Keppra 100 mg/ml concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Keppra 100 mg/ml concentrate for solution for infusion

Levetiracetam

Read the entire leaflet carefully before you or your child starts using this medicine, because it contains important information for you.

• Keep this leaflet as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor or pharmacist, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet contents

1. What Keppra is and what it is used for
2. What you need to know before using Keppra
3. How to use Keppra
4. Possible side effects
5. How to store Keppra
6. Contents of the pack and other information

1. What Keppra is and what it is used for

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

Keppra is used:

• as monotherapy in adults and adolescents aged 16 years or older with newly diagnosed epilepsy to treat a form of epilepsy. Epilepsy is a condition in which patients have seizures (fits). Levetiracetam is used for the type of epilepsy in which seizures initially affect only one side of the brain, but may then spread to broader areas on both sides of the brain (partial-onset seizures with or without secondary generalisation). Your doctor has prescribed levetiracetam to reduce the number of seizures.

• in combination with other antiepileptic medicines to treat:

• partial-onset seizures with or without generalisation in adults, adolescents, and children from 4 years of age.

• myoclonic seizures (brief, 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 seizures, including loss of consciousness) in adults and adolescents from 12 years of age with idiopathic generalised epilepsy (a type of epilepsy thought to have a genetic cause).

Keppra oral solution is an alternative for patients in whom oral administration is temporarily not feasible.

2. What you need to know before using Keppra

Do not use Keppra

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

Warnings and precautions

Consult your doctor before starting Keppra

• If you have kidney problems, follow your doctor's instructions, as your doctor will decide whether your dose needs to be adjusted.
• If you notice any growth delay in your child or unexpected development of puberty, contact your doctor.
• A small number of people taking antiepileptic medicines such as Keppra have had thoughts of harming themselves or of suicide. If you experience any symptoms of depression and/or suicidal thoughts, contact your doctor.
• If you have a personal or family medical history of irregular heartbeat (seen on electrocardiogram), or if you have a disease and/or are taking treatment(s) that make you prone to cardiac arrhythmias or electrolyte imbalances.

Inform your doctor or pharmacist if any of the following adverse effects worsen or last longer than a few days:

• Abnormal thoughts, feeling irritable, or reacting more aggressively than normal, 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, especially 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) causing multiple seizure types 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, seek medical advice as soon as possible.

Children and adolescents

• Treatment with Keppra alone (monotherapy) is not indicated in children and adolescents under 16 years of age.

Use of Keppra with other medicines

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

Do not take macrogol (a medicine used as a laxative) within one hour before or one hour after taking levetiracetam, as it could reduce its effect.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor before using this medicine. Levetiracetam may only be used during pregnancy if, after careful evaluation, your doctor considers it necessary.

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

The risk of birth defects for the baby cannot be completely ruled out. Two studies do not suggest an increased risk of autism or intellectual disability in children born to mothers treated with levetiracetam during pregnancy. However, available data on the impact of levetiracetam on infant neurological development are limited.

Breastfeeding is not recommended during treatment.

Driving and using machines

Keppra may impair your ability to drive or operate tools or machinery, as it may cause drowsiness. This is more likely at the beginning of treatment or when the dose is increased. You should not drive or use machinery until you are certain that your ability to perform these activities is not affected.

Keppra contains sodium

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

3. How to use Keppra

A doctor or nurse will administer Keppra by intravenous infusion.

Keppra should be given twice daily, once in the morning and once in the evening, approximately at the same time each day.

The intravenous formulation is an alternative to oral administration. You may switch directly from film-coated tablets or oral solution to the intravenous formulation, or vice versa, without the need for dose adjustment. Your total daily dose and frequency of administration should remain identical.

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

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

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

Recommended dose: between 20 mg per kg of body weight and 60 mg per kg of body weight per 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 on the correct use of Keppra is provided in section 6 for doctors and nurses.

Duration of treatment:

• There is no experience with administration of intravenous levetiracetam for longer than 4 days.

If you stop treatment with Keppra:

As with other antiepileptic medicines, Keppra treatment should be discontinued gradually to avoid an increase in seizures. If your doctor decides to stop your treatment with Keppra, you will be given instructions for gradual withdrawal of Keppra.

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

4. Possible adverse effects

Like all medicines, Keppra can cause adverse effects, although not everyone will experience them.

