ESTIRIPENTOL BILLEV 250 mg ORAL SUSPENSION POWDER IN SACHETS

2. What you need to know before your child starts taking Estiripentol Billev

Do not give Estiripentol Billev to your child if:

• your child is allergic to estiripentol or any of the other ingredients of this medicine (listed in section 6);
• your child has ever suffered from delirium (a mental state with confusion, emotion, restlessness, and hallucinations).

Warnings and precautions

Consult your child's doctor or pharmacist before giving your child Estiripentol Billev:

• Your child's liver function should be evaluated before starting treatment with estiripentol and checked every 6 months.
• Your child's blood count should be evaluated before starting treatment with estiripentol and checked every 6 months.
• Your child's growth rate should be carefully monitored due to gastrointestinal side effects with estiripentol, clobazam, and valproate, such as anorexia, loss of appetite, and vomiting.

Other medicines and Estiripentol Billev

Tell your child's doctor or pharmacist if your child is taking, has recently taken, or might take any other medicines.

Inform your child's doctor if your child is taking any of the following medicines:

• medicines containing:
  • cisapride (used to treat symptoms of nocturnal pyrosis);
  • pimozide (used to treat symptoms of Tourette's syndrome: vocal tics and repeated, uncontrolled body movements);
  • ergotamine (used to treat migraine);
  • dihydroergotamine (used to relieve signs and symptoms of reduced mental capacity due to the aging process);
  • halofantrine (an antimalarial drug);
  • quinidine (used to treat heart rhythm disorders);
  • bepridil (used to control chest pain);
  • ciclosporin, tacrolimus, sirolimus (all used to prevent rejection in liver, kidney, and heart transplants);
  • statins (simvastatin and atorvastatin, both used to reduce blood cholesterol levels).
  • antiepileptic medicines containing:

phenobarbital, primidone, phenytoin, carbamazepine, diazepam.

• medicines containing:

midazolam or triazolam (medicines used to reduce anxiety and insomnia – combined with estiripentol, they can cause significant drowsiness in your child);

chlorpromazine (used for mental illnesses such as psychosis).

• If your child is taking medicines containing:
  • caffeine (these substances help to restore mental alertness) or theophylline (this substance is used in case of asthma). Their combination with estiripentol should be avoided, as it can increase their blood levels, leading to digestive disorders, increased heart rate, and insomnia.

• If your child is taking medicines metabolized by certain liver enzymes:
  • citalopram (used to treat episodes of depression);
  • omeprazole (used for gastric ulcers);
  • HIV protease inhibitors (used to treat HIV);
  • astemizole, chlorphenamine (antihistamines);
  • calcium channel blockers (used to treat angina or heart rhythm problems);
  • oral contraceptives;
  • propranolol, carvedilol, timolol (used to treat high blood pressure);
  • fluoxetine, paroxetine, sertraline, imipramine, clomipramine (antidepressants);
  • haloperidol (antipsychotic);
  • codeine, dextromethorphan, tramadol (used to treat pain).

Taking Estiripentol Billev with food and drinks

Do not take estiripentol with milk or dairy products (yogurt, creamy cheeses, etc.), fruit juices, fizzy drinks, or foods and drinks containing caffeine or theophylline (e.g., cola, chocolate, coffee, tea, or energy drinks).

Pregnancy and breastfeeding

If your daughter is pregnant or breastfeeding, thinks she may be pregnant, or plans to become pregnant, consult her doctor before taking this medicine.

During pregnancy, antiepileptic treatment should not be interrupted.

Breastfeeding is not recommended during treatment with this medicine.

Driving and using machines

This medicine can cause drowsiness in your child.

Your child should not operate tools or machines or drive if they are affected in this way. Consult your child's doctor.

Estiripentol Billev containssucrose,aspartame (E951), benzyl alcoholand sodium

• Sucrose: If your doctor has told you that your child has an intolerance to some sugars, consult with them before giving this medicine.
• Aspartame (E 951): this medicine contains 2.5 mg of aspartame in each 250 mg sachet and 5 mg in each 500 mg sachet. Aspartame is a source of phenylalanine that may be harmful in people with phenylketonuria (PKU), a rare genetic disorder in which phenylalanine accumulates because the body cannot eliminate it properly.
• This medicine contains a fragrance with benzyl alcohol. Benzyl alcohol may cause allergic reactions.
• Sodium: this medicine contains less than 1 mmol of sodium (23 mg) per sachet; it is essentially "sodium-free".

3. How to take Estiripentol Billev

Your child should take this sachet exactly as their doctor has told them. If they are unsure, they should consult their doctor or pharmacist again.

Dose

The doctor will adjust the dose according to your child's age, weight, and condition, usually 50 mg per day per kilogram of body weight.

When to take Estiripentol Billev

Your child should take this medicine two or three times a day at regular intervals as indicated by their doctor: for example, in the mornings, at noon, and at bedtime to cover the night and daytime periods.

Dose adjustment

Dose increases should be gradual, replacing, over several weeks, the doses of the other antiepileptic medicines, which will be reduced at the same time. Your child's doctor will inform you of the new dose of the other antiepileptic medicines.

