Version July 2025
Absence (petit mal) seizures: Oral: Initial: 500 mg/day. Individualize dose based on patient response by increasing in small increments (eg, ≤250 mg); doses >1.5 g/day, in divided doses, should only be used under the strict supervision of a physician; higher doses may be necessary in some patients.
Note: Single daily doses have been shown to be effective and well tolerated in clinical trials (in children) and pharmacokinetic analysis (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; use with extreme caution.
There are no dosage adjustments provided in the manufacturer's labeling; use with extreme caution.
Refer to adult dosing.
(For additional information see "Ethosuximide: Pediatric drug information")
Absence seizures:
Note: Ethosuximide monotherapy or valproic acid monotherapy is considered an appropriate initial therapy for the treatment of absence seizures of childhood (Ref).
Children 2.5 to <3 years: Limited data available: Oral: Initial: 10 mg/kg/day in 2 or 3 divided doses, titrate to response in 5 to 10 mg/kg/day increments every 7 days; the reported mean daily dose was 33.5 ± 15.3 mg/kg/day in 2 to 3 divided doses in a population that included 155 subjects 2.5 to 13 years of age (39 patients were <6 years of age); reported maximum daily dose: 60 mg/kg/day or 2,000 mg/day in divided doses, whichever is less (Ref).
Children 3 to <6 years: Oral: Initial: 10 mg/kg/day in 2 or 3 divided doses, titrate to response in 5 to 10 mg/kg/day increments every 7 days; manufacturer labeling suggests an initial dose of 250 mg/day in 2 or 3 divided doses; titrate dose in small increments (eg, ≤250 mg) every 4 to 7 days to clinical response; usual daily dose range: 20 to 30 mg/kg/day in 2 to 3 divided doses; in a population that included 155 subjects 2.5 to 13 years of age (39 patients were <6 years of age), the reported mean daily dose was 33.5 ± 15.3 mg/kg/day (Ref); the maximum reported dose was 60 mg/kg/day or 2,000 mg/day in divided doses, whichever is less (Ref).
Children ≥6 years and Adolescents: Oral: Initial: 10 mg/kg/day in 2 or 3 divided doses, titrate to response in 5 to 10 mg/kg/day increments every 7 days; manufacturer labeling suggests an initial dose of 500 mg/day in 2 or 3 divided doses; titrate dose in small increments (eg, 250 mg) every 4 to 7 days to clinical response; usual daily dose: 20 to 30 mg/kg/day in divided doses (Ref); in trials, the maximum reported dose was 60 mg/kg/day or 2,000 mg/day in divided doses, whichever is less (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in manufacturer's labeling; use with extreme caution.
There are no dosage adjustments provided in manufacturer's labeling; use with extreme caution.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not defined:
Dermatologic: Pruritic erythematous rash, urticaria
Endocrine & metabolic: Hirsutism, increased libido, weight loss
Gastrointestinal: Abdominal cramps, abdominal pain, anorexia, diarrhea, epigastric pain, gastric distress, gingival hyperplasia, hiccups, nausea, vomiting
Genitourinary: Microscopic hematuria, vaginal hemorrhage
Hematologic & oncologic: Eosinophilia, leukopenia, pancytopenia
Hypersensitivity: Drug rash with eosinophilia and systemic symptoms, hypersensitivity reaction, swollen tongue
Nervous system: Aggressive behavior, ataxia, delusional paranoid disorder, depression, dizziness, drowsiness, euphoria, fatigue, headache, hyperactive behavior, irritability, lack of concentration, lethargy, night terrors, sleep disturbance
Ophthalmic: Myopia
Postmarketing:
Dermatologic: Stevens-Johnson syndrome (Matos 2021), toxic epidermal necrolysis (Matos 2021)
Hematologic & oncologic: Agranulocytosis (Imai 2003), immune thrombocytopenia (Shatara 2019), lymphadenopathy (Ojinnaka 2001)
Hepatic: Abnormal hepatic function tests (Coulter 1983)
Nervous system: Acute mania (Chien 2011), psychotic symptoms (Chien 2011), suicidal ideation (Chien 2011)
Neuromuscular & skeletal: Systemic lupus erythematosus (Crespel 2009)
Renal: Renal function test abnormality
Respiratory: Oropharyngeal edema (Shang 2021)
Hypersensitivity to ethosuximide, succinimides, or any component of the formulation.
