Consumer medicine information

Terbinafine-DRLA Tablets

Terbinafine

BRAND INFORMATION

Brand name

Terbinafine-DRLA

Active ingredient

Terbinafine

Schedule

What is in this leaflet

This leaflet answers some common questions about Terbinafine-DRLA tablets. It does not contain information about other forms of terbinafine that are available without a prescription from your pharmacy.

It does not contain all the available information about terbinafine tablets. 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 provide.

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

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

What Terbinafine-DRLA tablets are used for

Terbinafine-DRLA tablets are 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 the dermatophytes.

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

Terbinafine-DRLA tablets are only available with a doctor's prescription. This medicine is not addictive.

There is not enough information to recommend the use of this medicine in children.

Before you take Terbinafine-DRLA tablets

When you must not take it

Do not take Terbinafine-DRLA if you have ever had an allergic reaction to:

terbinafine, the active ingredient, or to any of the other ingredients listed at the end of this leaflet
any other medicines, foods, preservatives or dyes

Your doctor will want to know if you are prone to allergies.

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 Terbinafine-DRLA tablets:

if you have any problems with your kidneys
if you have or ever 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 terbinafine but may want to check your liver function before and during treatment with this medicine. 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 Terbinafine-DRLA.

Do not take Terbinafine-DRLA tablets after the expiry date printed on the pack, or if the packaging is torn or shows signs of tampering. In that case, return it to your pharmacist.

Before you start to take it

Tell your doctor if you:

are pregnant or intend to become pregnant

There is no experience with use of terbinafine tablets during pregnancy. If your doctor thinks it is necessary for you to take it, he/she will discuss with you the benefits and risks involved.

are breast-feeding

Breastfeeding is not recommended since terbinafine, the active ingredient in Terbinafine-DRLA tablets, passes into breast milk. There is a possibility that your baby could be affected.

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

or experience weakness, unusual bleeding, bruising or frequent infections

have or experience thickened patches of red/silver skin (psoriasis)

or facial rash, joint pain, muscle disorder, fever (cutaneous and systemic lupus erythematosus)

If you are not sure whether you should start taking Terbinafine-DRLA tablets, talk to your doctor or pharmacist.

Taking other medicines

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

Some medicines and Terbinafine-DRLA tablets may interfere with each other. These include:

some medicines used to treat depression and other mental disorders, including obsessive-compulsive disorders and panic attacks (e.g. some antidepressants such as tricyclic antidepressants, selective serotonin reuptake inhibitors including class 1A, 1B and 1C, monoamine oxidase inhibitors Type B, desipramine)
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)
some medicines called antibiotics used to treat infectious diseases (e.g. rifampicin)
caffeine
cyclosporin, a medicine used to help prevent organ transplant rejection or to treat certain problems with the immune system
oral contraceptives (birth control pills). You may have problems, such as bleeding between periods, while you are taking Terbinafine-DRLA tablets.
warfarin, a medicine used to prevent blood clots

You may need to take different amounts of your medicines or you may need to take different medicines.

Your doctor and pharmacist have more information.

If you have not told your doctor about any of these things, tell him/ her before you start taking this medicine.

How to take Terbinafine-DRLA tablets

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

If you do not understand the instructions on the label, ask your doctor or pharmacist for help.

How much to take

Follow your doctor's instructions on how many Terbinafine-DRLA tablets to take.

The usual dose of terbinafine is one tablet (250 mg) each day. If you have kidney problems, the dose may be reduced to one-half a tablet each day.

How to take it

Take the Terbinafine-DRLA tablet with a full glass of water. If you find that the tablet upsets your stomach, try taking it immediately after a light meal.

Take the tablet at about the same time each day. Taking your tablet 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

The length of your treatment will depend on the type of infection you have, what part of the body is affected and how well you respond to treatment.

Fungal skin infections (tinea):
If you have a tinea infection of the feet (athlete's foot), you will usually take the tablets for 2 to 6 weeks.

If you have a tinea infection of the body or groin, you will usually take the tablets for 2 to 4 weeks.

The signs and symptoms of infection may last for several weeks after the fungi (dermatophytes) have been killed.

Fungal nail infections:
Fungal nail infections usually take longer to heal than fungal skin infections. You will usually take the tablets for anywhere from 6 weeks to 3 months. But, if you have a nail infection of the big toe or your nails grow very slowly, you may need to take the tablets for up to 6 months.

It may take several months after you stop taking terbinafine tablets for your nail to look completely normal. That is because the deformed part of the nail has to grow out and be replaced by a healthy nail.

