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Methsuximide


General


Pronunciation

(meth SUKS i mide)


Brand Names: U.S.

  • Celontin

Indications


Use: Labeled Indications

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


Contraindications


History of hypersensitivity to succinimides


Dosing and Administration


Dosing: Adult

Anticonvulsant: Oral: 300 mg/day for the first week; may increase by 300 mg/day at weekly intervals up to 1.2 g/day in 2-4 divided doses/day


Dosing: Geriatric

Refer to adult dosing.


Dosing: Renal Impairment

No dosage adjustment provided in manufacturer 's labeling; use with caution.


Dosing: Hepatic Impairment

No dosage adjustment provided in manufacturer 's labeling; use with caution.


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).


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Celontin: 300 mg


Drug Interactions

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

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 patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy

CYP2C19 Inducers (Strong): May increase the metabolism of CYP2C19 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP2C19 Inhibitors (Moderate): May decrease the metabolism of CYP2C19 Substrates. Monitor therapy

CYP2C19 Inhibitors (Strong): May decrease the metabolism of CYP2C19 Substrates. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP2C19 Substrates. Management: Seek alternatives to the CYP2C19 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Dimethindene: 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 (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification

Enzalutamide: May decrease the serum concentration of CYP2C19 Substrates. Conversely, concentrations of active metabolites may be increased for those drugs activated by CYP2C19. Management: Concurrent use of enzalutamide with CYP2C19 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP2C19 substrate should be performed with caution and close monitoring. Consider therapy modification

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Consider starting with a 20% to 30% lower hydrocodone dose when using together with any other CNS depressant. Dose reductions in the other CNS depressant may also be warranted. 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

Luliconazole: May increase the serum concentration of CYP2C19 Substrates. Monitor therapy

Lumacaftor: May decrease the serum concentration of CYP2C19 Substrates. 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. 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 adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

Mianserin: May diminish the therapeutic effect of Anticonvulsants. Monitor therapy

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Orlistat: May decrease the serum concentration of Anticonvulsants. Monitor therapy

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: When oxycodone is combined with another CNS depressant, a dose reduction of one or both agents should be considered. The extended release oxycodone starting dose should be reduced 50% to 67% when initiated in patients already receiving CNS depressants. 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 [INT]: CNS Depressants may enhance the CNS depressant effect of Piribedil [INT]. 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

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification

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

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Start tapentadol at a dose of one-third to one-half of the normal dose if being initiated in a patient who is taking another drug with CNS depressant effects. Monitor closely for evidence of excessive CNS depression. Consider therapy modification

Tetrahydrocannabinol: 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


Monitoring Parameters

CBC, hepatic function tests, urinalysis; suicidality (eg, suicidal thoughts, depression, behavioral changes)


Adverse Reactions


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


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.


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).

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.


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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


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience fatigue, headache, abdominal pain, constipation, lack of appetite, weight loss, insomnia, or sensitivity to light. Have patient report immediately to prescriber signs of infection, signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), signs of lupus (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), signs of depression (suicidal ideation, anxiety, emotional instability, or illogical thinking), confusion, change in balance, vision changes, hematuria, severe nausea, severe vomiting, severe diarrhea, severe loss of strength and energy, bruising, bleeding, agitation, irritability, panic attacks, or mood changes (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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