SUMMARY CMI

SABRIL^®

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 Sabril?

Sabril contains the active ingredient vigabatrin. Sabril is used in addition to other medicines to treat epilepsy.

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

2. What should I know before I take Sabril?

Do not take if you have ever had an allergic reaction to Sabril 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 take Sabril? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Sabril 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 take Sabril?

• Sabril tablets and sachets are taken by mouth either once or twice a day.
• Take Sabril at about the same time each day.

More instructions can be found in Section 4. How do I take Sabril? in the full CMI.

5. What should I know while using Sabril?

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

6. Are there any side effects?

The less serious side effects are drowsiness, nervousness, irritability, depression, dizziness, confusion, headache, tiredness difficulty sleeping, joints pain, impaired concentration, weight gain, difficulty in speaking or slurred speech, lack of coordination agitation, excitation, aggression, tremors, nausea, vomiting, abdominal pain and unusual hair loss or thinning. Serious side effects are an increase in the number of seizures, changes in your behaviour or mood, severe tiredness or confusion, changes in your eyesight and suicidal thoughts/attempts.

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

SABRIL^®

Active ingredient(s): vigabatrin

Consumer Medicine Information (CMI)

This leaflet provides important information about using Sabril. 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 Sabril.

Where to find information in this leaflet:

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

1. Why am I using Sabril?

Sabril contains the active ingredient vigabatrin.

Sabril is a medicine used to help control epilepsy, a condition where you have repeated fits or convulsions.

Sabril is an anticonvulsant. It works by stopping the breakdown of an important chemical transmitter ("messenger") in the brain and this helps reduce seizure activity.

Sabril is used in addition to other medicines to treat epilepsy.

Your doctor, however, may have prescribed Sabril for another reason.

Ask your doctor if you have any questions about why it has been prescribed for you.

2. What should I know before I take Sabril?

Warnings

Do not take Sabril if:

• you are allergic to vigabatrin, or any of the ingredients listed at the end of this leaflet.
• you are pregnant or intend to become pregnant unless your doctor tells you to. It may affect your developing baby if you take it during pregnancy.
• you are breast-feeding or planning to breast-feed unless your doctor tells you to. Sabril passes into breast milk and there is a possibility your baby may be affected.
• Always check the ingredients to make sure you can use this medicine.

Check with your doctor if you:

• take any medicines for any other condition
• plan to have surgery
• have any other medical conditions, especially the following:
  - kidney problems
  - nervous or mental illness
  - depression
  - psychosis, a severe mental condition in which the person is unable to think and judge clearly.
• have allergies to:
  - any of the ingredients listed at the end of this leaflet
  - any other medicines
  - any other substances, such as foods, preservatives, or dyes

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

Tell your doctor if you are pregnant or intend to become pregnant.

Like most medicines for epilepsy, Sabril may affect your unborn baby. However, it is very important to control your epilepsy while you are pregnant since seizures may also affect your baby. Your doctor will help you decide whether you should take Sabril during pregnancy

Talk to your doctor if you are breastfeeding or intend to breastfeed.

Sabril passes into breast milk. Your doctor will discuss the risks and benefits of using it if you are breast-feeding or planning to breast-feed.

Eyesight

Your doctor may want to test your eyesight before you start taking Sabril and during the course of your treatment so that any changes in your sight can be detected.

Some anti-epilepsy medicines may affect eyesight. In rare cases, patients treated with Sabril have experienced changes to their peripheral vision (i.e., they had trouble seeing things that were not directly in front of them).

Please ask your doctor if you want more information about this.

• If you have not told your doctor about any of the above, tell them before you take Sabril.

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 interfere with the absorption of Sabril.

• These include phenytoin, a medicine used to treat seizures.

Other medicines can increase the drowsiness that Sabril causes.

• These include clonazepam, a medicine used as a sedative or to treat anxiety.

These medicines may be affected by Sabril. You may need to use different amounts of your medicine or take different medicines.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect Sabril.

4. How do I take Sabril?

How much to take

• Sabril tablets and sachets are taken by mouth either once or twice a day.
• The dose of Sabril varies between patients. Your doctor may have prescribed a different dose.

Follow all directions given to you by your doctor and pharmacist carefully.

These directions may differ from the information contained in this leaflet.

Ask your doctor or pharmacist if you are unsure of the correct dose for you.

If you take the wrong dose, Sabril may not work as well and your problem may not improve.

When to take Sabril

• Take Sabril at about the same time each day.
• Taking Sabril at the same time each day will have the best effect. It will also help you remember when to take it.
• You can take Sabril with or without food.

