Methsuximide
Medically reviewed by Drugs.com. Last updated on Nov 25, 2024.
Pronunciation
(meth SUKS i mide)
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Celontin: 300 mg [contains fd&c yellow #10 (quinoline yellow), fd&c yellow #6 (sunset yellow)]
Brand Names: U.S.
- Celontin
Pharmacologic Category
- Anticonvulsant, Succinimide
Pharmacology
Increases the seizure threshold and suppresses paroxysmal spike-and-wave pattern in absence seizures; depresses nerve transmission in the motor cortex
Metabolism
Metabolism: Hepatic; rapidly demethylated to N-desmethylmethsuximide (active metabolite)
Excretion
Urine (<1% as unchanged drug)
Time to Peak
Serum: 1 to 3 hours
Half-Life Elimination
2 to 4 hours
N-desmethylmethsuximide: Children: 26 hours; Adults: 28 to 80 hours
Use: Labeled Indications
Absence (petit mal) seizures, refractory: Control of absence (petit mal) seizures that are refractory to other drugs
Contraindications
History of hypersensitivity to succinimides
Dosing: Adult
Absence (petit mal) seizures, refractory: Oral: 300 mg daily for the first week; may increase by 300 mg/day at weekly intervals up to 1.2 g/day in 2 to 4 divided doses; slower titrations may be considered to avoid toxic accumulation of active metabolite (N-desmethylmethsuximide) (Brown 1983).
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Seizures, refractory; adjunct therapy: Limited data available in various seizure types except absence; has been found useful especially in Lennox-Gastaut syndrome and symptomatic focal epilepsies (Sigler 2001): Children and Adolescents: Oral: Initial: 5 mg/kg/day once daily; titrate at weekly intervals in 3.2 to 5.5 mg/kg/week increments as tolerated in divided doses every 6 to 8 hours to clinical response and target serum concentrations; maximum daily dose: 30 mg/kg/day not to exceed 1,200 mg/day in divided doses. For the active metabolite, N-desmethylmethsuximide (NDMSM), a therapeutic range of 25 to 45 mcg/mL in pediatric patients has been suggested; in a retrospective analysis of 15 patients, the reported mean dose was 20.4 mg/kg/day and mean serum concentration 34.3 mg/L (Nelson 1996; Sigler 2001; Tennison 1991)
Storage
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F); protect from excessive heat 40°C (104°F). Protect from light and moisture. Note: Methsuximide has a relatively low melting temperature (124°F); do not store in conditions that promote high temperatures (eg, in a closed vehicle).
Drug Interactions
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Avoid combination
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Consider therapy modification
Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Bromopride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Avoid combination
Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Consider therapy modification
Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy
Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Consider therapy modification
Esketamine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy
Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Consider therapy modification
Lisuride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Mefloquine: May diminish the therapeutic effect of Anticonvulsants. Mefloquine may decrease the serum concentration of Anticonvulsants. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of convulsions. If anticonvulsants are being used for another indication, monitor anticonvulsant concentrations and treatment response closely with concurrent use. Consider therapy modification
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Consider therapy modification
Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy
Mianserin: May diminish the therapeutic effect of Anticonvulsants. Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification
Orlistat: May decrease the serum concentration of Anticonvulsants. Monitor therapy
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Avoid combination
Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Consider therapy modification
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification
Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Monitor therapy
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification
Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification
Adverse Reactions
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not defined.
Cardiovascular: Hyperemia
Central nervous system: Aggressiveness, ataxia, confusion, depression, dizziness, drowsiness, hallucinations (auditory), headache, hypochondriacal behavior, insomnia, irritability, mental instability, mental slowness, nervousness, psychosis, suicidal behavior
Dermatologic: Pruritus, rash, Stevens-Johnson syndrome, urticaria
Gastrointestinal: Abdominal pain, anorexia, constipation, diarrhea, epigastric pain, nausea, vomiting, weight loss
Genitourinary: Hematuria (microscopic), proteinuria
Hematologic: Eosinophilia, leukopenia, monocytosis, pancytopenia
Ocular: Blurred vision, periorbital edema, photophobia
Miscellaneous: Hiccups, systemic lupus erythematosus
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Warnings/Precautions
Concerns related to adverse effects:
• Blood dyscrasias: Succinimides have been associated with severe blood dyscrasias (sometimes fatal). Monitor blood counts periodically, especially if signs/symptoms of infection develop.
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• SLE: Succinimides have been associated with cases of systemic lupus erythematosus (SLE).
• Suicidal ideation: Pooled analysis of trials involving various antiepileptics (regardless of indication) showed an increased risk of suicidal thoughts/behavior (incidence rate: 0.43% treated patients compared to 0.24% of patients receiving placebo); risk observed as early as 1 week after initiation and continued through duration of trials (most trials ≤24 weeks). Monitor all patients for notable changes in behavior that might indicate suicidal thoughts or depression; notify healthcare provider immediately if symptoms occur.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Renal impairment: Use with caution in patients with renal impairment.
Concurrent drug therapy issues:
• Sedatives: Effects with other sedative drugs or ethanol may be potentiated.
Other warnings/precautions:
• Appropriate use: Must be used in combination with other anticonvulsants in patients with both absence and tonic-clonic seizures. May increase tonic-clonic seizures when used alone in patients with mixed seizure disorders.
• Withdrawal: Anticonvulsants should not be discontinued abruptly because of the possibility of increasing seizure frequency; therapy should be withdrawn gradually to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal.
Monitoring Parameters
CBC, hepatic function tests, urinalysis; suicidality (eg, suicidal thoughts, depression, behavioral changes); serum concentrations of concomitant antiepileptic drugs (Besag 2000; Besag 2001; Browne 1983).
Reproductive Considerations
For women with epilepsy who are planning a pregnancy in advance, baseline serum concentrations should be measured once or twice prior to pregnancy during a period when seizure control is optimal (Patsalos 2008; Patsalos 2018).
Pregnancy Considerations
Epilepsy itself, the number of medications, genetic factors, or a combination of these may influence the teratogenicity of anticonvulsant therapy. In general, polytherapy may increase the risk of congenital malformations; monotherapy with the lowest effective dose is recommended (Harden 2009). For women with epilepsy who are planning a pregnancy in advance, baseline serum concentrations should be measured once or twice prior to pregnancy during a period when seizure control is optimal. Monitoring can then be continued up to once a month during pregnancy in women with stable seizure control (Patsalos 2008; Patsalos 2018).
Patients exposed to methsuximide during pregnancy are encouraged to enroll themselves into the NAAED Pregnancy Registry by calling 1-888-233-2334. Additional information is available at www.aedpregnancyregistry.org.
Patient Education
What is this drug used for?
• It is used to help control certain kinds of seizures.
All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
• Feeling sleepy
• Dizziness or headache
• Constipation, diarrhea, stomach pain, upset stomach, throwing up, or feeling less hungry
• Weight loss
• Trouble sleeping
• Hiccups
WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
• Infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal
• Liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes
• Lupus like a rash on the cheeks or other body parts, sunburn easy, muscle or joint pain, chest pain or shortness of breath, or swelling in the arms or legs
• Stevens-Johnson syndrome like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in the mouth, throat, nose, or eyes
• Feeling confused
• Change in balance
• Any unexplained bruising or bleeding
• Purple spots or redness of the skin
• Feeling very tired or weak
• Change in eyesight
• If bright lights bother your eyes
• Swollen gland
• Depression; feeling nervous, restless, or grouchy; panic attacks; or other changes in mood or behavior
• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.
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