Ethosuximide
Mechanism :
Ethosuximide suppresses the paroxysmal three cycle per second spike and wave activity associated with lapses of consciousness which is common in absence seizures. The frequency of seizures is reduced by depression of the motor cortex and elevation of the seizure threshold of the central nervous system to convulsive stimuli.
Binds to T-type voltage sensitive calcium channels.
Indication :
Contraindications :
Ethosuximide should not be used in patients with a history of hypersensitivity to succinimides.
Dosing :
Under 3 years:
Safety and efficacy not established.
3-6 years:
250 mg orally once daily initially; if needed, may increase by 250 mg every four hourly for 7 days; usual maintenance dose 20 mg/kg/day.
Above 6 years:
As adults, 500 mg orally once daily initially; may increase by 250 mg every four hourly for 7 days; Max: 1.5 g/day in divided doses.
Therapeutic range:
40-100 mg/L (steady state) is reached in 4-7 days.
Adverse Effect :
Nausea and vomiting, anorexia, epigastric and abdominal pain, cramps, weight loss, diarrhea, leukopenia, pancytopenia with or without bone marrow suppression, agranulocytosis, eosinophilia, drowsiness, dizziness, headache, hiccups, euphoria, irritability, hyperactivity, fatigue, lethargy, ataxia, urticaria, Stevens-Johnson syndrome, systemic lupus erythematosus, hirsutism, vaginal bleeding, microscopic hematuria.
Interaction :
Phenytoin: Ethosuximide may increase plasma levels of phenytoin.
Carbamazepine, Phenobarbitone, Primidone, Phenytoin: Ethosuximide plasma levels may be decreased.
Sodium Valproate, Vigabatrin and Isoniazid: Ethosuximide plasma levels may be increased
Antidepressants and antipsychotics: may antagonize effects of ethosuximide.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | Dose as in normal renal function |
| 10-20 | Dose as in normal renal function |
| <10 | Dose as in normal renal function |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Dialysed. Dose as in normal renal function |
| HD | Dialysed. Dose as in normal renal function |
| HDF/High flux | Dialysed. Dose as in normal renal function |
| CAV/VVHD | Dialysed. Dose as in normal renal function |
Hepatic Dose :
Dosage adjustments may be required in liver disease. Ethosuximide may cause hepatic dysfunction and discontinuation may need to be considered if significant hepatic impairment occurs during therapy.