Ethosuximide Neuraxpharm 500 mg/5 ml oral solution 100 mg/ml

• 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.

1. What Ethosuximide Neuraxpharm 500 mg/5 ml oral solution is and what it is used for
2. What you need to know before you take Ethosuximide Neuraxpharm 500 mg/5 ml oral solution
3. How to take Ethosuximide Neuraxpharm 500 mg/5 ml oral solution
4. Possible side effects
5. How to store Ethosuximide Neuraxpharm 500 mg/5 ml oral solution
6. Contents of the pack and other information

• if you are allergic to ethosuximide, other succinimides (group of medicines to which ethosuximide belongs) or any of the other ingredients of this medicine (listed in section 6).

Talk to your doctor before taking Ethosuximide Neuraxpharm 500 mg/5 ml oral solution.

If you experience movement disorders (see section 4) do not continue taking Ethosuximide Neuraxpharm 500 mg/5 ml oral solution. Please, contact the nearest doctor who, in the event of significant disturbances, can administer diphenhydramine as an antidote by the intravenous route.

Pay special attention to symptoms of bone marrow depression such as fever, inflammation of throat or pharynx tonsils as well as haemorrhagic tendency, and consult your doctor, if you experience any of these symptoms.

The blood count should be checked regularly (initially monthly, after one year every six months) to identify potential injury of the medulla. At a leucocyte count (number of white blood cells) of less than 3500/mm³ or a granulocyte ratio of less than 25 % the dose should be reduced or Ethosuximide 500 mg/5 ml discontinued completely. The liver enzymes should also be checked regularly.

Psychic side effects (anxiety, illusion) can occur in particular in patients with a history of psychiatric disorders. Special caution is required when Ethosuximide Neuraxpharm 500 mg/5 ml is administered to this group of patients.

A small number of patients treated with anti-epileptics such as ethosuximide have developed thoughts about self-harm or suicidal thoughts. If at any time during the treatment you have such thoughts, tell your doctor immediately.

Note:

To prevent grand mals which are often associated with complex and atypical absences, ethosuximide can be combined with effective anti-epileptics (e.g. primidone or phenobarbital). Additional grand mal prophylaxis can be dispensed with only in the case of pyknoleptic absence epilepsies in children of school age.

Serious skin reactions including Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported in association with ethosuximide treatment. Stop using Ethosuximide 500 mg/5 ml and seek medical attention immediately if you notice any of the symptoms described in section 4.

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

What other medicines affect the efficacy of Ethosuximide Neuraxpharm 500 mg/5 ml oral solution?

In patients also taking carbamazepine (medicine for the treatment of epileptic fits), the plasma clearance (excretion rate) of ethosuximide, the active substance of Ethosuximide 500 mg/5 ml oral solution, may be elevated. In patients taking valproic acid (medicine for the treatment of epileptic fits), the concentration of ethosuximide in blood may rise.

It cannot be excluded that CNS depressants and Ethosuximide Neuraxpharm 500 mg/5 ml oral solution mutually potentiate their sedative (calming and sleep inducing) effects.

The efficacy of what other medicines is affected by Ethosuximide Neuraxpharm 500 mg/5 ml oral solution?

Ethosuximide, the active substance of Ethosuximide Neuraxpharm 500 mg/5 ml oral solution, normally does not change the concentration of other medicines for the treatment of epileptic fits (e.g. primidone, phenobarbital, phenytoin) in blood. In individual cases the phenytoin level in blood may rise, however.

Alcohol can change and potentiate the effects of Ethosuximide Neuraxpharm 500 mg/5 ml oral solution in an unforeseeable manner.

Do not drink alcohol or consume alcohol-containing food while you take Ethosuximide Neuraxpharm 500 mg/5 ml oral solution!

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

If you are of childbearing age, you should be advised by your doctor regarding the necessity of planning and monitoring any pregnancy before starting the treatment with Ethosuximide 500 mg/5 ml oral solution. Do not discontinue Ethosuximide Neuraxpharm 500 mg/5 ml oral solution without first consulting your doctor as epileptic seizures might recur, which could harm you and/or your unborn child.

No specific malformations of babies are known, which were caused by the treatment with ethosuximide. However, patients treated with medicines against epileptic seizures generally have a higher risk for malformations than other women. The most commonly reported malformations are cleft lip, cardiovascular malformation and neural tube defects (spina bifida). This risk is even higher in patients treated with more than one anti-epileptic, and therefore combination treatment should be avoided during pregnancy.

Prenatal diagnostic measures like high level ultrasound and the determination of -fetoprotein are recommended for the early detection of foetal damage.

