LEVETIRACETAM HIKMA

Package Leaflet: Information for the patient

Levetiracetam Hikma 100 mg/ml concentrate for solution for infusion

Levetiracetam
Generic medicine
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 pharmacist.
• 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, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

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

Levetiracetam Hikma concentrate is an antiepileptic medicine (a medicine used to
treat epileptic seizures).
Levetiracetam Hikma 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 wider areas on both sides of the brain (partial-onset seizures with or without secondary generalization). Levetiracetam has been prescribed by your doctor to reduce the number of seizures.
• As add-on therapy to other antiepileptic medicines to treat:
  o Partial-onset seizures, with or without secondary generalization, in adults, adolescents and children from 4 years of age,
  o Myoclonic seizures (brief, shock-like muscle jerks of a single muscle or muscle group) in adults and adolescents from 12 years of age with juvenile myoclonic epilepsy,
  o Primary generalized tonic-clonic seizures (major seizures including loss of consciousness) in adults and adolescents from 12 years of age with idiopathic generalized epilepsy (the type of epilepsy believed to have a genetic cause).

Levetiracetam Hikma 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 Hikma

Do not use Levetiracetam Hikma

• 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 Hikma.

• If you have kidney problems, follow your doctor's instructions. Your doctor may decide whether the dose needs to be adjusted.
• If you notice slowed growth or unexpected development of puberty in the child, contact your doctor.
• A small number of people taking antiepileptic medicines such as Levetiracetam Hikma have experienced suicidal thoughts or self-harming ideas. If you have any symptoms of depression and/or suicidal thoughts, 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:

• Unusual thoughts, feeling irritable or more aggressive than usual, or if you or your family and friends notice significant changes in mood or behaviour.
• Worsening of epilepsy Seizures may rarely worsen or occur more frequently, mainly during the first month after starting treatment or increasing the dose. In a very rare early-onset form of epilepsy (epilepsy associated with SCN8A mutations), which causes multiple seizure types and loss of skills, you may notice that seizures persist or worsen during treatment.

If you experience any of these new symptoms while being treated with
Levetiracetam Hikma, consult a doctor as soon as possible.
Children and adolescents
Levetiracetam Hikma used alone (monotherapy) is not indicated in children and adolescents under 16
years of age.
Other medicines and Levetiracetam Hikma
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other
medicines, including those without a prescription.
Do not take macrogol (a medicine used as a laxative) within one hour before or one hour after
taking levetiracetam, as it may reduce the effectiveness of levetiracetam.
Pregnancy and breastfeeding
If you are pregnant or breastfeeding, suspect 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.
Two studies do not suggest an increased risk of autism or intellectual disability in children born to mothers treated with levetiracetam during pregnancy. However, available data on the impact of levetiracetam on neurological development in children are limited.
Breastfeeding is not recommended during treatment.
Driving and using machines
Levetiracetam Hikma may reduce your ability to drive or use tools or machinery, as Levetiracetam Hikma may cause drowsiness. This is more likely at the beginning of treatment or after a dose increase. You must not drive or use machinery until you have determined that your ability to perform these activities is not impaired.
Levetiracetam Hikma contains sodium
This medicine contains 19 mg of sodium (the main component of table salt) per vial, equivalent to 0.95% of the maximum daily sodium intake recommended in the adult diet.

3. How to use Levetiracetam Hikma
A doctor or nurse will administer Levetiracetam Hikma to you as an intravenous infusion.
Levetiracetam Hikma must be given 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 between film-coated tablets or oral solution and the intravenous formulation, or vice versa, without adjusting the dose. The total daily dose and frequency of administration remain the same.

Adjunctive therapy and monotherapy (from age 16 onwards)
Adults (≥18 years) and adolescents (12 to 17 years) weighing 50 kg or more:
Typical dose: between 1000 mg and 3000 mg per day.
When starting Levetiracetam Hikma for the first time, your doctor will prescribe a lower dose for 2 weeks before increasing to the lowest maintenance dose.

Dose for children (4 to 11 years) and adolescents (12 to 17 years) weighing less than 50 kg:
Standard 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 Hikma 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 Hikma are provided for doctors and nurses in section 6.

Duration of treatment:

• There is no experience with intravenous administration of levetiracetam for longer than 4 days.

