ETHOSUXIMIDE CRESCENT

Posology 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 incre-ments 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 μg/ml. How-ever, 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 treatment, gradual increase of dose) and by taking the medic-inal product during or after meals. Anti-epileptic therapies are principally long-term therapies.

A specialist (neurologist, neuro-paediatrician) 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.

Children between 2 and 6 years:

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 daily dose is 1000 mg.

1. Method of administration Ethosuximide Oral Solution is for oral use. The solution can be taken during or after meals. 5 ml steps) and an adapter for the oral syringe. A single dose of the oral solution is drawn into the oral syringe up to the re-quired level and transferred into a glass of water or mixed with milk pudding.

Alternatively, the oral solution can directly be applicated into the mouth. Afterwards, the patient should drink half a glass of water

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) *AE frequency estimated from post-marketing safety database Blood and lymphatic system disorders Uncommon: Leukopenia*, agranulocytosis*, eosinophilia*, aplastic anaemia*, pancytopenia*, bone marrow failure.

Not known:

Thrombocytopenia Immune system disorders Uncommon: Hypersensitivity* Metabolism and nutrition disorders common: Decreased appetite Psychiatric disorders Uncommon: Aggression*, sleep terror*, depression*,suicidal ideation*, psychotic disorder*, sleep disorders* Not known: Euphoric mood, apathy, libido increased.

Nervous system disorders common:

Headache, ataxia, dizziness, somnolence Uncommon: Psychomotor hyperactivity*, lethargy, disturbance in attention* Not known: Extrapyramidal side effects, increased frequency of grand mal convulsions Eye disorders Uncommon: Myopia* Respiratory, thoracic and mediastinal disorders Uncommon: Hiccups Gastrointestinal disorders common: Abdominal pain, abdominal pain upper, gastrointestinal disorder, Nausea, vomiting, abdominal discomfort Uncommon: Diarrhoea, gingival hypertrophy*, swollen tongue* Skin and subcutaneous tissue disorders common: Rash erythematous, urticaria Uncommon: Stevens-Johnson syndrome* Not known: Drug reaction with eosinophilia and systemic symptoms (DRESS) Musculoskeletal and connective tissue disorders Uncommon: Systemic lupus erythematous* Renal and urinary disorders Uncommon: Haematuria* Reproductive system and breast disorders Uncommon: Vaginal Haemorrhage* General disorders and administration Uncommon: Fatigue, irritability* Investigation Uncommon: Weight decreased If undesirable effects occur which are independent of the dose taken and reversible, the me-dicinal product should be discontinued.

They may reappear when the medicinal product is taken again. g. the performance in school of children and adolescents. 4). Psychiatric or psychological aberrations associated with ethosuximide administration may be noted particularly in patients who have previously exhibited psychological abnormalities.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is im-portant. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

8), ethosuximide must be discontinued and diphenhydra-mine administered by the intravenous route, if required. Special attention should be given to clinical symptoms of bone marrow damage (fever, an-gina, 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 a granulocyte ratio of less than 25%, the dose should be re-duced or the therapy discontinued. The liver enzymes should also be checked regularly. 8, paranoid and hallucinatory symptoms, anxiety, agitation) may occur, there-fore special caution is required when treating this group of patients with ethosuximide.

All patients treated with AEDs should be routinely evaluated for depression and anxiety. 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 antiepi-leptics also showed a slightly increased risk for suicidal thoughts and behaviour. The mecha-nism triggering this undesirable effect is unknown, and the data available do not exclude a potentially increased risk when taking ethosuximide.

Therefore, patients should be monitored for the emergence of suicidal thoughts and behav-iour, and an appropriate treatment should be considered. Patients (and their caregivers) should be advised to seek medical help if symptoms of suicidal thoughts or behaviour occur.

Severe Cutaneous Adverse Reactions (SCARs) Hypersensitivity Syndrome (HSS) and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Hypersensitivity Syndrome (HSS) or Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking anticonvulsant drugs, including ethosuximide.

Some of these events have been fatal or life threatening. HSS/DRESS typically, although not exclusively, presents with fever, rash, and/or lymphadenopathy, in association with other organ system involvement, such as hepatitis, nephritis, haematological abnormalities, myocarditis, myositis or pneumonitis.

Initial symptoms may resemble an acute viral infection. Other common manifestations include: arthralgias, jaundice, hepatomegaly, leucocytosis, and eosinophilia. The interval between the first drug exposure and symptoms is usually 2 to 4 weeks but has been reported in individuals receiving anticonvulsants for 3 or more months.

If such signs and symptoms occur, the patient should be evaluated immediately. Ethosuximide should be discontinued if an alternative aetiology for the signs and symptoms cannot be established. Patients at higher risk for developing HSS/DRESS include black patients, patients who have experienced this syndrome in the past (with ethosuximide or other anticonvulsant drugs), patients who have a family history of this syndrome and immuno-suppressed patients.

The syndrome is more severe in previously sensitized individuals. Stevens-Johnson syndrome (SJS) and Toxic epidermal necrolysis (TEN) Life-threatening cutaneous reactions Stevens-Johnson syndrome (SJS) and Toxic epidermal necrolysis (TEN) have been reported with the use of ethosuximide.

4), occurrence of rash and should be monitored closely for skin reactions. Patients should seek medical advice from their physician immediately when observing any indicative signs or symptoms. The highest risk for occurrence of SJS or TEN is within the first weeks of treatment.

g. progressive skin rash often with blisters or mucosal lesions) are present, ethosuximide treatment should be discontinued. The best results in managing SJS and TEN come from early diagnosis and immediate discontinuation of any suspect drug.

Early withdrawal is associated with a better prognosis. If the patient has developed SJS or TEN with the use of ethosuximide, ethosuximide must not be re-started in this patient at anytime. If the rash is of a milder type (measles-like or scarlatiniform), therapy may be resumed after the rash has completely disappeared.

If the rash recurs upon reinstitution of therapy, further ethosuximide medication is contraindicated. The risk of serious skin reactions and other hypersensitivity reactions to ethosuximide may be higher in black patients. Studies in patients of Chinese ancestry have found a strong association between the risk of developing SJS/TEN and the presence of human leukocyte antigen HLA- B*1502, an inherited allelic variant of the HLA-B gene, in patients using carbamazepine.

HLA-B*1502 may be associated with increased risk of developing SJS/TEN in patients of Thai and Han Chinese ancestry taking drugs associated with SJS/TEN, including ethosuximide. If these patients are known to be positive for HLA-B*1502, the use of ethosuximide should only be considered if the benefits are thought to exceed the risks.

In the Caucasian and Japanese population, the frequency of HLA-B*1502 allele is extremely low, and thus it is not possible at present to conclude on risk association. Adequate information about risk association in other ethnicities is currently not available.

Note:

Ethosuximide, when used alone in mixed types of epilepsy, may increase the frequency of generalised tonic clonic (grand mal) seizures in some patients. As with other anticonvulsants, it is important to proceed slowly when increasing or decreasing dosage, as well as when adding or eliminating other medication.

Abrupt withdrawal of anticonvulsant medication may precipitate absence (petit mal) seizures. Hepatic/Renal Impairment Ethosuximide should be used with extreme caution in patients with impaired hepatic […]

1. Porphyria.