Ethosuximide oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of ethosuximide.
Drugs List
Therapeutic Indications
Uses
Epilepsy - myoclonic seizures
Epilepsy absence seizures
Dosage
Effective plasma levels of ethosuximide lie between 40 and 100micrograms/ml but it is recommended that the dose should be adjusted according to 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 that the medicinal product is well tolerated. Higher doses should be taken in 2 or 3 single doses, however.
Adults
Initially 500mg daily.
The dose may be increased every five to seven days in increments of 250mg until the seizures are controlled.
A daily dose of 1g to 1.5g is usually sufficient. Occasionally 2g daily in divided doses may be necessary.
Children
Children aged 6 to 18 years
Initially 500mg daily.
The dose may be increased every five to seven days in increments of 250mg until the seizures are controlled.
A daily dose of 1g to 1.5g is usually sufficient. Occasionally 2g daily in divided doses may be necessary.
Children from 2 to 6 years
Initial dose: 250mg daily, increased by small increments until control is achieved.
Optimal dose for most children is 20mg/kg daily.
Maximum dose: 1g daily.
Children from birth to 2 years
Initial dose: 125mg daily, increased by small increments until control is achieved.
The following alternative dosing schedule may be suitable:
Children aged 6 to 18 years
Initially: 500mg daily, given in two divided doses.
Increase in increments of 250mg every 5 to 7 days to a usual dose of 1g to 1.5g daily.
Maximum dose: 1g twice a day.
Children aged 1 month to 6 years
Initially: 10mg/kg (250mg maximum) daily, given in two divided doses.
Increase gradually every 5 to 7 days to a maintenance dose of 20mg/kg to 40mg/kg (up to a maximum of 1g) daily, given in two divided doses.
If necessary, the total daily dose may be given in three divided doses.
Patients with Renal Impairment
Haemodialysis patients 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.
Additional Dosage Information
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 to 3 years.
Ethosuximide 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 changing the dose according to their age, however, it must be ensured that the EEG findings do not deteriorate.
Contraindications
Porphyria
Precautions and Warnings
Females of childbearing potential
Thai and Han Chinese ancestry positive for HLA-B 1502
Breastfeeding
Glucose-galactose malabsorption syndrome
Haemodialysis
Hepatic impairment
Hereditary fructose intolerance
History of psychiatric disorder
Pregnancy
Renal impairment
Advise ability to drive/operate machinery may be affected by side effects
Confirm HLA-B 1502 status in Han Chinese & Thai patients before initiating
Folic acid 5mg daily required pre-conception to end of 1st trimester
Not all formulations are suitable for all age groups/body weights
Treatment to be initiated and supervised by a specialist
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Some formulations contain hydroxybenzoate
Some formulations contain sucrose
Some products may contain soya or soya derivative
Monitor renal and hepatic function before and during treatment
Monitor closely for skin reactions
Monitor for Antiepileptic Hypersensitivity Syndrome
Monitor for signs of blood dyscrasias eg fever, sore throat, malaise etc
Monitor for signs of bone marrow depression
Monitor for signs of suicide ideation or behaviour
Monitor full blood count regularly
Monitor hepatic enzymes
Refer women considering pregnancy for specialist advice and monitoring
Advise patient to report symptoms of infection immediately
Advise patient to seek urgent medical advice if blood dyscrasias suspected
Discontinue treatment if DRESS is suspected
May induce systemic lupus erythematosus
Changeover to or from other anti-epileptic drugs should be gradual
Do not withdraw this drug suddenly
Advise patient to seek advice at first indications of pregnancy
Discontinue if severe skin reaction occurs
Discontinue or reduce dose if granulocyte ratio is less than 25%
Discontinue or reduce dose if leucocyte count is less than 3500/cubic mm
Discontinue if dyskinesias occur
Discontinue immediately if Antiepileptic Hypersensitivity Syndrome occurs
Advise that effects are potentiated by CNS depressants (including alcohol)
Pregnancy: Administer vitamin K in the last few weeks of pregnancy
Advise patient to brush teeth or rinse mouth after administering syrup
Advise patient/carers to report signs of suicide ideation or behaviour
The manufacturer recommends diphenhydramine administered by the intravenous route, if required in cases of dyskinesias.
Monitor patient routinely for depression and anxiety.
It is advised to monitor the blood count regularly (initially monthly, after one year every six months) to identify potential bone marrow damage.
Severe skin reactions, including Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), have been reported. Patients appear to be at a higher risk during the early stages of treatment, the majority of these reactions occur in the first month of treatment. Treatment of ethosuximide should be discontinued at the first appearance of signs and symptoms of severe skin reactions, such as skin rash, mucosal lesions, or any other sign of hypersensitivity. If the patient has developed SJS or TEN, ethosuximide must not be re-started at any time.
