Levetiracetam Sun

Package leaflet: Information for the user

Levetiracetam SUN 100 mg/mL concentrate for solution for infusion

levetiracetam
Please read all of this leaflet carefully before you or your child starts 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, ask your doctor or nurse.
• If you get any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

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

Levetiracetam SUN concentrate is an antiepileptic medicine (a medicine used to treat epileptic seizures).
Levetiracetam SUN 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 begins 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 seizures.
• in combination with other antiepileptic medicines (as adjunctive therapy) 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 muscle group) in adults and adolescents aged 12 years and older with juvenile myoclonic epilepsy
  • primary generalized tonic-clonic seizures (major 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 SUN concentrate for solution for infusion may be used when oral administration of levetiracetam is temporarily not possible.

2. What you need to know before using 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 using Levetiracetam SUN

• 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 the child, contact your doctor.
• A small number of people taking antiepileptic medicines such as Levetiracetam SUN have experienced self-harming thoughts or suicidal ideation. If you experience any symptoms of depression and/or have thoughts about suicide, contact your doctor.
• If you or a family member has a heart rhythm disorder (visible on electrocardiogram), or if you have a disease and/or are taking medicines that may cause irregular heartbeats or electrolyte imbalances.

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

• abnormal thoughts, feeling irritable, or more aggressive reactions than usual, or if you, your family, or friends notice the onset of significant changes in mood or behavior
• 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 skills, you may find that seizures persist or worsen during treatment.

If you experience any of these new symptoms while being treated with Levetiracetam SUN, consult a doctor as soon as possible.
Children and adolescents
Levetiracetam SUN used alone (monotherapy) is not indicated in children and adolescents under 16 years of age.
Other medicines and Levetiracetam SUN
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) within one hour before or one hour after taking levetiracetam, as it may cause a loss of effectiveness of levetiracetam.
Pregnancy and breastfeeding
If you are pregnant, breastfeeding, think you may be pregnant, or are planning to have a baby, consult your doctor 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 in the unborn child cannot be completely ruled out.
Breastfeeding is not recommended during treatment.
Driving and using machines
Levetiracetam SUN may reduce your ability to drive vehicles or operate tools or machinery, as it may cause drowsiness. This is more likely at the beginning of treatment or after a dose increase. You must not drive or operate machinery until you are certain that your ability to perform these activities is not impaired.
Levetiracetam SUN contains sodium
The excipients include sodium acetate trihydrate, glacial acetic acid, sodium chloride, and water for injections. A single maximum dose of concentrated Levetiracetam SUN 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 for patients on a low-sodium diet.

3. How to use Levetiracetam SUN

A doctor or nurse will administer Levetiracetam SUN to you as an intravenous infusion.
Levetiracetam SUN should 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. Switching from one formulation to the other can be done without changing the dose. 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:
When starting Levetiracetam SUN for the first time, your doctor will prescribe a lower dose for 2 weeks before increasing to the lowest daily dose.
Recommended dose: between 1,000 mg and 3,000 mg per day.
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 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.
More detailed instructions for appropriate use of Levetiracetam SUN are provided for doctors and nurses in section 6.
Duration of treatment
There is no experience with intravenous administration of levetiracetam for periods longer than 4 days.
If you stop treatment with Levetiracetam SUN
As with any other antiepileptic medicine, Levetiracetam SUN should be discontinued gradually to avoid an increase in seizures.
If your doctor decides to stop treatment with Levetiracetam SUN, they will provide you with instructions on how to gradually discontinue the medicine.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Contact your doctor immediately or go to the nearest emergency room 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, also known as Quincke's oedema)
• flu-like symptoms and a rash on the face followed by widespread rash with high fever, increased liver enzyme levels observed 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 worsening of kidney function
• a skin rash that may appear as blisters resembling small targets (dark spots in the center surrounded by a lighter area, with a dark ring around the edge) (erythema multiforme)
• a widespread rash with blisters 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 (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 uncontrolled 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, restlessness or irritability
• seizures, balance disorders, dizziness (feeling unsteady), lethargy (lack of energy and enthusiasm), tremor (involuntary shaking)
• 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
• suicide attempt and suicidal thoughts, mental disorder, abnormal behaviour, hallucinations, anger, confusion, panic attack, emotional lability/mood swings, agitation
• amnesia (memory loss), memory impairment (forgetfulness), abnormal coordination/ataxia (impaired motor coordination), paraesthesia (tingling sensations), attention disturbance (loss of concentration)
• diplopia (double vision), blurred vision
• elevated/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 serious allergic reaction], angioedema [swelling of face, lips, tongue, and throat])
• decreased concentration of sodium in the blood
• suicide, personality disorder (behavioural problems), disturbances in thinking (slowed thinking, inability to concentrate)
• delirium
• encephalopathy (see the section “Contact your doctor immediately” 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 worsening of kidney function
• skin rash that may appear as blisters resembling small targets (dark spots in the center surrounded by a lighter area, with a dark ring around the edge) (erythema multiforme), a widespread rash with blisters and skin peeling, 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 (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 or difficulty walking
• combination of fever, muscle rigidity, unstable blood pressure and heart rate, confusion, and 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 urges to perform actions repeatedly (obsessive-compulsive disorder)

