Sabril

Package leaflet: Information for the patient

Sabril, 500 mg, coated tablets
Vigabatrin
Please read this leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Table of contents:

1. What Sabril is and what it is used for
2. Important information before taking Sabril
3. How to take Sabril
4. Possible side effects
5. How to store Sabril
6. Contents of the pack and other information

1. What Sabril is and what it is used for

Sabril contains vigabatrin, which is a selective, irreversible inhibitor of GABA aminotransferase (an enzyme responsible for the breakdown of GABA). Vigabatrin increases the concentration of gamma-aminobutyric acid (GABA) in brain tissue, one of the main inhibitory neurotransmitters in the brain.
Sabril is indicated as an adjunctive treatment (in combination with other antiepileptic medicines) for treatment-resistant partial seizures, with or without secondary generalization, in patients for whom all other combination antiepileptic therapies have proved insufficient or poorly tolerated.
Additionally, it is used as monotherapy (as a single medicine) for epileptic seizures in infants (West syndrome).
(Sabril 500 mg granules for oral solution is also available).

2. Important information before using Sabril

When not to use Sabril

• If the patient has a known hypersensitivity to vigabatrin or to any of the other ingredients listed in section 6.

Warnings and precautions
Before starting treatment with Sabril, discuss with your doctor if:

• the patient has or has previously had psychotic, depressive, and/or behavioural disorders (see section 4),
• the patient has kidney problems or is elderly; in these patients, adverse effects such as sedation and confusion (disorientation) should be closely monitored (see section 3),
• the patient is taking clonazepam (a medicine used to treat epilepsy). Concomitant use of these medicines may enhance sedative effects or lead to coma. The doctor will decide, after careful evaluation, whether concomitant use is necessary.
• if the patient has vision problems.

Visual field defects have been observed in approximately 1/3 of patients receiving vigabatrin.
These visual field defects may be severe, up to tunnel vision or blindness,
and may be irreversible. It cannot be excluded that visual field defects may worsen after discontinuation of vigabatrin treatment.
The patient should immediately inform the doctor if any visual disturbances occur. In such a case, the doctor will refer the patient to an ophthalmologist and may decide to discontinue the treatment.
Vigabatrin should not be used concomitantly with other medicines known to have toxic effects on the retina.
Use of vigabatrin is not recommended in patients with existing visual field defects of clinical significance.
It is recommended that the doctor perform an eye examination (including assessment of peripheral vision) and visual acuity (i.e. the ability to read letters on an eye chart) before starting treatment with Sabril or within 4 weeks after initiation, and thereafter every 3 to 6 months throughout treatment. It is also recommended to perform an eye examination approximately 3 to 6 months after discontinuation of Sabril treatment.
Sabril may impair vision, causing eye disorders such as: retinal disorders, blurred vision, optic nerve atrophy, or optic neuritis (see section 4 "Undesirable effects"). If the patient notices any visual impairment, an ophthalmologist should be consulted.
Sabril should not be used as monotherapy except in the treatment of infantile spasms.
As with other antiepileptic medicines, abrupt discontinuation of Sabril may lead to increased seizure frequency. If treatment needs to be stopped, the doctor will recommend gradually reducing the dose over 2–4 weeks.
Patients treated with Sabril should remain under close medical supervision due to the risk of adverse neurological effects.
A small number of people taking antiepileptic medicines containing vigabatrin have had thoughts about harming themselves or committing suicide. If such thoughts occur at any time, contact the doctor immediately.
Children
Movement disorders and abnormalities on brain MRI have been observed in young infants treated for infantile spasms (West syndrome). If unusual movement disorders are observed in a child, contact the doctor, who will decide whether treatment modification should be considered.
Sabril with other medicines
Inform the doctor about all medicines currently or recently taken, as well as any medicines planned for future use.
Vigabatrin is not metabolized and does not bind to plasma proteins, nor does it induce cytochrome P450 liver enzymes involved in drug metabolism; therefore, interactions with other medicines are unlikely.
Vigabatrin may increase amino acid levels in urine, which may lead to false-positive results in tests used to detect certain rare genetic metabolic disorders.
Clonazepam
Concomitant use of vigabatrin and clonazepam may enhance the sedative effect of clonazepam or lead to coma (see section 2 "Warnings and precautions").
Taking Sabril with food and drink
The medicine may be taken before or after meals.
Pregnancy and breastfeeding
Pregnancy
If the patient becomes pregnant or plans to become pregnant, the doctor should reassess the necessity of treatment. Abruptly stopping effective antiepileptic treatment may worsen the disease in the mother, which may harm the fetus.
Vigabatrin may be used during pregnancy only if absolutely necessary.
Breastfeeding
Vigabatrin passes into breast milk. Therefore, breastfeeding is not recommended during treatment with vigabatrin.
Driving and operating machinery
Patients with uncontrolled epilepsy should not drive or operate potentially dangerous machinery. In clinical studies, somnolence has been observed in patients after administration of vigabatrin.
Visual field defects, which may significantly affect the ability to drive and operate machinery, have frequently been associated with the use of Sabril. Patients should be examined for visual field defects (see also section 2 "Warnings and precautions").
Sabril contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, which means the medicine is considered "sodium-free".

