Keppra 100 mg/ml concentrate for solution for infusion

Keppra concentrate is an antiepileptic medicine (a medicine used to treat seizures in epilepsy).

Keppra is used:

• on its own in patients from 16 years of age with newly diagnosed epilepsy, to treat partial onset seizures with or without secondary generalisation
• as an add-on to other antiepileptic medicines to treat: partial onset seizures with or without generalisation in patients from 4 years of age myoclonic seizures in patients from 12 years of age with juvenile myoclonic epilepsy. primary generalised tonic-clonic seizures in patients from 12 years of age with idiopathic generalised epilepsy

Keppra concentrate is an alternative for patients when administration of the antiepileptic oral Keppra medicine is temporarily not feasible.

Do not use Keppra

• If you are allergic (hypersensitive) to levetiracetam or any of the other ingredients of Keppra.

Take special care with Keppra

• If you suffer from kidney problems, follow your doctor?s instructions. He/she may decide if your dose should be adjusted.
• If you notice any slow down in the growth or unexpected puberty development of your child, please contact your doctor.
• If you notice an increase in seizure severity (e.g. increased number), please contact your doctor.
• A small number of people being treated with anti-epileptics such as Keppra have had thoughts of harming or killing themselves. If you have any symptoms of depression and/or suicidal ideation, please contact your doctor.

Taking other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Using Keppra with food and drink
You may take Keppra with or without food. As a safety precaution, do not use Keppra with alcohol.

Pregnancy and breast-feeding
Ask your doctor or pharmacist for advice before taking any medicine.
If you are pregnant or if you think you may be pregnant, please inform your doctor. Keppra should not be used during pregnancy unless clearly necessary. The potential risk to your unborn child is unknown. Keppra has shown unwanted reproductive effects in animal studies at dose levels higher than you would need to control your seizures.
Breast-feeding is not recommended during treatment.

Driving and using machines
Keppra may impair your ability to drive or operate any tools or machinery, as Keppra may make you feel sleepy. This is more likely at the beginning of treatment or after an increase in the dose. You should not drive or use machines until it is established that your ability to perform such activities is not affected.

Important information about some of the ingredients of Keppra

Other ingredients include sodium acetate, glacial acetic acid, sodium chloride, water for injections.

One maximum single dose of Keppra concentrate contains 2.5 mmol (or 57 mg) of sodium. This should be taken into consideration if you are on a controlled sodium diet.

A doctor or a nurse will administer you Keppra as an intravenous infusion.
Keppra must be administered twice a day, once in the morning and once in the evening, at about the same time each day.

The intravenous formulation is an alternative to your oral administration. You can switch from the film-coated tablets or from the oral solution to the intravenous formulation or reverse directly without dose adaptation. Your total daily dose and frequency of administration remain identical.

Monotherapy

Dose in adults and adolescents (from 16 years of age):

General dose: between 1000 mg and 3,000 mg each day.
When you will first start taking Keppra, your doctor will prescribe you a lower dose during 2 weeks before giving you the lowest general dose.

Add-on therapy

Dose in adults and adolescents (12 to 17 years) weighing 50 kg or more:

General dose: between 1,000 mg and 3,000 mg each day.

Dose in children (4 to 11 years) and adolescents (12 to 17 years) weighing less than 50 kg: General dose: between 20 mg per kg bodyweight and 60 mg per kg bodyweight each day.

Method and route of administration:

Keppra will be diluted in at least 100 ml of a compatible diluent and infused over 15-minutes. For doctors and nurses, more detailed direction for the proper use of Keppra is provided in section 6.

Duration of treatment:

• Keppra is used as a chronic treatment. You should continue Keppra treatment for as long as your doctor has told you.
• Do not stop your treatment without your doctor?s advice as this could increase your seizures. Should your doctor decide to stop your Keppra treatment, he/she will instruct you about the gradual withdrawal of Keppra.
• There is no experience with administration of intravenous levetiracetam for a longer period than 4 days.