Concerns related to adverse effects:
• Blood dyscrasias: Severe blood dyscrasias (some fatal) have been reported. Monitor CBC, especially if signs/symptoms of infection develop.
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Dermatologic reactions: Severe reactions, including Stevens-Johnson syndrome (SJS), have been reported with an onset usually within 28 days, but may be observed later. Drug should be discontinued if there are any signs of rash, unless the rash is clearly not drug-related. If SJS is suspected do not resume ethosuximide and consider alternative therapy.
• Drug-induced immune thrombocytopenia: Drug-induced immune thrombocytopenia (DITP) has been reported; may occur 1 to 3 weeks after initiation. Discontinue use and treat appropriately if DITP is suspected. Avoid use in patients with a history of ethosuximide-induced immune thrombocytopenia.
• Hepatic effects: Changes in hepatic function have been reported; monitor LFTs.
• Multiorgan hypersensitivity reactions: Potentially serious, sometimes fatal drug reaction with eosinophilia and systemic symptoms (DRESS), also known as multiorgan hypersensitivity reactions, have been reported. Monitor for signs and symptoms (eg, fever, rash, exfoliative dermatitis, lymphadenopathy, facial swelling, eosinophilia) in association with other organ system involvement (eg, hepatitis, nephritis, hematologic abnormalities, pneumonitis, myocarditis, myositis, pericarditis). If DRESS is suspected, discontinue therapy.
• Renal effects: Changes in renal function have been reported; monitor during therapy.
• Systemic lupus erythematous: Cases of systemic lupus erythematosus (SLE) have been reported.
• Suicidal ideation: Pooled analysis of trials involving various antiseizure medications (regardless of indication) showed an increased risk of suicidal thoughts/behavior (incidence rate: 0.43% treated patients compared to 0.24% of patients receiving placebo); risk observed as early as 1 week after initiation and continued through duration of trials (most trials ≤24 weeks). Monitor all patients for notable changes in behavior that might indicate suicidal thoughts or depression; notify healthcare provider immediately if symptoms occur.
Disease-related concerns:
• Hepatic impairment: Use with extreme caution in patients with hepatic impairment.
• Renal impairment: Use with extreme caution in patients with renal impairment.
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP 1997; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.
Other warnings/precautions:
• Withdrawal: Antiseizure medications should not be discontinued abruptly because of the possibility of increasing seizure frequency; therapy should be withdrawn gradually to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Zarontin: 250 mg [contains quinoline yellow (d&c yellow #10)]
Generic: 250 mg
Solution, Oral:
Zarontin: 250 mg/5 mL (474 mL) [contains fd&c red #40 (allura red ac dye), fd&c yellow #6 (sunset yellow), saccharin sodium, sodium benzoate; raspberry flavor]
Generic: 250 mg/5 mL (473 mL, 474 mL)
Yes
Capsules (Ethosuximide Oral)
250 mg (per each): $2.14 - $2.78
Capsules (Zarontin Oral)
250 mg (per each): $1.59
Solution (Ethosuximide Oral)
250 mg/5 mL (per mL): $0.50
Solution (Zarontin Oral)
250 mg/5 mL (per mL): $0.35
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Zarontin: 250 mg [contains quinoline yellow (d&c yellow #10)]
Generic: 250 mg
Syrup, Oral:
Zarontin: 250 mg/5 mL (500 mL) [contains alcohol, usp, fd&c yellow #6 (sunset yellow), saccharin sodium, sodium benzoate]
Oral: Administer with food or milk to decrease GI upset.
Oral: Administer with food or milk to decrease GI upset.
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/012380s034mg.pdf, must be dispensed with this medication.
Absence (petit mal) seizures: Management of absence (petit mal) seizures
Ethosuximide may be confused with ethionamide, methsuximide.
