LEVETIRACETAM KERN PHARMA 100 mg/ml CONCENTRATE FOR INFUSION

Introduction

Package Leaflet: Information for theuser

Levetiracetam Kern Pharma 100 mg/ml concentrate solution for infusion EFG

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

Contents of the pack

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

1. What is Levetiracetam Kern Pharma and what is it used for

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

Levetiracetam is used:

• on its own (without the need for another antiepileptic medicine) in patients from 16 years of age with newly diagnosed epilepsy to treat partial onset seizures with or without secondary generalisation,
• in combination with 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.

Levetiracetam concentrate is an alternative for patients when oral administration is temporarily not feasible.

2. What you need to know before you take Levetiracetam Kern Pharma

Do not use Levetiracetam Kern Pharma

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

Warnings and precautions

Consult your doctor before starting treatment with levetiracetam

• if you suffer from kidney problems, follow your doctor's instructions, who will decide whether to adjust your dose
• if you observe any decrease in your child's growth or an unexpected development of puberty, contact your doctor,
• if you notice an increase in the severity of your seizures (e.g. increase in number), contact your doctor
• a small number of people taking antiepileptics, such as levetiracetam, have had thoughts of harming themselves or suicide. If you have any symptoms of depression and/or suicidal thoughts, contact your doctor.

Tell your doctor or pharmacist if any of the following side effects get worse or last more than a few days:

• Abnormal thoughts, feeling irritable or reacting more aggressively than usual or if you or your family and friends notice significant changes in mood or behaviour.

Using Levetiracetam Kern Pharma with other medicines

Tell your doctor or pharmacist if you are using or have recently used other medicines, including those obtained without a prescription.

Using Levetiracetam Kern Pharma with food, drinks and alcohol

You can take levetiracetam with or without food. As a precautionary measure, do not take levetiracetam with alcohol.

Pregnancy, breastfeeding and fertility

Consult your doctor or pharmacist before taking any medicine.

If you are pregnant or think you may be pregnant, inform your doctor.

Levetiracetam should not be used during pregnancy unless clearly necessary. The risk to the baby is unknown. In animal studies, levetiracetam has shown undesirable effects on reproduction at doses higher than those you may need to control your seizures.

Breastfeeding is not recommended during treatment.

Driving and using machines

Levetiracetam may affect your ability to drive or use tools or machinery, as levetiracetam may cause drowsiness. This is more likely at the start of treatment or when the dose is increased. You should not drive or use machinery until it is established that your ability to perform these activities is not affected.

Levetiracetam Kern Pharma contains sodium

Other ingredients are sodium acetate, glacial acetic acid, sodium chloride, water for injectable preparations.

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

3. How to take Levetiracetam Kern Pharma

Levetiracetam Kern Pharma will be administered to you by a doctor or nurse through intravenous infusion.

Levetiracetam should be administered twice a day, 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 can switch from film-coated tablets or oral solution to the intravenous formulation, or vice versa, directly without dose adjustment. Your total daily dose and frequency of administration should be the same.

Monotherapy

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

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

When you start taking levetiracetam, your doctor will prescribe a lower dosefor two weeks before administering the lowest general dose.

Concomitant therapy

Dose in adults and adolescents (from 12 to 17 years) with a weight of 50 kg or more:

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

Dose in children (from 4 to 11 years) and adolescents (from 12 to 17 years) with a weight below 50 kg:

General dose: between 20 mg per kg of body weight and 60 mg per kg of body weight per day.

Method and route of administration:

Levetiracetam should be diluted to a minimum of 100 ml with a compatible diluent and administered by intravenous infusion over 15 minutes.

More detailed information for the correct use of Levetiracetam Kern Pharma is provided in section 6 for doctors and nurses.

Duration of treatment:

• Levetiracetam is used as a chronic treatment. You should continue treatment with Levetiracetam for the time indicated by your doctor.
• Do not stop your treatment without your doctor's advice, as your seizures may increase. If your doctor decides to stop your treatment with levetiracetam, he/she will give you instructions for the gradual withdrawal of levetiracetam, if he/she decides to suspend your treatment with this medicine.
• There is no experience with the administration of intravenous levetiracetam for a period longer than 4 days.

If you stop treatment with Levetiracetam Kern Pharma

As with other antiepileptic medicines, the discontinuation of treatment with levetiracetam should be done gradually to avoid an increase in seizures.

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

4. Possible side effects

Like all medicines, levetiracetam can cause side effects, although not everybody gets them.

Some of the side effects such as drowsiness, weakness and dizziness may be more frequent when starting treatment or increasing the dose. However, these side effects should decrease over time.

