Levetiracetam ratiopharm – patient leaflet, side effects, dosage

1. What Levetiracetam ratiopharm is and what it is used for

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

Levetiracetam ratiopharm is used:

• on its own in adults and adolescents from 16 years of age with newly diagnosed epilepsy, to treat a certain form of epilepsy. Epilepsy is a condition where the patients have repeated fits (seizures). Levetiracetam is used for the epilepsy form in which the fits initially affect only one side of the brain, but could thereafter extend to larger areas on both sides of the brain (partial onset seizure with or without secondary generalisation). Levetiracetam has been given to you by your doctor to reduce the number of fits.
• as an add-on to other antiepileptic medicines to treat:
• partial onset seizures with or without generalisation in adults, adolescents, children and infants from one month of age
• myoclonic seizures (short, shock-like jerks of a muscle or group of muscles) in adults and adolescents from 12 years of age with juvenile myoclonic epilepsy,
• primary generalised tonic-clonic seizures (major fits, including loss of consciousness) in adults and adolescents from 12 years of age with idiopathic generalised epilepsy (the type of epilepsy that is thought to have a genetic cause).

2. What you need to know before you take Levetiracetam ratiopharm

Do not take Levetiracetam ratiopharm

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

Warnings and precautions

Talk to your doctor before taking Levetiracetam ratiopharm

• 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.
• A small number of people being treated with anti-epileptics such as Levetiracetam ratiopharm have had thoughts of harming or killing themselves. If you have any symptoms of depression and/or suicidal ideation, please contact your doctor.
• If you have a family or medical history of irregular heart rhythm (visible on an electrocardiogram), or if you have a disease and/or take a treatment that make(s) you prone to heartbeat irregularities or salt imbalances.

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

• Abnormal thoughts, feeling irritable or reacting more aggressively than usually, or if you or your family and friends notice important changes in mood or behaviour.
• Aggravation of epilepsy

Your seizures may rarely become worse or happen more often, mainly during the first month after the start of the treatment or increase of the dose. If you experience any of these new symptoms while taking Levetiracetam ratiopharm, see a doctor as soon as possible.

Children and adolescents

• Levetiracetam ratiopharm is not indicated in children and adolescents below 16 years on its own (monotherapy)

Other medicines and Levetiracetam ratiopharm

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

Do not take macrogol (a drug used as laxative) for one hour before and one hour after taking levetiracetam as this may results in a reduction of its effect.

Pregnancy and breast-feeding

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 can be used during pregnancy, only if after careful assessment it is considered necessary by your doctor.

You should not stop your treatment without discussing this with your doctor.

A risk of birth defects for your unborn child cannot be completely excluded.

Breast-feeding is not recommended during treatment.

Driving and using machines

Levetiracetam ratiopharm may impair your ability to drive or operate any tools or machinery, as it 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.

Levetiracetam ratiopharm contains methyl parahydroxybenzoate, propyl parahydroxybenzoate, potassium and sodium.

Levetiracetam ratiopharm oral solution includes methyl parahydroxybenzoate (E218) and propyl parahydroxybenzoate (E216) which may cause allergic reactions (possibly delayed).

This medicine contains 1.2 mmol (or 46.65 mg) potassium per 15 ml. To be taken into consideration by patients with reduced kidney function or patients on a controlled potassium diet.

This medicine contains less than 1 mmol sodium (23 mg) per 15 ml that is to say essentially ‘sodium-free’.

3. How to take Levetiracetam ratiopharm

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

Levetiracetam ratiopharm must be taken twice a day, once in the morning and once in the evening, at about the same time each day.

Take the oral solution following your doctor’s instructions.

Monotherapy (from 16 years of age)

Adults (>18 years) and adolescents (from 16 years of age):

Measure the appropriate dosage using the 10 ml syringe included in the package for patients 4 years and above.

General dose: Levetiracetam ratiopharm is taken twice daily, in two equally divided doses, each individual dose being measured between 5 ml (500 mg) and 15 ml (1500 mg).

When you will first start taking Levetiracetam ratiopharm, 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):

Measure the appropriate dosage using the 10 ml syringe included in the package for patients of 4 years and above.

General dose: Levetiracetam ratiopharm is taken twice daily, in two equally divided doses, each individual dose being measured between 5 ml (500mg) and 15 ml (1500mg).

Dose in children 6 months and older:

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

For children 6 months to 4 years, measure the appropriate dosage using the 3 ml syringe included in the package.

For children above 4 years, measure the appropriate dosage using the 10 ml syringe included in the package.

General dose: Levetiracetam ratiopharm is taken twice daily, in two equally divided doses, each individual dose being measured between 0.1 ml (10 mg) and 0.3 ml (30 mg), per kg bodyweight of the child. (see table below for dose examples).

Dose in children 6 months and older

Dose in infants (1 month to less than 6 months):

For infants 1 month to less than 6 months, measure the appropriate dosage using the 1 ml syringe included in the package.

