KEPPRA 100 mg/ml CONCENTRATE FOR INFUSION SOLUTION

2. What you need to know before you take 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

Consult your doctor before starting to take Keppra

• If you have kidney problems, follow the advice of your doctor who will decide if you need a dose adjustment.
• 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 suicidal thoughts. If at any time you have these thoughts, talk to your doctor.
• If you have a medical history or a family history of abnormal ECG heart rhythm or if you have a condition or are taking a medicine that may affect the heart rhythm or electrolyte balance.

Tell your doctor or pharmacist if any of the following side effects gets serious or lasts longer than a few days:

• abnormal thoughts, feeling irritable or more aggressive than usual or if you, your family or friends notice any significant change in your mood or behaviour.
• worsening of epilepsy

On rare occasions, epileptic seizures may worsen or occur more frequently, mainly during the first month after start of treatment or dose increase. If you experience any of these new symptoms while taking Keppra, contact your doctor as soon as possible.

Children and adolescents

• Monotherapy (use of this medicine alone) is not indicated in children and adolescents below 16 years.

Use of 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 medicine used as a laxative) 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 can be used during pregnancy only if your doctor considers it is 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 impair your ability to drive or operate tools or machinery, as it may cause somnolence (sleepiness). This is more likely at the beginning of the 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). To be taken into consideration by patients on a controlled sodium diet.

3. How to use Keppra

A doctor or a nurse will administer Keppra to you by intravenous infusion. Keppra must be administered 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 the film-coated tablets or the oral solution to the intravenous formulation or vice versa, without dose adjustment. Your total daily dose and frequency of administration must 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 each day.

When you first start taking Keppra, your doctor will prescribe you a lower dose for two weeks before increasing to the lowest recommended 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 each day.

Method and route of administration:

Keppra is for intravenous use.

The recommended dose must 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 healthcare professionals.

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, the discontinuation of treatment with Keppra should be done gradually to avoid an increase in seizures. If your doctor decides to stop your treatment with Keppra, he/she will tell you how to gradually discontinue the treatment, if he/she decides 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 a rash on the face followed by a prolonged rash with high fever, high levels of liver enzymes in the blood tests and an increase in a type of white blood cell (eosinophilia) and swollen lymph nodes (Drug Reaction with Eosinophilia and Systemic Symptoms, DRESS)
• symptoms such as low urine output, tiredness, nausea, vomiting, confusion and swelling of the feet, ankles, or hands, as these may be signs of sudden kidney failure
• a skin rash which may form blisters and may be accompanied by fever, particularly if it appears as a so-called “target lesion” (a red spot with a paler centre, surrounded by an outer red ring) (erythema multiforme)
• a widespread rash with blisters and peeling of the 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, somnolence (drowsiness), amnesia (loss of memory), memory impairment (difficulty remembering), abnormal behaviour or other neurological signs including involuntary or uncontrolled movements. These may be signs of encephalopathy.

The most frequently reported side effects are nasopharyngitis, somnolence (sleepiness), headache, fatigue and dizziness. Side effects like sleepiness, 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 (sleepiness), headache.

Common:may affect up to 1 in 10 people

• loss of appetite;
• depression, hostility or aggression, anxiety, insomnia, restlessness or irritability;
• seizures, balance disorder, dizziness (unsteadiness), lethargy (lack of energy and enthusiasm), tremor (involuntary shaking);
• vertigo (spinning sensation);
• cough;
• abdominal pain, diarrhoea, dyspepsia (indigestion, heartburn), 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 the number of 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 (loss of memory), memory impairment (difficulty remembering), abnormal coordination/ataxia (impaired coordination), paraesthesia (tingling), attention deficit/hyperactivity disorder (disorders of attention and activity);
• diplopia (double vision), blurred vision;
• abnormal liver function tests;
• hair loss, eczema, pruritus;
• muscle weakness, myalgia (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 sodium levels in the blood;
• suicide, personality disorders (behavioural problems), abnormal thoughts (slow thinking, difficulty in 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 in controlling movements, hyperkinesia (hyperactivity);
• change in heart rhythm (electrocardiogram);
• pancreatitis (inflammation of the pancreas);
• liver failure, hepatitis (inflammation of the liver);
• sudden kidney failure;
• skin rash which may form blisters and may be accompanied by fever, particularly if it appears as a so-called “target lesion” (a red spot with a paler centre, surrounded by an outer red ring) (erythema multiforme), a widespread rash with blisters and peeling of the 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 consciousness (these 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 get 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.

This medicine does not require any special storage conditions.

6. Packaging Contents and Additional Information

Composition of Keppra

The active ingredient 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 Packaging Contents

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 medication 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 medication is available on the European Medicines Agency website: http://www.ema.europa.eu

This information is intended only 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, 1000 mg, 2000 mg, or 3000 mg divided into two doses.

Table 1. Preparation and Administration of Keppra Concentrate

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

Shelf life 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 performed under validated and controlled aseptic conditions.

It has been 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