Patient Information Leaflet

Levetiracetam Zentiva 100 mg/ml Concentrate for Solution for Infusion EFG

Levetiracetam

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

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

1.What Levetiracetam Zentiva is and what it is used for

2.What you need to know before you start taking Levetiracetam Zentiva

3.How to use Levetiracetam Zentiva

4.Possible side effects

5.Storage of Levetiracetam Zentiva

6.Contents of the pack and additional information

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

Levetiracetam Zentiva is used:

• alone in adults and adolescents of 16 years of age or older with recently diagnosed epilepsy to treat a form of epilepsy. Epilepsy is a disease where patients have seizures (crises). Levetiracetam is used for the form of epilepsy in which the seizures initially affect only one side of the brain, but may later extend to wider areas in both sides of the brain (partial onset seizures with or without secondary generalization). Your doctor has prescribed levetiracetam to reduce the number of seizures.
• in combination with other antiepileptic medications to treat:
• • partial onset seizures with or without generalization in adults, adolescents, and children aged 4 years or older.
  • myoclonic seizures (shock-like, short, muscle or group of muscle seizures) in adults and adolescents aged 12 years or older with juvenile myoclonic epilepsy.
  • primary generalized tonic-clonic seizures (major seizures, including loss of consciousness) in adults and adolescents aged 12 years or older with idiopathic generalized epilepsy (a type of epilepsy thought to have a genetic cause).

Levetiracetam Zentiva concentrate is an alternative for patients in whom oral administration is not temporarily viable.

Do not use Levetiracetam Zentiva

•If you are allergic to levetiracetam, pyrrolidone derivatives, or any of the other components of this medication (listed in section 6).

Warnings and precautions

Consult your doctor before starting to use levetiracetam

• 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 onset of puberty, contact your doctor.
• A small number of people taking antiepileptic medications 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.
• If you have a family or medical history of irregular heart rhythm (visible on an electrocardiogram), or if you have a disease or are taking a treatment that makes you prone to cardiac irregularities or electrolyte imbalances.

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

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

• Worsening of epilepsy

In rare cases, seizures may worsen or occur more frequently, mainly during the first month after starting treatment or increasing the dose. If you experience any of these new symptoms while taking Levetiracetam Zentiva, visit a doctor as soon as possible.

Children and adolescents

•Monotherapy with levetiracetam (exclusive treatment) is not indicated in children and adolescents under 16 years old.

Other medications and Levetiracetam Zentiva

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication, including those obtained without a prescription.

Do not take macrogol (laxative medication) within one hour before and one hour after taking levetiracetam, as it may reduce its effect.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor before using this medication.

Pregnancy

Levetiracetam can only be used during pregnancy if, after careful evaluation, your doctor considers it necessary.

Do not stop your treatment without discussing it with your doctor first.

The risk of birth defects for the baby cannot be completely ruled out.

Breastfeeding

It is not recommended to breastfeed naturally during treatment.

Driving and operating machinery

Levetiracetam Zentiva may affect your ability to drive or operate tools or machinery, as it may cause drowsiness. This is more likely at the start of treatment or when increasing the dose. Do not drive or operate machinery until it is confirmed that your ability to perform these activities is not impaired.

Levetiracetam Zentiva contains sodium

This medication contains 19.1 mg of sodium (main component of table salt/for cooking) in each vial (5 ml). This is equivalent to 0.796% of the maximum daily sodium intake recommended for an adult.

A doctor or nurse will administer levetiracetam through intravenous infusion. Levetiracetam should be administered twice a day, once in the morning and once at night, approximately at the same time each day.

The intravenous formulation is an alternative to oral administration. You can switch from coated tablets or oral solution to the intravenous formulation, or vice versa, directly without adjusting the dose. Your total daily dose and administration frequency must be identical.

Concomitant therapy and monotherapy (from 16 years of age)

Adults (≥18 years) and adolescents (12 to 17 years) with a weight of 50 kg or more:

Recommended dose: between 1,000 mg and 3,000 mg per day.

When starting to take Levetiracetam Zentiva, your doctor will prescribe a lower dose for two weeks before administering the general lowest dose.

Dose in children (4 to 11 years) and adolescents (12 to 17 years) with a weight less than 50 kg:

Recommended dose: between 20 mg per kg of body weight and 60 mg per kg of body weight per day.

Method and form of administration:

Levetiracetam Zentiva is for intravenous administration.

The recommended dose must be diluted in at least 100 ml of a compatible diluent and administered by intravenous infusion over 15 minutes.

Further detailed information for the correct use of Levetiracetam Zentiva is provided in the section 6 for doctors and nurses.

Treatment duration:

No experience is available with the administration of levetiracetam intravenously for periods exceeding 4 days.

If treatment with Levetiracetam Zentiva is interrupted:

Like with other antiepileptic medications, the discontinuation of levetiracetam treatment should be done gradually to avoid an increase in seizures. If your doctor decides to stop your treatment with levetiracetam, they will give you instructions for the gradual withdrawal of levetiracetam.