General dose: Levetiracetam ratiopharm is taken twice daily, in two equally divided doses, each individual dose being measured between 0.07 ml (7 mg) and 0.21 ml (21 mg), per kg bodyweight of the infant. (see table below for dose examples).

Dose in infants (1 month to less than 6 months):

Method of administration

After measuring the correct dose with an appropriate syringe, Levetiracetam ratiopharm oral solution may be diluted in a glass of water or baby’s bottle. You may take Levetiracetam ratiopharm with or without food. After oral administration the bitter taste of levetiracetam may be experienced.

Instructions for use:

• Open the bottle: press the cap and turn it anticlockwise.
• Take the syringe and put it in the opening of the bottle.

For this the piston must be completely pushed into the syringe (figure ©)

©

Hold bottle and syringe securely tight. Then turn bottle and syringe upside down (figure ®).

®

Fill the syringe with the liquid by pulling the piston to the graduation mark corresponding to the quantity in millilitre (ml) prescribed by your doctor.

You can read the corresponding millilitre at the beginning of the thicker part of the piston figure ®).

®

If bubbles occur push the piston into the syringe again and fill the syringe once more slowly.

Move bottle and the filled syringe back in starting position.

Remove the filled syringe from the bottle (figure @).

Empty the contents of the syringe in a glass of water by pushing the piston into the syringe (figure ©).

• Close the bottle with the plastic screw cap after every usage.
• Drink the whole contents of the glass.
• Wash the syringe afterwards with clear water by filling and emptying the syringe repeatedly.

Duration of treatment

• Levetiracetam ratiopharm is used as a chronic treatment. You should continue Levetiracetam ratiopharm 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.

If you take more Levetiracetam ratiopharm than you should

The possible side effects of an overdose of Levetiracetam ratiopharm are sleepiness, agitation, aggression, decrease of alertness, inhibition of breathing and coma.

Contact your doctor if you took more Levetiracetam ratiopharm than you should. Your doctor will establish the best possible treatment of overdose.

If you forget to take Levetiracetam ratiopharm

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 Levetiracetam ratiopharm

If stopping treatment, Levetiracetam ratiopharm should be discontinued gradually to avoid an increase of seizures. Should your doctor decide to stop your Levetiracetam ratiopharm treatment, he/she will instruct you about the gradual withdrawal of Levetiracetam ratiopharm.

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 your nearest emergency department, if you experience:

• weakness, feel light-headed or dizzy or have difficulty breathing, as these may be signs of a serious allergic (anaphylactic) reaction
• swelling of the face, lips, tongue and throat (Quincke’s oedema)
• flu-like symptoms and a rash on the face followed by an extended rash with a high temperature, increased levels of liver enzymes seen in blood tests and an increase in a type of white blood cell (eosinophilia) and enlarged lymph nodes (Drug Reaction with Eosinophilia and Systemic Symptoms [DRESS]).
• symptoms such as low urine volume, tiredness, nausea, vomiting, confusion and swelling in the legs, ankles or feet, as this may be a sign of sudden decrease of kidney function
• a skin rash which may form blisters and look like small targets (central dark spots surrounded by a paler area, with a dark ring around the edge) (erythema multiforme)
• a widespread rash with blisters and peeling 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 around you notices signs of confusion, somnolence (sleepiness), amnesia (loss of memory), memory impairment (forgetfulness), abnormal behaviour or other neurological signs including involuntary or uncontrolled movements. These could be symptoms of an encephalopathy.

The most frequently reported adverse reactions were nasopharyngitis, somnolence (sleepiness), headache, fatigue and dizziness. At the beginning of the treatment or at dose increase side effects like sleepiness, tiredness and dizziness may be more common. These effects should however 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

• anorexia (loss of appetite);
• depression, hostility or aggression, anxiety, insomnia, nervousness or irritability;
• convulsion, balance disorder (equilibrium disorder), dizziness (sensation of unsteadiness), lethargy (lack of energy and enthusiasm), tremor (involuntary trembling);
• vertigo (sensation of rotation);
• cough;
• abdominal pain, diarrhoea, dyspepsia (indigestion), vomiting, nausea;
• rash;
• asthenia/fatigue (tiredness).

Uncommon: may affect up to 1 in 100 people

• decreased number of blood platelets, decreased number of white blood cells;
• weight decrease, weight increase;
• suicide attempt and suicidal ideation, mental disorder, abnormal behaviour, hallucination, anger, confusion, panic attack, emotional instability/mood swings, agitation;
• amnesia (loss of memory), memory impairment (forgetfulness), abnormal coordination/ataxia (impaired coordinated movements), paraesthesia (tingling), disturbance in attention (loss of concentration);
• diplopia (double vision), vision blurred;
• elevated/abnormal values in a liver function test;
• hair loss, eczema, pruritus;
• muscle weakness, myalgia (muscle pain);
• injury.

