Levetiracetam Noridem

Package leaflet: Information for the patient

Levetiracetam Noridem 100 mg/mL concentrate for solution for infusion

levetiracetam
Generic medicine
Read this leaflet carefully before you or your child start taking this medicine
because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

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

Levetiracetam is an antiepileptic medicine (a medicine used to treat epileptic seizures).
Levetiracetam Noridem is used:

• as monotherapy in adults and adolescents aged 16 years and older with newly diagnosed epilepsy, to treat a specific type of epilepsy. Epilepsy is a condition in which patients experience repeated seizures. Levetiracetam is used for the type of epilepsy in which the seizure starts in only one part of the brain but may subsequently spread to broader areas on both sides of the brain (partial-onset seizures with or without secondary generalization). Your doctor has prescribed Levetiracetam to reduce the number of your seizures.
• as add-on therapy to other antiepileptic medicines to treat:
  • partial-onset seizures, with or without secondary generalization, in adults, adolescents, and children aged 4 years and older
  • myoclonic seizures (brief, shock-like jerks of a muscle or group of muscles) in adults and adolescents aged 12 years and older with juvenile myoclonic epilepsy
  • primary generalized tonic-clonic seizures (grand mal seizures, including loss of consciousness) in adults and adolescents aged 12 years and older with idiopathic generalized epilepsy (the type of epilepsy believed to have a genetic cause).

Levetiracetam Noridem concentrate for solution for infusion is an alternative for patients when oral administration of the antiepileptic medicine levetiracetam is temporarily not possible.

2. What you need to know before using Levetiracetam Noridem

Do not use Levetiracetam Noridem

• 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 using Levetiracetam Noridem

• If you have kidney problems, follow your doctor's instructions. Your doctor may decide whether your dose needs to be adjusted.
• If you notice slowed growth or unexpected onset of puberty in a child, contact your doctor.
• A small number of people taking antiepileptic medicines such as levetiracetam have experienced self-harming thoughts or suicidal ideas. If you experience any symptoms of depression and/or have suicidal thoughts, contact your doctor.
• If you or a family member has a heart rhythm disorder (detectable on electrocardiogram), or if you have a disease and/or are taking medicines that may cause irregular heartbeat or electrolyte imbalances.

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

• Unusual thoughts, feeling irritable, or more aggressive reactions than usual, or if you or your family and friends notice the onset of significant changes in mood or behaviour.
• Worsening of epilepsy: Seizures may rarely 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), which causes multiple seizure types and loss of existing abilities, you may notice that seizures persist or worsen during treatment.

If you experience any of these new symptoms while being treated with Levetiracetam Noridem,
consult a doctor as soon as possible.
Children and adolescents
Levetiracetam Noridem as monotherapy (used alone) is not indicated in children and adolescents under 16 years of age.
Other medicines and Levetiracetam Noridem
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) one hour before or one hour after taking levetiracetam, as it may reduce the effect of levetiracetam.
Pregnancy and breastfeeding
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 may be used during pregnancy only if, after careful evaluation, your doctor considers it necessary.
Do not stop your treatment without discussing it with your doctor.
A risk of birth defects for the unborn child cannot be completely ruled out.
Breastfeeding is not recommended during treatment.
Driving and using machines
Levetiracetam Noridem may reduce your ability to drive or operate tools or machinery, as it may cause drowsiness. This is more likely at the beginning of treatment or after a dose increase. Do not drive or operate machinery until you know how this medicine affects your ability to perform these activities.
Levetiracetam Noridem contains sodium
This medicine contains 57 mg (2.5 mmol) of sodium (the main component of table salt) in each maximum single dose. This corresponds to 2.85% of the maximum recommended daily dietary intake for an adult. This should be taken into consideration for patients on a low-sodium diet.

3. How to use Levetiracetam Noridem

A doctor or nurse will administer Levetiracetam Noridem to you as an intravenous infusion.
Levetiracetam Noridem must be administered 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 the film-coated tablets or oral solution to the intravenous formulation, or vice versa, without the need for dose adjustment. The total daily dose and frequency of administration remain unchanged.

Adjunctive therapy and monotherapy (from age 16 onwards)
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 starting Levetiracetam Noridem for the first time, your doctor will prescribe a lower dose for 2 weeks before increasing to the lowest daily maintenance dose.

