LEVETIRACETAM TARBIS 100 mg/ml CONCENTRATE FOR INFUSION SOLUTION

2. What you need to know before you use Levetiracetam Tarbis

Do not use Levetiracetam Tarbis

• if you are allergic to levetiracetam, to pyrrolidone derivatives or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Tell your doctor before you start taking this medicine

• if you have kidney problems, follow your doctor's instructions, as he/she will decide if you need to adjust your dose.
• if you notice any decrease in your child's growth or an unexpected delay in puberty, contact your doctor.
• a small number of people taking antiepileptics such as levetiracetam have had thoughts of harming themselves or suicide. If you have any symptoms of depression and/or suicidal thoughts, contact your doctor.
• if you have a medical history or a family history of abnormal heart rhythms (visible on an electrocardiogram), or if you have a disease and/or take a treatment that makes you prone to cardiac arrhythmias or electrolyte imbalances.

Tell your doctor or pharmacist if any of the following side effects get worse or last more than a few days:

Abnormal thoughts, feeling irritable or behaving more aggressively than usual, or if you or your family and friends notice significant changes in mood or behaviour.Worsening of epilepsy:

Rarely, epileptic 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 (epilepsy associated with SCN8A mutations) 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 medicine, go to a doctor as soon as possible.

Children and adolescents

• Monotherapy with levetiracetam is not indicated in children and adolescents under 16 years.

Other medicines and Levetiracetam Tarbis

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including those without a prescription.

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

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. Levetiracetam should only be used during pregnancy if, after a careful evaluation, your doctor considers it necessary.

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

The risk of birth defects for your baby cannot be completely excluded.

Breast-feeding is not recommended during treatment with levetiracetam.

Driving and using machines

Levetiracetam Tarbis may affect your ability to drive or use tools or machines, as it may cause drowsiness. This is more likely at the start of treatment or when the dose is increased. You should not drive or use machines until it is established that your ability to perform these activities is not affected.

Levetiracetam Tarbis contains sodium

This medicine contains 19 mg of sodium (a major component of cooking/table salt) per vial, which is equivalent to 0.95% of the maximum recommended daily intake of sodium for an adult.

3. How to use Levetiracetam Tarbis

This medicine will be administered to you by a doctor or nurse through intravenous infusion.

Levetiracetam should be taken twice daily, once in the morning and once in the evening, approximately at the same time every day.

The intravenous formulation is an alternative to oral administration. You can switch from film-coated tablets or oral solution to the intravenous formulation, or vice versa, directly without dose adjustment. Your total daily dose and frequency of administration should be the same.

Concomitant therapy and monotherapy (from 16 years of age)

Adults (≥18 years) and adolescents (12-17 years) weighing 50 kg or more:Recommended dose: 1000-3000 mg daily.

When you first start taking Levetiracetam Tarbis, your doctor will prescribe a lower dose for two weeks before giving you the lowest daily dose.

Dose in children (4-11 years) and adolescents (12-17 years) weighing less than 50 kg:

Recommended dose: 20-60 mg/kg body weight daily.

Method and route of administration:

This medicine is for intravenous use.

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

More detailed information for the correct use of levetiracetam is provided in section 6 for healthcare professionals.

Duration of treatment:

• There is no experience with the intravenous administration of levetiracetam for a period longer than 4 days.

If you stop treatment with Levetiracetam Tarbis:

As with other antiepileptic medicines, stopping treatment with this medicine should be done gradually to avoid an increase in seizures. If your doctor decides to stop your treatment with levetiracetam, he/she will give you instructions for the gradual withdrawal of levetiracetam.

If you have any further questions on 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.

Tell your doctor immediately, or go to the casualty department 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 oedema)
• flu-like symptoms and 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 decreased urine output, tiredness, nausea, vomiting, confusion and swelling of the legs, arms or feet, as this may be a sign of sudden decrease in kidney function
• a skin rash which may form blisters and may look like targets (central dark spot surrounded by a paler area, with a dark ring on the edge) (erythema multiforme)
• a widespread rash with blisters and peeling skin, particularly around the mouth, nose, eyes and genitals (Stevens-Johnson syndrome)
• a more severe form causing skin peeling over more than 30% of the body surface (toxic epidermal necrolysis)
• signs of serious mental changes or if someone around you notices signs of confusion, drowsiness (drowsiness), amnesia (memory loss), memory impairment (forgetfulness), abnormal behaviour or other neurological signs including involuntary or uncontrolled movements. These may be symptoms of encephalopathy.

