LEVETIRACETAM HIKMA 100 mg/ml CONCENTRATE FOR INFUSION SOLUTION

2. What you need to know before you start using Levetiracetam Hikma

Do not use Levetiracetam Hikma:

• 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

Talk to your doctor before starting to use Levetiracetam Hikma:

• If you have kidney problems, follow your doctor's instructions, who will decide if you need to adjust the dose to be taken.
• If you notice any decrease in your child's growth or an unexpected development of puberty, contact your doctor.
• A small number of people taking antiepileptics, such as Levetiracetam Hikma, 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 history of heart rhythm disorders (visible on an electrocardiogram) or if you have a disease and/or are taking a treatment that makes you prone to cardiac arrhythmias or electrolyte imbalances.

Tell your doctor or pharmacist if any of the following side effects gets worse or lasts 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 your 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 epileptic seizures and loss of skills, you may notice that seizures persist or worsen during treatment.

If you experience any of these new symptoms while taking Levetiracetam, go to a doctor as soon as possible.

Children and adolescents

Monotherapy with Levetiracetam Hikma is not indicated in children and adolescents under 16 years.

Use of Levetiracetam Hikma withother medicines

Tell your doctor or nurse if you are taking, have recently taken or might take any other medicines.

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

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, 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 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 excluded.

Breastfeeding is not recommended during treatment.

Driving and using machines

Levetiracetam Hikma may affect your ability to drive or use tools or machinery, 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 machinery until it is established that your ability to perform these activities is not affected.

Levetiracetam Hikma contains sodium

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

3. How to use Levetiracetam Hikma

A doctor or nurse will administer levetiracetam to you by intravenous infusion.

Levetiracetam should be administered twice a day, once in the morning and once in the evening, approximately at the same time each day.

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

Concomitant therapy andmonotherapy (from 16 years of age)

Adults (≥18 years) and adolescents (from 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 you start taking levetiracetam, your doctor will prescribe a lower dosefor two weeks before administering the lowest general dose.

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

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

Method and route of administration:

Levetiracetam is for intravenous administration.

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 doctors and nurses.

Duration of treatment:

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

If you stop treatment with Levetiracetam Hikma

As with other antiepileptic medicines, stopping treatment with levetiracetam 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 he/she decides to discontinue your treatment with this medicine.

If you have any further questions on the use of this medicine, ask your doctor or nurse.

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 (anaphylactic reaction)
• 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 cells (eosinophilia) and enlarged lymph nodes (Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS))
• symptoms such as low urine output, tiredness, nausea, vomiting, confusion and swelling of legs, arms or feet, as this may be a sign of sudden decrease in kidney function
• a skin rash that may form blisters and may appear as small targets (dark spots surrounded by a paler area, with a dark ring around the edge) (erythema multiforme)
• a widespread rash with blisters and peeling of the skin, especially around the mouth, nose, eyes and genitals (Stevens-Johnson syndrome)
• a more severe form causing peeling of the skin on 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 (memory loss), abnormal coordination/ataxia (altered movement coordination), paraesthesia (tingling); 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 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;
• somnolence (feeling drowsy), 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 (feeling unsteady), lethargy (lack of energy and enthusiasm), tremor (involuntary shaking);
• 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 platelet count, decrease in white blood cell count;
• weight loss, weight gain;
• suicidal attempt and suicidal thoughts, mental disorders, abnormal behaviour, hallucinations, anger, confusion, panic attack, emotional instability/mood changes, agitation;
• amnesia (memory loss), memory impairment (memory loss), abnormal coordination/ataxia (altered movement coordination), paraesthesia (tingling);
• 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 subsection “Tell your doctor immediately” for a detailed description of the symptoms);
• epileptic seizures may worsen or occur more frequently;
• 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 failure, hepatitis (inflammation of the liver);
• sudden decrease in kidney function;
• skin rash, which may lead to blisters that may appear as small targets (dark spots surrounded by a paler area, with a dark ring around the edge) (erythema multiforme), a widespread rash with blisters and peeling of the skin, especially around the mouth, nose, eyes and genitals (Stevens-Johnson syndrome) and a more severe form causing peeling of the skin on 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, low level of consciousness (may be signs of a disorder 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

• unwanted and repetitive thoughts or urges to do something over and over again (obsessive-compulsive disorder).

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse, even if they are 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 Hikma

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 label and on the carton after EXP. The expiry date refers to the last day of the month shown.

This medicine does not require any special storage conditions.

6. Container Contents and Additional Information

Composition of Levetiracetam Hikma

• The active ingredient is levetiracetam.

Each ml of solution for infusion contains 100 mg of levetiracetam.

• The other components are: sodium acetate, glacial acetic acid, sodium chloride, and water for injectable preparations.

Appearance of the Product and Container Contents

Levetiracetam Hikma concentrate for solution for infusion is a sterile, transparent, and colorless liquid.

Levetiracetam Hikma concentrate for solution for infusion is packaged in cardboard boxes containing 10 vials of 5 ml.

Marketing Authorization Holder and Manufacturer

Hikma Farmacêutica (Portugal), S.A.

Estrada do Rio da Mó nº8, 8A, 8B

Fervença

2705-906 Terrugem SNT

Portugal

This Medicinal Product is Authorized in the Member States of the European Economic Area under the Following Names:

Austria: Levetiracetam Hikma 100 mg/ml, Konzentrat zur Herstellung einer Infusionslösung

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

France: Lévétiracétam Hikma 100 mg/ml Solution à diluer pour perfusion

Italy: Levetiracetam Hikma, 100 mg/ml, Concentrato per soluzione per infusione

Portugal: Levetiracetam Hikma 100 mg/ml, Concentrado para solução para perfusão

Spain: Levetiracetam Hikma 100 mg/ml Concentrado para solución para perfusión

United Kingdom/Northern Ireland: Levetiracetam 100 mg/ml Concentrate for solution for infusion

Date of the Last Revision of this Leaflet:August 2024

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This Information is Intended Only for Healthcare Professionals:

Instructions for the proper use of Levetiracetam Hikma are provided in section 3.

A vial of concentrate contains 500 mg of levetiracetam (5 ml of 100 mg/ml concentrate). See Table 1 for the recommended preparation and administration of Levetiracetam Hikma 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 Hikma Concentrate for Solution for Infusion

This medicinal product is for single use only, so the unused solution should 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 at room temperature (15-25°C), unless the dilution has been performed under validated and controlled aseptic conditions.

It was found that Levetiracetam Hikma concentrate for solution for infusion was physically compatible and chemically stable for at least 24 hours when mixed with the following diluents 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's lactate injection solution
• Dextrose 50 mg/ml (5%) injection solution