If you forget to take it

If it is almost time for your next dose (within 4 hours), skip the dose you missed and take the next dose when you are meant to.

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

Do not take a double dose to make up for the one that you missed. This may increase the chance of you getting an unwanted side effect.

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

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

If you take too much (Overdose)

Immediately telephone your doctor or Poisons Information Centre (telephone number 13 11 26), or go to Accident and Emergency at your nearest hospital if you think that you or anyone else may have taken too many Terbinafine-DRLA tablets. Do this even if there are no signs of discomfort or poisoning. Keep the telephone numbers for these places handy.

Some of the symptoms of an overdose may include headache, nausea (feeling sick), stomach pain and dizziness.

While you are taking Terbinafine-DRLA tablets

Things you must do

Make sure to take 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.

Make sure to have any blood tests done that are ordered by your doctor. Any side effects on your liver, kidneys or blood can be detected by blood tests.

Tell your doctor immediately if you notice any of the following:

fever
sore throat
mouth ulcers
"flu-like" symptoms (chills, aching joints, swollen glands, lack of energy)
any other signs of infection, apart from the fungal infection you are being treated for

If you become pregnant while taking Terbinafine-DRLA tablets, tell your doctor immediately. Your doctor can discuss with you the risks and benefits of taking it during pregnancy.

Remind your doctor and pharmacist that you are taking Terbinafine-DRLAl tablets if you are about to be started on any new medicine.

Tell any other doctor, dentist or pharmacist who treats you that you are taking Terbinafine tablets.

Things you must not do

Do not give this medicine to anyone else, even if their condition seems similar to yours.

Do not use it to treat any other complaints unless your doctor tells you to.

Things to be careful of

Be careful driving, operating machinery or doing jobs that require you to be alert while you are taking Terbinafine-DRLA tablets until you know how it affects you. This medicine can cause tiredness, sleepiness, dizziness or light-headedness in some people. If you have any of these symptoms, do not drive, use machines, 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 that 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 Terbinafine-DRLA tablets, even if you do not think it is connected with the medicine.

All medicines can have side effects. Sometimes they are serious, but most of the time they are not. You may need medical treatment if you get some of the side effects.

Do not be alarmed by these lists of possible side effects. You may not experience any of them. Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor immediately or go to Accident and Emergency at your nearest hospital if you notice any of the following:

chest pain
signs of a severe allergic reaction such as swelling of the face, lips, tongue, throat or other part of the body; shortness of breath, wheezing or troubled breathing; dizziness, redness, itching or rash on the skin; flushing, crampy abdominal pain, loss of consciousness; joint pain, stiffness, rash, fever or swollen/ enlarged lymph nodes
possible signs of a 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
possible 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
possible signs of a blood problem such as constant "flu-like" symptoms (fever, sore throat, mouth ulcers, chills, swollen glands, lack of energy)
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.

The above are serious side effects that need medical attention. Serious side effects are rare.

Tell your doctor if you notice any of the following and they worry you:

nausea (feeling sick) or vomiting
upset stomach (heartburn, cramps, wind, belching)
loss of appetite
diarrhoea
aching joints or muscles
headache
light headedness
tiredness, sleepiness
skin rash due to high level of a specific type of white blood cells
loss of or change in sense of taste, which usually returns to normal within several weeks of stopping terbinafine tablet treatment
blurred vision, decreased sharpness of vision
other skin problems
psoriasis (thickened patches of red skin, often with silvery scales)
hair loss
tingling or numbness
decreased physical sensitivity
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) due to taste disturbances
decreased hearing, impaired hearing and/or perception of noises in the absence of sound (e.g. hissing, ringing) in ears.

Tell your doctor if you notice anything else that is making you unwell. Some people may have other side effects not yet known or mentioned in this leaflet.

After using Terbinafine-DRLA tablets

Storage

Keep your medicine in the originalcontainer until it is time to take it.

Store it in a cool, dry place below 30°C and protected from light.

Do not store Terbinafine-DRLA tablets or any other medicine in the bathroom or near a sink.

Do not leave it in the car or on window sills.

Keep the 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 you have left over.

Product description

What it looks like

Terbinafine-DRLA: AUST R 167575: White to off white round tablet embossed “R250” on one side and score (bisect) line on the other side; pack of 42

Ingredients

The active ingredient in Terbinafine-DRLA is terbinafine (as hydrochloride). Each Terbinafine-DRLA tablet contains 250 mg of terbinafine.

