patients had underlying systemic conditions (see Section 4.8 Adverse Effects (Undesirable Effects)). Patients prescribed terbinafine tablets should be warned to report immediately 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.

Use in renal impairment.

The use of terbinafine tablets in patients with impaired renal function (creatinine clearance less than 50 mL/min or serum creatinine of more than 300 micromol/L) has not been adequately studied and, therefore, is not recommended.

Effect on vision.

During high dose studies in monkeys, refractile irregularities were observed in the retina at doses that were 30 to 60 times the human dose (nontoxic effect level 50 mg/kg). The clinical relevance of this observation is unknown. However, the ocular effects in monkeys were not confirmed in humans in the placebo controlled trials, where the incidence of ophthalmic abnormalities was lower in the terbinafine tablet treated patients (1.1%) compared with those who received placebo (1.5%).

Effect on blood.

Patients taking terbinafine tablets are at risk of developing agranulocytosis, thrombocytopenia, neutropenia and pancytopenia which are very rarely associated with terbinafine. The problem usually resolves within a few days to a week of withdrawal of terbinafine. Patients taking terbinafine should be advised to report any symptoms of infections. Prescribers should examine the patient to determine the correct aetiology of any blood dyscrasias that occurs in patients treated with terbinafine, and consideration should be given to a possible change in medication regimen, including discontinuation of treatment with terbinafine.

Transient decreases in absolute lymphocyte counts (ALC).

Transient decreases in absolute lymphocyte counts (ALC) 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 1,000/mm3 on two or more occasions. The clinical significance of this observation is unknown. However, in patients with known or suspected immunodeficiency, physicians should consider monitoring complete blood counts in individuals using terbinafine therapy for greater than six weeks.

Dermatological effects.

Serious skin reactions (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms) have been very rarely reported in patients taking terbinafine tablets.
If progressive skin rash occurs, treatment with terbinafine tablets should be discontinued.
Terbinafine should be used with caution in patients with pre-existing psoriasis or lupus erythematosus as precipitation and exacerbation of psoriasis and cutaneous and systemic lupus erythematosus have been reported in a postmarketing setting.

Effect on lipids.

In chronic toxicity studies in rats, oral terbinafine, at a dose of 309 mg/kg per day, increased serum cholesterol levels.
This effect was more marked in female, than in male rats. Effects on triglyceride levels were not consistent among the various studies. In monkeys a daily dose of 300 mg/kg increased triglyceride levels and chylomicron concentrations. In a small clinical study, a daily dose of 250 mg for 8 weeks did not result in detectable changes in the plasma lipid profile. In other clinical trials there was no evidence of a significant change in the plasma lipid profile of patients.

Paediatric use.

There is no experience with terbinafine in children and its use cannot be recommended.
This product should be kept out of reach of children.

Use in the elderly.

There is no evidence to suggest that elderly patients require different dosages or experience side effects different from those in younger patients. When using tablets in this age group the possibility of impairment of liver or kidney function should be considered (see Section 4.4 Special Warnings and Precautions for Use).

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

The plasma clearance of terbinafine may be accelerated by drugs that induce metabolism (see Rifampicin), and may be inhibited by drugs that inhibit (see Cimetidine) cytochrome P450. Where co-administration of such agents is necessary, the dosage of terbinafine may need to be adjusted accordingly.
Cautious use of terbinafine is advised in women taking oral contraceptives since a few cases of menstrual disorders have been reported in patients taking this drug combination, although the incidence of these disorders remains within the background incidence of patients taking oral contraceptives alone.
There have been spontaneous reports of increase or decrease in prothrombin times in patients concomitantly taking oral terbinafine and warfarin, however, a causal relationship between terbinafine tablets and these changes has not been established.

The following medicinal products may increase the effect or plasma concentration of terbinafine.

Cimetidine.

Cimetidine decreased the clearance of terbinafine by 33%. Where co-administration of such agents is necessary, the dosage of terbinafine may need to be adjusted accordingly.

Fluconazole.

Fluconazole significantly increased the Cmax and AUC of terbinafine, due to inhibition of both CYP2C9 and CYP3A4 enzymes. Similar increase in exposure may occur when other drugs which may inhibit both CYP2C9 and CYP3A4, such as ketoconazole and amiodarone, are concomitantly administered with terbinafine.

The following medicinal products may decrease the effect or plasma concentration of terbinafine.

Rifampicin.

Rifampicin increased the clearance of terbinafine by 100%. Where co-administration of such agents is necessary, the dosage of terbinafine may need to be adjusted accordingly.

Effect of terbinafine on other medicinal products.