Hypersensitivity syndrome and drug reaction with eosinophilia and systemic symptoms have been seen in patients taking ethosuximide. The interval between treatment initiation and symptoms is usually two to four weeks but has been reported in patients with three or more months with the treatment. If such signs and symptoms occur, the patient should be evaluated immediately and treatment should be discontinued if an alternative aetiology for the signs and symptoms cannot be established.
If 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.
Pregnancy and Lactation
Pregnancy
Use ethosuximide with caution during pregnancy.
The manufacturer does not recommend using ethosuximide during pregnancy and the prescribing physician should weigh the benefits versus the risk of ethosuximide in treating women of childbearing potential. Ethosuximide crosses the placenta. Congenital malformations have not been observed in children of mothers exposed to ethosuximide monotherapy during pregnancy but animal studies have shown reproductive toxicity. 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 drugs therapies are associated with a higher risk of congenital malformation, monotherapy should be practised during pregnancy when possible.
The lowest effective dose ensuring seizure control must not be exceeded, particularly during the 20th and 40th day of pregnancy. Serum concentration of pregnant women 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 of haemorrhages in newborn infants, women should be given vitamin K1 during the last month of pregnancy.
Lactation
Use ethosuximide with caution during breastfeeding.
The manufacturer recommends avoiding breastfeeding during treatment with ethosuximide.
Ethosuximide is excreted in breast milk. Sedation, poor suckling and irritability have been observed in individual breast-fed infants. Exposed infants should be monitored for drowsiness, adequate weight gain and developmental milestones. Briggs (2015) indicates that ethosuximide is compatible with breastfeeding.
Side Effects
Abdominal cramps
Abdominal pain
Aggression
Agitation
Agranulocytosis
Alopecia
Anorexia
Anxiety
Apathy
Aplastic anaemia
Ataxia
Attention disturbances
Behavioural disturbances
Blood dyscrasias
Bone marrow failure
Constipation
Decreased appetite
Depression
Diarrhoea
Dizziness
Drowsiness
Drug rash with eosinophilia and systemic symptoms (DRESS)
Dyskinesia
Eosinophilia
Epigastric pain
Epileptic seizures
Erythema nodosum
Euphoria
Extrapyramidal effects
Fatigue
Gastric upset
Gingival hypertrophy
Haematuria
Hallucinations
Headache
Hepatic disorders
Hiccough
Hiccups
Hyperactivity
Hypersensitivity reactions
Impaired concentration
Increase in antinuclear antibodies (ANA)
Increased libido
Irritability
Lethargy
Leucocytosis
Leucopenia
Lupus erythematosus-like syndrome
Monocytosis
Myopia
Nausea
Nephrotic syndrome
Night terrors
Pancytopenia
Paranoia
Photophobia
Psychomotor excitation
Psychosis
Raised neutrophil count
Rash
Renal disorders
Skin reactions
Sleep disturbances
Somnolence
Stevens-Johnson syndrome
Suicidal tendencies
Systemic lupus erythematosus
Thrombocytopenia
Tongue swelling
Tonic-clonic seizures (generalised)
Toxic epidermal necrolysis
Urticaria
Vaginal bleeding
Vomiting
Weight loss
Withdrawal symptoms
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: March 2021
Reference Sources
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.
Summary of Product Characteristics: Emeside 250mg Capsules. Chemidex Pharma Ltd. Revised December 2021.
Summary of Product Characteristics: Emeside 250mg/5ml Syrup. Essential Pharma Ltd. Revised November 2021.
Summary of Product Characteristics: Epesri 250mg Capsules. Strides Pharma UK Ltd. Revised June 2021.
Summary of Product Characteristics: Ethosuximide 250mg Capsules. Essential Pharma. Revised November 2018.
Summary of Product Characteristics: Ethosuximide 250mg/5ml Oral solution. Aristo Pharma. Revised August 2018.
Summary of Product Characteristics: Ethosuximide 250mg/5ml Oral solution. Neuraxpharm Arzneimittal GmbH. Revised August 2019.
Summary of Product Characteristics: Ethosuximide 250mg/5ml Syrup. Essential Pharma. Revised August 2019.
MHRA Drug Safety Update Vol 2, Issue 1, August 2008
Antiepileptics: risk of suicidal thoughts and behaviour
Available at: www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/CON023078
Last accessed: 08 November 2018
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 17 September 2021
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://www.ncbi.nlm.nih.gov/books/NBK501922/
Ethosuximide Last revised: 15 February 2021
Last accessed: 05 March 2021
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