Dose for 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:
Levetiracetam Noridem is for intravenous use (infusion into a vein).
The recommended dose must be diluted in at least 100 mL of a compatible diluent and infused over 15 minutes.
More detailed instructions for the appropriate use of Levetiracetam Noridem are provided in the section for healthcare professionals.

Duration of treatment:
There is no experience with intravenous administration of levetiracetam for periods longer than 4 days.

If you stop treatment with Levetiracetam Noridem:
As with any other antiepileptic medicine, Levetiracetam Noridem must be discontinued gradually to avoid an increase in seizures. If your doctor decides to stop treatment with Levetiracetam Noridem, they will provide you with specific instructions for gradually tapering off the medication.

If you have any doubts about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Immediately contact your doctor or go to the nearest emergency department if you experience:

• weakness, feeling faint or dizzy, or have difficulty breathing, as these may be signs of a severe allergic reaction (anaphylactic)
• swelling of the face, lips, tongue and throat (angioedema, Quincke's oedema)
• flu-like symptoms and rash on the face followed by widespread rash with high fever, increased liver enzyme levels found in blood tests, increase in a type of white blood cells (eosinophilia), and swollen lymph nodes (drug reaction with eosinophilia and systemic symptoms [DRESS, Drug Reaction with Eosinophilia and Systemic Symptoms])
• symptoms such as reduced urine volume, fatigue, nausea, vomiting, confusion, and swelling of legs, ankles or feet, as these may indicate sudden decrease in kidney function
• a skin rash which may appear as blisters resembling small targets (dark central spots surrounded by a paler area, with a dark ring around the edge) (erythema multiforme)
• widespread blistering rash and peeling of the skin, particularly around the mouth, nose, eyes and genitals (Stevens-Johnson syndrome)
• a more severe form of skin rash causing skin peeling over more than 30% of the body surface area (toxic epidermal necrolysis)
• signs of serious mental disturbances or if someone around you notices confusion, drowsiness, amnesia (memory loss), memory impairment (forgetfulness), abnormal behaviour or other neurological signs including involuntary or uncontrollable movements. These could be symptoms of encephalopathy.

The most frequently reported side effects are: nasopharyngitis, drowsiness, headache, fatigue and dizziness. At the beginning of treatment or when the dose is increased, side effects such as drowsiness, fatigue and dizziness may be more common. However, these effects should decrease over time.
Very common: may affect more than 1 in 10 people

• nasopharyngitis
• drowsiness, 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 disorders, dizziness (feeling of unsteadiness), lethargy (lack of energy and enthusiasm), tremor (involuntary tremors)
• vertigo (sensation of spinning)
• cough
• abdominal pain, diarrhoea, dyspepsia (indigestion), vomiting, nausea
• rash
• asthenia/fatigue (feeling weak).

Uncommon: may affect up to 1 in 100 people

• decreased number of platelets in the blood, decreased number of white blood cells in the blood
• weight loss, weight gain
• suicidal attempt and suicidal ideation, mental disorder, abnormal behaviour, hallucinations, anger, confusion, panic attack, affective lability/mood swings, agitation
• amnesia (memory loss), memory impairment (forgetfulness), abnormal coordination/ataxia (impaired motor coordination), paresthesia (tingling), attention disturbance (loss of concentration)
• diplopia (double vision), blurred vision
• elevated or abnormal liver function test results
• hair loss, eczema, pruritus (itching)
• muscle weakness, myalgia (muscle pain)
• trauma.

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

• infection
• decreased number of all types of blood cells
• severe allergic reactions (DRESS, anaphylactic reaction [severe and important allergic reaction], angioedema [swelling of face, lips, tongue and throat])
• decreased concentration of sodium in the blood
• suicide, personality disorder (behavioural problems), thought disturbances (slowed thinking, inability to concentrate)
• delirium
• encephalopathy (see subsection “Immediately contact your doctor” for a detailed description of symptoms)
• seizures may worsen or occur more frequently
• uncontrollable muscle spasms involving the head, trunk and limbs, difficulty controlling movements, hyperkinesia (hyperactivity)
• changes in heart rhythm (electrocardiogram)
• pancreatitis
• liver failure, hepatitis
• sudden decrease in kidney function
• skin rash which may appear as blisters resembling small targets (dark central spots surrounded by a paler area, with a dark ring around the edge) (erythema multiforme), widespread blistering rash and peeling of the skin, particularly 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 area (toxic epidermal necrolysis)
• rhabdomyolysis (breakdown of muscle tissue) and associated increase in blood creatine phosphokinase. The prevalence is significantly higher in Japanese patients compared to non-Japanese patients
• limping gait or difficulty walking
• combination of fever, muscle rigidity, unstable blood pressure and heart rate, confusion, reduced level of consciousness (may be signs of a disorder called neuroleptic malignant syndrome). The prevalence is significantly higher in Japanese patients compared to non-Japanese patients.