Tell your doctor immediately, or go to the emergency 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 rash on the face followed by a prolonged rash with high temperature, elevated liver enzymes 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 output, fatigue, nausea, vomiting, confusion and swelling of legs, arms or feet, as this may be a sign of sudden decrease in kidney function
• a skin rash that may form blisters and appears as small targets (central dark spots surrounded by a paler area, with a dark ring on the edge) (erythema multiforme)
• a widespread rash with blisters and skin peeling, especially around the mouth, nose, eyes and genitals (Stevens-Johnson syndrome)
• a more severe form causing skin peeling on more than 30% of the body surface (toxic epidermal necrolysis)
• signs of severe mental changes or if someone around you notices signs of confusion, drowsiness (drowsiness), amnesia (memory loss), memory impairment (forgetfulness), abnormal behaviour or other neurological signs including uncontrolled or involuntary movements. These may be symptoms of encephalopathy

Very common:may affect more than 1 in 10 people

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

Common:may affect up to 1 in 10 people

• loss of appetite (anorexia);
• depression, hostility or aggression, anxiety, insomnia, nervousness or irritability;
• seizures, balance disorder, dizziness (feeling unsteady), lethargy, tremor (involuntary trembling);
• vertigo (feeling of spinning);
• cough;
• abdominal pain, diarrhoea, dyspepsia (indigestion), vomiting, nausea;
• skin rash;
• asthenia/fatigue (feeling weak).

Uncommon:may affect up to 1 in 100 people

• decrease in platelet count, decrease in white blood cell count;
• weight loss, weight gain;
• suicidal attempt and suicidal thoughts, mental disorders, abnormal behaviour, hallucinations, anger, confusion, emotional instability/mood changes, agitation;
• amnesia (memory loss), memory impairment (lack of memory), abnormal coordination/ataxia (altered movement coordination), paraesthesia (tingling), attention disorders (lack of concentration);
• double vision, blurred vision;
• abnormal liver function tests;
• 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;
• suicide, personality disorders (behavioural problems), abnormal thinking (slow thinking, difficulty concentrating);
• uncontrolled muscle spasms affecting the head, torso and limbs, difficulty controlling movements, hyperkinesia (hyperactivity);
• pancreatitis (inflammation of the pancreas);
• liver failure, hepatitis (inflammation of the liver);
• skin rash, which may form blisters and appears as small targets (central dark spots surrounded by a paler area, with a dark ring on the edge) (erythema multiforme), a widespread rash with blisters and skin peeling, especially around the mouth, nose, eyes and genitals (Stevens-Johnson syndrome) and a more severe form causing skin peeling on more than 30% of the body surface (toxic epidermal necrolysis)
• decrease in sodium levels in the blood.
• sudden decrease in kidney function;
• rhabdomyolysis (muscle tissue breakdown) and increased creatine phosphokinase in the blood.

The prevalence is significantly higher in Japanese patients compared to non-Japanese patients.

Reporting of side effects

If you experience 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 Spanish Medicines and Healthcare Products Agency's website: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

If you experience side effects, talk to your doctor, pharmacist or nurse, even if they are not listed in this leaflet.

5. Storage of Levetiracetam Kern Pharma

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

No special storage conditions are required.

Do not use this medicine after the expiry date which is stated on the vial and carton after "EXP". The expiry date is the last day of the month shown.

Medicines should not be disposed of via wastewater or household waste. Place the vials and medicines you no longer need in the SIGRE collection point at your pharmacy. If you have any doubts, ask your pharmacist how to dispose of the vials and medicines you no longer need. This will help protect the environment.

6. Levetiracetam Kern Pharma

Composition of Levetiracetam Kern Pharma

The active substance is 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 injectable preparations.

Appearance and packaging

Levetiracetam Kern Pharma concentrate for solution for infusion is a sterile, clear and colourless liquid.

The 5 ml vials of Levetiracetam Kern Pharma concentrate are packaged in cardboard boxes of 10 vials.

Marketing authorisation holder and manufacturer:

Kern Pharma, S.L.

Venus, 72 - Pol. Ind. Colón II,

08228 Terrassa - Barcelona

Spain

Date of last revision of this leaflet: October 2019

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency for Medicines and Healthcare Products (AEMPS) http://www.aemps.gob.es/

This information is intended only for healthcare professionals:

Instructions for the correct use of levetiracetam are provided in section 3.

A vial of Levetiracetam concentrate contains 500 mg of levetiracetam (5 ml of 100 mg/ml concentrate). See Table 1 for the recommended preparation and administration of levetiracetam concentrate to achieve the total daily dose of 500 mg, 1,000 mg, 2,000 mg or 3,000 mg divided into two doses.

Table 1. Preparation and administration of Levetiracetam Kern Pharma concentrate

This medicinal product is for single use, so the 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 time and storage conditions before 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 performed under validated and controlled aseptic conditions.

It has been found that levetiracetam 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 injection (0.9%)
• Lactated Ringer's injection
• 5% Dextrose injection