If you stop using Keppra:
If stopping treatment, as with other antiepileptic medicines, Keppra should be discontinued gradually to avoid an increase of seizures.

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

Like all medicines, Keppra can cause side effects, although not everybody gets them. Tell your doctor if you have any of the following and they worry you.

Some of the side effects like sleepiness, tiredness and dizziness may be more common at the beginning of the treatment or at dose increase. These effects should however decrease over time.

The frequency of possible side effects listed below is defined using the following convention: Very common (affects more than 1 user in 10)
Common (affects 1 to 10 users in 100)
Uncommon (affects 1 to 10 users in 1,000)
Rare (affects 1 to 10 users in 10,000)
Very rare (affects less than 1 user in 10,000)
Not known (frequency cannot be estimated from the available data)

Very common:

• somnolence (sleepiness);
• asthenia/fatigue (tiredness).

Common:

• infection, nasopharyngitis;
• decreased number of blood platelets;
• anorexia (loss of appetite), weight increase;
• agitation, depression, emotional instability/mood swings, hostility or aggression, insomnia, nervousness or irritability, personality disorders (behavioral problems), thinking abnormal (slow thinking, unable to concentrate);
• dizziness (sensation of unsteadiness), convulsion, headache, hyperkinesia (hyperactivity), ataxia (impaired coordinated movements), tremor (involuntary trembling), amnesia (loss of memory), balance disorder (equilibrium disorder), disturbance in attention (loss of concentration), memory impairment (forgetfulness);
• diplopia (double vision), vision blurred;
• vertigo (sensation of rotation);
• cough (increase of pre-existing cough);
• abdominal pain, nausea, dyspepsia (indigestion), diarrhoea, vomiting;
• rash, eczema, pruritus;
• myalgia (muscle pain);
• accidental injury.

Not known:

• decreased number of red blood cells, and/or white blood cells;
• weight loss;
• abnormal behaviour, anger, anxiety, confusion, hallucination, mental disorder, suicide, suicide attempt and suicidal ideation;
• paraesthesia (tingling);
• pancreatitis, hepatic failure, hepatitis, liver function test abnormal;
• hair loss, blistering of the skin, mouth, eyes and genital area, skin eruption.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Keep out of the reach and sight of children.

Do not use after the expiry date stated on the vial and carton box after EXP:.
The expiry date refers to the last day of the month.

This medicine does not require any special storage conditions.

What Keppra contains

The active substance is called levetiracetam. Each ml of solution for infusion contains 100 mg of levetiracetam.
The other ingredients are: sodium acetate, glacial acetic acid, sodium chloride, water for injections.

What Keppra looks like and contents of the pack

Keppra concentratefor solution for infusion (Keppra concentrate) is a clear, colourless, sterile liquid. Keppra concentrate 5 ml vial is packed in a cardboard box of 10 vials.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder: UCB Pharma SA, Allée de la Recherche 60, B-1070 Brussels, Belgium.
Manufacturers: UCB Pharma SA, Chemin du Foriest, B-1420 Braine-l?Alleud, Belgium or UCB Pharma S.p.A., Via Praglia, 15, I-10044 Pianezza, Italy.

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder.

BelgiëBelgiqueBelgien UCB Pharma SANV TelTél 32 02 559 92 00 LuxembourgLuxemburg UCB Pharma SANV TélTel 32 02 559 92 00

Te. 359 0 2 962 30 49 Magyarország UCB Magyarország Kft. Tel. 36-1 391 0060

eská republika UCB s.r.o. Tel 420 221 773 411 Malta Pharmasud Ltd. Tel 356 21 37 64 36

Danmark Nederland

UCB Nordic AS Tlf 45 32 46 24 00 UCB Pharma B.V. Tel. 31 076-573 11 40

Deutschland UCB Pharma GmbH Tel 49 0 2173 48 4847 Norge UCB Nordic AS Tlf 45 32 46 24 00

