ethosuximide
Zarontin

Available forms
Available by prescription only
Capsules: 250 mg
Syrup: 250 mg/5 ml

Indications and dosages
 Absence seizures. Adults and children age 6 and older: Initially, 250 mg P.O. b.i.d. May increase by 250 mg q 4 to 7 days up to 1.5 g daily.
Children ages 3 to 6: 250 mg P.O. daily. Optimal dosage is 20 mg/kg/day.

Pharmacodynamics
Anticonvulsant action: Ethosuximide raises the seizure threshold; it suppresses characteristic spike-and-wave pattern by depressing neuronal transmission in the motor cortex and basal ganglia. It’s indicated for absence seizures refractory to other drugs.

Pharmacokinetics
Absorption: Absorbed from the GI tract; steady state plasma levels occur in 4 to 7 days.
Distribution: Distributed widely throughout the body; protein-binding is minimal.
Metabolism: Metabolized extensively in the liver to several inactive metabolites.
Excretion: Excreted in urine, with small amounts in bile and feces. Plasma half-life is about 60 hours in adults and about 30 hours in children.

Contraindications and precautions
Contraindicated in patients hypersensitive to succinimide derivatives. Use extremely cautiously in patients who have hepatic or renal disease.

Interactions
Drug-drug. CNS depressants (antidepressants, antipsychotics, anxiolytics, other anticonvulsants, narcotics): Causes additive CNS depression and sedation. Monitor patient closely.
Phenobarbital, primidone: Decreases primidone and phenobarbital levels. Monitor patient closely for seizure activity. Dosage adjustments may be needed.
Phenytoin: Increases serum phenytoin levels. Monitor patient carefully.
Valproic acid: Alters serum ethosuximide levels. Monitor patient closely.
Drug-lifestyle. Alcohol use: Causes additive CNS depression and sedation. Discourage alcohol use.

Adverse reactions
CNS: drowsiness, headache, fatigue, dizziness, ataxia, irritability, euphoria, lethargy, depression, psychosis.
EENT: myopia, tongue swelling, gingival hyperplasia.
GI: nausea, vomiting, diarrhea, weight loss, cramps, anorexia, epigastric and abdominal pain.
GU: vaginal bleeding, urinary frequency, microscopic hematuria.
Hematologic: leukopenia, eosinophilia, agranulocytosis, pancytopenia, aplastic anemia.
Respiratory: hiccups.
Skin: urticaria, pruritic and erythematous rash, hirsutism, Stevens-Johnson syndrome.

Effects on lab test results
• May increase liver enzyme levels.
• May increase eosinophil count. May decrease WBC, granulocyte, RBC, and platelet counts.

Overdose and treatment
Signs and symptoms of ethosuximide overdose, given alone or with other anticonvulsants, include CNS depression, ataxia, stupor, and coma.
 Treatment is symptomatic and supportive. Carefully monitor vital signs and fluid and electrolyte balance.

Special considerations
• Ethosuximide may cause false-positive Coombs’ test results. It also may cause abnormal results in renal function tests.
 ALERT Abrupt discontinuation of drug may precipitate absence seizures.
• Observe patient for skin reactions, joint pain, unexplained fever, or unusual bruising or bleeding (which may signal hematologic or other severe adverse reactions).
• Perform CBC, liver function tests, and urinalysis periodically.
• Therapeutic plasma levels range from 40 to 100 mcg/ml.
Pregnant patients
• Safety hasn’t been established.
Breast-feeding patients
• Safety hasn’t been established. Advise breast-feeding women to use an alternative to breast-feeding during ethosuximide therapy.
Pediatric patients
• Don’t use drug in children younger than age 3.
Geriatric patients
• Use cautiously in elderly patients.

Patient education
• Advise patient to take drug with food or milk to prevent GI distress, to avoid use with alcoholic beverages, and to avoid hazardous tasks that require alertness if drug causes drowsiness, dizziness, or blurred vision.
• Tell patient to report the following effects: rash, joint pain, fever, sore throat, or unusual bleeding or bruising.
• Advise patient to call immediately if pregnancy is suspected.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use