Ethosuximide

Pronunciation: ETH-oh-SUX-i-mide
Class: Succinimide

Trade Names

Zarontin
- Capsules, oral 250 mg
- Solution, oral 250 mg per 5 mL

Pharmacology

Suppresses paroxysmal spike and wave activity associated with lapses of consciousness common in absence seizures and elevates seizure threshold.

Slideshow: Flashback: FDA Drug Approvals 2013

Pharmacokinetics

Absorption

Readily absorbed from the GI tract. T max is approximately 3 h.

Metabolism

Extensively metabolized to inactive metabolites.

Elimination

Approximately 12% to 20% is excreted unchanged by the kidneys. The half-life is approximately 40 to 60 h (adults) and 30 h (children).

Indications and Usage

For the control of absence seizures.

Contraindications

Hypersensitivity to succinimides.

Dosage and Administration

Adults and Children 6 y and older

PO 500 mg/day initially; individualize dose based on response. Increase daily dose by 250 mg every 4 to 7 days until control is achieved with minimal adverse reactions. Administer dosages exceeding 1.5 g/day in divided doses under strict medical supervision. Optimal dosage for most children is 20 mg/kg/day.

Children 3 to 6 y of age

PO 250 mg/day initially; individualize dose based on response. Increase daily dose by 250 mg every 4 to 7 days until control is achieved with minimal adverse reactions. Administer dosages exceeding 1.5 g/day in divided doses under strict medical supervision. Optimal dosage for most children is 20 mg/kg/day.

General Advice

  • Increase dosage by small increments.
  • Abrupt withdrawal of anticonvulsant medications may precipitate absence status.
  • May be administered with other anticonvulsants when other forms of epilepsy coexist with absence seizures.
  • The accepted therapeutic range is 40 to 100 mcg/mL.

Storage/Stability

Store capsules between 59° and 86°F and oral solution between 68° and 77°F. Protect oral solution from freezing and light.

Drug Interactions

Carbamazepine

Ethosuximide concentrations and pharmacologic effects may be decreased. Monitor closely and adjust the ethosuximide dosage as needed.

Hydantoins (eg, phenytoin)

Coadministration may decrease ethosuximide concentrations and increase phenytoin serum levels. Monitor for signs of phenytoin toxicity and phenytoin plasma concentrations. Adjust the dosage accordingly.

Isoniazid

Ethosuximide plasma concentrations may be elevated, possibly with GI, CNS, and psychotic symptoms. If an interaction is suspected, measure ethosuximide plasma levels, assess the patient's clinical status, and adjust the dose accordingly.

Valproic acid

Valproic acid has been reported to both increase and decrease ethosuximide serum levels. If an interaction is suspected, measure ethosuximide levels and adjust the dose accordingly.

Adverse Reactions

CNS

Aggressiveness; ataxia; dizziness; drowsiness; euphoria; fatigue; headache; hyperactivity; increased depression with overt suicidal intentions; increased libido; irritability; lethargy; night terrors; poor concentration; sleep disorders.

Dermatologic

Hirsutism; pruritic erythematous rash; SLE; Stevens-Johnson syndrome; urticaria.

GI

Anorexia; cramps; diarrhea; epigastric and abdominal pain; GI upset; gum hypertrophy; nausea; tongue swelling; vomiting; weight loss.

Genitourinary

Microscopic hematuria; vaginal bleeding.

Hematologic

Agranulocytosis; bone marrow suppression; eosinophilia; leukopenia; pancytopenia.

Miscellaneous

Allergic reaction; hiccups; myopia.

Precautions

Monitor

Perform periodic urinalysis and LFTs in all patients. Monitor blood cell counts periodically for blood dyscrasias. Monitor patients for emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts or behavior, or thoughts about self-harm.


Pregnancy

Category undetermined . Anticonvulsant drugs have been observed to increase the incidence of birth defects.

Lactation

Excreted in breast milk. The American Academy of Pediatrics classifies ethosuximide as compatible with breast-feeding.

Children

Safety and effectiveness in pediatric patients younger than 3 y not established.

Renal Function

Use with extreme caution.

Hepatic Function

Use with extreme caution.

Hazardous Tasks

May impair mental and/or physical ability required to perform potentially hazardous tasks, such as driving or other activities requiring alertness.

Hematologic effects

Blood dyscrasias, including some with fatal outcomes, have occurred.

Hepatic effects

Abnormal LFTs have been reported.

Renal effects

Abnormal renal function studies have been reported.

Suicidal behavior and ideation

AEDs, including ethosuximide, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Increased risk has been observed as early as 1 wk after starting treatment with AEDs.

Systemic lupus erythematosus

Cases have been reported.

Withdrawal seizures

Do not withdraw drug abruptly as this may precipitate absence status; proceed slowly when increasing or decreasing dose.

Overdosage

Symptoms

CNS depression; coma; nausea; respiratory depression; vomiting.

Patient Information

  • Advise patients or caregivers to read the Medication Guide before starting therapy and with each refill.
  • Counsel patients, families, or caregivers that antiepileptic drugs may increase the risk of suicidal thoughts and behavior and to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts or behavior, or thoughts about self-harm, and to immediately report any of these symptoms to their health care provider.
  • Advise patients with epilepsy to carry medical identification (eg, card, bracelet) indicating medication usage and epilepsy.
  • Advise patients that the drug may cause drowsiness and to use caution while driving or performing other tasks requiring mental alertness.
  • Instruct patients to report these symptoms to their health care provider: skin rash, sore throat, fever, unusual bleeding or bruising, swollen glands, pregnancy.
  • Tell patients to avoid intake of alcoholic beverages or other CNS depressants.
  • Advise pregnant patients taking ethosuximide to enroll in the North American Antiepileptic Drug Pregnancy Registry. This can be done by calling 1-888-233-2334.

Copyright © 2009 Wolters Kluwer Health.

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