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex 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 bottle and
on the carton after EXP. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.

6. Package contents and other information

What Levetiracetam SUN contains

• The active substance is called 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 SUN 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 packaged in a cardboard box containing 10 vials of 5 mL each.

Marketing Authorisation Holder and Manufacturer
Sun Pharmaceutical Industries Europe B.V.
Polarisavenue 87
2132 JH Hoofddorp
The Netherlands

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder.

België/Belgique/Belgien/България/Česká republika/
Danmark/Eesti/Ελλάδα/Ireland/Ísland/
Κύπρος/Latvija/Lietuva/Luxembourg/Luxemburg/Magyarország/
Malta/Nederland/Norge/Österreich/Portugal/
Slovenská republika/Suomi/Finland/Sverige
Sun Pharmaceutical Industries Europe B.V.
Polarisavenue 87
2132 JH Hoofddorp
Nederland/Pays-Bas/Niederlande/Нидерландия/Nizozemsko/
Nederlandene/Holland/Ολλανδία/The Netherlands/Holland/
Ολλανδία/Nīderlande/Nyderlandai/Pays-Bas/Niederlande/Hollandia/
L-Olanda/Nederland/Nederland/Niederlande/Países Baixos/
Holandsko/Alankomaat/Nederländerna/Nederländerna
Tel./тел./tlf./τηλ./Sími/τηλ./Tlf./Puh./
+31 (0)23 568 5501

Deutschland Polska
Sun Pharmaceuticals Germany GmbH Ranbaxy (Poland) Sp. Z o. o.
Hemmelrather Weg 201 ul. Kubickiego 11
51377 Leverkusen 02-954 Warszawa
Germany Poland
Tel. +49 214 403 99 0 tel. +48 22 642 07 75

Basics GmbH România
Hemmelrather Weg 201 Terapia S.A.
51377 Leverkusen Str. Fabricii nr 124
Germany Cluj-Napoca, Judeţul Cluj
Tel. +49 214 403 99 0 Romania
tel. +40 (264) 501 500

España
Sun Pharma Laboratorios, S.L. Slovenija
Rambla de Catalunya 53-55 Lenis farmacevtika d.o.o.
08007 Barcelona Litostrojska cesta 52
Spain 1000 Ljubljana
tel. +34 93 342 78 90 Slovenia
tel. +386 (0)1 235 07 00

France
Sun Pharma France United Kingdom (Northern Ireland)
11-15, Quai Dion Bouton Ranbaxy UK Ltd
92800 Puteaux a Sun Pharma Company
France Millington Road 11
tel. +33 (0) 1 41 44 44 50 Hyde Park, Hayes 3
5 Floor
Hrvatska UB3 4AZ HAYES
Medicopharmacia d.o.o. United Kingdom
Ulica Pere Budmanija 5 tel. +44 (0) 208 848 8688
10000 Zagreb
Croatia
tel. +385 1 5584 604

Italia
Sun Pharma Italia Srl
Viale Giulio Richard, 1
20143 Milano
Italy
tel. +39 02 33 49 07 93

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu/

The following information is intended exclusively for healthcare professionals:

Instructions for the correct use of Levetiracetam SUN are provided in section 3.
A vial of Levetiracetam SUN 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 SUN 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 SUN concentrate.

This medicinal product is intended for single use and any unused solution must be discarded.
In-use shelf life: From a microbiological point of view, the product should be used immediately after dilution. If not used immediately, the in-use storage time and conditions prior to use are the responsibility of the user and should normally 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 SUN concentrate has been shown to be physically and chemically compatible and stable for at least 24 hours when mixed with the following diluents and stored in PVC bags at a controlled room temperature of 15–25°C.
Diluents:

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