Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: neuraxpharm Arzneimittel GmbH, Elisabeth-Selbert-Str. 23, 40764, Langenfeld, Germany
Hypersensitivity to the active substance, other succinimides or to any of the excipients listed in section 6.1.
If dyskinesias occur (see section 4.8), ethosuximide must be discontinued and diphenhydramine 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 a granulocyte ratio of less than 25%, the dose should be reduced or the therapy discontinued. The liver enzymes should also be checked regularly.
In particular in patients with a history of psychiatric disorders psychic undesirable effects (see section 4.8, paranoid and hallucinatory symptoms, anxiety, agitation) may occur, therefore special caution is required when treating this group of patients with ethosuximide.
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.
Therefore, patients should be monitored for the emergence of suicidal thoughts and behaviour, 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.
Note:
To prevent grand fits which are often associated with complex and atypical absences, ethosuximide can be combined with effective anticonvulsives (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.
Ethosuximide contains Methyl-4-hydroxybenzoate (E218), which may cause allergic reactions (possibly delayed).
In particular the following interaction of ethosuximide with other medicinal products should be considered:
The concomitant administration of carbamazepine increases the plasma clearance of ethosuximide. Valproic acid may increase the plasma concentration of ethosuximide in most patients.
Ethosuximide normally does not change the plasma concentration of other anti-epileptics such as primidone, phenobarbital and phenytoine since ethosuximide is not an enzyme inductor. However, individual cases of elevated phenytoin concentration were reported when ethosuximide was administered concomitantly.
The simultaneous use of medicinal products affecting the central nervous system, alcohol or convulsion-inducing substances and ethosuximide should be avoided.
Women of childbearing potential should be advised by their doctor of the necessity of planning and monitoring a pregnancy before starting the treatment with ethosuximide. Patients should be advised to tell their doctor immediately if they have become pregnant during the treatment.
The treatment with ethosuximide should not be interrupted during pregnancy without the consent of a physician as the sudden discontinuation of the treatment or uncontrolled reduction of the dose may result in recurrence of epileptic seizures which may harm the pregnant woman and/or the unborn child. Ethosuximide crosses the placenta. Studies in animals have shown reproductive toxicity (see section 5.3). Specific congenital malformations have not been observed in children of mothers exposed to ethosuximide monotherapy during pregnancy. The risk of malformations during anti-epileptic therapy is increased by a factor of 2 to 3 compared to the expected incidence of about 3% in the general population. Most common malformations reported are cleft lip, cardiovascular malformations and neural tube defects. Multiple antiepileptic drug therapies are associated with a higher risk of congenital malformation so that monotherapy should be practised during pregnancy whenever possible.
Patients should be informed of the increased risk of malformations and prenatal diagnostic measures should be offered.
The lowest effective dose ensuring seizure control must not be exceeded, particularly during the 20th and 40th day of pregnancy. The ethosuximide serum concentration of the pregnant woman must be regularly monitored.
Folic acid supplementation is recommended in patients planning to have a baby and during pregnancy. To prevent vitamin K1 deficiency and reduce the risk for haemorrhages in newborn infants, women should be given vitamin K1 during the last month of pregnancy.
Ethosuximide is excreted into breast milk reaching concentrations up to 94% of the maternal serum concentrations (see section 5.2). Sedation, poor suckling and irritability have been observed in individual breast-fed infants.
Breast-feeding should be discontinued during treatment with ethosuximide.
During the adjustment phase, at higher doses and in combination with other medicinal products affecting the central nervous system reactivity can be impaired to an extent that the ability to drive or operate machines is affected. This may even be the case when ethosuximide is taken as prescribed, and especially in connection with alcohol.
Therefore patients should not drive, operate machines or perform any other potentially hazardous activities, at least not during the adjustment phase of the treatment. The decision will be taken in each case by the attending doctor considering the patient’s individual response and the respective dose.
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 <1/100)
Rare (≥1/10,000 to <1/1,000)
Very rare (<1/10,000)
Not known (frequency cannot be estimated from the available data)
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.
Rare: Leucopenia*, thrombocytopenia*, agranulocytosis*, eosinophilia*
Not known: In individual cases aplastic anaemia* and pancytopenia* have been observed.
Uncommon: Loss of weight, loss of appetite
Uncommon: Withdrawal, anxiety, sleep disturbances
Rare: Paranoid and hallucinatory phenomena developing over days and weeks.
Uncommon: Severe headache, ataxia, lethargy
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.
Common to very common: Singultus
Common to very common: Nausea, vomiting, abdominal pain
Uncommon: Diarrhoea, constipation
Rare: Lupus erythematodes of varying extent*
Not known: Allergic skin reactions* such as exanthema, but also the severe generalised form of Stevens-Johnson syndrome* may occur.
* Effect independent of the dose (also see section 4.2)
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.
Long-term treatment may affect the patient’s performance, e.g. the performance in school of children and adolescents.
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. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme, Website: 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.
Not applicable.
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