In vitro and in vivo studies showed negligible potential for interaction with the drugs that are metabolised via the CYP450 system except those with CYP2D6-mediated metabolism.
Terbinafine does not interfere with the metabolism of antipyrine or digoxin. Terbinafine clearance is unaffected by cyclosporine.
There was no effect of terbinafine on the pharmacokinetics of fluconazole. Further there was no clinically relevant interaction between terbinafine and the potential comedications cotrimoxazole (trimethoprim and sulfamethoxazole), zidovudine or theophylline.

Terbinafine may increase the effect or plasma concentration of the following medicinal products.

Compounds predominantly metabolised by CYP2D6.

Terbinafine inhibits the CYP2D6-mediated metabolism. Therefore, patients receiving concomitant treatment with drugs predominantly metabolised by this enzyme, such as tricyclic antidepressants (TCAs; e.g. desipramine), beta-blockers, selective serotonin reuptake inhibitors (SSRIs), antiarrhythmics Class 1A, 1B and 1C and monoamine oxidase inhibitors (MAOIs) Type B, should be followed, if the co-administered drug has a narrow therapeutic window.
In studies in healthy subjects characterised as extensive metabolisers of dextromethorphan (antitussive drug and CYP2D6 probe substrate), terbinafine significantly increased the dextromethorphan/dextrorphan metabolic ratio in urine. Thus terbinafine may convert extensive CYP2D6 metabolisers to poor metaboliser status.

Caffeine.

Terbinafine decreased the clearance of caffeine administered intravenously by 19%.

Terbinafine may decrease the effect or plasma concentration of the following medicinal products.

Cyclosporin.

Terbinafine increased the clearance of cyclosporin by 15%.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B1)
Foetal toxicity and fertility studies in animals suggest no adverse effects.
Since clinical experience in pregnant women is not available, terbinafine tablets should not be used during pregnancy unless the potential benefits outweigh any potential risks.
Terbinafine is excreted in breast milk. Therefore, mothers receiving oral treatment with terbinafine tablets should not breastfeed.

4.8 Adverse Effects (Undesirable Effects)

In general, terbinafine is well tolerated. In clinical trials, adverse events occurred in 10.4% of patients taking terbinafine and 5.6% of patients taking placebo. Most adverse events were mild to moderate in severity and of a short duration.
Adverse drug reactions from clinical trials experience are listed by MedDRA system organ class. Within each system organ class, the adverse drug reactions are ranked under heading by frequency, with the most frequent reactions first. The frequency category for each adverse drug reaction is based on the following convention (CIOMS III): very common (≥ 1/10); common (≥ 1/100 to, < 1/10); uncommon (≥ 1/1,000 to, < 1/100); rare (≥ 1/10,000 to, < 1/1,000); very rare (< 1/10,000).

Blood and lymphatic system disorders.

Transient decrease in haematocrit, haemoglobin, leucocytes.
Uncommon: anaemia.
Very rare: haematological disorders such as neutropenia, agranulocytosis, pancytopenia, thrombocytopenia.

Gastrointestinal disorders.

Very common: nausea, vomiting, flatulence, mild abdominal discomfort, abdominal cramps, anorexia, diarrhoea, dyspepsia/gastritis, belching, abdominal distension, decreased appetite.
Uncommon: taste disturbances, including taste loss, which usually recover within several weeks after discontinuation of the drug. Isolated cases of prolonged taste disturbances have been reported. A decrease of food intake leading to significant weight loss was observed in very few cases.

Hepatobiliary disorders.

Rare: transient increases in liver enzymes, hepatobiliary dysfunction, cholestatic jaundice, liver failure (some leading to liver transplant or death). In the majority of liver failure cases, the patients had underlying systemic conditions (see Section 4.3 Contraindications).

Immune system disorders.

Very rare: anaphylactoid reactions (including angioedema), cutaneous and systemic lupus erythematosus.

Musculoskeletal and connective tissue disorders.

Very common: musculoskeletal reactions (arthralgia, myalgia).

Psychiatric disorders.

Common: depression.
Very rare: anxiety.

Skin and subcutaneous tissue disorders.

Very common: urticaria, rash.
Common: pruritus, erythema.
Uncommon: photosensitivity reactions.
Very rare: psoriaform eruptions or exacerbation of psoriasis, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, acute generalised exanthematous pustulosis, cutaneous and systemic lupus erythematosus, anaphylactoid reactions (including angioedema), toxic skin eruption, dermatitis exfoliative, dermatitis bullous, alopecia. In the event of an allergic or severe skin reaction, terbinafine treatment should be discontinued.

Nervous system disorders.

