Levetiracetam Sun - patient leaflet, side effects, dosage

2. What you need to know before you are given Levetiracetam SUN

Do not use Levetiracetam SUN

• – 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 SUN

• – 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 slowdown in growth, or if there is unexpected puberty development in your child, please contact your doctor.

• – A small number of people being treated with anti-epileptics such as Levetiracetam SUN have had thoughts of harming or killing themselves. If you have any symptoms of depression and/or thoughts about committing suicide, 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. If you experience any of these new symptoms while taking Levetiracetam SUN, see a doctor as soon as possible.

Children and adolescents

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

Other medicines and Levetiracetam SUN

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 results 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.

Breast-feeding is not recommended during treatment.

Driving and using machines

Levetiracetam SUN 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 SUN contains sodium

One maximum single dose of Levetiracetam SUN 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 Levetiracetam SUN is given

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

Levetiracetam SUN 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 the oral formulation. You can be switched from one to the other without changing dose. Your total daily dose and frequency of administration remain the same.

Adjunctive therapy and Monotherapy (from 16 years of age).

Adults (>18 years) and adolescents (12 to 17 years) weighing 50 kg or more:

When you will first start taking Levetiracetam SUN, your doctor will prescribe a lower dose for 2 weeks before adjusting the dose as necessary.

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

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

General dose: between 20 mg per kg bodyweight and 60 mg per kg bodyweight each day.

Method and route of administration

Levetiracetam SUN 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 SUN 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 SUN

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

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.

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 of the 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.

Reporting of side effects

If you get 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 national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Levetiracetam SUN

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 box after EXP: The expiry date refers to the last day of the month.

Do not refrigerate or freeze.

6. Contents of the pack and other information

What Levetiracetam SUN contains

• - The active substance is called levetiracetam. Each ml contains 100 mg of levetiracetam.

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

What Levetiracetam SUN looks like and contents of the pack

Levetiracetam SUN concentrate for solution for infusion (sterile concentrate) is a clear, colourless liquid.

Levetiracetam SUN concentrate for solution for infusion is packed in a cardboard box containing 10 vials of 5 ml.

Marketing Authorisation Holder and Manufacturer

Sun Pharmaceutical Industries Europe B.V.

Polarisavenue 87

2132 JH Hoofddorp

The Netherlands

For any information about this medicine, please contact the local representative of the Marketing

Authorisation Holder.

Belgiě/Belgiqu­e/Belgien/Et.nra­pun/Česká republika/

Danmark/Eesti/EX­XáSa/Ireland/Ís­land/

Kúnpog/Latvija/Li­etuva/Luxembou­rg/Luxemburg/Ma­gyarország/

Malta/Nederlan­d/Norge/Osterre­ich/Portugal/

Slovenská republika/Suo­mi/Finland/Sve­rige

Sun Pharmaceutical Industries Europe B.V.

Polarisavenue 87

2132 JH Hoofddorp

Nederland/Pays-Bas/Niederian­de/HugepaaHgu­a/Nizozemsko/

Nederlandene/Ho­lland/OXXav8i­a/The Netherlands/Ho­lland/

OZZavôia/Nïder­lande/Nyderlan­dai/Pays-Bas/Niederlan­de/Hollandia/

L-Olanda/Nederlan­d/Nederland/Ni­ederlande/Paí­ses Baixos/

Holandsko/Alan­komaat/Nederländer­na/Nederländer­na

Tel./men./tlf­./TnX./Simi/TnX­./Tlf./Puh./

+31 (0)23 568 5501

Deutschland Sun Pharmaceuticals Germany GmbH Hemmelrather Weg 201 51377 Leverkusen Deutschland Tel. +49 214 403 99 0	Polska Ranbaxy (Poland) Sp. Z o. o. ul. Kubickiego 11 02–954 Warszawa Polska tel. +48 22 642 07 75
Basics GmbH Hemmelrather Weg 201 51377 Lever­kusen Deutschland Tel. +49 214 403 99 0	Romania Terapia S.A. Str. Fabricii nr 124 Cluj-Napoca, Judetul Cluj Romania tel. +40 (264) 501 500
España Sun Pharma Laboratorios, S.L. Rambla de Catalunya 53–55 08007 Barcelona España tel. +34 93 342 78 90	Slovenija Lenis farmacevtika d.o.o. Litostrojska cesta 52 1000 Ljubljana Slovenija tel. +386 (0)1 235 07 00
France Sun Pharma France 11–15, Quai Dion Bouton 92800 Puteaux France tel. +33 (0) 1 41 44 44 50	United Kingdom (Northern Ireland) Ranbaxy UK Ltd a Sun Pharma Company Millington Road 11 Hyde Park, Hayes 3 5th Floor
Hrvatska Medicopharmacia d.o.o. Ulica Pere Budmanija 5 10000 Zagreb Hrvatska	UB3 4AZ HAYES United Kingdom tel. +44 (0) 208 848 8688

tel. +385 1 5584 604

Italia

Sun Pharma Italia Srl

Viale Giulio Richard, 1 20143 Milano

Italia

tel. +39 02 33 49 07 93

This leaflet was last revised in {month/YYYY}

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:.

The following information is intended for healthcare professionals only:

Directions for the proper use of Levetiracetam SUN is provided in section 3.

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

Dose	Withdrawal Volume	Volume of Diluent	Infusion 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

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

In use shelf life: from a microbiological point of view, the product should be used immediately after dilution. If not used immediately, in-use storage time and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless dilution has taken place in controlled and validated aseptic conditions.

Levetiracetam SUN concentrate was found to be physically compatible and chemically stable when mixed with the following diluents for at least 24 hours and stored in PVC bags at controlled room temperature 15–25°C.

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