If you stop treatment with Levetiracetam Hikma:
As with any other antiepileptic medicine, Levetiracetam Hikma should be discontinued gradually to avoid an increase in seizures.
If your doctor decides to stop treatment with Levetiracetam Hikma, they will give you specific instructions on how to gradually discontinue the medicine.
If you have any doubts about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
Contact your doctor immediately or go to the nearest emergency room if you experience:

• weakness, dizziness or lightheadedness, or have difficulty breathing, as these may be signs of a severe allergic (anaphylactic) reaction
• swelling of the face, lips, tongue, and throat (Quincke's edema)
• flu-like symptoms and facial rash followed by widespread rash with high fever, elevated liver enzymes observed in blood tests, increased levels of a type of white blood cells (eosinophilia), swollen lymph nodes, and involvement of other organs (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 blistering lesions resembling small targets (dark central spots surrounded by a lighter area, with a dark ring around the edge) (erythema multiforme)
• 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 rash causing skin peeling affecting more than 30% of the body surface (toxic epidermal necrolysis)
• signs of severe mental disturbances, or if someone around you notices confusion, drowsiness, amnesia (memory loss), impaired memory (forgetfulness), abnormal behavior, 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 patients

• nasopharyngitis
• drowsiness, headache

Common: may affect up to 1 in 10 patients

• anorexia (loss of appetite)
• depression, hostility or aggression, anxiety, insomnia, nervousness or irritability
• seizures, balance disorders (imbalance), dizziness (sensation of unsteadiness), lethargy (lack of energy and enthusiasm), tremor (involuntary tremors)
• vertigo (spinning sensation)
• cough
• abdominal pain, diarrhoea, dyspepsia (indigestion), vomiting, nausea
• rash
• asthenia/fatigue (feeling weak)

Uncommon: may affect up to 1 in 100 patients

• decreased platelet count in blood, decreased white blood cell count
• weight loss, weight gain
• suicide attempt and suicidal ideation, mental disorder, abnormal behavior, 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 patients

• infection
• decreased number of all types of blood cells
• severe allergic reactions (DRESS, anaphylactic reaction [severe and significant allergic reaction], Quincke's edema [swelling of face, lips, tongue, and throat])
• reduced sodium concentration in blood (hyponatremia)
• suicide, personality disorder (behavioral problems), thought disturbances (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)
• change in heart rhythm (electrocardiogram abnormalities)
• pancreatitis
• liver failure, hepatitis
• sudden worsening of kidney function
• skin rash that may blister and appear as small targets (central dark spot surrounded by a lighter area, with a dark ring at the edge) (erythema multiforme), widespread rash with blisters and skin peeling, especially 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 levels. 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, 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 patients
repetitive unwanted thoughts or sensations, or an urge to repeatedly perform certain actions (obsessive-compulsive disorder).

Reporting of side effects
If you experience any side effect, 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 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 Hikma

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 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 Hikma contains

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

Description of the appearance of Levetiracetam Hikma and contents of the pack
Levetiracetam Hikma concentrate for solution for infusion is a clear, colourless, sterile liquid.
Levetiracetam Hikma 5 ml concentrate vials are packaged in a cardboard box containing 10 vials.

Marketing Authorisation Holder and Responsible Person for Batch Release
Hikma Farmacêutica (Portugal), S.A.
Estrada do Rio da Mó nº8, 8A, 8B
Fervença
2705-906 Terrugem SNT
Portugal

Selling Agent for Italy
Hikma Italia SpA
Viale Certosa 10
27100 Pavia (Italy)

This medicinal product is authorised in the European Economic Area countries under the following names:
Austria: Levetiracetam Hikma 100 mg/ml, Konzentrat zur Herstellung einer Infusionslösung
France: Lévétiracétam Hikma 100 mg/ml Solution à diluer pour perfusion
Germany: Levetiracetam Hikma 100 mg/ml, Konzentrat zur Herstellung einer Infusionslösung
Italy: Levetiracetam Hikma 100 mg/ml, Concentrato per soluzione per infusione
Portugal: Levetiracetam Hikma 100 mg/ml, Concentrado para solução para perfusão
Spain: Levetiracetam Hikma 100 mg/ml Concentrado para solución para perfusión
United Kingdom: Levetiracetam 100 mg/ml Concentrate for solution for infusion

The following information is intended exclusively for doctors and/or healthcare professionals:

Instructions for the correct use of Levetiracetam Hikma are provided in section 3.
One vial of Levetiracetam Hikma 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 Hikma concentrate to achieve a total daily dose of 500 mg, 1000 mg, 2000 mg, or 3000 mg divided into two doses.
Table 1 - Preparation and administration of Levetiracetam Hikma concentrate

This medicinal product is intended for single use and any unused solution must be discarded.
Shelf life during use: From a microbiological standpoint, the product should be used immediately after dilution. If not used immediately, the duration of storage during use and the conditions prior to use are the responsibility of the user and should normally not exceed 24 hours at room temperature (15–25°C), unless the dilution has been carried out under controlled and validated aseptic conditions.
Levetiracetam Hikma 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 under controlled room temperature conditions 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