If you think that the effect of this medicine is too strong or too weak, consult your child's doctor or pharmacist. The doctor will adjust the dose according to your child's condition.

If your child experiences side effects, consult their doctor, as it may be necessary to adjust the dose of this medicine and the other antiepileptic medicines.

There are slight differences between the capsules and the powder for oral suspension of Estiripentol Billev. Please consult your child's doctor if they experience any problems when switching from the capsules to the powder for oral suspension or vice versa. If switching between the capsule and powder formulations, it should be done under the strict supervision of your child's doctor.

In case of vomiting in the first minutes after taking the medicine, it is considered that the medicine has not been absorbed and a new dose should be given.

However, the situation changes if the vomiting occurs more than an hour after taking the medicine, as estiripentol is rapidly absorbed.

If this is the case, it is considered that a significant fraction of the administered dose has been systemically absorbed in the digestive tract. Therefore, there will be no need to take a new dose to adjust the next dose.

How to take the Estiripentol Billev powder

The powder should be dissolved in a glass of water and taken immediately after dissolution during a meal. Your child should take Estiripentol Billev with food and not on an empty stomach. To know which foods and drinks to avoid, see the previous section "Taking Estiripentol Billev with food and drinks".

If your child takes more Estiripentol Billev than they should

Consult your child's doctor if you know or think that your child has taken more of the medicine than they should.

In case of overdose or accidental ingestion, consult your child's doctor or pharmacist immediately or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medicine and the amount ingested.

If your child forgets to take Estiripentol Billev

It is important that your child takes this medicine regularly at the same time every day. If your child forgets to take a dose, they should take it as soon as you remember, unless it is time for the next dose. In that case, continue with the next dose as usual. Your child should not take a double dose to make up for forgotten doses.

If your child stops taking Estiripentol Billev

Your child should not stoptaking this medicine unless their doctor tells them to. Stopping treatment can cause a seizure crisis.

If you have any other questions about the use of this medicine, ask your child's doctor or pharmacist.

4. Possible side effects

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

Very common side effects(may affect more than 1 in 10 people):

• loss of appetite, weight loss (especially in combination with the antiepileptic medicine valproate sodium);
• insomnia, drowsiness;
• ataxia (inability to coordinate muscle movements), hypotonia (low muscle strength), dystonia (involuntary muscle contractions).

Common side effects(may affect up to 1 in 10 people):

• increased liver enzyme levels, especially when administered with the antiepileptic medicines carbamazepine or valproate sodium;
• aggression, irritability, agitation, hyperexcitability (state of unusual excitability);
• sleep disorders (sleep anomalies);
• hyperkinesia (exaggerated movements);
• nausea, vomiting;
• low number of a type of white blood cell.

Uncommon side effects(may affect up to 1 in 100 people):

• double vision when used with the antiepileptic medicine carbamazepine;
• photosensitivity;
• rash, skin allergy, urticaria (skin inflammation with a pink tone and accompanied by itching);
• fatigue (tiredness).

Rare side effects(may affect up to 1 in 1,000 people):

• decrease in blood platelet count;
• abnormal liver function test.

To eliminate these side effects, your child's doctor may need to adjust the dose of estiripentol or one of the other prescribed medicines.

Reporting of side effects

If your child experiences any side effects, consult their doctor or pharmacist, even if they are not listed in this leaflet. You can also report side effects directly through the Spanish Medicines Monitoring System: https://www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Estiripentol Billev

Keep this medicine out of the sight and reach of children.

Do not give this medicine to your child after the expiry date stated on the label and carton. The expiry date is the last day of the month stated.

Store in the original packaging to protect from light. This medicine does not require any special storage temperature.

Medicines should not be disposed of via wastewater or household waste. Return the containers and any unused medicines to the pharmacy's SIGRE point. If you are unsure, ask your pharmacist how to dispose of the containers and any unused medicines. This will help protect the environment.

6. Contents of the pack and further information

Composition of Estiripentol Billev

• The active substance is estiripentol.

Estiripentol Billev 250 mg: each sachet contains 250 mg of estiripentol.

Estiripentol Billev 500 mg: each sachet contains 500 mg of estiripentol.

• The other ingredients are:

Sachet contents: sodium carboxymethyl starch type A, povidone K30, sodium lauryl sulfate, and magnesium stearate, sodium croscarmellose, hydroxyethyl cellulose, sucrose, aspartame (E951), titanium dioxide (E171), tutti frutti flavor [contains propylene glycol (E1520), benzyl alcohol], erythrosine (E127).

Appearance and packaging

Estiripentol Billev is a light pink crystalline powder for oral suspension packaged in sachets.

Estiripentol Billev is supplied in cartons containing 30, 60, or 90 sachets.

Not all pack sizes may be marketed.

Estiripentol Billev is also available in the form of hard capsules of 250 mg and 500 mg.

Marketing authorization holder

Billev Pharma ApS

Slotsmarken 10

2970 Hoersholm

Denmark

Manufacturer

Misom Labs Limited

Malta Life Sciences Park

LS2.01.06, Industrial Estate

San Gwann

SGN 3000

Malta

Date of last revision of this leaflet:05/2024

Detailed information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS): http://www.aemps.gob.es/.