KEPPRA 250 mg FILM-COATED TABLETS

2. What you need to know before you take Keppra

Do not take 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 taking Keppra

• If you have kidney problems, follow your doctor's instructions, as your dose may need adjusting.
• If you notice any slowing of growth or unexpected pubertal delay in your child, 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 at any time you have these thoughts, contact your doctor.
• If you have a history of heart rhythm problems, or if you are taking medicines that may cause heart rhythm problems, or if you have any other medical condition that may increase the risk of heart rhythm problems, your doctor may want to monitor your heart while you are taking this medicine.

Tell your doctor if any of the following side effects get serious or last longer than a few days:

• abnormal thoughts, feeling irritable or more aggressive than usual or if you or your family and friends notice any changes in your mood or behaviour
• worsening of seizures:

Very rarely, the seizures may become worse or more frequent, mainly during the first month after starting treatment or after a dose increase.

In very rare cases, a very severe form of epilepsy (epilepsy associated with SCN8A gene mutation) that causes multiple types of seizures and developmental delays, may not improve and may even worsen during treatment.

If you experience any of these new symptoms while taking Keppra, contact your doctor as soon as possible.

Children and adolescents

• Monotherapy (use of only one medicine to treat epilepsy) with Keppra is not indicated for children and adolescents under 16 years of age.

Using Keppra with other medicines

Tell your doctor or pharmacist 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 the effect of levetiracetam.

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 or pharmacist for advice before taking this medicine. Levetiracetam can be used during pregnancy only if your doctor considers it to be clearly necessary.

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

It is not known whether the possible risk of birth defects associated with the use of levetiracetam is higher than with other antiepileptic medicines.

It is recommended to use effective contraception during treatment with levetiracetam.

Breast-feeding is not recommended during treatment with Keppra.

Driving and using machines

Keppra may cause drowsiness or other symptoms that may affect your ability to drive or operate machinery. This is more likely at the beginning of treatment or when the dose is increased. Do not drive or use machinery until you are sure that your ability to perform such activities is not affected.

Keppra 750 mg tablets contain the colouring agent sunset yellow FCF (E110)

Sunset yellow FCF (E110) may cause allergic reactions.

Keppra contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per tablet, i.e. essentially 'sodium-free'.

3. How to take Keppra

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Take the number of tablets as instructed by your doctor.

Keppra must be taken twice a day, once in the morning and once in the evening, at approximately the same time each day.

Concomitant therapy and monotherapy (from 16 years of age)

• Adults (≥18 years) and adolescents (12 to 17 years) weighing 50 kg or more:

Recommended dose: 1000 to 3000 mg per day.

When you first start taking Keppra, your doctor will prescribe you a lower dose during 2 weeks before reaching the recommended daily dose.

For example, for a 1000 mg daily dose, the initial dose would be 1 x 250 mg tablet in the morning and 1 x 250 mg tablet in the evening, and then the dose would be gradually increased to 1000 mg per day after 2 weeks of treatment.

• Adolescents (12 to 17 years) weighing less than 50 kg:

Your doctor will prescribe the most appropriate pharmaceutical form of Keppra according to the weight and dose.

• Dose in infants (1 month to 23 months) and children (2 to 11 years) weighing less than 50 kg:

Your doctor will prescribe the most appropriate pharmaceutical form of Keppra according to the age, weight and dose.

Keppra 100 mg/ml oral solution is a more appropriate formulation for infants and children under 6 years and for children and adolescents (6 to 17 years) weighing less than 50 kg and when tablets are not appropriate.

Method of administration

Swallow Keppra tablets with a sufficient amount of liquid (e.g. a glass of water). You may take Keppra with or without food. After oral administration, the bitter taste of levetiracetam may be experienced.

Duration of treatment

• Keppra is used as chronic treatment. You should continue to take it for as long as your doctor has told you.
• Do not stop your treatment without your doctor's advice, as this may increase your seizures.

If you take more Keppra than you should

Adverse effects after an overdose are similar to those of other antiepileptics: drowsiness, agitation, aggression, decrease in alertness, inhibition of respiratory function and coma.

Contact your doctor if you have taken more tablets than you should. Your doctor will decide on the best course of action to take.

If you forget to take Keppra

Contact your doctor if you have missed one or more doses.

Do not take a double dose to make up for a forgotten dose.

If you stop taking Keppra

It is very important that your treatment is stopped gradually, unless your doctor tells you otherwise. If your doctor decides to stop your treatment with Keppra, your doctor will tell you how to gradually reduce the dose.

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
• swelling of the face, lips, tongue or throat (Quincke's oedema)
• symptoms of flu and 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), 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 these may be signs of sudden kidney failure
• a rash that may form blisters and looks like the centre of a target (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 of rash causing skin peeling in more than 30% of the body surface (toxic epidermal necrolysis)
• signs of serious mental changes or if someone else notices signs of confusion, somnolence (drowsiness), amnesia (loss of memory), memory impairment (forgetfulness), abnormal behaviour or other neurological signs including involuntary movements or uncontrolled movements. These may be symptoms of encephalopathy.

