Methsuximide

Pronunciation: meth-SUX-i-mide
Class: Succinimide

Trade Names

Celontin
- Capsules 300 mg

Pharmacology

Elevates seizure threshold and suppresses paroxysmal spike wave activity associated with lapses of consciousness common in absence (petit mal) seizures.

Slideshow: Flashback: FDA Drug Approvals 2013

Pharmacokinetics

Absorption

T max is 1 to 4 h and is readily absorbed.

Elimination

The half-life is 2.6 to 4 h. Less than 1% recovered unchanged in urine.

Indications and Usage

Control of absence (petit mal) seizures that are refractory to other drugs.

Contraindications

Hypersensitivity to succinimides.

Dosage and Administration

Adults and Children

PO 300 mg/day for the first week. Dosage may be increased at weekly intervals by 300 mg/day for 3 wk following to a daily dosage of 1,200 mg/day.

General Advice

  • Optimal dosing is the amount of methsuximide that is barely sufficient to control seizures so that side effects may be kept to a minimum.
  • May be administered with other anticonvulsants when other forms of epilepsy coexist with absence (petit mal).
  • Administer with or without food.

Storage/Stability

Store at 59° to 86°F. Protect from excessive heat (104°F), moisture, and light.

Drug Interactions

Carbamazepine, hydantoins (eg, phenytoin)

Methsuximide plasma concentrations may be reduced, decreasing the efficacy. Additionally, plasma concentrations of phenytoin may be elevated by methsuximide, increasing the risk of adverse reactions. Monitor methsuximide and phenytoin concentrations and observe the clinical response of the patient. Adjust the dose of methsuximide and phenytoin as needed.

Lamotrigine

Plasma concentrations may be reduced by methsuximide, decreasing the therapeutic effects. Monitor lamotrigine concentrations and observe the clinical response of the patient. Adjust the lamotrigine dose as needed.

Phenobarbital, primidone

Plasma concentrations of the active metabolite of primidone, phenobarbital, may be elevated by methsuximide, increasing the risk of adverse reactions. Monitor phenobarbital concentrations and observe the clinical response of the patient. Adjust the dose of primidone or phenobarbital as needed.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hyperemia.

CNS

Aggressiveness; ataxia; auditory hallucinations; confusion; depression; dizziness; drowsiness; headache; hypochondriacal behavior; insomnia; instability; irritability; mental slowness; nervousness; psychosis; suicidal behavior.

Dermatologic

Pruritic erythematous rash; Stevens-Johnson syndrome; urticaria.

EENT

Blurred vision; periorbital edema; photophobia.

GI

Anorexia; constipation; diarrhea; epigastric and abdominal pain; hiccups; nausea; vomiting; weight loss.

Genitourinary

Microscopic hematuria; proteinuria.

Hematologic

Eosinophilia; leukopenia; monocytosis; pancytopenia (with and without bone marrow suppression).

Precautions

Monitor

Closely monitor patients for clinical worsening (including development of new symptoms) and suicidality, especially at the beginning of treatment or at the time of dose changes. Perform periodic blood cell counts, urinalysis, and liver function studies.


Pregnancy

Category C . Anticonvulsant drugs have been associated with an increase in the incidence of birth defects.

Lactation

Undetermined.

Renal Function

Use with extreme caution.

Hepatic Function

Use with extreme caution.

Dosage adjustment

Proceed slowly when increasing or decreasing the dose, as well as when adding or eliminating other medications.

Grand mal seizures

May increase frequency of grand mal seizures when used alone in mixed types of epilepsy.

Hematologic

Blood dyscrasias, including fatal cases, have occurred.

Suicidal behavior and ideation

Antiepileptic drugs increase the risk of suicidal thoughts and behaviors in patients taking these drugs for any indication.

Systemic lupus

Systemic lupus has occurred.

Withdrawal

Withdraw slowly if unusual depression, aggressiveness, or other behavioral alterations occur. Do not withdraw drug abruptly as this may precipitate absence (petit mal) seizures.

Overdosage

Symptoms

CNS depression (including coma with respiratory depression), nausea, vomiting, .

Patient Information

  • Instruct patient to take exactly as prescribed and to not change the dose or stop taking unless advised by health care provider.
  • Advise patient that dose may be gradually increased no more often than every week until max benefit is achieved.
  • Advise patient to swallow capsule whole and to not chew or break the capsule.
  • Advise patient that each dose may be taken without regard to meals but to take with food if GI upset occurs.
  • Advise patient that if medication needs to be discontinued it will be slowly withdrawn over a period of several weeks unless safety concerns (eg, rash) require a more rapid withdrawal.
  • Inform patients that methsuximide may increase the risk of suicidal thoughts and behavior.
  • Caution patient that drug may cause drowsiness, dizziness, or blurred vision and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
  • Instruct patient to contact health care provider immediately if any of the following occur: rash; joint pain; fever, sore throat, or other signs of infection; unusual bruising or bleeding; depression; aggressive behavior or other behavioral changes.
  • Instruct patient to inform health care provider if seizures get worse of if new types of seizures occur.

Copyright © 2009 Wolters Kluwer Health.

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