The lowest effective ethosuximide dose ensuring seizure control must not be exceeded, particularly during the 20^th and 40^th day of pregnancy. Your ethosuximide serum concentration must be checked regularly. You should take extra folic acid, if you are planning to have a baby or if you are pregnant.

To prevent vitamin K1 deficiency in your baby and bleeding caused by this deficiency, you should also be given vitamin K1 during the last month of your pregnancy.

Breast-feeding

Ethosuximide passes into breast milk and might lead to sedation, poor suckling and irritability in breast-fed infants. Therefore, you should stop breast-feeding during treatment with Ethosuximide 500 mg/5 ml oral solution.

Ethosuximide Neuraxpharm 500 mg/5 ml oral solution can impair reactivity. Therefore, the following should be considered throughout the treatment period, in particular, however, during the adjustment phase: You are not able to respond quickly and purposefully to unexpected and sudden events. Do not drive cars or other vehicles! Do not operate dangerous electric tools or machines! Do not work without a secure hold!

The decision about whether you are able to drive and use machines will be taken in each case by your doctor considering your individual response to the medicine.

Be advised that alcohol further impairs your driving capacity.

This medicine contains less than 1 mmol sodium (23 mg) per 5 ml, that is to say essentially ‘sodium-free’.

The dosing syringe provided has only been demonstrated to deliver doses accurately starting at 250 mg. For starting doses of 125 mg, the 250 mg/5 mL strength is recommended. .

Unless otherwise prescribed by your doctor, the recommended dose is:

Adults, elderly patients and children over 6 years of age: The treatment is started at a daily dose of 500 mg (5 ml). Depending on the patient’s tolerance, the dose is increased every five to seven days in increments of max. 250 mg (2.5 ml) until the fits are controlled by a daily dose of 1000-1500 mg (10-15 ml). In an individual case, a daily dose of 2000 mg (20 ml), taken in several single doses, may be required.

The therapeutic plasma level of ethosuximide is normally between 40 and 100 mcg/ml. However, the dose depends on the patient’s clinical response. The half-life of ethosuximide in plasma is more than 24 hours so that the daily dose can be taken as a single dose provided the medicine is well tolerated. Higher daily doses should be taken in 2 or 3 single doses, however.

The decision about changes to the dosage regimen can be taken by your doctor only.

The risk of side effects which depend on the dose taken can be reduced by taking small initial doses of Ethosuximide 500 mg/5 ml oral solution and increasing them gradually to optimum amounts (increasing the amounts slowly from day to day) and by taking them during or after meals.

Haemodialysis patients

Ethosuximide is dialysable. Haemodialysis patients therefore require a supplementary dose or a modified dosage regimen. During a dialysis period of four hours, 39 % to 52 % of the dose taken is removed.

Children and adolescents

Children between 2 and 6 years of age: The treatment is started at a daily dose of 250 mg (2.5 ml). The dose is increased gradually in small increments every few days until the fits are controlled.

The optimum daily dose for most children is 20 mg/kg. The maximum dose is 1000 mg (10 ml).

• The pack contains a graduated oral syringe (0.5 ml steps) and an adapter for the oral syringe.
• Opening of the bottle: Turn the screw cap anti-clockwise.
• Insert the adapter in the bottle neck (Fig. 1). Make sure that the adapter is tightly fitted.
• Insert the oral syringe in the opening of the adapter (Fig. 1).
• Turn the bottle upside down (Fig. 2).
• Transfer a small amount of the solution into the syringe by pulling out the piston a short distance (Fig. 3A). Push the piston back to remove any air bubbles (Fig. 3B). Now pull the piston as far as to the millilitre (ml) level corresponding to the dose prescribed by your doctor (Fig. 3C).
• Place the bottle in upright position. Remove the syringe from the adapter.
• Transfer the content of the syringe into a glass of water by pushing the piston into the syringe as far as to stop position (Fig. 4). The dose can also be mixed with milk pudding.
• Drink up the glass.
• Alternatively, the drug dose can directly be applied into the mouth. The patient should sit upright and the syringe piston should slowly be pressed into the syringe so that the patient can swallow well (Fig. 5). After having taken the medicine, the patient should drink half a glass of water.
• Rinse the syringe using water only (Fig. 6).
• Close the bottle with the screw cap.

How long to take Ethosuximide Neuraxpharm 500 mg/5 ml oral solution

The treatment of epileptic fits is principally a long-term treatment.

The dose, the distribution of the daily dose, the duration of treatment and discontinuation of Ethosuximide 500 mg/5 ml oral solution are determined by a specialist with experience in the treatment of epilepsy.

