ethosuximide
antiepileptic drug· Brands: Zarontin, Emeside, PetnidanPO
Mechanism of action
Ethosuximide reduces T-type calcium currents in thalamic neurons, which suppresses the abnormal oscillatory activity that underlies absence seizures. It is selective for this current and has minimal effect on other ion channels.
Pharmacokinetics
Ethosuximide is well absorbed after oral administration, reaching peak plasma concentrations within 3 to 7 hours. It has a long elimination half-life of approximately 40 to 60 hours in adults. The drug is extensively metabolised in the liver, and the metabolites and unchanged drug are excreted in urine.
Indications & dosing
Absence seizures (typical)
Given in two divided doses; increase gradually by 250 mg every 2-3 weeks.
- adult · PO: 500–1000 mg daily · Given in two divided doses; increase gradually by 250 mg every 2-3 weeks.
Absence seizures (typical)
Given in two divided doses; adjust according to response and serum levels.
- pediatric · PO: 10–30 mg/kg/day daily · Given in two divided doses; adjust according to response and serum levels.
Contraindications & precautions
- Hypersensitivity to ethosuximide or other succinimides · May cause cross-sensitivity
- Porphyria
- Hepatic impairment · Caution, may require dose adjustment
- Renal impairment · Caution, may require dose adjustment
- Monitor complete blood count, hepatic and renal function periodically.
- Avoid abrupt withdrawal to prevent precipitation of seizures.
- Use caution in patients with hepatic or renal impairment.
- Use caution in patients with a history of psychiatric disorders or depression.
- Advise patients to report signs of infection, rash, or mood changes.
- Ethosuximide may interact with other antiepileptic drugs, monitor serum levels if co-prescribed.
Adverse effects
- Nausea, vomiting, abdominal pain
- Anorexia, weight loss
- Drowsiness, dizziness, ataxia
- Blood dyscrasias (leukopenia, agranulocytosis, pancytopenia)serious
- Stevens-Johnson syndromeserious
- Lupus-like syndromeserious
- Psychiatric disturbances (hallucinations, depression, psychosis)serious
- Increased frequency of generalized tonic-clonic seizuresserious
Renal & hepatic adjustment
- Hepatic impairment (moderate): Use with caution; consider reducing dose and monitor plasma concentrations.
- Hepatic impairment (severe): Reduce dose; monitor plasma concentrations closely.
Monitoring, pregnancy & toxicity
- Plasma ethosuximide concentration · Periodically, especially after dose adjustment or if inadequate response
- Seizure frequency · Regularly
- Liver function tests · Periodically
- Renal function tests · Periodically
- Complete blood count · Periodically, as blood dyscrasias have been reported
- Mood and behaviour changes · Regularly
- Pregnancy: Use only if the benefit outweighs the risk. Ethosuximide has been associated with foetal malformations, including neural tube defects. If used during pregnancy, use the lowest effective dose, provide folic acid supplementation, and involve a specialist.
- Toxicity: Nausea, vomiting, and abdominal pain · Supportive care; consider antiemetics.
- Toxicity: Sedation, ataxia, and dizziness · Monitor; reduce dose or discontinue.
- Toxicity: Severe toxicity: respiratory depression, coma, hypotension · Urgent supportive measures including airway management, intravenous fluids, and activated charcoal if recent ingestion.
- Toxicity: Rarely, liver dysfunction or blood dyscrasias · Monitor liver function and blood counts; discontinue if severe.
Clinical notes
Ethosuximide is indicated for the treatment of absence seizures and may be used as monotherapy or in combination with other antiepileptics. Common adverse effects include gastrointestinal disturbances, drowsiness, dizziness, and headache. Rarely, it can cause blood dyscrasias, so periodic blood cell counts are recommended. It should not be used in patients with a history of porphyria. Caution is needed when switching to or from ethosuximide, as it may exacerbate tonic-clonic seizures.
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BNF; local formulary