ONTOZRY 25 mg /12.5 Mg Film-Coated Tablets

Зміст інструкції

1. Ontozry 12.5 mg tablets, 25 mg film-coated tablets, 50 mg film-coated tablets, 100 mg film-coated tablets, 150 mg film-coated tablets, 200 mg film-coated tablets
   1. What is Ontozry and what is it used for
   2. What you need to know before taking Ontozry
   3. How to take Ontozry
   4. Possible side effects
   5. How to store Ontozry
   6. Package contents and other information

Ontozry 12.5 mg tablets, 25 mg film-coated tablets, 50 mg film-coated tablets, 100 mg film-coated tablets, 150 mg film-coated tablets, 200 mg film-coated tablets

cenobamate

Medicinal product subject to additional monitoring. This will allow the rapid identification of new safety information. You can contribute by reporting any adverse effects encountered during the use of this medicine. See the end of section 4 for information on how to report adverse effects.

Read this leaflet carefully before you start taking this medicine as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

• 1. What Ontozry is and what it is used for
• 2. What you need to know before you take Ontozry
• 3. How to take Ontozry
• 4. Possible side effects
• 5. How to store Ontozry
• 6. Contents of the pack and other information

1. What is Ontozry and what is it used for

Ontozry contains the active substance cenobamate. It belongs to a group of medicines called
antiepileptics. These medicines are used to treat epilepsy, a condition in which you have
seizures or convulsions due to abnormal brain activity.
Ontozry is used in combination with other antiepileptic medicines in adult patients with epilepsy who
have not been adequately controlled, despite previous treatment with at least two
antiepileptic medicines, to treat a type of epilepsy that manifests with epileptic seizures with
focal onset with or without secondary generalization. Focal onset seizures
are those caused by abnormal brain activity that begins in one part of the brain, on one side,
while secondary generalization means that the abnormal activity spreads to both sides of the
brain. The medicine can only be used in adults.

2. What you need to know before taking Ontozry

Do not take Ontozry

• if you are allergic tocenobamate or any of the other ingredients of this medicine (listed in section 6)
• if you have congenital heart problems, with changes in the electrical activity of the heart, related to a rare condition called short QT syndrome.

Warnings and precautions
Talk to your doctor or pharmacist before taking Ontozry or during treatment if:

• at any time you have thoughts of self-harm or suicide. Some people treated with antiepileptic drugs like Ontozry have had thoughts of self-harm or suicide. If you have any of these thoughts at any time, contact your doctor immediately
• you have a severe skin reaction that can include high temperature and flu-like symptoms, rash on the face, rash that spreads to other parts of the body, swelling of the glands (enlarged lymph nodes) and blood tests showing an increase in liver enzyme levels and a type of white blood cells (eosinophilia).

Children and adolescents
Ontozry is not recommended in children and adolescents under 18 years of age, as it has not
been studied in this age group.

Other medicines and Ontozry
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicines.
Taking Ontozry with some other medicines may affect the action of other medicines or how Ontozry
works. Do not start or stop taking other medicines without talking to your doctor or
pharmacist.
Tell your doctor if you are taking any of the following medicines, as it may be necessary to adjust
the dose:

• medicines used to help you sleep such as barbiturates and benzodiazepines
• other medicines to treat epilepsy, such as clobazam, phenytoin and phenobarbital, lamotrigine
• medicines for birth control (oral contraceptives), as these may become less effective when taken with Ontozry. Your doctor may prescribe alternative methods to prevent pregnancy while taking this medicine and for up to 4 weeks after stopping the medicine
• medicines that are known to be broken down in the body by specific groups of enzymes such as midazolam (a medicine used to stop prolonged, acute (sudden) seizures, for sedation and for sleep problems), bupropion (a medicine used to help you quit smoking), omeprazole (a medicine used to treat heartburn or stomach ulcers), baricitinib (a medicine used to treat painful inflammation of the joints or eczema), cefaclor (an antibiotic), empagliflozin (a medicine used to treat high blood sugar in diabetes), penicillin G (an antibiotic), ritobegron (a medicine used to treat overactive bladder), sitagliptin (a medicine used to control high blood sugar in diabetes).

