Patient leaflet - Ethosuximide Brown & Burk 250 mg/5 ml oral solution

1. What Ethosuximide Brown & Burk is and what it is used for

Ethosuximide Brown & Burk is a medicine for the treatment of epileptic ﬁts (anti-epileptic).

Ethosuximide Brown & Burk is used to treat

Pyknoleptic absences and complex and atypical
absences.
Myoclonic-astatic petit mal and myoclonic ﬁts of
adolescents (impulsive petit mal), if other medicines are not effective and/or are not tolerated.

2. What you need to know before you take Ethosuximide Brown & Burk

Do not take Ethosuximide Brown & Burk

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

Warnings and precautions

Talk to your doctor before taking Ethosuximide Brown & Burk.

If you experience movement disorders (see section 4) do not continue taking Ethosuximide Brown & Burk. 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/mm or a granulocyte ratio of less than 25% the dose should be reduced or Ethosuximide Brown & Burk 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 Brown & Burk 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 Brown & Burk and seek medical attention immediately if you notice any of the symptoms described in section 4.

Other medicines and Ethosuximide Brown & Burk

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

What other medicines affect the efﬁcacy of Ethosuximide Brown & Burk?

In patients also taking carbamazepine (medicine for the treatment of epileptic ﬁts), the plasma clearance (excretion rate) of ethosuximide, the active substance of Ethosuximide Brown & Burk, 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 mutually potentiate their sedative (calming and sleep inducing) effects.

The efﬁcacy of what other medicines is affected by Ethosuximide Brown & Burk?

Ethosuximide, the active substance of Ethosuximide

Brown & Burk, 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.

Ethosuximide Brown & Burk with alcohol

Alcohol can change and potentiate the effects of Ethosuximide Brown & Burk in an unforeseeable manner.

Do not drink alcohol or consume alcohol-containing food while you take Ethosuximide Brown & Burk!

Pregnancy and breast-feeding

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 Brown & Burk. Do not discontinue Ethosuximide Brown & Burk 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 α-fetoprotein are recommended for the early detection of foetal damage.

The lowest effective ethosuximide dose ensuring seizure control must not be exceeded, particularly

th th during the 20 and 40 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 Brown & Burk.

Driving and using machines

Ethosuximide Brown & Burk 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.

Ethosuximide Brown & Burk contains sodium benzoate (E211), propylene glycol (E1520) and Sodium

This medicine contains 2.50 mg sodium benzoate (E211) in each 5 mL oral solution which is equivalent to 0.5 mg/mL. Sodium benzoate (E211) may increase jaundice (yellowing of the skin and eyes) in newborn babies (up to 4 weeks old).

This medicine contains 2.40 mg – 2.85 mg propylene glycol (E1520) in each 5 mL oral solution which is equivalent to 0.48 mg/mL – 0.57 mg/mL. If your baby is less than 4 weeks old, talk to your doctor or pharmacist before giving them this medicine, in particular if the baby is given other medicines that contain propylene glycol or alcohol.

This medicine contains less than 1 mmol sodium (23 mg) per 5 mL oral solution, this is to say essentially 'sodium-free'.

3. How to take Ethosuximide Brown & Burk

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

Shake the bottle vigorously before you measure your dose. The pack contains a graduated measuring cup. Use the measuring cup to take the dose prescribed by your doctor. Wash and dry the measuring cup after each use.

Dosage

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 (10 mL). Depending on the patient's tolerance, the dose is increased every ﬁve to seven days in increments of max. 250 mg (5 mL) until the ﬁts are controlled by a daily dose of 1000-1500 mg (20-30 mL).

In an individual case, a daily dose of 2000 mg (40 mL), taken in several single doses, may be required. The therapeutic plasma level of ethosuximide is normally between 40 and 100 μg/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 Brown & Burk 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 under 2 years: The treatment is started at a daily dose of 125 mg (2.5 mL). The dose is increased gradually in small increments every few days until the ﬁts are controlled.

Children between 2 and 6 years of age: The treatment is started at a daily dose of 250 mg (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 (20 mL).

Method of administration

Ethosuximide Brown & Burk is for oral use. The solution can be taken during or after meals.

How long to take Ethosuximide Brown & Burk 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 Brown & Burk are determined by a specialist with experience in the treatment of epilepsy.

If you take more Ethosuximide Brown & Burk than you should

If by mistake you have taken a double dose Ethosuximide Brown & Burk, do not change your dosage regimen, but continue taking Ethosuximide Brown & Burk 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 μg 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.

If you forget to take Ethosuximide Brown & Burk

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 Brown & Burk will control your state safely and appropriately only when taken regularly!

If you stop taking Ethosuximide Brown & Burk

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 Brown & Burk, please contact your doctor!

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 too, although not everybody gets them.

Serious side effects

Stop using Ethosuximide Brown & Burk 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.
Other side-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 Brown & Burk is taken again.

Note:

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

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 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.

5. How to store Ethosuximide Brown & Burk

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

This medicinal product does not require any special storage conditions

Do not use this medicine after the expiry date which is stamped on the carton after EXP. The expiry date refers to the last day of that month.

After ﬁrst opening, use within 90 days.

Do not throw away medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Ethosuximide Brown & Burk oral solution contains

The active ingredient is ethosuximide

Each 5 mL dose contains 250 mg of ethosuximide The other ingredients are sodium benzoate, glycerol, sucralose, ﬂavadew caramel (contains propylene glycol), citric acid monohydrate, sodium citrate, puriﬁed water.

What Ethosuximide Brown & Burk oral solution looks like and contents of the pack

Ethosuximide 250 mg/5 mL oral solution is a clear colourless solution with characteristic caramel odour. Ethosuximide oral solution is available in 200 mL amber glass bottle with a child-resistant polypropylene cap. The pack contains a graduated measuring cup.

Marketing Authorisation Holder

Brown & Burk UK Limited,

Micro House, Bury Street,

Ruislip, HA4 7TL,

United Kingdom

Manufacturer