Consumer medicine information

APO Terbinafine

Terbinafine

BRAND INFORMATION

Brand name

APO-Terbinafine

Active ingredient

Terbinafine

Schedule

SUMMARY CMI

APO-TERBINAFINE

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. WHY AM I USING APO-TERBINAFINE?

APO-TERBINAFINE contains the active ingredient terbinafine hydrochloride and is used to treat fungal infections of the fingernails and toenails, tinea (ringworm) infections of the groin, body, tinea infections of the feet - referred to as "athlete's foot".

For more information, see Section 1. Why am I using APO-TERBINAFINE? in the full CMI.

2. What should I know before I use APO-TERBINAFINE?

Do not use if you have ever had an allergic reaction to APO-TERBINAFINE or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use APO-TERBINAFINE? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with APO-TERBINAFINE and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use APO-TERBINAFINE?

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.

More instructions can be found in Section 4. How do I use APO-TERBINAFINE? in the full CMI.

5. What should I know while using APO-TERBINAFINE?

Things you should do	Make sure you are taking your tablet every day, continue taking it until your doctor tells you to stop. This will ensure that all the infection is gone and will lessen the chance of the infection coming back once you stop taking this medicine.
Things you should 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.
Driving or using machines	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
Drinking alcohol	Tell your doctor if you drink alcohol.
Looking after your medicine	Keep your medicine in a cool dry place where the temperature will stay below 25°C. Protect from light. Heat and dampness can destroy some medicines.

For more information, see Section 5. What should I know while using APO-TERBINAFINE? in the full CMI.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention. Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking this medicine

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

FULL CMI

APO-TERBINAFINE

Active ingredient(s): Terbinafine hydrochloride

Consumer Medicine Information (CMI)

This leaflet provides important information about using APO-TERBINAFINE. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using APO-TERBINAFINE.

Where to find information in this leaflet:

1. Why am I using APO-TERBINAFINE?
2. What should I know before I use APO-TERBINAFINE?
3. What if I am taking other medicines?
4. How do I use APO-TERBINAFINE?
5. What should I know while using APO-TERBINAFINE?
6. Are there any side effects?
7. Product details

1. Why am I using APO-TERBINAFINE?

APO-TERBINAFINE contains the active ingredient terbinafine hydrochloride. APO-TERBINAFINE is used to treat:

fungal infections of the fingernails 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

2. What should I know before I use APO-TERBINAFINE?

Warnings

Do not use APO-TERBINAFINE 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
if you take any medicines for any other condition
if you are pregnant or whilst pregnant until you and your doctor have discussed the risks and benefits involved
if you are breastfeeding. This medicine passes into breast milk. Do not take this medicine whilst breastfeeding as there is a possibility that your baby could be affected
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

Check with your doctor:

if you have allergies to any other medicines, foods, preservatives or dyes.
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
if you are pregnant or plan to become pregnant or are breastfeeding.
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).
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.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

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.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy 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. Your doctor can discuss with you the risks and benefits involved.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if this may affect APO-TERBINAFINE.

4. How do I use APO-TERBINAFINE?

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.
Follow the instructions provided and use APO-TERBINAFINE until your doctor tells you to stop. [for antibiotics, replace with ‘Follow the instructions provided when APO-TERBINAFINE was prescribed, including the number of days it should be taken.

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 APO-TERBINAFINE

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 APO-TERBINAFINE

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

If you forget to use APO-TERBINAFINE

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 use too much APO-TERBINAFINE

If you think that you have used too much APO-TERBINAFINE, you may need urgent medical attention.

You should immediately:

phone the Poisons Information Centre
(by calling 13 11 26), or
contact your doctor, or
go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

You may need urgent medical attention.

5. What should I know while using APO-TERBINAFINE?

Things you should 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 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 start 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 should 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.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how APO-TERBINAFINE affects you.

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.

Drinking alcohol

Tell your doctor if you drink alcohol.

Looking after your medicine

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.
Heat and dampness can destroy some medicines.

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

in the bathroom or near a sink, or
in the car or on windowsills.

Keep it where young children cannot reach it.

When to discard your medicine

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.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

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

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.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effects

What to do

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

Speak to your doctor if you have any of these less serious side effects and they worry you.

Very Serious side effects

Very Serious side effects

What to do

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

Call your doctor straight away or go straight to the Emergency Department at your nearest hospital if you notice any of these very serious side effects.
You may need urgent medical attention or hospitalisation.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people. Some of these side effects can only be found when your doctor does tests from time to time to check your progress.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What APO-TERBINAFINE contains

Active ingredient (main ingredient)	Each tablet contains 250 mg of terbinafine (as hydrochloride) as the active ingredient.
Other ingredients (inactive ingredients)	methylcellulose croscarmellose sodium magnesium stearate colloidal anhydrous silica

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

Do not take this medicine if you are allergic to any of these ingredients.

What APO-TERBINAFINE looks like

APO-TERBINAFINE is a 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

SPONSOR

Arrotex Pharmaceuticals Pty Ltd
15-17 Chapel Street Cremorne VIC 3121
Australia
Web: www.arrotex.com.au

This leaflet was prepared in October 2024

Published by MIMS December 2024

BRAND INFORMATION

Brand name

APO-Terbinafine

Active ingredient

Terbinafine

Schedule

1 Name of Medicine

Terbinafine (as hydrochloride).

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.

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.

4.2 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.

4.3 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 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 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.

4.7 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 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: psoriasiform 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.

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 Arrotex Medical Information Enquiries/Adverse Drug Reaction Reporting on 1800 195 055.

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).

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.

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.

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: (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.

CAS number.

78628-80-5.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

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APO-Terbinafine 250 mg Tablets