The most frequently reported side effects are nasopharyngitis, somnolence (feeling drowsy), headache, fatigue and dizziness. Side effects such as drowsiness, weakness and dizziness are more frequent at the start of treatment or when the dose is increased. However, these side effects should decrease over time.

Very common:may affect more than 1 in 10 people

• nasopharyngitis;
• somnolence (feeling drowsy), headache.

Common:may affect up to 1 in 10 people

• loss of appetite;
• depression, hostility or aggression, anxiety, insomnia, nervousness or irritability;
• seizures, balance disorder, dizziness (feeling unsteady), lethargy (lack of energy and enthusiasm), tremor (involuntary trembling);
• vertigo (feeling of spinning);
• cough;
• abdominal pain, diarrhoea, dyspepsia (indigestion), vomiting, nausea;
• skin rash;
• asthenia/fatigue (feeling weak).

Uncommon:may affect up to 1 in 100 people

• decrease in the number of platelets, decrease in white blood cells;
• weight loss, weight gain;
• suicidal attempt and suicidal thoughts, mental disorders, abnormal behaviour, hallucinations, anger, confusion, panic attack, emotional instability/mood swings, agitation;
• amnesia (memory loss), memory impairment (forgetfulness), abnormal coordination/ataxia (impaired coordination), paraesthesia (tingling), attention disturbances (loss of concentration);
• diplopia (double vision), blurred vision;
• elevated/abnormal liver function tests;
• 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, Quincke's oedema);
• decrease in sodium levels in the blood;
• suicide, personality disorders (behavioural problems), abnormal thinking (slow thinking, difficulty concentrating);
• delirium;
• encephalopathy (see sub-section "Tell your doctor immediately" for a detailed description of symptoms);
• epileptic seizures may worsen or occur more frequently;
• involuntary muscle contractions affecting the head, torso and limbs, difficulty controlling movements, hyperkinesia (hyperactivity);
• change in heart rhythm (electrocardiogram);
• pancreatitis (inflammation of the pancreas);
• liver failure, hepatitis (inflammation of the liver);
• sudden decrease in kidney function;
• skin rash, which may lead to blisters that may look like targets (central dark spot surrounded by a paler area, with a dark ring on the edge) (erythema multiforme), a widespread rash with blisters and peeling skin, particularly around the mouth, nose, eyes and genitals (Stevens-Johnson syndrome) and a more severe form causing skin peeling over more than 30% of the body surface (toxic epidermal necrolysis);
• rhabdomyolysis (breakdown of muscle tissue) and increased creatine phosphokinase in the blood. The prevalence is significantly higher in Japanese patients compared to non-Japanese patients;
• limping or difficulty walking;
• a combination of fever, muscle stiffness, unstable blood pressure and heart rate, confusion, decreased level of consciousness (may be signs of a condition called malignant neuroleptic 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

?

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Spanish Medicines Monitoring System for Human Use: www.notificaRAM.es.

By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Levetiracetam Tarbis

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 vial and carton after EXP. The expiry date is the last day of the month shown.

This medicine does not require any special storage conditions.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Container Content and Additional Information

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 injectable preparations.

Appearance of the Product and Container Content

Levetiracetam Tarbis 100 mg/ml concentrate for solution for perfusion EFG (sterile concentrate) is a clear and colorless liquid.

Levetiracetam Tarbis 100 mg/ml concentrate for solution for perfusion 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

Manufacturer

Pharmadox Healthcare Ltd.

KW20A Kordin Industrial Park

Paola, PLA 3000

Malta

Amarox Pharma B.V.

Rouboslaan 32

Voorschoten, 2252TR

Netherlands

This medicinal product is authorized in the Member States of the European Economic Area under 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

Date of the Last Revision of this Leaflet: October 2023

Detailed and updated information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es

-------------------------------------------------------------------------------------------------------------------------

This information is intended only for healthcare professionals:

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 medicinal product 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 Tarbis Concentrate

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

Shelf life after first opening: from a microbiological point of view, the product should be used immediately after dilution. If not used immediately, the storage time and conditions before 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 carried out under validated and controlled aseptic conditions.

It has been 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 a controlled room temperature of 15-25°C.

Diluents:

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

Dextrose 50 mg/ml (5%) injection solution