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Milpharm

Package leaflet: Information for the user

Levetiracetam Milpharm 100 mg/ml concentrate for solution for infusion

Levetiracetam

Read all of this leaflet carefully before you 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 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. See section 4.

What is in this leaflet

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

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

3.    How to take Levetiracetam Milpharm

4.    Possible side effects

5.    How to store Levetiracetam Milpharm

6.    Contents of the pack and other information

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

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

Levetiracetam Milpharm 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 seizures with or without secondary generalisation). Levetiracetam has been given to you by your doctor to reduce the number of fits.

•    as an add-on to other antiepileptic medicines to treat:

-    partial onset seizures with or without generalisation in in adults, adolescents and children from

4 years of age

-    myoclonic seizures (short, shocklike 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 Milpharm concentrate for solution for infusion is an alternative for patients when administration of the antiepileptic oral Levetiracetam Milpharm medicine is temporarily not feasible.

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

Do not use

Levetiracetam Milpharm:

- 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 Milpharm.

•    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 Milpharm have had thoughts of harming or killing themselves. If you have any symptoms of depression and/ or suicidal ideation, please contact your doctor.

Children and adolescents

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

Other medicines and Levetiracetam Milpharm

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines,

Do not take macrogol (a drug used as laxative) for one hour before and one hour after taking levetiracetam as this may results in a reduction of its effect.

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 Milpharm should not be used during pregnancy unless clearly necessary. A risk of birth defects for your unborn child cannot be completely excluded. Levetiracetam Milpharm has shown unwanted reproductive effects in animal studies at dose levels higher than you would need to control your seizures. Breast-feeding is not recommended during treatment.

Driving and using machines

Levetiracetam Milpharm 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 Milpharm contains sodium

One maximum single dose of Levetiracetam Milpharm concentrate contains 2.5 mmol (or 57 mg) of sodium (0.8 mmol (or 19 mg) of sodium per vial). This should be taken into consideration if you are on a controlled sodium diet.

3. How to take Levetiracetam Milpharm

A doctor or a nurse will administer you Levetiracetam Milpharm as an intravenous infusion.

Levetiracetam Milpharm 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.

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

General dose: between 1000 mg and 3,000 mg each day.

When you will first start taking Levetiracetam Milpharm, your doctor will prescribe you a lower dose during 2 weeks before giving you the lowest general dose.

Add-on therapy Dose in adults and adolescents (12 to 17 years) weighing 50 kg or more:

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

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

General dose: between

The following information is intended for healthcare professionals only:

Direction for the proper use of Levetiracetam Milpharm is provided in section 3.

One vial of Levetiracetam Milpharm concentrate contains 500 mg levetiracetam (5 ml concentrate of 100 mg/ ml). See Table 1 for the recommended preparation and administration of Levetiracetam Milpharm 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 Milpharm concentrate

Dose	Withd rawal Volume	Volume of Diluent	Infu sion Time	Frequency of administration	Total Daily Dose
250 mg	2.5 ml (half 5 ml 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 5 ml 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

Black

20 mg per kg bodyweight and 60 mg per kg bodyweight each day.

Method and route of administration:

Levetiracetam Milpharm 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 Milpharm 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 Levetiracetam Milpharm:

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

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

4. Possible side effects

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

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 user in 10 people

•    nasopharyngitis;

•    somnolence (sleepiness), headache.

Common: may affect 1 to 10 users in 100 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 1 to 10 users in 1000 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 1 to 10 users in 10,000 people

•    infection;

•    decreased number of all blood cell types;

•    severe hypersensitivity 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);

•    uncontrollable muscle

K...........................

spasms affecting the head, torso and limbs, difficulty in controlling movements, hyperkinesia (hyperactivity);

•    pancreatitis;

•    liver failure, hepatitis;

•    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).

Reporting of side effects

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

5. How to store Levetiracetam Milpharm

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, inuse storage times and conditions prior to use are the responsibility of the user.

Do not use Levetiracetam Milpharm 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 Milpharm 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 Milpharm looks like and contents of the pack

Levetiracetam Milpharm concentrate for solution for infusion is a clear, colourless solution.

Levetiracetam Milpharm 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

Milpharm Limited Ares block, Odyssey Business Park West End Road Ruislip HA4 6QD United Kingdom

Manufacturer

APL Swift Services (Malta) Limited

HF26, Hal Far Industrial Estate, Hal Far Birzebbugia, BBG 3000 Malta

This leaflet was last revised in 10/2016.

This medicinal product is for single use only, any unused solution should be discarded.

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 15-25°C, over the concentration range of 2.5 mg/ml to 13 mg/ml.

Diluents:

•    Sodium chloride 9 mg/ ml (0.9%) solution for injection

•    Lactated Ringer's solution for injection

•    Dextrose 50 mg/ ml (5%) solution for injection