ETHOSUXIMIDE NEURAXPHARM

Posology Pay attention to the strength of Ethosuximide. Dosage errors in the use of this medicinal product can result in serious adverse reactions. Please read this section of the summary of product characteristics very carefully.

Adults, elderly patients and children over 6 years of age:

The treatment is started at a daily dose of 500 mg. Depending on the patient’s tolerance, the dose is increased every five to seven days in increments of max. 250 mg until the seizures are controlled by a daily dose of 1000-1500 mg. In an individual case, a daily dose of 2000 mg, 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 medicinal product is well tolerated.

Higher daily doses should be taken in 2 or 3 single doses, however. The probability of dose-dependent undesirable effects can be reduced by careful dosing (small initial dose at the start of the treatment, gradual increase of dose) and by taking the medicinal product during or after meals.

Anti-epileptic therapies are principally long-term therapies. A specialist (neurologist, neuropaediatrician) should decide about the start, duration and discontinuation of ethosuximide on an individual basis. In general, reduction of the dose and discontinuation of the medicinal product should not be considered before the patient has been free from fits for 2-3 years.

The medicinal product must be discontinued by reducing the dose gradually over a period of one to two years. Children may be allowed to outgrow the dose per kg body weight instead of adjusting the dose according to their age, however, it must be ensured that the EEC findings do not deteriorate.

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

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 daily dose is 1000 mg. 1. Method of administration Ethosuximide Neuraxpharm 500 mg/5 ml oral solution is for oral use.

4). Within the therapeutic dose range undesirable effects are common and have been observed in about 1/6 of patients. These are mainly nausea, vomiting, singultus and abdominal pain. Tabulated list of adverse reactions The frequency of possible undesirable effects is defined using the following convention: Very common (≥ 1/10) Common (≥ 1/100 to < 1/10) Uncommon (> 1/1,000 to < /100) Rare (> 1/10,000 to < 1/1,000) Very rare (< 1/10,000) Not known (frequency cannot be estimated from the available data) MedDRA System Organ Class Frequency Undesirable Effects Rare Leucopenia*, thrombocytopenia*, agranulocytosis*, eosinophilia* Blood and lymphatic system disorders Not known In individual cases aplastic anaemia* and pancytopenia* have been observed Metabolism and nutrition disorders Uncommon Loss of weight, loss of appetite Uncommon Withdrawal, anxiety, sleep disturbancesPsychiatric disorders Rare Paranoid and hallucinatory phenomena developing over days and weeks Uncommon Severe headache, ataxia, lethargyNervous systems disorders Not known A few individual cases of dyskinesia have been reported for the period of the first 12 hours after start of the treatment, it disappeared soon after discontinuation of ethosuximide or the administration of diphenhydramine.

Respiratory, thoracic and mediastinal disorders Common to very common Singultus Common to very common Nausea, vomiting, abdominal painGastrointestinal disorders Uncommon Diarrhoea, constipation Rare Lupus erythematodes of varying extent*Skin and subcutaneous tissue disorders Not known Allergic skin reactions* such as exanthema, but also the severe generalised from of Stevens-Johnson syndrome* or drug reaction with eosinophilia and systemic symptoms (DRESS) may occur.

2) If undesirable effects occur which are independent of the dose taken and reversible, the medicinal product should be discontinued. They may reappear when the medicinal product is taken again. g. the performance in school of children and adolescents.

8), ethosuximide must be discontinued and diphenydramine administered by the intravenous route, if required. Special attention should be given to clinical symptoms of bone marrow damage (fever, angina, haemorrhage). It is recommended to check the blood count regularly (initially monthly, after one year every six months) to identify potential bone marrow damage.

At a leucocyte count of less than 3500/mm3 or granulocyte ratio of less than 25 %, the dose should be reduced or the therapy discontinued. The liver enzymes should aslo be checked regularly. 8, paranoid and hallucinatory symptoms, anxiety, agitation) may occur, therefore special caution is required when treating this group of patients with ethosuximide.

Suicidal ideation and behaviour Suicidal thoughts and behaviour have been reported in patients treated with anti-epileptics for various indications. A meta-analysis of randomised, placebo-controlled studies with antiepileptics also showed a slightly increased risk for suicidal thoughts and behaviour.

The mechanism triggering this undesirable effect is unknown, and the data available do not exclude a potentially increased risk when taking ethosuximide. Threfore, patients should be monitored for the emerge of suicidal thoughts and behaviour, and a appropriate treatment should be considered.

Patients (and their caregivers) should be advised to seek medical help if symptoms of suicidal thoughts or behaviour occur. 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.

Severe skin reactions Serious dermatologic reactions, including Stevens-Johnsons Syndrome (SJS) and drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported with ethosuximide treatement. SJS and DRESS can be fatal.

Patients appear to be at highest risk of these reactions early in the course of therapy, the onset of the reaction occuring in the majority of cases within the first month of treatment. Ethosuximide should be discontinued at the first appearance of signs and symptoms of sever skin reactions, such as skin rash, mucosal lesions, or any other sign of hypersensitivity.

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