Contact your doctor immediately, or go to the nearest hospital emergency department if you experience:

• weakness, dizziness or difficulty breathing, as these may be signs of a severe allergic (anaphylactic) reaction
• swelling of the face, lips, tongue or throat (angioedema)
• flu-like symptoms and rash on the face followed by a widespread rash with high temperature, elevated liver enzymes in blood tests, and an increase in a type of white blood cells (eosinophilia), enlarged lymph nodes and involvement of other organs (Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS))
• symptoms such as low urine output, tiredness, nausea, vomiting, confusion and swelling of legs, ankles or feet, as these may be signs of sudden worsening of kidney function
• a skin rash that may blister and may appear as small targets (dark central spots surrounded by a paler area, with a dark ring around the edge) (erythema multiforme)
• a widespread rash with blisters and peeling of the skin, especially 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 (memory loss), memory impairment (forgetfulness), abnormal behaviour or other neurological signs including involuntary or uncontrolled movements. These may be symptoms of encephalopathy.

The most frequently reported adverse effects are nasopharyngitis, somnolence (feeling sleepy), headache, fatigue and dizziness. Adverse effects such as drowsiness, feeling weak and dizziness may be more common when treatment is started or when the dose is increased. However, these adverse effects should decrease over time.

Very common: may affect more than 1 in 10 people

• nasopharyngitis;
• somnolence (feeling sleepy), headache.

Common: may affect up to 1 in 10 people

• anorexia (loss of appetite);
• depression, hostility or aggression, anxiety, insomnia, nervousness or irritability;
• seizures, balance disorder, dizziness (feeling of unsteadiness), lethargy (lack of energy and enthusiasm), tremor (involuntary shaking);
• vertigo (sensation of spinning);
• cough;
• abdominal pain, diarrhoea, dyspepsia (indigestion, burning and acid regurgitation), vomiting, nausea;
• skin rash;
• asthenia/fatigue (feeling of weakness).

Uncommon: may affect up to 1 in 100 people

• decrease in platelet count, decrease in white blood cells;
• weight loss, weight gain;
• suicide attempt and suicidal thoughts, mental disturbances, abnormal behaviour, hallucinations, anger, confusion, panic attack, emotional instability/mood changes, agitation;
• amnesia (memory loss), memory impairment (forgetfulness), abnormal coordination/ataxia (impaired coordination of movement), paraesthesia (tingling), attention disturbances (loss of concentration);
• diplopia (double vision), blurred vision;
• elevated/abnormal liver function test results;
• hair loss, eczema, itching;
• muscle weakness, myalgia (muscle pain);
• injury.

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

• infection;
• decrease in all types of blood cells;
• severe allergic reactions (DRESS, anaphylactic reaction (severe and serious allergic reaction), angioedema (swelling of face, lips, tongue and throat));
• decrease in blood sodium concentration;
• suicide, personality disorders (behavioural problems), abnormal thinking (slow thinking, difficulty concentrating);
• delirium;
• encephalopathy (see subsection “Contact your doctor immediately” for a detailed description of symptoms);
• epileptic seizures may worsen or occur more frequently;
• uncontrollable muscle spasms affecting the head, trunk 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 worsening of kidney function;
• skin rash, which may lead to blisters that may appear as small targets (dark central spots surrounded by a paler area, with a dark ring around the edge) (erythema multiforme), a widespread rash with blisters and peeling of the skin, especially 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 associated increase in blood creatine phosphokinase. Prevalence is significantly higher in Japanese patients compared to non-Japanese patients;
• limping or difficulty walking;
• combination of fever, muscle rigidity, unstable blood pressure and heart rate, confusion, and reduced level of consciousness (may be signs of a disorder called neuroleptic malignant syndrome). Prevalence is significantly higher in Japanese patients compared to non-Japanese patients.

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

• unwanted and repeated thoughts or sensations, or the urge to do something repeatedly (obsessive-compulsive disorder).

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system listed in Appendix V. By reporting adverse 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 indicated.

This medicine does not require any special storage conditions.

6. Contents of the pack and other 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 injections.

Nature of the product and contents of the container

Keppra concentrate for solution for infusion (sterile concentrate) is a clear, colourless liquid.

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

Marketing Authorisation 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.

More information about this medicinal product can be obtained by contacting the local representative of the Marketing Authorisation Holder.

Date of the most recent review of this summary:

Other sources of information

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

This information is intended for healthcare professionals only:

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 a total daily dose of 500 mg, 1,000 mg, 2,000 mg, or 3,000 mg given in two divided doses.

Table 1. Preparation and administration of Keppra concentrate

This medicinal product is for single use; therefore, any unused solution must be discarded.

In-use shelf life: From a microbiological point of view, the product should be used immediately after dilution. If not used immediately, the duration and conditions of storage prior to the next use are the responsibility of the user and should not exceed 24 hours between 2 and 8°C, unless the dilution has been carried out under validated and controlled 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 under controlled room temperature of 15–25°C.

Diluents:

• Sodium chloride injection solution 9 mg/ml (0.9%)
• Ringer lactate injection solution
• Dextrose injection solution 50 mg/ml (5%)