Zarontin may be confused with Neurontin, Xalatan, Zantac, Zaroxolyn.
Substrate of CYP3A4 (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Cobicistat: May increase serum concentration of Ethosuximide. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of Ethosuximide. Risk C: Monitor
Desmopressin: Hyponatremia-Associated Agents may increase hyponatremic effects of Desmopressin. Risk C: Monitor
Fosphenytoin-Phenytoin: Ethosuximide may increase serum concentration of Fosphenytoin-Phenytoin. Fosphenytoin-Phenytoin may decrease serum concentration of Ethosuximide. Risk C: Monitor
LamoTRIgine: Ethosuximide may increase CNS depressant effects of LamoTRIgine. Ethosuximide may decrease serum concentration of LamoTRIgine. Risk C: Monitor
Mefloquine: May decrease therapeutic effects of Antiseizure Agents. Mefloquine may decrease serum concentration of Antiseizure Agents. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of seizures. If antiseizure drugs are being used for another indication, monitor antiseizure drug concentrations and treatment response closely with concurrent use. Risk D: Consider Therapy Modification
MetyraPONE: Coadministration of Antiseizure Agents and MetyraPONE may alter diagnostic results. Management: Consider alternatives to the use of the metyrapone test in patients taking antiseizure agents. Risk D: Consider Therapy Modification
Mianserin: May decrease therapeutic effects of Antiseizure Agents. Risk C: Monitor
Orlistat: May decrease serum concentration of Antiseizure Agents. Risk C: Monitor
Phenobarbital-Primidone: May decrease serum concentration of Ethosuximide. Risk C: Monitor
Valproic Acid and Derivatives: Ethosuximide may decrease serum concentration of Valproic Acid and Derivatives. Valproic Acid and Derivatives may increase serum concentration of Ethosuximide. Risk C: Monitor
Patients with epilepsy who are planning to become pregnant in advance should have baseline serum concentrations measured once or twice prior to pregnancy during a period when seizure control is optimal (Patsalos 2008; Patsalos 2018).
Ethosuximide crosses the placenta. Birth defects have been reported in infants. Epilepsy itself, the number of medications, genetic factors, or a combination of these may influence the teratogenicity of antiseizure therapy. In general, polytherapy may increase the risk of congenital malformations; monotherapy with the lowest effective dose is recommended (Harden 2009). Monitoring of serum concentrations should begin prior to pregnancy and continue up to once a month during pregnancy in patients with stable seizure control (Patsalos 2008; Patsalos 2018).
Patients exposed to ethosuximide during pregnancy are encouraged to enroll themselves into the NAAED Pregnancy Registry by calling 1-888-233-2334. Additional information is available at www.aedpregnancyregistry.org.
Ethosuximide is present in breast milk. The manufacturer recommends that caution be exercised when administering ethosuximide to breastfeeding patients. The Canadian label recommends against breastfeeding while taking ethosuximide.
Serum concentrations, CBC, platelets, liver enzymes (periodic), urinalysis (periodic); serial platelet counts and presence of drug-dependent antiplatelet antibodies (if possible) in patients with suspected drug-induced immune thrombocytopenia; signs of rash; suicidality (eg, suicidal thoughts, depression, behavioral changes).
Therapeutic: 40 to 100 mcg/mL (SI: 283.2 to 708 micromole/L); levels up to 150 mcg/mL (SI: 1,062 micromole/L) have been reported without toxicity.
Increases the seizure threshold and suppresses paroxysmal spike-and-wave pattern in absence seizures; depresses nerve transmission in the motor cortex
Absorption: Complete and rapid.
Distribution: Vd: 0.7 L/kg (Battino 1995).
Protein binding: 21.8% (Patsalos 2017).
Metabolism: Hepatic via CYP3A to >40% inactive glucuronide conjugates (Patsalos 2018).
Half-life elimination, serum: Children: 30 hours; Adults: 50 to 60 hours.
Time to peak, serum: 1 to 7 hours.
Excretion: Urine, slowly (12% to 20% as unchanged drug).
