Patient leaflet - Levetiracetam Eugia 100 mg/ml concentrate for solution for infusion

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:

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.

an add-on to other antiepileptic medicines to treat:
- partial onset seizures with or without generalisation in adults, adolescents and
  children from 4 years 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).

Levetiracetam Eugia concentrate for solution for infusion is an alternative for patients when administration of the antiepileptic oral Levetiracetam Eugia medicine is temporarily not feasible.

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

Do not use Levetiracetam Eugia:

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 you are given Levetiracetam Eugia.

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
Eugia 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.

In a very rare form of early-onset epilepsy (epilepsy associated with SCN8A mutations) that causes multiple types of seizures and loss of skills you may notice that the seizures remain present or are becoming worse during your treatment

If you experience any of these new symptoms while taking Levetiracetam Eugia, see a doctor as soon as possible.

Children and adolescents

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

Other medicines and Levetiracetam Eugia

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription.

Do not take macrogol (a drug used as laxative) for one hour before and one hour after taking levetiracetam as this may result 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. Two studies do not suggest an increased risk of autism or intellectual disability in children born to mothers treated with levetiracetam during pregnancy. However, the available data regarding the impact of levetiracetam on neurodevelopment in children is limited.

Breast-feeding is not recommended during treatment.

Driving and using machines

Levetiracetam Eugia 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 Eugia contains sodium

For 250 mg & 500 mg dose:

This medicine contains less than 1 mmol sodium (23 mg) per unit volume, that is to say essentially sodium-free.

For 1000 mg dose:

This medicine contains 38 mg sodium (main component of cooking/table salt) in each unit volume. This is equivalent to 1.9% of the recommended maximum daily dietary intake of sodium for an adult.

For 1500 mg dose:

This medicine contains 57 mg sodium (main component of cooking/table salt) in each unit volume. This is equivalent to 2.85% of the recommended maximum daily dietary intake of sodium for an adult.

3. How to take Levetiracetam Eugia

A doctor or a nurse will administer you Levetiracetam Eugia as an intravenous infusion. Levetiracetam Eugia must be administered twice a day, once in the morning and once in the evening, at about the same time each day.

The intravenous formulation is an alternative to your oral administration. You can switch from the film- coated tablets or from the oral solution to the intravenous formulation or reverse directly without dose adaptation. Your total daily dose and frequency of administration remain identical.

Adjunctive 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 1000 mg and 3,000 mg each day.

When you will first start taking Levetiracetam Eugia, your doctor will prescribe you a lower dose during 2 weeks before giving you 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 bodyweight and 60 mg per kg bodyweight each day.

Method and route of administration:

Levetiracetam Eugia is for intravenous use.

The recommended dose must be diluted in at least 100 ml of a compatible diluent and infused over 15- minutes.

For doctors and nurses, more detailed direction for the proper use of Levetiracetam Eugia is provided in section 6.

Duration of treatment:

There is no experience with administration of intravenous levetiracetam for a longer

period than 4 days.

If you stop using LevetiracetamEugia:

If stopping treatment, as with other antiepileptic medicines, Levetiracetam Eugia should be discontinued gradually to avoid an increase of seizures. Should your doctor decide to stop your Levetiracetam Eugia treatment, he/she will instruct you about the gradual withdrawal of LevetiracetamEugia.

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

The following information is intended for healthcare professionals only: Direction for the proper use of Levetiracetam Eugia is provided in section 3.

One vial of Levetiracetam Eugia concentrate contains 500 mg levetiracetam (5 ml concentrate of 100 mg/ml). See Table 1 for the recommended preparation and administration of Levetiracetam Eugia concentrate to achieve a total daily dose of 500 mg, 1000 mg, 2000 mg, or 3000 mg in two divided doses.

Table 1. Preparation and administration of Levetiracetam Eugia concentrate

Dose Withdrawal Volume Volume of

Diluent

Infusion Time

Frequency of administration

Total Daily Dose

250 mg 2.5 ml (half 5ml vial) 100 ml 15 minutes Twice daily 500 mg/day 500 mg 5 ml (one 5 ml vial) 100 ml 15 minutes Twice daily 1000 mg/day 1000 mg 10 ml (two 5ml vials) 100 ml 15 minutes Twice daily 2000 mg/day 1500 mg 15 ml (three 5 ml

vials)

100 ml 15 minutes Twice daily 3000 mg/day

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 1,000 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.
- Combination of fever, muscle stiffness, unstable blood pressure and heart rate, confusion, low level of consciousness (may be signs of a disorder called neuroleptic malignant syndrome). Prevalence is significantly higher in Japanese patients when compared to non-Japanese patients.

Very rare: may affect up to 1 in 10000 people

repeated unwanted thoughts or sensations or the urge to do something over and over again (Obsessive Compulsive Disorder).

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

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, which is stated on the vial and carton box after EXP. The expiry date refers to the last day of that month.

This medicinal product does not require any special storage conditions.

Chemical and physical in-use stability has been demonstrated for 24 hours at 2-8°C and at 15-25°C.

From a microbiological point of view, unless the method of opening/dilution precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user.

Do not use Levetiracetam Eugia if you notice any particulate matter or discoloration

Do not throw away any medicines via wastewater. 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 Eugia contains

The active substance is levetiracetam,

Each ml of solution for infusion contains 100 mg of levetiracetam.

The other ingredients are: Sodium chloride, sodium acetate trihydrate, acetic acid, glacial, water for injection.

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 vial is packed in a cardboard box of 1 and 10 vials.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Eugia (UK) Limited

Milpharm Limited

1 Roundwood Avenue,

Stockley Park,

Uxbridge, UB11 1AF,

United Kingdom

Manufacturer

APL Swift Services (Malta) Limited

HF26, Hal Far Industrial Estate,

Hal Far, Birzebbugia, BBG 3000 Malta