3. How to use Sabril

The medicine should be used as directed by the physician. If in doubt, consult your
doctor.
Sabril should be taken orally once or twice daily, either before or after meals.
Sabril should be used in combination with other antiepileptic medicines currently taken by the
patient.
Adults
Maximum efficacy is usually observed with a daily dose of 2 to 3 g. Vigabatrin at an initial dose of
1 g per day should be added to the antiepileptic medicines currently used by the patient. The daily
dose should then be gradually increased by 0.5 g weekly, depending on clinical response and
patient tolerance. The recommended maximum dose is 3 g per day.
Children
Drug-resistant partial seizures
The recommended initial dose in infants, children, and adolescents is 40 mg/kg body weight/day.
Dosing should be based on body weight:

Do not exceed the maximum recommended dose in each of the groups.
Monotherapy for infantile spasms (West syndrome):
The recommended initial dose is 50 mg/kg body weight/day. If necessary, it may be gradually
increased over one week.
Doses up to 150 mg/kg body weight/day may be used.
Elderly patients and patients with renal impairment:
The medicinal product should be used with caution in elderly patients and in patients with creatinine
clearance less than 60 ml/min. In such cases, the physician should consider dose adjustment and
frequency of administration. A lower maintenance dose may be effective in these patients.
These patients should be closely monitored for adverse effects such as sedation or confusion
(see section 2 and section 4).
Method of administration
For oral use.
Tablets should be swallowed with a small amount of water.
Sabril may be taken before or after meals.
If you feel that the effect of Sabril is too strong or too weak, consult your doctor.
Use of a higher than recommended dose of Sabril
In case of overdose, contact your doctor immediately.
In the event of overdose, the physician will provide symptomatic treatment, as there is no specific
antidote for vigabatrin.
The most commonly observed symptoms of overdose included somnolence or coma. Other, less common
symptoms included: dizziness, headache, psychosis, respiratory depression or apnoea, bradycardia,
hypotension, agitation, irritability, confusion, behavioural disturbances or speech disorders.
Missed dose of Sabril
If a dose of Sabril is missed, it should be taken as soon as possible, except when it is almost time for
the next dose. Do not take a double dose to make up for a missed dose.
If you have any doubts concerning the use of this medicinal product, consult your doctor.

