Package Insert: Information for the User

Levetiracetam Combix 500 mg Film-Coated Tablets

Read this package insert carefully before starting to take the medication, as it contains important information for you.

• Keep this package insert, as you may need to refer to it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed for you and should not be given to others who may have the same symptoms, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

Contents of the package and additional information

Levetiracetam Combix is an antiepileptic medication (a medication for the treatment of seizures in epilepsy).

Levetiracetam Combixis used:

• alone (without the need for another antiepileptic medication) in adults and adolescents 16 years of age or older with recently diagnosed epilepsy to treat partial onset seizures with or without secondary generalization.
• in combination with other antiepileptic medications to treat:
• partial onset seizures with or without secondary generalization in adults, adolescents, children, and infants 1 month of age or older.
• myoclonic seizures in adults and adolescents 12 years of age or older with juvenile myoclonic epilepsy.
• primary generalized tonic-clonic seizures in adults and adolescents 12 years of age or older with idiopathic generalized epilepsy.

Do not takeLevetiracetam Combix

• If you are allergic to levetiracetam or any of the other ingredients (listed in section 6).

Warnings and precautions

Consult your doctor or pharmacist before starting to take Levetiracetam Combix.

• If you have kidney problems, follow your doctor's instructions who will decide if you need to adjust your dose.
• If you notice any decrease in your child's growth or an unexpected development of puberty, contact your doctor.
• If you notice an increase in the severity of seizures (e.g. increase in frequency), contact your doctor.
• A small number of people taking antiepileptic drugs such as Levetiracetam have had thoughts of self-harm or suicide. If you have any symptoms of depression and/or suicidal thoughts, contact your doctor.

Inform your doctor or pharmacist if any of the following side effects worsen or last more than a few days:

• Abnormal thoughts, feeling irritable or reacting more aggressively than normal or if you or your family and friends notice significant changes in mood or behavior.

Taking Levetiracetam Combix with other medicines

Inform your doctor or pharmacist if you are using or have recently used other medicines, including those purchased without a prescription.

Taking Levetiracetam Combix with food, drinks, and alcohol

You can take Levetiracetam Combix with or without food. As a precaution, do not take Levetiracetam Combix with alcohol.

Pregnancy and breastfeeding

Consult your doctor or pharmacist before using any medicine.

If you are pregnant or think you may be pregnant, inform your doctor.

Levetiracetam Combix should not be used during pregnancy unless strictly necessary. The risk to the baby during pregnancy is unknown. In animal studies, Levetiracetam Combix has shown unwanted effects on reproduction at doses higher than those you may need to control your seizures.

It is not recommended to breastfeed naturally during treatment.

Driving and operating machinery

Levetiracetam may cause symptoms such as drowsiness, dizziness, or visual disturbances, and may impair your reaction time. These effects, as well as the underlying condition, may make it difficult for you to drive vehicles or operate machinery. Therefore, do not drive, operate machinery, or engage in other activities that require special attention, until your doctor assesses your response to this medicine.

Follow exactly the administration instructions for Levetiracetam Combix as indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

Levetiracetam Combix should be taken twice a day, once in the morning and once at night, approximately at the same time each day.

Take the number of tablets prescribed by your doctor.

Monotherapy

Dosage in adults and adolescents (from 16 years of age):

General dosage: between 1,000 mg (2 tablets) and 3,000 mg (6 tablets) per day.

When starting to take Levetiracetam Combix, your doctor will prescribe alower dosefor two weeks before administering the general lowest dose.

For example: for a daily dose of 2,000 mg, you should take 2 tablets in the morning and 2 tablets at night.

Concomitant therapy

Dosage in adults and adolescents (from 12 to 17 years) with a weight of50 kg or more:

General dosage: between 1,000 mg (2 tablets) and 3,000 mg (6 tablets) per day.

For example, for a daily dose of 1,000 mg, you should take one tablet in the morning and one tablet at night.

Dosage in infants (from 6 to 23 months), children (from 2 to 11 years), and adolescents (from 12 to 17 years) with a weight less than 50 kg:

Your doctor will prescribe the most appropriate pharmaceutical form of Levetiracetam according to age, weight, and dosage.

Levetiracetam 100 mg/ml oral solution is a more suitable presentation for infants and children under 6 years old.

General dosage: between 20 mg per kg of body weight and 60 mg per kg of body weight per day.

Dosage in infants (from 1 month to less than 6 months):

Oral solution is a more suitable presentation for infants under 6 months.

Administration form

Swallow the Levetiracetam Combix tablets with a sufficient amount of liquid (e.g. a glass of water).

Treatment duration

• Levetiracetam Combix is used as a chronic treatment. Continue treatment with Levetiracetam Combix for the time indicated by your doctor.
• Do not stop treatment without your doctor's recommendation, as this may increase your seizures.If your doctor decides to stop your treatment with Levetiracetam Combix, they will give you instructions for the gradual withdrawal of Levetiracetam Combix.

If you take more Levetiracetam Combix than you should

The possible adverse effects of a Levetiracetam overdose are drowsiness, agitation, aggression, decreased alertness, respiratory inhibition, and coma.

Contact your doctor if you have taken more tablets than you should. Your doctor will establish the best possible treatment for the overdose.

In case of overdose or accidental ingestion, consult your doctor or pharmacist or call the Toxicological Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

If you forgot to take Levetiracetam Combix

Contact your doctor if you have missed one or more doses.

Do not take a double dose to compensate for the missed doses.

If you interrupt treatment with Levetiracetam Combix

Like with other antiepileptic medications, the discontinuation of treatment with Levetiracetam Combix should be done gradually to avoid an increase in seizures.