Terbinafine-DRLA tablets (AUSTR 167575) also contain:

Microcrystalline cellulose
Colloidal anhydrous Silica
Hypromellose
Magnesium stearate
Croscarmellose sodium

If you are concerned about which tablet you are taking or any of the above ingredients, talk to your doctor or pharmacist before starting to take Terbinafine-DRLA.

Sponsor

Terbinafine-DRLA 250 mg is supplied in Australia by:

Dr Reddy's Laboratories (Australia) Pty Ltd
Level 9, 492 St Kilda Road Melbourne 3004

Australian Registration Number:

Terbinafine-DRLA 250 mg Tablets AUSTR 167575

This leaflet was prepared in October 2016.

Published by MIMS February 2018

BRAND INFORMATION

Brand name

Terbinafine-DRLA

Active ingredient

Terbinafine

Schedule

1 Name of Medicine

Terbinafine hydrochloride.

2 Qualitative and Quantitative Composition

Each tablet contains terbinafine hydrochloride equivalent to 250 mg terbinafine base. For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Terbinafine-DRLA Tablets are white to off white round, flat bevelled edge tablets embossed "R250" on one side and Score (bisect) line on the other side.

4 Clinical Particulars

4.1 Therapeutic Indications

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.

4.2 Dose and Method of Administration

Terbinafine 250 mg once a day, taken orally.
The bioavailability of terbinafine is not affected by a light meal.
The duration if treatment varies according to the indication and the severity of the infection.

Skin infections.

Likely treatment durations are as follows.

Tinea pedis (interdigital, planar/moccasin type).

Two to six weeks.

Tinea corporis, cruris.

Two to four 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 six weeks and three months.
Infections of fingers 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, for infections in the big toe, or if the nail growth is very poor, treatment for up to six 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.

4.3 Contraindications

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

4.4 Special Warnings and Precautions for Use

Identified precautions.

Effect on blood.

Patients taking terbinafine tablets are at risk of developing agranulocytosis, thrombocytopenia, pancytopenia and neutropenia, which are very rarely associated with terbinafine. The problem usually resolves within a few days to a week of withdrawal of terbinafine tablets. Patients taking terbinafine 250 mg tablets should be advised to report symptoms of infections. Prescribers should examine the patient to determine the correct aetiology of any blood dyscrasias that occur in patients treated with terbinafine tablets, and consideration should be given to a possible change in medication regimen, including discontinuation of treatment with terbinafine tablets.

Dermatological effects.

Serious skin reactions (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis) have been very rarely reported in patients taking terbinafine tablets. If progressive skin rash occurs, terbinafine tablet treatment 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 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 (non-toxic 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 hydrochloride treated patients (1.1%) compared with those who received placebo (1.5%).

Use in hepatic impairment.

Terbinafine tablets are 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 liver transplant or death) have been reported with the use of terbinafine. In the majority of hepatic failure cases, the patients had underlying systemic conditions (see Section 4.8 Adverse Effects (Undesirable Effects)). Patients prescribed terbinafine 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 hepatic function should be immediately evaluated.

Use in renal impairment.

The elimination of terbinafine in patients with impaired renal function is lower compared to healthy volunteers.
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 terbinafine is not recommended.

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 terbinafine 250 mg 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, Use in hepatic impairment, Use in renal impairment).

Paediatric use.

There is no experience with terbinafine in children and its use cannot be recommended. Terbinafine 250 mg should be kept out of reach of children.

Effects on laboratory tests.

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 tablet treated patients (1.7%) and 3/137 placebo-treated patients (2.2%) had decreases in ALC 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, doctors should consider monitoring complete blood counts in individuals using terbinafine tablet therapy for greater than six weeks.
See Section 4.8 Adverse Effects (Undesirable Effects), Effect on laboratory tests.

Effect on lipids.

In chronic toxicity studies in rats, oral terbinafine, at a dose of 309 mg/kg/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 eight 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.

4.5 Interactions with Other Medicines and Other Forms of Interactions

The plasma clearance of terbinafine may be accelerated by drugs which induce metabolism and may be decreased by drugs which inhibit cytochrome P450. Where co-administration of such agents is necessary, the dosage of terbinafine may need to be adjusted accordingly.
There have been spontaneous reports of increase or decrease in prothrombin time in patients taking oral terbinafine and warfarin concomitantly. However, a causal relationship between terbinafine tablets and these changes has not been established.
Cautious use of terbinafine tablets 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.

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

Cimetidine.

Decreased the clearance of terbinafine by 33%.

Fluconazole.

Significantly increased the C_max and AUC of terbinafine, due to inhibition of both CYP2C9 and CYP3A4 enzymes. Similar increase in exposure may occur when other drugs which 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.