If you are not sure when to take it, ask your doctor or pharmacist.

How to take Sabril

Tablets

• Swallow your tablet(s) whole with plenty of water. Do not crush or chew the tablet(s).

Sachets

• The contents of the sachets should be dissolved in half a glass of water, juice or soft drink just before you plan to take it.
• Once dissolved, the solution should be taken immediately. It will dissolve easily and has no taste or smell.
• Once mixed, any remaining solution should be discarded within 24 hours.

How long to take Sabril

• Do not stop taking Sabril until your doctor tells you to.
• Ask your doctor or pharmacist if you are not sure how long to take the medicine for.

If you forget to take Sabril

Do not take a double dose to make up for the dose you missed.

• If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.
• If there is still a long time to go before your next dose, take it as soon as you remember, and then go back to taking your dose as you would normally.

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 hints.

If you take too much Sabril

If you think that you have taken too much Sabril, you may need urgent medical attention.

You should immediately:

• phone the Poisons Information Centre for advice
  - Australia 13 11 26 or
  - New Zealand 0800 POISON or 0800 764766), 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.

5. What should I know while using Sabril?

Things you should do

• Tell all the doctors, dentists and pharmacists that are treating you that you are taking Sabril.
• If you are about to start taking any new medicine, tell your doctor and pharmacist that you are taking Sabril.
• If you plan to have surgery that needs a general anaesthetic, tell your doctor or dentist that you are taking this medicine.
• If you become pregnant while you are taking Sabril, tell your doctor immediately.
• Tell your Doctor immediately or go to the Accident and Emergency department of your nearest hospital if you have any thoughts of harming yourself or committing suicide.

Things you should not do

• Do not stop taking Sabril until your doctor tells you to.
• Do not give this medicine to anyone else, even if they have the same condition as you.
• Do not take more than the recommended dose unless your doctor or pharmacist tells you to.
• Do not use this medicine to treat any other complaints unless your doctor tells you to.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Sabril affects you.

Sabril may cause dizziness or light-headedness in some people. Make sure you know how you react to Sabril before you drive a car, operate machinery or do anything else that could be dangerous if you are dizzy or light-headed. This effect decreases with time.

Drinking alcohol

Tell your doctor if you drink alcohol.

Looking after your medicine

• Keep your tablets or sachets in the container until it is time to take them.
• Keep Sabril in a cool dry place where the temperature stays below 30°C.
• Do not store Sabril or any other medicine in the bathroom or near a sink.
• Do not leave it in the car or on window sills.
• Heat and dampness can destroy some medicines.

Keep it where young children cannot reach it.

Do not take it after the expiry date (EXP) printed on the pack.

If you take this medicine after the expiry date has passed, it may not work as well.

Do not take it if the packaging is torn or shows signs of tampering.

Getting rid of any unwanted medicine

If your doctor tells you to stop taking Sabril tablets or sachets or the expiry date has passed, ask your pharmacist what to do with any tablets or sachets that are left over.

Return any unused medicine to your pharmacist.

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.

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

Serious side effects

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.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects as follows. Australia: Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. New Zealand: Medsafe online at www.medsafe.govt.nz/safety/report-a-problem.asp

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 Sabril contains

Sabril does not contain gluten, sucrose, tartrazine or any other azo dyes.

Tablets

Sachets

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

What Sabril looks like

Tablets

Sabril 500 mg are white to off-white, oval biconvex, film-coated tablets with a break-mark on one side and "SABRIL" or "SABRILEX" engraved on the other side. They come in a blister pack of 100 tablets (AUST R 150021).

Sachets

Sabril sachets contain 500 mg of vigabatrin. They come in a pack of 60 sachets (AUST R 52985).

Who distributes Sabril

Distributed in Australia by:

sanofi-aventis australia pty ltd
12-24 Talavera Road
Macquarie Park NSW 2113
Freecall: 1800 818 806
Email: [email protected]

Distributed in New Zealand by:

Pharmacy Retailing (NZ) Ltd t/a Healthcare Logistics
PO Box 62027
Sylvia Park Auckland 1644
Freecall: 0800 283 684
Email: [email protected]

This leaflet was prepared in August 2023.

sabril-ccdsv14-cmiv12-04aug23

Published by MIMS October 2023

1 Name of Medicine

Vigabatrin.

2 Qualitative and Quantitative Composition

Each tablet contains 500 mg vigabatrin.
Each oral powder sachet contains 500 mg vigabatrin.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Tablets.