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

• repetitive unwanted thoughts or sensations or urge to repeat certain actions (obsessive-compulsive disorder).

Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system at:
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse .
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Levetiracetam Noridem

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial/bottle and the outer packaging after Exp. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
The diluted product is chemically and physically stable for 24 hours at 15 – 25 °C and 2 – 8 °C.
From a microbiological standpoint, the product should be used immediately after dilution.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Levetiracetam Noridem contains

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

Description of the appearance of Levetiracetam Noridem and contents of the pack
Levetiracetam Noridem is a clear, colourless concentrate for solution for infusion.
Levetiracetam Noridem is available in two pack types:

• Glass vials (containing 5 mL of concentrate for solution for infusion) with 500 mg of levetiracetam (10 or 50 vials per pack).
• Polypropylene vials (containing 5 mL of concentrate for solution for infusion) with 500 mg of levetiracetam (10 or 50 vials per pack).

Not all pack sizes may be marketed.

Marketing Authorisation Holder:
Noridem Enterprises Limited
Evagorou & Makariou, Mitsi Building 3, Office 115,
1065 Nicosia, Cyprus

Manufacturer:
DEMO S.A. PHARMACEUTICAL INDUSTRY
21st Km National Road Athens – Lamia
14568 Krioneri, Attiki, Greece

This medicinal product is authorised in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Germany: Levetiracetam Noridem 100 mg/ml Konzentrat zur Herstellung einer Infusionslösung
United Kingdom (Northern Ireland): Levetiracetam 100 mg / mL Concentrate for solution for infusion
Ireland: Levetiracetam 100 mg / mL Concentrate for solution for infusion
France: LEVETIRACETAM NORIDEM 100 mg/mL, solution à diluer pour perfusion
Belgium: Levetiracetam Noridem 100 mg/ml solution à diluer pour perfusion – concentraat voor oplossing voor infusie – Konzentrat zur Herstellung einer Infusionslösung
Cyprus: Levetiracetam Noridem 100 mg / mL Πυκνό διάλυμα για παρασκευή διαλύματος προς έγχυση
Greece: LEVETIRACETAM/DEMO 100 mg / mL Πυκνό διάλυμα για παρασκευή διαλύματος προς έγχυση
Austria: Levetiracetam Noridem 100 mg / ml Konzentrat zur Herstellung einer Infusionslösung
Spain: Levetiracetam Noridem 100 mg/ml concentrado para solución para perfusión
Finland: Levetiracetam Noridem 100 mg/ml infuusiokonsentraatti, liuosta varten
Italy: Levetiracetam Noridem
Norway: Levetiracetam Noridem
Portugal: Levetiracetam Noridem
Sweden: Levetiracetam Noridem
Denmark: Levetiracetam Noridem

The following information is intended for healthcare professionals only:

Preparation and handling

Instructions for the correct use of Levetiracetam Noridem are provided in section 3.
A vial of Levetiracetam Noridem concentrate contains 500 mg of levetiracetam (5 mL of concentrate at 100 mg/mL). See Table 1 for the recommended preparation and administration of Levetiracetam Noridem concentrate to achieve a 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 Noridem concentrate.

This medicinal product is intended for single use and any unused solution must be discarded.
The diluted product is physically and chemically stable for 24 hours at 15 – 25 °C and 2 – 8 °C.
From a microbiological standpoint, the product should be used immediately after dilution. If not used immediately, the in-use storage duration and conditions prior to use are the responsibility of the user and normally should not exceed 24 hours at a temperature between 2 and 8 °C, unless the dilution has been carried out under controlled and validated aseptic conditions.
Levetiracetam Noridem concentrate for solution for infusion has been shown to be physically compatible and chemically stable for 24 hours at 15 – 25 °C and 2 – 8 °C at concentrations of Levetiracetam Noridem 2.5 mg/mL and 15.0 mg/mL.
Diluents:

• Sodium chloride 9 mg/mL (0.9%) injection
• Lactated Ringer's injection
• Dextrose 50 mg/mL (5%) injection