ETHOSUXIMIDE ARISTO

Posology Adults, the elderly and paediatric population over 6 years of age Start with a small dose - 500 mg daily with increments of 250 mg every five to seven days until control is achieved with 1000-1500 mg daily. Occasionally, 2000 mg, in divided doses may be required.

Paediatric population aged 0-6 years Children aged 0-6 years old and those who are unable to swallow capsules should be given ethosuximide oral liquid. Effective plasma levels of ethosuximide normally lie between 40 and 100 μg/ml but the clinical response should be the criteria for the regulation of the dosage.

The half- life of ethosuximide in plasma is more than 24 hours but the daily dose if large, is more comfortably divided between morning and evening. 1. Method of administration Ethosuximide Aristo is for oral use. The soft capsules can be taken during or after meals with some liquid.

Frequencies reported are as follows:

Common (≥ 1/100 to < 1/10); Uncommon (> 1/1,000 to < /100); Rare (> 1/10,000 to < 1/1,000); Not known (frequency cannot be estimated from the available data) * AE frequency estimated from post-marketing safety database Blood and lymphatic system disorders Uncommon Agranulocytosis*, aplastic anaemia*, eosinophilia*, leukopenia* 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 disorder* 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, abdominal discomfort, vomiting 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).

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 important.

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.

General Suicidal ideation and behaviour have been reported in patients treated with anti- epileptic agents in several indications. A meta-analysis of randomised placebo controlled trials of antiepileptic drugs (AEDs) has also shown a small increased risk of suicidal ideation and behaviour.

The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for ethosuximide. Therefore, patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered.

Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge. All patients treated with AEDs should be routinely evaluated for depression and anxiety. 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.

8). It is recommended to check the blood count regularly (initially monthly, after one year every six months) to identify potential medulla injury. At a leucocyte count of less than 3500/mm³ or a granulocyte ratio of less than 25%, the dose should be reduced or the therapy discontinued.

The liver enzymes should also be checked regularly. Hepatic/Renal Impairment Ethosuximide should be used with extreme caution in patients with impaired hepatic or renal function. Periodic urinalysis and liver function studies are advised for all patients receiving the drug.

Ethosuximide is capable of producing morphological and functional changes in the animal liver. In humans, abnormal liver and renal function studies have been reported. Autoimmune Disorders Cases of systemic lupus erythematosus have been reported with the use of ethosuximide.

The physician should be alert to this possibility. Additionally, lupus- like reactions have been reported in children given ethosuximide. They vary in severity from systemic immunological disorders, which include the nephrotic syndrome, to the asymptomatic presence of antinuclear antibodies.

The nephrotic syndrome is rare and a complete recovery has usually been reported on drug withdrawal. 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 any time. 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 […]

1. Porphyrias.