Increased the clearance of terbinafine by 100%.

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 (see below).
Terbinafine does not interfere with the clearance of antipyrine or digoxin. Terbinafine clearance is unaffected by cyclosporin.
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 IC, and monoamine oxidase inhibitors (MAOIs) Type B, should be followed, especially if the co-administered drug has a narrow therapeutic window.
In studies in healthy subjects characterized 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.

Foetal toxicity and fertility studies in animals suggest no adverse effects.
(Category B1)
Since clinical experience in pregnant women is not available, terbinafine 250 mg 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 250 mg should not breastfeed.

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.

4.8 Adverse Effects (Undesirable Effects)

In general, terbinafine hydrochloride 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.
The following adverse reactions have been observed during clinical trials and/or post marketing surveillance.
Frequency estimate. Very common: greater than or equal to 10%; common: greater than or equal to 1% to < 10%; Uncommon: greater than or equal to 0.1% to < 1%; Rare: greater than or equal to 0.01% to < 0.1%; Very rare: < 0.01%.

Gastrointestinal disorders.

Very common: nausea, vomiting, flatulence, mild abdominal discomfort, abdominal cramps, anorexia, diarrhoea, dyspepsia/gastritis, belching, abdominal distension, decreased appetite.

Immune system disorders.

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

Psychiatric disorders.

Common: depression.
Uncommon: 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, toxic skin eruption, dermatitis exfoliative, dermatitis bullous, alopecia. In the event of an allergic or severe skin reaction, terbinafine treatment should be discontinued.

Musculoskeletal and connective tissue disorders.

Very common: musculoskeletal reactions (arthralgia, myalgia).

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).

Blood and lymphatic system disorders.

Uncommon: anemia.
Very rare: haematological disorders such as neutropenia, agranulocytosis, pancytopenia and thrombocytopenia.

Nervous system disorders.

Very common: headache.
Common: dysgeusia* including ageusia*, dizziness, tiredness/fatigue.
Uncommon: paraesthesia and hypoaesthesia.
Very rare: sedation, light-headedness, chest pain.

Eye disorders.

Common: visual impairment.

Ear and labyrinth disorders.

Uncommon: tinnitus.

General disorders.

Uncommon: pyrexia.

Investigations.

Uncommon: weight decreased**.

Effect on laboratory tests.

Transient increases in serum urea, serum creatinine, and liver enzymes. 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.

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 www.tga.gov.au/reporting-problems.

4.9 Overdose

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

Signs and symptoms.

Studies in animals suggest that in a high dose situation such as accidental overdose, central nervous system (CNS) symptoms 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 absorption of the drug if given within one or two hours after ingestion. In patients who are not fully conscious or have 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 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Terbinafine is an allylamine with antifungal activity mainly against dermatophytes.

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 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 given orally, the drug concentrates in skin and nails at levels associated with antifungal activity.

Clinical trials.

No information available.

5.2 Pharmacokinetic Properties

Absorption.

Following oral administration, terbinafine is well absorbed (> 70%) and the bioavailability of terbinafine hydrochloride tablets, as the result of first-pass metabolism is approximately 40%. A single oral dose of terbinafine 250 mg results in peak plasma concentrations of 0.83 microgram/mL within two 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 tablets are administered with food. At steady state, in comparison to a single dose, 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 approximately 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 tablets have been reported in humans.

Metabolism.

Terbinafine is extensively metabolised in the body. Biotransformation results in metabolites with no antifungal activity, which are excreted predominantly in the urine.

Excretion.

No age dependent changes in pharmacokinetics have been observed. In patients with renal impairment (creatine clearance less than or equal to 50 mL/minute) or with pre-existing liver disease, the clearance of terbinafine is decreased by approximately 50% compared to normal volunteers.

5.3 Preclinical Safety Data

Genotoxicity.

No information available.

Carcinogenicity.

In a two 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/day. No increase in hepatic tumours was seen in female rats at a dietary dose of 97 mg/kg/day.

6 Pharmaceutical Particulars

6.1 List of Excipients

Cellulose - microcrystalline, croscarmellose sodium, silica - colloidal anhydrous, hypromellose, magnesium stearate.

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

Blister packs of 14, 28 and 42 tablets.

6.6 Special Precautions for Disposal

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

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 structure.

Chemical name.

Terbinafine hydrochloride.

Molecular formula.

C₂₁H₂₅N.

Molecular weight.

291.44.

CAS number.

91161-71-6.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Medicine.

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Terbinafine-DRLA Tablets

Terbinafine

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Terbinafine-DRLA 250 mg Tablets