LEVETIRACETAM EUGIA

Package leaflet: Information for the user

Levetiracetam Eugia, 100 mg/mL, concentrate for solution for infusion
Levetiracetamum
Please read all of this leaflet carefully before using this medicine or administering it to a child, as it contains important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm someone else, even if their symptoms are the same.
• If the patient experiences any adverse reactions, including any possible adverse reactions not listed in this leaflet, please inform the doctor or pharmacist. See section 4.

Contents of the leaflet

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

1. What Levetiracetam Eugia is and what it is used for
Levetiracetam is an antiepileptic medicine (a medicine used to treat seizures in epilepsy).
Levetiracetam Eugia is used:

• as monotherapy (using Levetiracetam Eugia alone) in the treatment of adults and adolescents aged 16 years and older with newly diagnosed epilepsy, for certain types of epilepsy. Epilepsy is a condition in which patients have recurrent seizures (fits). Levetiracetam is used to treat forms of epilepsy in which seizures start in one part of the brain but may then spread to larger areas of both brain hemispheres (secondarily generalized or non-generalized partial seizures). Your doctor has prescribed levetiracetam to reduce the number of seizures.
• as an add-on therapy to another antiepileptic medicine:
  • in adults, adolescents and children from 4 years of age, for the treatment of partial seizures with or without secondary generalization,
  • in adults and adolescents from 12 years of age, for the treatment of juvenile myoclonic epilepsy, for myoclonic seizures (brief, shock-like jerks of a muscle or group of muscles),
  • in adults and adolescents from 12 years of age with idiopathic generalized epilepsy (a type of epilepsy likely to have a genetic basis), for the treatment of primary generalized tonic-clonic seizures (major seizures, including loss of consciousness).

Levetiracetam Eugia, concentrate for solution for infusion, is an alternative for patients when oral administration is temporarily not possible.

2. Important information before using Levetiracetam Eugia

When not to use Levetiracetam Eugia

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

Warnings and precautions
Before starting treatment with Levetiracetam Eugia, please discuss this with your doctor.

• If the patient has a kidney disease, Levetiracetam Eugia should be used according to the doctor's recommendations. The doctor may decide to adjust the dosage.
• If any growth retardation or unexpected early puberty in a child is observed, please contact the doctor.
• In some patients treated with antiepileptic medicines such as Levetiracetam Eugia, thoughts of self-harm or suicidal thoughts have occurred. If symptoms of depression and/or suicidal thoughts occur, please contact the doctor.
• If the patient has a family history or personal history of irregular heart rhythm (visible on electrocardiogram), or if the patient has a disease and/or is taking medicines that may predispose to irregular heart rhythm or electrolyte imbalance.

Please inform your doctor or pharmacist if any of the following adverse reactions worsen or persist for longer than a few days:

• Abnormal thoughts, irritability, more aggressive reactions than usual, or significant changes in mood or behaviour noticed by the patient or their family and friends.
• Worsening of epilepsy. In rare cases, seizures may worsen or occur more frequently, especially during the first month of treatment or after increasing the dose. In a very rare form of early-onset epilepsy (epilepsy associated with SCN8A gene mutations) causing various types of seizures and loss of skills, the patient may notice that seizures continue or worsen during treatment.

If any of these new symptoms occur while taking Levetiracetam Eugia, please contact your doctor as soon as possible.
Children and adolescents
Levetiracetam Eugia is not recommended for use as monotherapy (using Levetiracetam Eugia alone) in children and adolescents under 16 years of age.
Levetiracetam Eugia and other medicines
Please inform your doctor or pharmacist about all medicines currently being taken, recently taken, or planned to be taken.
Do not take macrogol (a laxative used for bowel cleansing) one hour before and one hour after taking levetiracetam, as this may reduce its effectiveness.
Pregnancy and breastfeeding
If the patient is pregnant, breastfeeding, suspects she may be pregnant, or is planning to have a baby, she should consult her doctor before using this medicine.
Levetiracetam may be used during pregnancy only if, after careful evaluation, the treating doctor considers it necessary. Do not discontinue treatment without discussing it with the treating doctor.
A risk of congenital malformations in the unborn child cannot be completely ruled out.
Breastfeeding is not recommended during treatment.
Driving and operating machinery
Levetiracetam Eugia may impair the ability to drive and operate tools or machinery, as this medicine may cause drowsiness. This is more likely at the beginning of treatment or after increasing the dose. Driving and operating machinery should not be undertaken until the effect of the medicine on the patient's ability to perform these activities is known.
Levetiracetam Eugia contains sodium
For doses of 250 mg and 500 mg:
This medicine contains less than 1 mmol (23 mg) of sodium per unit volume, meaning the medicine is considered "sodium-free".
For dose of 1000 mg:
This medicine contains 38 mg of sodium (the main component of table salt) in each unit volume.
This corresponds to 1.9% of the maximum recommended daily dietary sodium intake for adults.
For dose of 1500 mg:
This medicine contains 57 mg of sodium (the main component of table salt) in each unit volume.
This corresponds to 2.85% of the maximum recommended daily dietary sodium intake for adults.