Very common: headache.
Common: dysgeusia* including ageusia*, dizziness, tiredness/fatigue.
Uncommon: paraesthesia and hypoaesthesia.
Very rare: sedation, light-headedness, chest pain, hair loss and allergic reactions (including anaphylaxis).

Eye disorders.

Common: visual impairment.

Ear and labyrinth disorders.

Uncommon: tinnitus.

General disorders.

Uncommon: pyrexia.

Investigations.

Uncommon: weight decreased**.

Laboratory test.

Transient rises in serum urea/serum creatinine and liver enzyme. Transient decreases in haematocrit, haemoglobin, and leucocytes.
*Hypogeusia, including ageusia, which usually recover within several weeks after discontinuation of the drug. Isolated cases of prolonged hypogeusia have been reported.
**Weight decreased secondary to dysgeusia.

Other adverse drug reactions from post-marketing spontaneous reports.

The following adverse drug reactions have been identified based on post-marketing spontaneous case reports and literature cases. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency which is therefore categorised as not known. Adverse drug reactions are listed according to system organ classes in MedDRA.

Blood and lymphatic system disorders.

Anaemia.

Ear and labyrinth disorders.

Hypoacusis, impaired hearing tinnitus.

Eye disorders.

Vision blurred, visual acuity reduced.

Gastrointestinal disorders.

Pancreatitis.

General disorders and administration site conditions.

Influenza-like illness, pyrexia.

Immune system disorders.

Anaphylactic reaction, serum sickness-like reaction.

Investigations.

Blood creatine phosphokinase increased.

Musculoskeletal and connective tissue disorders.

Rhabdomyolysis.

Nervous system disorders.

Anosmia including permanent anosmia, hyposmia.

Psychiatric disorders.

Anxiety and depressive symptoms secondary to taste disturbances.

Skin and subcutaneous tissue disorders.

Photosensitivity reactions (e.g. photodermatosis, photosensitivity allergic reaction and polymorphic light eruption), drug rash with eosinophilia and systemic symptoms.

Vascular disorders.

Vasculitis.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at http://www.tga.gov.au/reporting-problems and contact Apotex Medical Information Enquiries/Adverse Drug Reaction Reporting on 1800 195 055.

4.2 Dose and Method of Administration

APO-Terbinafine tablets are intended for oral administration.

Dosage.

Skin infections.

250 mg once a day.

Onychomycosis.

250 mg once a day.

Administration.

Terbinafine tablets should be taken orally. The bioavailability of terbinafine is not affected by a light meal.

Duration of treatment.

Oral terbinafine should be prescribed only after topical therapy has failed and for the shortest time possible.
The duration of treatment varies according to the indication and the severity of the infection.

Skin infections.

Likely durations of treatment are as follows:
tinea pedis (interdigital, plantar/moccasin type): 2 to 6 weeks;
tinea corporis, cruris: 2 to 4 weeks.
Complete resolution of the signs and symptoms of infection may not occur until several weeks after mycological cure.

Onychomycosis.

For most patients the duration for successful treatment is between 6 weeks and 3 months.
Infections of finger and toenails (other than big toe) usually respond to the shorter duration of treatment, particularly in patients of younger age with a normal rate of nail outgrowth. In patients with slow nail growth, treatment for up to three months is usually adequate. However, infections in the big toe, or if nail growth is very poor, treatment for up to 6 months may be necessary.
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 tissue.

4.7 Effects on Ability to Drive and Use Machines

No studies on the effects of terbinafine tablets treatment on the ability to drive and use machines have been performed. Patients who experience dizziness as an undesirable effect should avoid driving vehicles or using machines.

4.9 Overdose

A few cases of overdosage (up to 5 g) have been reported.

Symptoms.

Studies in animals suggest that in a high dose situation, such as accidental overdose, central nervous symptoms (CNS) may appear. The relevance of those effects to man is unknown. However, these effects can be monitored.

Central nervous system.

Headache and dizziness.

Gastrointestinal system.

Nausea, and epigastric pain.

Treatment.

The recommended treatment of overdosage consists in eliminating the drug, primarily by the administration of activated charcoal and giving symptomatic supportive therapy, if needed. Activated charcoal may reduce the absorption of the drug if given within one or two hours of ingestion. In patients who are not fully conscious or have an impaired gag reflex, consideration should be given to administering activated charcoal via a nasogastric tube, once the airway is protected.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Methylcellulose, croscarmellose sodium, magnesium stearate, colloidal anhydrous silica.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C. Protect from light.

6.5 Nature and Contents of Container

250 mg tablets.

APO-Terbinafine tablets.

Blister pack (PVC/PVDC/Al) of 42 tablets (AUST R 100025).

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

Summary Table of Changes