Methsuximide (Celontin) is a succinimide like ethosuximide. It is used in the treatment of patients with absence seizures or petit mal seizures (in which the patient suddenly becomes blank and unresponsive for a brief period of time)

Methsuximide (Celontin) Uses:

• Absence (petit mal) seizures, refractory:

  • It is prescribed to treat absence (petit mal) seizures that are resistant to other medications.

Methsuximide (Celontin) Dose in Adults:

Methsuximide (Celontin) Dose in refractory Absence (petit mal) seizures:

• 300 mg orally daily for the first week;
• The maximum daily dose is 30 mg/kg/day not to exceed 1,200 mg/day in divided doses. 
• A slower titration may be considered to avoid toxicity and rapid accumulation of the active metabolite (N-desmethylmethsuximide).

Methsuximide (Celontin) Dose in childrens:

Methsuximide (Celontin) Dose in refractory Seizures; adjunct therapy:

The data is limited in various seizure types except absence seizures. It has been found useful especially in Lennox-Gastaut syndrome and symptomatic focal epilepsies.

• Children and Adolescents:

  • Initial: 5 mg/kg/day orally once a day.
  • The dose is titrated at weekly intervals in 3.2 to 5.5 mg/kg/week increments as tolerated in three or four divided doses to achieve clinical response and target serum concentrations.
  • The maximum daily dose is 30 mg/kg/day not to exceed 1,200 mg/day in divided doses. 
  • A therapeutic range of 25 to 45 mcg/mL for the active metabolite, N-desmethylmethsuximide (NDMSM) in pediatric patients has been suggested.

Pregnancy Risk Category: C

• Due to multiple factors, including genetics and medications, teratogenecity in epileptic patients is higher.
• Monotherapy with one drug is usually recommended. Avoid polytherapy with higher doses.
• Once seizure control is at its best, patients should be tested for antiepileptic medication levels before they are allowed to have a planned pregnancy.

Use of methsuximide during breastfeeding

• • It is unknown whether the drug can be excreted into breastmilk. 
  • It is important to weigh the benefits and risks of treating the mother as well as the potential for drug exposure in the infant.

Dose in Kidney Disease:

There is no dosage modification specified in the manufacturer's labelling; people with kidney problems should use it cautiously.

Dose in Liver disease:

There is no dosage modification specified in the manufacturer's labelling; patients with liver problems should use it cautiously.

Side effects of Methsuximide (Celontin):

• Cardiovascular:

  • Hyperemia

• Central Nervous System:

  • Psychosis
  • Ataxia
  • Depression
  • Mental Slowness
  • Dizziness
  • Irritability
  • Hallucinations (Auditory)
  • Insomnia
  • Headache
  • Mental Instability
  • Drowsiness
  • Nervousness
  • Hypochondriacal Behavior
  • Confusion
  • Suicidal Behavior
  • Aggressiveness

• Dermatologic:

  • Urticaria
  • Rash
  • Pruritus
  • Stevens-Johnson Syndrome

• Gastrointestinal:

  • Anorexia
  • Constipation
  • Epigastric Pain
  • Nausea
  • Vomiting
  • Diarrhea
  • Weight Loss
  • Abdominal Pain

• Genitourinary:

  • Hematuria (Microscopic)
  • Proteinuria

• Hematologic:

  • Pancytopenia
  • Eosinophilia
  • Monocytosis
  • Leukopenia

• Ocular:

  • Photophobia
  • Periorbital Edema
  • Blurred Vision

• Miscellaneous:

  • Hiccups
  • Systemic Lupus Erythematosus

Contraindications to Methsuximide (Celontin):

• History of hypersensitivity to succinimides

Warnings and precautions

• Blood dyscrasias

  • Sometimes, severe blood dyscrasias can be caused by the treatment.
  • It is important to monitor blood counts regularly, especially if there are clinical signs of infection.

• Depression in the CNS:

  • It can cause sleepiness, CNS depression, and other symptoms that could impair mental or physical abilities.
  • Patients who are required to be alert for driving or operating heavy machinery should be cautious about taking the drug.

• SLE:

  • Systemic lupus, also known as SLE, has been linked to methsuximide and succinimides.

• Suicidal thoughts:

  • Most antiepileptics have suicide risk, with a rate of 0.43 percent in patients who received placebo.
  • Suicidal tendencies can be more common with long-term treatment, but they can be detected as soon as one week after treatment began.
  • Patients must be monitored for any changes in behavior that could indicate depression or suicidal thoughts. 
  • If any symptoms are noticed, healthcare personnel must be notified immediately.

• Hepatic impairment

  • Patients with impaired liver function or liver disease should be cautious.

Methsuximide: Drug Interaction Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• CBC,
• Liver function tests,
• Urinalysis;
• Monitor for suicidal tendencies such as suicidal thoughts, depression, and behavioral changes
• Monitor the serum concentrations of concomitant antiepileptic drugs.

How to administer Methsuximide (Celontin)?

• It is given without consideration for meals.
• It may be administered after meals to reduce the gastrointestinal side effects.

Mechanism of action of Methsuximide (Celontin):

• It decreases motor cortex neuronal transmission and increases seizure threshold. It reduces absence seizures patients' spike and wave patterns.

Metabolism:

• It undergoes fast demethylation in the liver, where it is converted to N-desmethylmethsuximide (the active metabolite).

Half-life elimination:

• 2 to 4 hours
• N-desmethylmethsuximide:
  • Children: 26 hours;
  • Adults: 28 to 80 hours

Time to peak, serum:

• Within 1 to 3 hours

Excretion:

• Urine (<1% as unchanged drug)

International Brand Names of Methsuximide:

• Celontin

Methsuximide Brand Names in Pakistan:

No Brands Available in Pakistan.