3. How to use Levetiracetam Eugia

Levetiracetam Eugia is administered as an intravenous infusion by a doctor or nurse.
Levetiracetam Eugia must be given twice daily, in the morning and evening, approximately at the same time each day.
The intravenous formulation of the medicine provides an alternative to oral administration. Switching from oral tablets or oral solution to the intravenous form of the medicine, or vice versa, may be performed directly, without gradual dose adjustment. The total daily dose and frequency of administration remain unchanged.

Adjunctive therapy and monotherapy (in patients aged 16 years and older)
Adults (aged ≥ 18 years) and adolescents (aged 12 to 17 years) with body weight of 50 kg or more:
Recommended dose: 1000 mg to 3000 mg per day.
If a patient is starting Levetiracetam Eugia for the first time, the doctor will initially recommend a lower dose for 2 weeks, followed by the lowest daily maintenance dose.

Dosing in children (aged 4 to 11 years) and adolescents (aged 12 to 17 years) with body weight below 50 kg:
Recommended dose: 20 mg/kg body weight to 60 mg/kg body weight per day.

Method and route of administration:
Levetiracetam Eugia is administered intravenously.
The recommended dose should be diluted in at least 100 mL of an appropriate diluent and infused over a period of more than 15 minutes.
Further detailed information for doctors and nurses on the proper administration of Levetiracetam Eugia can be found in section 6.

Duration of treatment:

• There are no data on the intravenous administration of levetiracetam for periods longer than 4 days.

Discontinuation of Levetiracetam Eugia:
If treatment with Levetiracetam Eugia is to be discontinued, the medicine should be withdrawn gradually in order to avoid an increase in the frequency of epileptic seizures. If the doctor decides to discontinue treatment with Levetiracetam Eugia, they will also provide instructions on how to taper the medicine gradually.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
You should immediately inform your doctor or contact the nearest hospital emergency department (A&E) if the patient experiences:

• weakness, dizziness or breathing difficulties, as these symptoms may indicate 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 rash spreading over the entire body, accompanied by high fever, increased liver enzyme activity observed in blood tests, increased number of certain white blood cells (eosinophilia), enlarged lymph nodes and involvement of other organs (drug rash with eosinophilia and systemic symptoms - DRESS syndrome)
• symptoms such as reduced urine output, fatigue, nausea, vomiting, confusion, and swelling of the legs, ankles or feet, as these may indicate sudden worsening of kidney function
• skin rash which may lead to blister formation and appear as small target-like lesions (dark center surrounded by a lighter area and a dark ring around it) (erythema multiforme)
• extensive rash with blisters and peeling skin, occurring mainly around the mouth, eyes, nose and genital organs (Stevens-Johnson syndrome)
• a more severe form of rash causing skin detachment affecting over 30% of the body surface (toxic epidermal necrolysis)
• signs of serious mental changes, or if the patient shows signs of disorientation, drowsiness, amnesia (memory loss), memory disturbances (forgetfulness), behavioural disturbances or other neurological symptoms including involuntary or uncontrolled movements. These may be symptoms of encephalopathy.

The most commonly reported adverse reactions are: inflammation of the mucous membranes of the nose and throat, drowsiness, headache, fatigue and dizziness. During the initial treatment period or when the dose is increased, adverse reactions such as drowsy, fatigue or dizziness may occur more frequently. These effects should gradually diminish over time.
Very common: may affect more than 1 in 10 people

• inflammation of the mucous membranes of the nose and throat
• drowsiness, headache

Common: may affect up to 1 in 10 people

• loss of appetite
• depression, feeling of hostility or aggression, anxiety, insomnia, nervousness or irritability
• seizures, balance disorders, dizziness (feeling of unsteadiness), somnolence (lack of energy and motivation), tremor (involuntary shaking)
• dizziness (spinning sensation)
• cough
• abdominal pain, diarrhoea, dyspepsia (indigestion), vomiting, nausea
• rash
• asthenia/fatigue (tiredness)

Uncommon: may affect up to 1 in 100 people

• decreased platelet count, decreased white blood cell count
• weight decrease, weight increase
• suicidal thoughts and suicide attempts, mental disorders, abnormal behaviour, hallucinations, feeling of anger, disorientation, panic attacks, emotional instability/mood changes, agitation
• amnesia (memory loss), memory disturbances (forgetfulness), ataxia (impaired coordination of movement), paresthesia (tingling), difficulty concentrating
• double vision, blurred vision
• elevated/abnormal liver function test results
• hair loss, skin eruption, itching
• muscle weakness, muscle pain
• injuries

