Methsuximide

Treatment should include emesis (unless the patient is or could rapidly become obtunded, comatose, or convulsing) or gastric lavage, activated charcoal, cathartics, and general supportive measures. Charcoal hemoperfusion may be useful in removing the N-desmethyl metabolite of methsuximide. Forced diuresis and exchange transfusions are ineffective. (L1712)

Concurrent use /with alcohol; central nervous system depression-producing medications; tricyclic antidepressants; loxapine; maprotiline; molindone; monoamine oxidase inhibitors; phenothiazines; pimozide; thioxanthenes/ may lower the convulsive threshold, enhance CNS depression, and decrease the effects of the anticonvulsant medication. /Succinimide anticonvulsants/

Requirements for folic acid may be increased in patients receiving anticonvulsant therapy. /Succinimide anticonvulsants/

Induction of hepatic microsomal enzyme activity resulting in increased metabolism and decreased serum concentrations and elimination half-lives of succinimide anticonvulsants and/or these medications /carbamazepine, phenobarbital, phenytoin, primidone/ may occur during concurrent therapy; monitoring of serum concentrations as a guide to dosage is recommended, especially when any anticonvulsant is added to or withdrawn from an existing regimen. /Succinimide anticonvulsants/

Concurrent use /with haloperidol/ may cause a change in the pattern and/or the frequency of epileptiform seizures; dosage adjustments of the anticonvulsant may be necessary; serum concentrations of haloperidol may be significantly reduced. /Succinimide anticonvulsants/

For more Interactions (Complete) data for METHSUXIMIDE (9 total), please visit the HSDB record page.

Prospective studies suggest that chronic methsuximide therapy is not accompanied by significant elevations in serum aminotransferase levels, although it has been shown to have hepatotoxicity in animals. Clinically apparent hepatotoxicity from methsuximide has not been reported, although hypersensitivity reactions with fever and rash are not uncommon (1% to 5%). The product label for methsuximide warns of hepatic dysfunction and recommends periodic liver function studies. Nevertheless, clinically apparent liver injury from methsuximide must be very rare, if it occurs at all.

Methsuximide suppresses the paroxysmal three cycle per second spike and wave activity associated with lapses of consciousness which is common in absence (petit mal) seizures. The frequency of epileptiform attacks is reduced, apparently by depression of the motor cortex and elevation of the threshold of the central nervous system to convulsive stimuli.

/SIGNS AND SYMPTOMS/ Adverse hematologic effects associated with methsuximide include eosinophilia, leukopenia, monocytosis, and pancytopenia. Adverse dermatologic effects may include urticaria, pruritic erythematous rash, and Steven-Johnson syndrome. Adverse genitourinary effects associated with methsuximide include proteinuria and microscopic hematuria. Periorbital edema and hyperemia have also occurred. Systemic lupus erythematosus has been associated with succinimide use.

/SIGNS AND SYMPTOMS/ GI disturbances such as ... diarrhea, wt loss, epigastric & abdominal pain, & constipation occur frequently. Hemopoietic complications including eosinophilia ... Monocytosis, & pancytopenia have been reported. Neurologic & sensory reactions observed including ... irritability, nervousness ... blurred vision, photophobia...and insomnia.

/SIGNS AND SYMPTOMS/ Dermatologic disturbances including urticaria, Stevens-Johnson syndrome, & pruritic erythematous rashes.

/SIGNS AND SYMPTOMS/ Drowsiness, gastrointestinal disturbance, hiccups, irritability, and headache /are/ the common side effects of methsuximide.

For more Human Toxicity Excerpts (Complete) data for METHSUXIMIDE (9 total), please visit the HSDB record page.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Methsuximide

vNo-DILI-concern

0

No match

DOI:10.1016/j.drudis.2016.02.015

/LABORATORY ANIMALS: Acute Exposure/ Phensuximide (PSX), methsuximide (MSX) and ethosuximide (ESX) are succinimide antiepileptie agents used worldwide in the treatment of absence seizures. A previous study ... demonstrated that PSX (0.3 or 0.6 mmol/kg/day ip) induced urotoxicity following daily administration for 5-7 days in Fischer 344 rats, but PSX (1.25 mmol/kg, ip) induced only minimal urotoxicity following acute administration. The purpose of this study was to determine the acute nephrotoxic potential of MSX and ESX in male Fischer 344 rats and if antiepileptic succinimide induced urotoxicity is potentiated by phenobarbital pretreatment. In one set of experiments, rats (four rats per group) were administered a single ip injection of a succinimide (0.4 or 1.0 mmol/kg) or vehicle (sesame oil, 2.5 mL/kg), and the renal function was monitored at 24 and 48 hr. Neither ESX or MSX induced substantial changes in renal function or morphology, which suggests that neither compound is acutely nephrotoxic. Similar results were obtained with PSX, whiCh supported ... earlier findings with this antiepileptic agent. In a second set of experiments, rats (four rats per group) were pretreated for 3 days with phenobarbital (75 mg kg/day, ip) prior to receiving a succinimide (0.4 or 1.0 mmol/kg, ip) or vehicle (sesame oil, 2.5 mL/kg, ip). Renal function was monitored at 24 and 48 hr after the last injection. Phenobarbital pretreatment had only minor effects on ESX or MSX induced renal effects, with no significant morphological changes detected between treated and pair fed control groups.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ ... Drugs of widely differing pharmacological activity have been administered to partially hepatectomized male rats and the extent of liver regeneration ascertained over a period of ten days. ... The following fed ad lib in diets supplemented in a basal ration at the weight percent 0.15 methsuximide ... was hepatotrophic. ...

While data specific to methsuximide were not located(SRC, 2007), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2).

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl methsuximide, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Anticonvulsant

Anticonvulsant succinimide

MEDICATION

Use (kg; approx.) in Germany (2009): >100

For the control of absence (petit mal) seizures that are refractory to other drugs.

2-methyl-2-phenylsuccinic acid is dissolved in excess of 40% methylamine. Water & excess amine are distilled off & residue consisting of di(methylamine) salt of acid is pyrolized at about 250 °C until no more distillate is formed. Residue of crude methsuximide may be purified by vacuum dist or by...precipitation...

Prepd by action of methylamine on alpha-methyl-alpha-phenylsuccinic acid.

Acetophenone + ethyl cyanoacetate + hydrogen cyanide + methylamine (Cope reaction/addition/nitrile hydrolysis/decarboxylation/amide formation).

CELONTIN

MESUXIMIDE

MESUXIMIDUM

METHSUXIMID

For more Formulations/Preparations (Complete) data for METHSUXIMIDE (6 total), please visit the HSDB record page.