Rare: may affect up to 1 in 1000 people

• infection;

decreased number of all blood cell types;

severe allergic reactions (DRESS, anaphylactic reaction [severe and important allergic reaction], Quincke’s oedema [swelling of the face, lips, tongue and throat]);

decreased blood sodium concentration;

suicide, personality disorders (behavioural problems), thinking abnormal (slow thinking, unable to concentrate);

delirium;

encephalopathy (see sub-section “Tell your doctor immediately” for a detailed description of symptoms);

seizures may become worse or happen more often;

uncontrollable muscle spasms affecting the head, torso and limbs, difficulty in controlling movements, hyperkinesia (hyperactivity);

change of the heart rhythm (Electrocardiogram);

pancreatitis;

liver failure, hepatitis;

sudden decrease in kidney function;

skin rash, which may form blisters and looks like small targets (central dark spots surrounded by a paler area, with a dark ring around the edge) (erythema multiforme), a widespread rash with blisters and peeling skin, particularly around the mouth, nose, eyes and genitals (Stevens-

Johnson syndrome), and a more severe form causing skin peeling in more than 30% of the body surface (toxic epidermal necrolysis).

rhabdomyolysis (breakdown of muscle tissue) and associated blood creatine phosphokinase increase. Prevalence is significantly higher in Japanese patients when compared to non-Japanese patients.

limp or difficulty walking.

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. How to store Levetiracetam ratiopharm

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the cardboard box and bottle after EXP.

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

Keep the bottle in the outer carton in order to protect from light.

Do not use after 4 months of first opening the bottle.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Levetiracetam ratiopharm contains

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

The other ingredients are: methyl parahydroxybenzoate (E 218), propyl parahydroxybenzoate (E 216), citric acid monohydrate, sodium hydroxide, purified water, acesulfame potassium (E 950), grape flavour.

What Levetiracetam ratiopharm looks like and contents of the pack Levetiracetam ratiopharm oral solution is a clear liquid.

The 300 ml glass bottle of Levetiracetam ratiopharm oral solution (for children aged 4 years and above, adolescents and adults) is packed in a cardboard box containing a 10 ml oral syringe (graduated every 0.25 ml) and an adaptor for the syringe.

The 150 ml glass bottle of Levetiracetam ratiopharm oral solution (for infants aged 6 months and above and children aged 2 to 4 years) is packed in a cardboard box containing a 3 ml oral syringe (graduated every 0.1 ml) and an adaptor for the syringe.

The 150 ml glass bottle of Levetiracetam ratiopharm oral solution (for infants aged 1 month to less than 6 months) is packed in a cardboard box containing a 1 ml oral syringe (graduated every 0.05 ml) and an adaptor for the syringe.

Marketing Authorisation Holder

ratiopharm GmbH

Graf-Arco-Str. 3

89079 Ulm

Germany e-mail: info@ratiopharm.de

Manufacturer

Merckle GmbH

Ludwig-Merckle-Str. 3

89143 Blaubeuren

Germany

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

Tql: +30 2118805000

This leaflet was last revised in {month/YYYY}

Detailed information on this medicine is available on the European Medicines Agency web site:

http://www.ema.europa.eu

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¹

Prevalence is significantly higher in Japanese patients when compared to non-Japanese patients.

Description of selected adverse reactions

The risk of anorexia is higher when levetiracetam is coadministered with topiramate.

In several cases of alopecia, recovery was observed when levetiracetam was discontinued.

Bone marrow suppression was identified in some of the cases of pancytopenia.

²

Levetiracetam ratiopharm 100 mg/ml oral solution should be used for doses under 250 mg, for doses not multiple of 250 mg when dosing recommendation is not achievable by taking multiple tablets and for patients unable to swallow tablets.

³

A 10.5 mg/kg (0.105 ml/kg) loading dose is recommended on the first day of treatment with levetiracetam.

⁴

Following dialysis, a 3.5 to 7 mg/kg (0.035 to 0.07 ml/kg) supplemental dose is recommended.

⁵

A 15 mg/kg (0.15 ml/kg) loading dose is recommended on the first day of treatment with levetiracetam.

⁶

Following dialysis, a 5 to 10 mg/kg (0.05 to 0.10 ml/kg) supplemental dose is recommended.

Hepatic impairment

No dose adjustment is needed in patients with mild to moderate hepatic impairment. In patients with severe hepatic impairment, the creatinine clearance may underestimate the renal insufficiency.

Therefore a 50 % reduction of the daily maintenance dose is recommended when the creatinine clearance is < 60 ml/min/1.73 m².

⁷

Children 25 kg or less should preferably start the treatment with Levetiracetam ratiopharm 100 mg/ml oral solution.

⁸

Dose in children and adolescents 50 kg or more is the same as in adults.

Add-on therapy for infants aged from 1 month to less than 6 months

The initial therapeutic dose is 7 mg/kg twice daily.

Depending upon the clinical response and tolerability, the dose can be increased by 7 mg/kg twice daily every 2 weeks up to recommended dose of 21 mg/kg twice daily. Dose changes should not 23