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

Like all medicines, this medicine can 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 (anaphylaxis);
• 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 high 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 low 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, drowsiness (drowsiness), amnesia (memory loss), memory decline (forgetfulness), abnormal behavior, or other neurological signs including involuntary or uncontrolled movements. These may be symptoms of encephalopathy.

The most frequently reported side effects are nasopharyngitis, drowsiness (feeling sleepy), headache, fatigue, and dizziness. Side effects such as feeling sleepy, feeling weak, 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 people

• nasopharyngitis;
• drowsiness (feeling sleepy), headache.

Common: may affect up to 1 in 10 people

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

Rare: may affect up to 1 in 100 people

• decrease in platelet count, decrease in white blood cell count;
• weight loss, weight gain;
• suicidal thoughts and attempts, mental changes, 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 disturbances (loss of concentration);
• diplopia (double vision), blurred vision;
• elevated/anomalous liver function test values;
• hair loss, eczema, itching;
• muscle weakness, myalgia (muscle pain);
• injury.

Rare: may affect up to 1 in 1,000 people

• infection;
• decrease in all types of blood cells;
• severe allergic reactions (DRESS, anaphylactic reaction (severe and serious allergic reaction), Quincke's edema (swelling of the face, lips, tongue, and throat));
• decrease in sodium concentration in blood;
• suicide, personality disorders (behavior problems), abnormal thinking (slow thinking, difficulty concentrating), delirium;
• encephalopathy(see "Inform your doctor immediately" subsection for a detailed description of symptoms);
• epileptic seizures may worsen or occur more frequently;
• involuntary and uncontrolled muscle spasms affecting the head, trunk, and limbs, difficulty controlling movements, hyperkinesia (hyperactivity);
• change in heart rhythm (electrocardiogram);
• pancreatitis (inflammation of the pancreas);
• hepatic insufficiency, hepatitis (inflammation of the liver);
• sudden decline in kidney function;
• 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);
• rhabdomyolysis (muscle tissue breakdown) and elevated creatine phosphokinase associated. The prevalence is significantly higher in Japanese patients compared to non-Japanese patients;
• gait disturbance or difficulty walking.
• combination of fever, muscle rigidity, unstable blood pressure and heart rate, confusion, and low level of consciousness (may be signs of a condition called neuroleptic malignant syndrome). 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 Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the vial and on the carton after CAD.

The expiration date is the last day of the month indicated.

This medication does not require special conditions for conservation.

Composition of Levetiracetam Zentiva

• The active ingredient is levetiracetam.

Each ml contains 100 mg of levetiracetam.

Each vial of 5 ml contains 500 mg of levetiracetam.

• The other components are: sodium chloride, sodium acetate trihydrate, glacial acetic acid, water for injections.

Appearance of the product and contents of the pack

Levetiracetam Zentiva concentrate for solution for infusion is a transparent and colourless liquid.

Levetiracetam Zentiva concentrate for solution for infusion is packaged in carton boxes containing 1 or 10 vials of 5 ml.

Only some pack sizes may be marketed.

Marketing authorisation holder and manufacturer responsible

Marketing authorisation holder

Zentiva k.s.,

U kabelovny 130,

Prague 10 – Dolní Mecholupy,

102 37 Czech Republic

Manufacturer responsible1

MIAS Pharma Limited

Suite 2, Stafford House, Strand Road

Portmarnock, Co. Dublin

Ireland

Tillomed Malta Limited,

Malta Life Sciences Park,

LS2.01.06 Industrial Estate,

San Gwann, SGN 3000, Malta

Zentiva S.A.

Bulevardul Pallady Theodor Nr. 50,

Bucharest, 032266

Romania

You can request more information about thismedicamentby contacting the local representative of the marketing authorisation holder:

ZentivaSpain S.L.U.

Avenida de Europa, 19, Edificio 3, Planta 1.

28224 Pozuelo de Alarcón, Madrid

Spain

This medicinal product is authorised in the member states of the European Economic Area with the following names:

Last review date of this leaflet: January 2023

Other sources of information

The detailed information on this medicinal product is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/).

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This information is intended solely for healthcare professionals:

The instructions for the proper use of Levetiracetam Zentiva are provided in section 3.

Each vial of 5 ml contains 500 mg of levetiracetam.See Table 1 for the recommended preparation and administration of Levetiracetam Zentiva concentrate for solution for infusion to achieve the total daily dose of 500 mg, 1,000 mg, 2,000 mg or 3,000 mg divided into two doses.

Table 1. Preparation and administration of Levetiracetam Zentiva concentrate for solution for infusion:

This medicinal product is for single use only, so the unused solution must be discarded.

Shelf life in use:

From a microbiological point of view, the product must be used immediately after dilution. If not used immediately, the time and conditions of storage prior to the next use are the responsibility of the user and should not exceed 24 hours between 2 and 8°C, unless the dilution has been made in validated and controlled aseptic conditions.

It has been found that Levetiracetam Zentiva concentrate is physically compatible and chemically stable when mixed with the following diluents for at least 24 hours and stored in PVC bags at controlled room temperature of 15-25°C.

Diluent:

• Sodium chloride injection (0.9%)
• Lactate Ringer's injection
• Dextrose injection 5%