The most frequently reported adverse reactions are nasopharyngitis, somnolence (feeling drowsy), headache, fatigue and dizziness. Adverse reactions such as somnolence, fatigue and dizziness may be more frequent at the beginning of 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 (involuntary shaking)
• vertigo (feeling of spinning)
• cough
• abdominal pain, diarrhoea, dyspepsia (indigestion), vomiting, nausea
• skin rash
• asthenia/fatigue (feeling of weakness)

Uncommon: may affect up to 1 in 100 people

• decrease in the number of blood platelets, decrease in the number of white blood cells
• weight decrease, weight increase
• suicidal ideation and attempt, mental disorders, abnormal behaviour, hallucinations, anger, confusion, panic attack, emotional instability/mood swings, agitation
• amnesia (loss of memory), memory impairment (forgetfulness), abnormal coordination/ataxia (impaired coordination of movements), paraesthesia (tingling), attention deficit/hyperactivity disorder (inability to concentrate)
• diplopia (double vision), blurred vision
• abnormal liver function tests
• hair loss, eczema, pruritus (itching)
• 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 blood sodium levels
• 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 become worse or more frequent
• uncontrolled muscle spasms affecting the head, torso and limbs, difficulty in controlling movements, hyperkinesia (hyperactivity)
• abnormal heart rate (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 looks like the centre of a target (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 of rash causing skin peeling in more than 30% of the body surface (toxic epidermal necrolysis):
• rhabdomyolysis (breakdown of muscle tissue) and increased creatine phosphokinase in the blood, more frequently observed in Japanese patients compared to non-Japanese patients
• gait disturbance or difficulty walking
• a combination of fever, muscle stiffness, unstable blood pressure and heart rate and confusion, a condition known as the neuroleptic malignant syndrome, more frequently observed in Japanese patients compared to non-Japanese patients

Very rare: may affect up to 1 in 10,000 people

• unwanted thoughts or impulses and repetitive thoughts or impulses to perform a specific action, obsessive-compulsive disorder

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 carton after EXP and on the blister after EXP.

The expiry date refers to the last day of that month.

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 to protect the environment.

6. Package Contents and Additional Information

Composition of Keppra

The active substance is levetiracetam. Each tablet contains 250 mg of levetiracetam.

A 250 mg Keppra tablet contains 250 mg of levetiracetam.

A 500 mg Keppra tablet contains 500 mg of levetiracetam.

A 750 mg Keppra tablet contains 750 mg of levetiracetam.

A 1000 mg Keppra tablet contains 1000 mg of levetiracetam.

The other ingredients are:

Tablet core: sodium croscarmellose, macrogol 6000, anhydrous colloidal silica, magnesium stearate.

Coating: partially hydrolyzed polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, colorants*.

• The colorants are:

250 mg tablets: aluminum lake with carmine indigo (E132)

500 mg tablets: yellow iron oxide (E172)

750 mg tablets: aluminum lake with orange yellow S (E110), red iron oxide (E172)

Appearance and Packaging of the Product

Keppra 250 mg film-coated tablets are blue, 13 mm, oblong, scored and marked with “ucb” and “250” on one side.

The score line is only to facilitate breaking for ease of swallowing and not to divide into equal doses.

Keppra 500 mg film-coated tablets are yellow, 16 mm, oblong, scored and marked with “ucb” and “500” on one side.

The score line is only to facilitate breaking for ease of swallowing and not to divide into equal doses.

Keppra 750 mg film-coated tablets are orange, 18 mm oblong, scored and marked with “ucb” and “750” on one side.

The score line is only to facilitate breaking for ease of swallowing and not to divide into equal doses.

Keppra 1000 mg film-coated tablets are white, 19 mm, oblong, scored and marked with “ucb” and “1.000” on one side.

The score line is only to facilitate breaking for ease of swallowing and not to divide into equal doses.

Keppra tablets are packaged in blisters included in cardboard boxes containing:

• 250 mg: 20, 30, 50, 60, 100 x 1, 100 film-coated tablets and multiple packs containing 200 (2 packs of 100) film-coated tablets

• 500 mg: 10, 20, 30, 50, 60, 100 x 1, 100, 120 film-coated tablets and multiple packs containing 200 (2 packs of 100) film-coated tablets

• 750 mg: 20, 30, 50, 60, 80, 100 x 1, 100 film-coated tablets and multiple packs containing 200 (2 packs of 100) film-coated tablets

• 1000 mg: 10, 20, 30, 50, 60, 100 x 1, 100 film-coated tablets and multiple packs containing 200 (2 packs of 100) film-coated tablets

The pack of 100 x 1 tablets is available in precut unit-dose aluminum/PVC blisters. The other packs are available in standard aluminum/PVC blisters.

Not all pack sizes may be marketed.

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

For further information about this medicinal product, please contact the local representative of the marketing authorization holder.

Date of Last Revision of this Leaflet:

Other Sources of Information

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