If by mistake you have taken a double dose Ethosuximide Neuraxpharm 500 mg/5 ml oral solution, do not change your dosage regimen, but continue taking Ethosuximide Neuraxpharm 500 mg/5 ml oral solution as prescribed. Significantly higher doses potentiate effects such as tiredness, lethargy (lack of drive, apathy), depressive states and states of agitation, in some cases also irritability as well as any other side effects depending on the quantity taken (overdose effects may occur at concentrations over 150 mcg ethosuximide per ml blood).

Overdose symptoms are potentiated by alcohol and other CNS depressants.

If any of these symptoms occur, contact the nearest doctor and, if possible, present the medicine taken and the package leaflet.

If a significant overdose was taken, the doctor will perform gastric lavage and administer medicinal charcoal. Monitoring of the cardiovascular and respiratory systems in an intensive care unit is required.

Do not take a double dose to make up for the forgotten dose.

Normally no symptoms will appear when you forgot to take a single dose. Continue taking the medicine as prescribed, i.e. do not take the forgotten dose at a later time. Be advised, however, that Ethosuximide 500 mg/5 ml oral solution will control your state safely and appropriately only when taken regularly!

If you wish to discontinue the treatment, talk to your doctor first. Do not stop taking the medicine without checking with your doctor, as this may jeopardise the success of the treatment.

Strictly follow the treatment recommendations of your doctor, as otherwise you may have again epileptic fits! If you think that you do not tolerate Ethosuximide 500 mg/5 ml oral solution, please contact your doctor!

Stop using Ethosuximide 500 mg/5 ml oral solution and seek medical attention immediately if you notice any of the following symptoms:

• Reddish patches on the trunk, the patches are target-like macules or circular, often with central blisters, skin peeling, ulcers of mouth, throat, nose, genitals and eyes. These serious skin rashes can be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome).
• Widespread rash, high body temperature and enlarged lymph nodes (drug reaction with eosinophilia and systemic symptoms (DRESS)).

Seek medical attention if you notice any of the following symptoms:

• Changes in your blood (bruising or bleeding more easily, fever, sore throat, mouth ulcers, fatigue, repeated infections or infections that will not go away). Your doctor may take regular blood samples to test for these effects.

Common (may affect up to 1 in 10 patients) to very common (may affect more than 1 in 10 patients):

• Nausea, vomiting, hiccup and abdominal pain.

Uncommon (may affect up to 1 in 100 patients):

• Severe headache, sleep disturbances, lethargy (lack of drive, apathy), ataxia (movement disorders)
• Withdrawal, anxiety
• Loss of appetite, loss of weight
• Diarrhoea, constipation

Rare (may affect up to 1 in 1000 patients):

• Paranoid and hallucinatory phenomena developing over days and weeks (illusion, persecution complex)
• Lupus erythematodes* of varying extent (skin disease that may involve internal organs)
• Leucopenia* (shortage of white blood cells), eosinophilia* (increase of a certain type of white blood cells), thrombocytopenia* (shortage of blood platelets) or agranulocytosis* (absence of certain defensive cells)

Not known (frequency cannot be estimated from the available data):

• In individual cases dyskinesias (movement disorders, see section 2) may occur during the first 12 hours of the treatment
• Allergic skin reactions* such as rash, Stevens-Johnson syndrome (very severe allergic skin reaction) or DRESS (drug reaction with eosinophilia and systemic symptoms)
• In individual cases aplastic anaemia* (shortage of red blood cells due to failure of body to produce new cells) and pancytopenia* (shortage of all blood cells) may occur (see section 2).

* Side effects which are independent of the dose of the medicine.

If side effects occur which are independent of the dose taken, the medicine is usually discontinued and the side effects disappear. They may reappear when Ethosuximide 500 mg/5 ml oral solution is taken again.

Note:

Long-term treatment may affect the patient’s performance, e.g. the performance in school of children and adolescents.

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 Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects, you can help provide more information on the safety of this medicine.

• The active substance is ethosuximide. 1 ml oral solution contains 100 mg ethosuximide
• The other ingredients are sodium citrate dihydrate, citric acid monohydrate, saccharin sodium, hypromellose, strawberry flavour, sweet boster (50SW10) and purified water.

Ethosuximide Neuraxpharm 500 mg/5 ml oral solution is a clear, colourless to slightly yellow solution.

Ethosuximide Neuraxpharm 500 mg/5 ml oral solution is presented in amber glass bottles with a child resistant screw cap and a dosing syringe with adapter.

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