Ontozry with alcohol
Do not take this medicine with alcohol. Ontozry can increase the effects of alcohol such as feeling
tired or sleepy; do not drink alcohol while taking this medicine.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant or are planning to become pregnant, or if you are
breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
Take Ontozry during pregnancy only if you and your doctor consider it absolutely necessary.
You must use effective contraception during the use of cenobamate and for up to 4 weeks after
stopping this medicine. Ask your doctor about effective contraceptive measures.
You must stop breastfeeding during the use of Ontozry.

Driving and using machines

• While taking Ontozry you may experience drowsiness, dizziness or fatigue and blurred vision.
• These effects are more likely to occur at the beginning of treatment or after an increase in dose.
• Do not drive, ride a bicycle or use tools or machines if your reactions are impaired until you know how the medicine affects you.

Ontozry contains lactose
If you have been told by your doctor that you have an intolerance to some sugars, consult your doctor
before taking this medicine.

3. How to take Ontozry

Take this medicine following exactly the instructions of your doctor. If you have any doubts, ask your
doctor or pharmacist.
You will take Ontozry with other medicines to treat epilepsy.

Recommended dose
You will start Ontozry with a daily dose of one 12.5 mg tablet for the first 2 weeks,
followed by one 25 mg tablet once a day for the next 2 weeks. Afterwards
your dose will be gradually adjusted every 2 weeks until you reach the dose that has the
best effect. Your doctor will calculate the right daily dose for you and may need to
modify it over time.
The recommended daily dose is between 200 mg and 400 mg once a day.

Method of use
Take the recommended dose once a day, at about the same time. You can take Ontozry in
any time of the day or in the evening, with food or away from meals.
Swallow the tablets whole with a glass of water. Do not break the tablets in half because they are not
suitable for being divided into two equal parts.

If you take more Ontozry than you should
Talk to your doctor. You may experience dizziness, fatigue and drowsiness.

If you forget to take Ontozry
Take the forgotten dose as soon as you remember, if less than 12 hours have passed since the time it
was scheduled to be taken. If more than 12 hours have passed, skip the forgotten dose and take the next
dose at the usual time. Do not take a double dose to make up for a missed dose.

If you stop taking Ontozry
Do not reduce the dose or stop taking Ontozry without asking your doctor for advice. The
doctor will explain to you how to stop taking Ontozry by gradually reducing the
dose.
If you have any doubts about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Seek immediate medical attentionif you experience any of the following serious side effects:

Rare side effects(may affect up to 1 in 1,000 people):

• severe skin reaction which can include fever and other flu-like symptoms, rash on the face, rash spreading to other areas of the body and swelling of the glands (enlarged lymph nodes). Blood tests may show an increase in liver enzymes and a type of white blood cells (eosinophilia).

The following side effects may also occur with this medicine. Tell your doctor if any of the following effects occur:

Very common side effects(may affect more than 1 in 10 people):

• feeling sleepy, sedated or extremely tired
• dizziness
• vertigo
• problems with coordination of movements, problems walking or maintaining balance (ataxia, gait disturbance, abnormal coordination)
• headache

Common side effects(may affect up to 1 in 10 people):

• memory impairment, confusion
• excitement
• difficulty pronouncing words or difficulty speaking
• rapid and involuntary movements of the eyes (nystagmus), blurred vision, double vision
• nausea, vomiting, constipation or diarrhoea
• dry mouth
• rash, itching
• swelling of the eyelids, swelling of the limbs
• blood tests showing increases in levels of certain liver enzymes

Uncommon side effects(may affect up to 1 in 100 people):

