KEPPRA 100 mg/ml CONCENTRATE FOR INFUSION SOLUTION

2. What you need to know before you use Keppra

Do not use Keppra

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

Warnings and precautions

Tell your doctor before you start using Keppra

• If you have kidney problems, follow your doctor's instructions. Your doctor will decide if you need to adjust the 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 Keppra 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 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 Keppra, see a doctor as soon as possible.

Children and adolescents

• Monotherapy with Keppra is not indicated for children and adolescents below 16 years.

Using Keppra with other medicines

Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines.

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 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 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 Keppra.

Driving and using machines

Keppra 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 such activities is not affected.

Keppra contains sodium

A single maximum dose of Keppra concentrate contains 2.5 mmol (or 57 mg) of sodium (0.8 mmol (or 19 mg) of sodium per vial). This is equivalent to 2.85% of the maximum recommended daily sodium intake for an adult. This should be taken into account for patients on a low sodium diet.

3. How to use Keppra

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

Keppra 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 (from 12 to 17 years) weighing 50 kg or more:

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

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

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

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

Method and route of administration:

Keppra 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 Keppra is provided in section 6 for doctors and nurses.

Duration of treatment:

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

If you stop treatment with Keppra:

As with other antiepileptic medicines, stopping treatment with Keppra should be done gradually to avoid an increase in seizures. If your doctor decides to stop your treatment with Keppra, they will tell you how to gradually reduce the dose, if they decide to stop your treatment with this medicine.

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

4. Possible side effects

Like all medicines, Keppra 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), swollen lymph nodes and involvement of other body organs (Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS))
• symptoms such as low urine output, tiredness, nausea, vomiting, confusion and swelling of feet, ankles or hands, as this may be a sign of sudden decrease in kidney function
• a skin rash which may form blisters and may be preceded by fever, flu-like symptoms and aching of joints and muscles (Stevens-Johnson syndrome), a more severe form causing skin peeling (toxic epidermal necrolysis)
• signs of serious mental changes or if someone around you notices signs of confusion, somnolence (drowsiness), amnesia (loss of memory), memory impairment (memory loss), 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 somnolence, fatigue and dizziness are more likely to occur when you first start treatment or when the dose is increased. However, these 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 (uncontrollable 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 the number of platelets, decrease in white blood cells;
• weight loss, weight gain;
• suicidal thoughts and behaviour, mental disorders, abnormal behaviour, hallucinations, anger, confusion, panic attacks, emotional instability/mood swings, agitation;
• amnesia (loss of memory), memory impairment (memory loss), abnormal coordination/ataxia (lack of coordination), paraesthesia (tingling), attention deficit (lack of concentration);
• diplopia (double vision), blurred vision;
• abnormal liver function tests;
• hair loss, eczema, itching;
• muscle weakness, muscle pain;
• injury.

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

• infection;
• decrease in all blood cell types;
• severe allergic reactions (DRESS, anaphylactic reaction, Quincke's oedema);
• decrease in blood sodium levels;
• suicide, personality disorders (behavioural problems), abnormal thinking (slow thinking, difficulty concentrating);
• delirium;
• encephalopathy (see section “Tell your doctor immediately” for a detailed description of the symptoms);
• 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 form blisters and may be preceded by fever, flu-like symptoms and aching of joints and muscles, a more severe form causing skin peeling (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 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

• unwanted thoughts or feelings and repetitive or compulsive actions (obsessive-compulsive disorder).

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Keppra

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 refers to the last day of the month shown.

This medicine does not require any special storage conditions.

6. Container Content and Additional Information

Composition of Keppra

The active substance is levetiracetam. Each ml contains 100 mg of levetiracetam.

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

Appearance of the Product and Container Content

Keppra concentrate for solution for infusion (sterile concentrate) is a clear and colorless liquid.

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

Marketing Authorization Holder

UCB Pharma SA, Allée de la Recherche 60, B-1070 Brussels, Belgium.

Manufacturer

UCB Pharma SA, Chemin du Foriest, B-1420 Braine l'Alleud, Belgium

or Aesica Pharmaceuticals S.r.l., Via Praglia, 15, I-10044 Pianezza, Italy.

You can request more information about this medicine by contacting the local representative of the marketing authorization holder.

Date of Last Revision of this Prospectus:

Other Sources of Information

Detailed information about this medicine is available on the European Medicines Agency website: https://www.ema.europa.eu.

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This information is intended solely for healthcare professionals:

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

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

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

Validity period after opening: from a microbiological point of view, the product must 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 must not exceed 24 hours between 2 and 8°C, unless the dilution has been carried out under validated and controlled aseptic conditions.

It was found that Keppra 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