If you have any other doubts about the use of this product, ask your doctor or pharmacist.

Like all medications, Levetiracetam Combix may cause side effects, although not everyone will experience them.

Inform your doctor immediately, or go to the emergency service of your nearest hospital if you experience:

• weakness, dizziness, or difficulty breathing, as these may be signs of a severe allergic reaction (anaphylactic)
• swelling of the face, lips, tongue, or throat (Quincke's edema)
• flu-like symptoms and a rash on the face followed by a prolonged rash with elevated temperature, elevated liver enzymes in blood tests, and an increase in a type of white blood cell (eosinophilia) and enlarged lymph nodes (drug reaction with eosinophilia and systemic symptoms (DRESS))
• symptoms such as decreased urine output, fatigue, nausea, vomiting, confusion, and swelling of the legs, arms, or feet, as it may be a sign of sudden kidney function decline
• a skin rash that can form blisters and may appear as small dots (central dark spots surrounded by a lighter area, with a dark ring around the edge) (erythema multiforme)
• a generalized rash with blisters and skin peeling, especially around the mouth, nose, eyes, and genitals (Stevens-Johnson syndrome)
• a more severe form that causes skin peeling on more than 30% of the body surface (toxic epidermal necrolysis)
• signs of severe mental changes or if someone around you notices signs of confusion, somnolence (drowsiness), amnesia (memory loss), memory decline (forgetfulness), abnormal behavior, or other neurological signs including involuntary or uncontrolled movements. These may be symptoms of encephalopathy.

Some side effects such as drowsiness, weakness, and dizziness may be more frequent when starting treatment or increasing the dose. However, these side effects should decrease over time.

Very common: may affect more than 1 in 10 patients

• nasopharyngitis;
• drowsiness (drowsiness), headache.

Common: may affect up to 1 in 10 patients

• anorexia (loss of appetite);
• depression, hostility or aggression, anxiety, insomnia, nervousness, or irritability;
• seizures, balance disorder, dizziness (sensation of instability), lethargy, tremor (involuntary shaking);
• vertigo (sensation of rotation);
• cough;
• abdominal pain, diarrhea, dyspepsia (heavy digestion, burning, and acidity), vomiting, nausea;
• skin rash;
• asthenia/ fatigue (sensation of weakness).

Rare: may affect up to 1 in 100 patients

• decreased platelet count, decreased white blood cell count;
• weight loss, weight gain;
• suicidal attempt and suicidal thoughts, mental alterations, abnormal behavior, hallucinations, anger, confusion, panic attack, emotional instability/mood changes, agitation;
• amnesia (memory loss), memory decline (forgetfulness), abnormal coordination/ataxia (coordinated movement altered), paresthesia (tingling), attention alterations (loss of concentration);
• diplopia (double vision), blurred vision;
• abnormal results in liver function tests;
• hair loss, eczema, itching;
• muscle weakness, myalgia (muscle pain);
• injury.

Rare: may affect up to 1 in 1000 patients

• infection;
• decreased count of all types of blood cells;
• suicide, personality disorders (behavioral problems), abnormal thinking (slow thinking, difficulty concentrating);
• involuntary muscle spasms affecting the head, torso, and limbs, difficulty controlling movements, hyperkinesia (hyperactivity);
• pancreatitis (inflammation of the pancreas);
• hepatic insufficiency, hepatitis (inflammation of the liver);
• skin rash, which may lead to blisters that may appear as small dots (central dark spots surrounded by a lighter area, with a dark ring around the edge) (erythema multiforme), a generalized rash with blisters and skin peeling, especially around the mouth, nose, eyes, and genitals (Stevens-Johnson syndrome), and a more severe form that causes skin peeling on more than 30% of the body surface (toxic epidermal necrolysis).
• decreased sodium concentration in blood.
• sudden decline in kidney function.
• rhabdomyolysis (muscle tissue breakdown) and associated elevated creatine phosphokinase in blood.

The prevalence is significantly higher in Japanese patients compared to non-Japanese patients.

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use:www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

Keep this medication out of the sight and reach of children.

This medication does not require special conditions for conservation.

Do not use Levetiracetam after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Medications should not be disposed of through drains or in the trash. Dispose of the packaging and medications you no longer need at the SIGRE collection point of the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. By doing so, you will help protect the environment.

Composition of Levetiracetam Combix 500 mg film-coated tablets

• The active ingredient is levetiracetam. Each tablet contains 500 mg of levetiracetam.
• The other components are pregelatinized cornstarch, sodium starch glycolate (type A) from potato, povidone K-30, cornstarch, anhydrous colloidal silica, magnesium stearate, coating agent Instacoat Universal ICG-U-10276 Yellow (hypromellose-E464-, macrogol, talc-E553b-, titanium dioxide-E171-, iron oxide yellow-E172).

Appearance of the product and contents of the packaging

Levetiracetam Combix 500 mg film-coated tablets are yellow, oval, biconvex, with the number “500” engraved on one face and scored on the other.

OPA/Al/PVC/Al blisters and PVC/PVDC/Al blisters.

Containers containing 60 film-coated tablets.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Laboratorios Combix, S.L.U.

C/ Badajoz 2. Edificio 2.

28223 Pozuelo de Alarcón (Madrid)

Spain

Responsible for manufacturing

Zydus France

ZAC Les Hautes Patures

Parc d’activités des Peupliers

25 Rue des Peupliers

92000 Nanterre

France

or

Centre Spécialités Pharmaceutiques

ZAC des Suzots

35 rue de la Chapelle

63450 Saint Amant Tallende

France

Last reviewed date of this leaflet: September 2019.

“Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/ ”.