methsuximide (Celontin, Kapseal)

Introduction

Tradename: Celontin, Kapseals. Methsuximide was introduced in 1956 for treatment of absence seizures. Ethosuximide subsequently proved more effective.

Indications

• absence (petit mal) seizures
• adjunctive therapy for refractory complex-partial seizures

Dosage

• adults: start 300 mg PO QD for 1st week
• may increase by 300 mg/day at weekly intervals up to 1.2 g/day divided BID-QID

Tabs: 150 & 300 mg.

Pharmacokinetics

• metabolized in liver to active metabolite N-desmethyl- methsuximide
• t1/2 of 2-4 hours
• t1/2 of N-desmethylmethsuximide is 28-36 hours

elimination via liver

elimination via kidney

1/2life = 2-4 hours

1/2life = 30-50 hours N-desmethyl methsuximide

protein binding = <5 % small

Monitor

• liver function tests periodically

• monitor with anticonvulsants

Adverse effects

• common (> 10%)
  • Stevens-Johnson syndrome, lupus-like syndrome, anorexia, ataxia, dizziness, drowsiness, hiccups, headache, nausea/vomiting, weight loss
• less common (1-10%)
  • aggressiveness, depression, nightmares, weakness, lethargy
• uncommon (< 1%)
  • agranulocytosis, leukopenia, aplastic anemia, thrombocytopenia, pancytopenia, paranoid psychosis, urticaria, exfoliative dermatitis

• drug adverse effects of anticonvulsants

Drug interactions

• increases phenytoin level
• enhances conversion of primidone to phenobarbital
• agents which may increase methsuximide metabolism
  • carbamazepine
  • phenobarbital
  • phenytoin
  • primidone
• valproic acid may increase or decrease methsuximide levels

• drug interaction(s) anticonvulsants with anti-bacterial agents
• drug interaction(s) anticonvulsants with statins

Laboratory

• specimen: serum
• methods: HPLC, GLC

More general terms

• succinimide
• anticonvulsant

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=6476