Eesti UCB Pharma Oy Finland Tel 358 10 234 6800 Soome Österreich UCB Pharma GmbH Tel 43 1 291 80 00

UCB .. 30 2109974000 Polska UCB Pharma Sp. z o.o. Tel. 48 22 696 99 20

España UCB Pharma, S.A. Tel 34 91 570 34 44 Portugal UCB Pharma Produtos Farmacêuticos, Lda Tel 351 21 302 5300

France UCB Pharma S.A. Tél 33 01 47 29 44 35 România UCB Pharma România S.R.L. Tel 40 21 300 29 04

Ireland UCB Pharma Ireland Ltd. Tel 353 01-46 37 395 Slovenija Medis, d.o.o. Tel 386 1 589 69 00

Ísland Vistor hf. Tel 354 535 7000 Slovenská republika UCB s.r.o., organizaná zloka Tel 421 0 2 5920 2020

Italia UCB Pharma S.p.A. Tel 39 02 300 791 SuomiFinland UCB Pharma Oy Finland PuhTel 358 10 234 6800

Lifepharma Z.A.M. Ltd 357 22 34 74 40 Sverige UCB Nordic AS Tel 46 0 40 29 49 00

Latvija UCB Pharma Oy Finland Tel 358 10 234 6800 Somija United Kingdom UCB Pharma Ltd. Tel 44 01753 534 655

Lietuva
UCB Pharma Oy Finland
Tel: + 358 10 234 6800 (Suomija)

This leaflet was last approved in

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The following information is intended for doctor and nurses only:
Direction for the proper use of Keppra is provided in section 3.

One vial of Keppra concentrate contains 500 mg levetiracetam (5 ml concentrate of 100 mg/ml). See Table 1 for the recommended preparation and administration of Keppra concentrate to achieve a total daily dose of 500 mg, 1000 mg, 2000 mg, or 3000 mg in two divided doses.

Table 1. Preparation and administration of Keppra concentrate

Dose Withdrawal Volume Volume of Diluent Infusion Time Frequency of administration Total Daily Dose 250 mg 2.5 ml half 5 ml vial 100 ml 15 minutes Twice daily 500 mgday 500 mg 5 ml one 5 ml vial 100 ml 15 minutes Twice daily 1000 mgday 1000 mg 10 ml two 5 ml vials 100 ml 15 minutes Twice daily 2000 mgday 1500 mg 15 ml three 5 ml vials 100 ml 15 minutes Twice daily 3000 mgday

This medicinal product is for single use only, any unused solution should be discarded.

In use shelf life: from a microbiological point of view, the product should be used immediately after dilution. If not used immediately, in-use storage time and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless dilution has taken place in controlled and validated aseptic conditions.

Keppra concentrate was found to be 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 15-25°C.
Diluents:

• Sodium chloride (0.9%) injection
• Lactated Ringer?s injection
• Dextrose 5% injection

ANNEX IV

GROUNDS FOR ONE ADDITIONAL RENEWAL

Grounds for one additional renewal

Based upon the data that have become available since the last renewal of the Marketing Authorisation, the CHMP considers that the benefit-risk balance of Keppra remains positive, but considers that its safety profile is to be closely monitored for the following reasons:

Keppra has been authorised for children from 4 years old (approved September 2005) and more recently for children from 1 month to 4 years old (approved September 2009). Due to the recent addition of these sensitive populations to the therapeutic indication, limited safety information is available in these age groups. The CHMP considers that more safety experience needs to be gained in children, and decided that the MAH should continue to submit yearly PSURs and 6-monthly specific safety reports for children < 4 years old in between yearly PSURs.

Therefore, based upon the safety profile of Keppra, which requires the submission of yearly PSURs and 6-monthly specific safety reports for children < 4 years old in between yearly PSURs, the CHMP concluded that the MAH should submit one additional renewal application in 5 years time.