4. Possible adverse reactions

Like all medicines, Sabril may cause adverse reactions, although not everyone experiences them.
The following adverse reactions have been observed in patients treated with vigabatrin:
Visual field defects (mild to severe), which may impair functioning, are commonly observed in patients receiving vigabatrin. Symptoms typically begin after several months or years of vigabatrin treatment. Studies indicate that visual field defects may develop in up to 1 in 3 patients treated with vigabatrin (see also section 2).
Adverse reactions occurred in approximately 50% of patients during controlled clinical trials with vigabatrin. In adults, these were mainly central nervous system-related effects such as sedation, somnolence, fatigue, and impaired concentration. In children, however, excitation or psychomotor agitation are frequent. The frequency of these adverse reactions is generally higher at the beginning of treatment and decreases over time.
As with other antiepileptic drugs, vigabatrin may in some patients lead to an increase in seizure frequency, including status epilepticus. This is particularly observed in patients with myoclonic seizures. In rare cases, new-onset or worsening of pre-existing myoclonic seizures may occur.
The adverse reactions are listed below, classified according to the following frequency categories:
very common (at least 1 in 10 people), common (less than 1 in 10 people), uncommon (less than 1 in 100 people), rare (less than 1 in 1,000 people), very rare (less than 1 in 10,000 people), frequency not known (cannot be estimated from available data).

Very common adverse reactions:

• somnolence
• visual field defects
• fatigue
• joint pain

Common adverse reactions:

• weight gain
• speech disorders, headache, tremor, dizziness, paresthesia (tingling sensation), concentration and memory impairment, thinking disorders
• blurred vision, double vision, nystagmus
• nausea, vomiting, abdominal pain
• edema, irritability
• psychomotor agitation, aggression, restlessness, depression, paranoid reaction (delusions, hallucinations), insomnia
• anaemia
• alopecia

Uncommon adverse reactions:

• ataxia (lack of coordination of movement), movement disorders
• rash
• hypomania, mania (mood disorders associated with hyperactivity and excitement), psychosis

Rare adverse reactions:

• encephalopathic symptoms (marked sedation, stupor, and confusion)
• retinal disorders (mainly peripheral)
• angioedema, urticaria
• suicide attempt

Very rare adverse reactions:

• optic neuritis
• optic nerve atrophy
• hepatitis
• hallucinations

Adverse reactions with frequency not known:

• cases of abnormalities on brain MRI, which may indicate cytotoxic edema
• decreased visual acuity
• swelling in the protective layer of nerve cells in the brain, observed on brain MRI

Additional adverse reactions observed in children:
Very common adverse reactions:

• excitation, psychomotor agitation

Adverse reactions with frequency not known:

• movement disorders in young infants treated for infantile spasms
• cases of abnormalities on brain MRI, particularly in infants
• swelling in the protective layer of nerve cells in the brain, observed on brain MRI, particularly in infants

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, patients should inform their doctor or pharmacist. Adverse reactions can be reported directly to the Department for Monitoring Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, Poland
Tel: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder or its representative in Poland.
Reporting adverse reactions contributes to the further accumulation of safety information regarding the use of this medicine.

5. How to store the medicine Sabril

Before use, check the expiry date stated on the packaging.
Keep the medicine out of sight and reach of children.
Do not use the medicine Sabril after the expiry date indicated on the packaging.
Storage - no special requirements.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist
how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Sabril contains
One film-coated tablet contains as the active substance:
500 mg vigabatrin
and excipients:
povidone K30, microcrystalline cellulose, sodium carboxymethyl starch (type A) and magnesium stearate.
Coating composition: hypromellose, titanium dioxide, polyethylene glycol 8000.

What Sabril looks like and contents of the pack
Sabril 500 mg film-coated tablets are packed in blisters and cardboard cartons.
The pack contains 10 blisters with 10 film-coated tablets each.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Sanofi Winthrop Industrie
82, Avenue Raspail
94250 Gentilly
France

Manufacturer
Patheon France S.A.
40, Boulevard de Champaret
38300 Bourgoin-Jallieu
France

For further information, please contact the representative of the Marketing Authorisation Holder in Poland:
Sanofi Sp. z o.o.
Marcina Kasprzaka 6 Street
01-211 Warsaw
Tel.: +48 22 280 00 00