Oral powder.

4 Clinical Particulars

4.1 Therapeutic Indications

For the treatment of epilepsy which is not satisfactorily controlled by other antiepileptic drugs.

4.2 Dose and Method of Administration

Vigabatrin is intended for oral administration once or twice daily. Initiation of treatment should be as add-on therapy in epilepsy which is not satisfactorily controlled by other drugs. Thus, the starting daily dose of 2 g (4 tablets) should be added on to the patient's current antiepileptic drug regimen. If necessary, the daily dose may be increased or decreased in 0.5 g or 1.0 g increments at weekly or greater intervals depending on clinical response and tolerability. Increasing the dose beyond 4 g/day does not usually result in greater efficacy.
Use of vigabatrin should be under the general direction of a specialist practitioner who is experienced in the treatment of epilepsy (see Section 4.4 Special Warnings and Precautions for Use).

Therapeutic dose.

3-9 years old.

> 10 years old.

4.3 Contraindications

Contraindicated for patients who have a history of hypersensitivity to vigabatrin or any of the components.

4.4 Special Warnings and Precautions for Use

Animal safety studies indicate that vigabatrin causes intramyelinic oedema in the brain of some species. Currently, there is no evidence to suggest that this effect occurs in man. However, it is recommended that patients treated with vigabatrin are closely observed for adverse effects on neurological functions.
Drowsiness has been observed in clinical trials and patients should be warned of this possibility at the start of treatment.
Vigabatrin should be used with caution in patients with a history of psychosis, depression or behavioural problems. Psychiatric events (agitation, depression, abnormal thinking, paranoid reactions) have been reported during vigabatrin therapy. These events occurred in patients with and without a psychiatric history and were usually reversible when vigabatrin doses were reduced or gradually discontinued. It is advisable that in patients who may be susceptible to such reactions (e.g. patients with a previous history), vigabatrin be introduced cautiously at low dose with frequent monitoring. In clinical trials, depression occurred in less than 10% of patients and seldom required discontinuation of vigabatrin. Less common events included psychotic symptoms.
Cases of abnormal brain magnetic resonance imaging (MRI) findings have been reported, particularly in young infants treated for infantile spasms with high doses of vigabatrin. The clinical significance of these findings is currently unknown. Additionally, cases of intramyelinic oedema (IME) have been reported, particularly in infants treated for infantile spasms (see Section 4.8 Adverse Effects (Undesirable Effects)).
Movement disorders including dystonia, dyskinaesia and hypertonia have been reported in patients treated for infantile spasms. The benefit/ risk of vigabatrin should be evaluated on an individual patient basis. If new movement disorders occur during treatment with vigabatrin, consideration should be given to dose reduction or a gradual discontinuation of treatment.
As with other antiepileptic drugs, some patients may experience an increase in seizure frequency, including status epilepticus with vigabatrin, or the onset of new types of seizures with vigabatrin. New onset myoclonus and exacerbation of existing myoclonus may occur in rare cases.
As with other antiepileptic drugs, abrupt withdrawal may lead to rebound seizures; therefore, it is recommended that withdrawal from vigabatrin treatment occurs by gradual dose reduction over a 2 to 4 week period.
Vigabatrin is eliminated via the kidney and, therefore, caution should be exercised when administering the product to elderly patients and more particularly to patients with a creatinine clearance of less than 60 mL/min. Reduced doses should be used and patients monitored closely for adverse events such as sedation and confusion.
Rare reports of encephalopathic symptoms such as marked sedation, stupor and confusion in association with nonspecific slow wave activity on electroencephalogram (EEG) have been described soon after the initiation of vigabatrin treatment. Risk factors for the development of these reactions include higher than recommended starting dose, faster dose escalation at higher steps than recommended and renal failure. These events have been reversible following dose reduction or discontinuation of vigabatrin.

Visual disorders.

Visual acuity.

Suicidal behaviour and ideation.

Use in renal impairment.

Use in the elderly.

Paediatric use.

Effects on laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

As vigabatrin is neither extensively metabolised, nor plasma protein bound, and is not an inducer of hepatic cytochrome P450, interactions with other drugs are unlikely. However, during controlled clinical studies a gradual reduction of about 20% in the plasma concentration of phenytoin has been observed. The exact nature of this interaction is presently not understood and the therapeutic significance is not known.
The plasma concentrations of carbamazepine, phenobarbital (phenobarbitone) and sodium valproate have also been monitored during controlled clinical trials and no clinically significant interactions have been detected.
The concomitant use of vigabatrin and clonazepam may exacerbate the sedative effect or lead to coma. Need for concomitant use must be carefully assessed.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

4.7 Effects on Ability to Drive and Use Machines

Special care should be taken by patients driving, operating machinery or performing any hazardous task. Visual field defects, which can significantly affect the ability to drive and use machines, have frequently been reported in association with vigabatrin. Patients should be evaluated for the presence of visual field defect.