• allergic reactions
• thoughts of self-harm or suicide

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Annex V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Ontozry

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the box and blister after
Exp. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Ontozry contains

• The active ingredient is cenobamate. One 12.5 mg Ontozry tablet contains 12.5 mg of cenobamate. One film-coated Ontozry 25 mg tablet contains 25 mg of cenobamate. One 50 mg film-coated tablet contains 50 mg of cenobamate. One 100 mg film-coated tablet contains 100 mg of cenobamate. One 150 mg film-coated tablet contains 150 mg of cenobamate. One 200 mg film-coated tablet contains 200 mg of cenobamate.
• The other excipients are microcrystalline cellulose (E460), lactose monohydrate, sodium starch glycolate, anhydrous colloidal silica (E551), magnesium stearate (E470b)

25 mg and 100 mg film-coated tablets: aluminium lake containing indigo carmine (E132), red iron oxide (E172), yellow iron oxide (E172), macrogol, partially hydrolysed polyvinyl alcohol (E1203), talc (E553b), titanium dioxide (E171)
50 mg film-coated tablets: yellow iron oxide (E172), macrogol, partially hydrolysed polyvinyl alcohol (E1203), talc, titanium dioxide (E171)
150 mg and 200 mg film-coated tablets: red iron oxide (E172), yellow iron oxide (E172), macrogol, partially hydrolysed polyvinyl alcohol (E1203), talc (E553b), titanium dioxide (E171)

Description of the appearance of Ontozry and contents of the pack
Ontozry 12.5 mg is supplied as round, uncoated tablets, of colour from white to off-white, with AV on one side and ‘12’ on the other side.
Ontozry 25 mg is supplied as round, film-coated tablets, of brown colour, with AV on one side and ‘25’ on the other side.
Ontozry 50 mg is supplied as round, film-coated tablets, of yellow colour, with AV on one side and ‘50’ on the other side.
Ontozry 100 mg is supplied as round, film-coated tablets, of brown colour, with AV on one side and ‘100’ on the other side.
Ontozry 150 mg is supplied as round, film-coated tablets, of light orange colour, with AV on one side and ‘150’ on the other side.
Ontozry 200 mg is supplied as oval-shaped, film-coated tablets, of light orange colour, with AV on one side and ‘200’ on the other side.
The starter pack of Ontozry contains 14 tablets of 12.5 mg and 14 film-coated tablets of 25 mg.
Ontozry 50 mg, 100 mg, 150 mg and 200 mg film-coated tablets are available in packs of 14, 28 or 84.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Angelini Pharma S.p.A
Viale Amelia 70, 00181
Rome - Italy

Manufacturer
Swiss Caps GmbH
Grassingerstrasse 9
83043 Bad Aibling
Germany
Aziende Chimiche Riunite Angelini Francesco ACRAF SPA
Via Vecchia del Pinocchio, 22 60100
Ancona (AN), Italy

Other sources of information
More detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu .

Annex IV
Scientific conclusions and justification for the variation(s) to the marketing authorisation(s)
Scientific conclusions
Considering the PRAC assessment of the PSUR for cenobamate, the scientific conclusions are as follows:
Following review of the available data from clinical studies and spontaneous reports, including 11 reports of single case reports of adverse reactions with a close temporal association and a positive de-challenge, the PRAC considers that a causal relationship between cenobamate and “suicidal ideation” is at least reasonably possible.
The PRAC concluded that the medicine information for products containing cenobamate should be updated accordingly.
Following review of the PRAC recommendations, the CHMP agrees with the PRAC’s conclusions and justification for the recommendation.

Justification for the variation(s) to the marketing authorisation(s)
Based on the scientific conclusions on cenobamate, the CHMP considers that the benefit/risk ratio of the medicine(s) containing cenobamate remains unchanged, save for the proposed changes to the medicine information.
The CHMP recommends the variation(s) to the marketing authorisation(s).