Patient Information Leaflet

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

Read this leaflet carefully before you start using 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, ask your doctor or pharmacist.
• This medicine has been prescribed for you only, and you must not give it to others even if they have the same symptoms as you, as it may harm them.
• 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 Tarbis is and what it is used for

2. What you need to know before using Levetiracetam Tarbis

3. How to use Levetiracetam Tarbis

4. Possible side effects

5. Storage of Levetiracetam Tarbis

6. Contents of the pack and additional information

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

Levetiracetam is used:

• alone in adults and adolescents 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 spread 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 4 years of age or older.
  • myoclonic seizures (shock-like, short, muscle or group of muscles) in adults and adolescents 12 years of age or older with juvenile myoclonic epilepsy.
  • primary generalized tonic-clonic seizures (major seizures, including loss of consciousness) in adults and adolescents 12 years of age or older with idiopathic generalized epilepsy (a type of epilepsy thought to have a genetic cause).

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

No use Levetiracetam Tarbis

• 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 this medication

• 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 medical history or family history of irregular heart rhythm (visible on an electrocardiogram), or if you have a disease and/or treatment that makes you prone to cardiac arrhythmias 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. In a very rare form of early-onset epilepsy (SCN8A mutation-associated epilepsy) that causes multiple types of seizures and loss of skills, it may be observed that seizures continue or worsen during treatment.

If you experience any of these new symptoms while taking this medication, see a doctor as soon as possible.

Children and adolescents

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

Other medications and Levetiracetam Tarbis

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication, including non-prescription medications.

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. 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 is not recommended during treatment.

Driving and operating machinery

Levetiracetam Tarbis may impair 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 affected.

Levetiracetam Tarbis contains sodium

This medication contains 19 mg of sodium (main component of table salt/for cooking) in each vial. This is equivalent to 0.95% of the maximum daily sodium intake recommended for an adult.

A doctor or nurse will administer this medication 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 should 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 Tarbis, your doctor will prescribe a lower dose for two weeks before administering the lowest daily 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:

This medication is for intravenous administration.

The recommended dose should be diluted to a minimum of 100 ml in a compatible diluent and administered by intravenous infusion over 15 minutes.

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

Treatment duration:

• No experience is available in the administration of intravenous levetiracetam for a period exceeding 4 days.

If you interrupt treatment with Levetiracetam Tarbis:

Like with other antiepileptic medications, the discontinuation of treatment with this medication 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 they decide to discontinue your treatment with this medication.

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 (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 high temperature, elevated liver enzyme levels 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 deterioration (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 (drowsiness), headache, fatigue, and dizziness. 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 people

• nasopharyngitis;
• drowsiness (drowsiness), headache.

Common:may affect up to 1 in 10 people

• anorexia (loss of appetite);
• depression, hostility, or aggression, anxiety, insomnia, nervousness, or irritability;
• seizures, balance disorder, dizziness (sensation of instability), lethargy (lack of energy and enthusiasm), 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 people

• decreased platelet count, decreased 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 deterioration (forgetfulness), abnormal coordination/ataxia (coordinated movement altered), paresthesia (tingling), attention alterations (loss of concentration);
• diplopia (double vision), blurred vision;
• abnormal liver function test results;
• hair loss, eczema, itching;
• muscle weakness, myalgia (muscle pain);
• injury.

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

• infection;
• decreased count of all types of blood cells;
• severe allergic reactions (DRESS, anaphylactic reaction (severe and life-threatening allergic reaction), Quincke's edema (swelling of the face, lips, tongue, and throat));
• decreased sodium concentration in blood;
• suicide, personality disorders (behavior problems), abnormal thinking (slow thinking, difficulty concentrating);
• delirium;
• encephalopathy (see "Inform your doctor immediately" for a detailed description of symptoms);
• seizures may worsen or occur more frequently;
• involuntary and uncontrolled muscle spasms affecting the head, torso, and limbs, difficulty controlling movements, hyperkinesia (hyperactivity);
• change in heart rhythm (electrocardiogram);
• pancreatitis (inflammation of the pancreas);
• liver 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.

Very rare:may affect up to 1 in 10,000 people

?Repetitive unwanted thoughts or sensations or the urge to do something over and over (Obsessive-Compulsive Disorder).

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 leaflet. You can also report them directly through the Spanish System for the Vigilance of Medicines for Human Use: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.

Medications should not be thrown down the drain or in the trash. If in doubt, ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Composition of Levetiracetam Tarbis

The active ingredient is levetiracetam.

Each ml contains 100 mg of levetiracetam.

The other components are: Sodium acetate trihydrate (E262), glacial acetic acid (E260) (for pH adjustment), sodium chloride, water for injection preparations.

Appearance of the product and contents of the package

Levetiracetam Tarbis 100 mg/ml concentrated solution for infusion EFG (sterile concentrate) is a transparent and colorless liquid.

Levetiracetam Tarbis 100 mg/ml concentrated solution for infusion EFG is packaged in cardboard boxes containing 10 vials and 25 vials of 5 ml.

Only some package sizes may be marketed.

Marketing Authorization Holder

Tarbis Farma S.L.

Gran Vía Carlos III, 94

08028 Barcelona

Spain

Responsible for manufacturing

Pharmadox Healthcare Ltd.

KW20A Kordin Industrial Park

Paola, PLA 3000

Malta

Amarox Pharma B.V.

Rouboslaan 32

Voorschoten, 2252TR

Netherlands

This medicine is authorized in the member states of the European Economic Area with the following names:

Germany:Levetiracetam Amarox 100 mg/ml Konzentrat zur Herstellung einer Infusionslösung

Netherlands:Levetiracetam Amarox 100 mg/ml, concentraat voor oplossing voor infusie

Spain:Levetiracetam Tarbis 100 mg/ml concentrado para solución para perfusión EFG

Last review date of this leaflet: October 2023

The 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

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This information is intended solely for healthcare professionals:

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

A vial of Levetiracetam Tarbis concentrate contains 500 mg of levetiracetam (5 ml of 100 mg/ml concentrate). See Table 1 for the recommended preparation and administration of this medication to achieve a daily total 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 Tarbis concentrate

This drug is for single use, 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 storage conditions 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 was found that Levetiracetam 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.

Diluents:

• Sodium chloride injection solution 9 mg/ml (0.9%)
• Ringer lactate injection solution

Dextrose injection solution 50 mg/ml (5%)