4.8 Adverse Effects (Undesirable Effects)

Pooled data from prevalence surveys suggest that as many as 1/3 of patients receiving vigabatrin therapy develop visual field defects.
Adverse events are mainly CNS related, such as sedation, somnolence, fatigue and impaired concentration and probably a secondary consequence of increased GABA levels caused by vigabatrin. The most commonly reported adverse effects in children are excitation and agitation. The incidence of these undesirable effects is generally higher at the beginning of treatment and decreases with time.
As with other antiepileptic drugs, some patients may experience an increase in seizure frequency, including status epilepticus, or the onset of new types of seizures with vigabatrin treatment. Patients with myoclonic seizures may be particularly liable to this effect. New onset myoclonus and exacerbation of existing myoclonus may occur in rare cases.
Undesirable effects, ranked under heading of frequency, are listed below in CIOMS format.
The following CIOMS frequency rating is used: Very common: ≥ 10%; common: ≥ 1 and < 10%; uncommon: ≥ 0.1 and < 1%; rare: ≥ 0.01 and < 1.0%; very rare: < 0.01%.

Investigations*.

Nervous system disorders.

Eye disorders.

Gastrointestinal disorders.

Skin and subcutaneous tissue disorders.

General disorders and administration site conditions.

Psychiatric disorders****.

Blood and lymphatic system disorders.

Musculoskeletal and connective tissue disorders.

Reporting suspected adverse effects.

4.9 Overdose

Symptoms.

Treatment.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Actions: anticonvulsant.

Mechanism of action.

Clinical trials.

5.2 Pharmacokinetic Properties

Vigabatrin is a water soluble compound and is rapidly absorbed from the gastrointestinal tract; absorption is unaffected by the presence of food. The drug is widely distributed with an apparent volume of distribution slightly greater than total body water. Plasma and CSF concentrations are linearly related to dose over the recommended dose range.
There is no direct correlation between plasma concentration and efficacy. Duration of drug effect is thought to be dependent on the rate of enzyme resynthesis rather than the plasma concentration of drug.
Vigabatrin is eliminated from the plasma with a terminal half-life of 5-8 hours with approximately 70% of a single oral dose being recovered in the urine as unchanged drug in the first 24 hours postdose.
Vigabatrin does not induce the hepatic cytochrome P450 enzymes nor is it extensively metabolised or plasma protein bound, therefore, drug interactions are unlikely.

5.3 Preclinical Safety Data

Animal safety studies carried out in rat, mouse, dog and monkey have indicated that vigabatrin has no significant adverse effects on the liver, kidney, lung, heart or gastrointestinal tract. In the brain, microvacuolation has been observed in white matter tracts of rat, mouse and dog at doses of 30-50 mg/kg/day. This effect is caused by a separation of the outer lamellar sheath of myelinated fibres, a change characteristic of intramyelinic oedema.
In both rat and dog (mouse, not tested), the intramyelinic oedema was reversible on stopping vigabatrin treatment. However, in rodents, residual changes consisting of swollen axons and mineralised microbodies have been observed. In the monkey, no lesions were noted after 6 years of treatment at 50 and 100 mg/kg. In monkeys receiving 300 mg/kg for 16 months, minimal microvacuolation was noted with equivocal differences between treated and control animals. In the dog, results of an electrophysiological study indicate that intramyelinic oedema is associated with increased latency of the somatosensory evoked potential which is reversible when the drug is withdrawn.

Genotoxicity.

Carcinogenicity.

6 Pharmaceutical Particulars

6.1 List of Excipients

Sabril tablets contain the following inactive ingredients: povidone, microcrystalline cellulose, sodium starch glycollate, magnesium stearate, hypromellose, titanium dioxide, macrogol 8000 and Opadry White OY-S-7298.
Sabril sachets contain the inactive ingredient povidone.

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 30°C.

6.5 Nature and Contents of Container

Tablets.

Oral powder.

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

Chemical structure.

CAS number.

7 Medicine Schedule (Poisons Standard)

Prescription Only Medicine (S4).

Summary Table of Changes