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

• infection
• decreased number of all types of blood cells
• severe hypersensitivity reactions (drug rash with eosinophilia and systemic symptoms - DRESS syndrome, Quincke's oedema (swelling of face, lips, tongue and throat))
• decreased sodium concentration in blood
• suicide, personality disorders (behavioural disturbances), thought disorders (slow thinking, inability to concentrate)
• delirium
• encephalopathy (a detailed description of symptoms is provided in the section "You should immediately inform your doctor")
• seizures may worsen or occur more frequently
• involuntary muscle contractions of the head, trunk and limbs, difficulty controlling movements, hyperkinesia (hyperactivity)
• change in heart rhythm (electrocardiographic examination)
• pancreatitis
• liver function disorders, hepatitis
• sudden worsening of kidney function
• skin rash which may lead to blister formation and appear as small target-like lesions (dark center surrounded by a lighter area and a dark ring around it) (erythema multiforme), extensive rash with blisters and peeling skin, occurring mainly around the mouth, eyes, nose and genital organs (Stevens-Johnson syndrome), and a more severe form of rash causing skin detachment affecting over 30% of the body surface (toxic epidermal necrolysis)
• rhabdomyolysis (breakdown of striated muscles) and associated increase in creatine phosphokinase activity in blood. Occurrence is significantly more frequent in Japanese patients compared to other (non-Japanese) patients
• limping or difficulty walking
• concurrent occurrence of: fever, muscle stiffness, unstable blood pressure and heart rate, disorientation, low level of consciousness (these may be symptoms of a disorder known as neuroleptic malignant syndrome). The frequency of occurrence is significantly higher in Japanese patients compared to non-Japanese patients.

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

• recurrent unwanted thoughts or feelings or inner compulsion to repeatedly perform the same action (obsessive-compulsive disorder)

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, phone: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the responsible entity.
By reporting adverse reactions, additional information on the safety of the medicine can be collected.

5. How to store Levetiracetam Eugia

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial and carton after EXP.
The expiry date refers to the last day of the stated month.
No special storage conditions are required for this medicine.
Chemical and physical in-use stability has been demonstrated for 24 hours at temperatures of
2-8°C and 15-25°C.
From a microbiological point of view, unless the method of opening/dilution excludes the risk of
microbiological contamination, the product should be used immediately. If the product is not used
immediately, the user is responsible for the storage time and conditions prior to use.
Do not use Levetiracetam Eugia if any particulate matter or discoloration is observed.
Medicines should not be disposed of via wastewater. Ask your pharmacist how to dispose of
medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Levetiracetam Eugia contains

• The active substance is levetiracetam. Each mL of infusion solution contains 100 mg of levetiracetam.
• Other ingredients are: sodium chloride, sodium acetate trihydrate, glacial acetic acid, water for injections.

What Levetiracetam Eugia looks like and contents of the pack
Levetiracetam Eugia, concentrate for solution for infusion is a clear, colourless solution.
Levetiracetam Eugia, concentrate for solution for infusion 5 mL is supplied in cardboard boxes containing 10 vials.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Eugia Pharma (Malta) Limited
Vault 14, level 2
Valletta Waterfront
Floriana, FRN 1914
Malta
e-mail: [email protected]

Manufacturer/Importer:
APL Swift Services (Malta) Limited
HF26, Hal Far Industrial Estate, Hal Far
Birzebbugia, BBG 3000
Malta

This medicinal product is authorised in the European Economic Area countries under the following names:
Belgium: Levetiracetam AB 100 mg/ml, concentraat voor oplossing voor infusie
France: LEVETIRACETAM ARROW LAB 100 mg/ml, solution à diluer pour perfusion
Italy: Levetiracetam Aurobindo Italia 100 mg/ml concentrato per soluzione per infusione
Netherlands: Levetiracetam Eugia 100 mg/ml, concentraat voor oplossing voor infusie
Portugal: Levetiracetam Aurovitas 100 mg/ml concentrado para solução para perfusão
Spain: Levetiracetam Aurovitas 100 mg/ml concentrado para solución para perfusión EFG
Poland: Levetiracetam Eugia

Information intended exclusively for medical professionals:

Instructions for the proper use of Levetiracetam Eugia are provided in section 3.
One vial of Levetiracetam Eugia concentrate contains 500 mg of levetiracetam (5 mL of concentrate at 100 mg/mL). Table 1 provides recommendations for the preparation and administration of Levetiracetam Eugia concentrate to achieve a total daily dose of 500 mg, 1000 mg, 2000 mg, or 3000 mg, divided into two doses.
Table 1. Preparation and administration of Levetiracetam Eugia concentrate

This medicine is intended for single use; any unused portion of the solution should be discarded.
The levetiracetam concentrate for solution for infusion is physically compatible and chemically stable when mixed with the following diluents for at least 24 hours at controlled room temperature of 15-25°C, within a concentration range of 2.5 mg/mL to 13 mg/mL.
Diluents:

• Sodium chloride 9 mg/mL (0.9%) solution for injection
• Ringer's solution with lactate solution for injection
• Dextrose 50 mg/mL (5%) solution for injection