Methsuximide
FDA Drug Information • Also known as: Celontin, Methsuximide
- Brand Names
- Celontin, Methsuximide
- Dosage Form
- POWDER
- Product Type
- BULK INGREDIENT
Description
DESCRIPTION Celontin (methsuximide) is an anticonvulsant succinimide, chemically designated as N,2-Dimethyl-2-phenylsuccinimide, with the following structural formula: Each Celontin capsule contains 300 mg methsuximide, USP. Also contains starch, NF. The capsule contains colloidal silicon dioxide, NF; D&C yellow No. 10; FD&C yellow No. 6; gelatin, NF; and sodium lauryl sulfate, NF. Molecular structure.jpg
What Is Methsuximide Used For?
INDICATIONS AND USAGE Celontin is indicated for the control of absence (petit mal) seizures that are refractory to other drugs.
Dosage and Administration
DOSAGE AND ADMINISTRATION Optimum dosage of Celontin must be determined by trial. A suggested dosage schedule is 300 mg per day for the first week. If required, dosage may be increased thereafter at weekly intervals by 300 mg per day for the three weeks following to a daily dosage of 1.2 g. Because therapeutic effect and tolerance vary among patients, therapy with Celontin must be individualized according to the response of each patient. Optimal dosage is that amount of Celontin which is barely sufficient to control seizures so that side effects may be kept to a minimum. Celontin may be administered in combination with other anticonvulsants when other forms of epilepsy coexist with absence (petit mal).
Side Effects (Adverse Reactions)
ADVERSE REACTIONS Gastrointestinal System: Gastrointestinal symptoms occur frequently and have included nausea or vomiting, anorexia, diarrhea, weight loss, epigastric and abdominal pain, and constipation. Hemopoietic System: Hemopoietic complications associated with the administration of methsuximide have included eosinophilia, leukopenia, monocytosis, and pancytopenia with or without bone marrow suppression. Nervous System : Neurologic and sensory reactions reported during therapy with methsuximide have included drowsiness, ataxia or dizziness, irritability and nervousness, headache, blurred vision, photophobia, hiccups, and insomnia. Drowsiness, ataxia, and dizziness have been the most frequent side effects noted. Psychologic abnormalities have included confusion, instability, mental slowness, depression, hypochondriacal behavior, and aggressiveness. There have been rare reports of psychosis, suicidal behavior, and auditory hallucinations. Integumentary System : Dermatologic manifestations which have occurred with the administration of methsuximide have included urticaria, Stevens-Johnson syndrome, and pruritic erythematous rashes. Cardiovascular : Hyperemia. Genitourinary System : Proteinuria, microscopic hematuria. Body as a Whole : Periorbital edema.
Warnings and Precautions
WARNINGS Blood dyscrasias Blood dyscrasias, including some with fatal outcome, have been reported to be associated with the use of succinimides; therefore, periodic blood counts should be performed. Should signs and/or symptoms of infection (eg, sore throat, fever) develop, blood counts should be considered at that point. Effects on Liver It has been reported that succinimides have produced morphological and functional changes in animal liver. For this reason, methsuximide should be administered with extreme caution to patients with known liver or renal disease. Periodic urinalysis and liver function studies are advised for all patients receiving the drug. Systemic Lupus Erythematosus Cases of systemic lupus erythematosus have been reported with the use of succinimides. The physician should be alert to this possibility. Suicidal Behavior and Ideation Antiepileptic drugs (AEDs), including Celontin, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide. The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed. The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5–100 years) in the clinical trials analyzed. Table 1 shows absolute and relative risk by indication for all evaluated AEDs. Table 1 Risk by indication for antiepileptic drugs in the pooled analysis Indication Placebo Patients with Events Per 1000 Patients Drug Patients with...
Drug Interactions
Drug Interactions Since Celontin (methsuximide) may interact with concurrently administered antiepileptic drugs, periodic serum level determinations of these drugs may be necessary (eg, methsuximide may increase the plasma concentrations of phenytoin and phenobarbital).
Contraindications
CONTRAINDICATIONS Methsuximide should not be used in patients with a history of hypersensitivity to succinimides.
Pregnancy and Breastfeeding
Usage in Pregnancy Reports suggest an association between the use of anticonvulsant drugs by women with epilepsy and an elevated incidence of birth defects in children born to these women. Data are more extensive with respect to phenytoin and phenobarbital, but these are also the most commonly prescribed anticonvulsants; less systematic or anecdotal reports suggest a possible similar association with the use of all known anticonvulsant drugs. The reports suggesting an elevated incidence of birth defects in children of drug-treated epileptic women cannot be regarded as adequate to prove a definite cause and effect relationship. There are intrinsic methodologic problems in obtaining adequate data on drug teratogenicity in humans; the possibility also exists that other factors, eg, genetic factors or the epileptic condition itself, may be more important than drug therapy in leading to birth defects. The great majority of mothers on anticonvulsant medication deliver normal infants. It is important to note that anticonvulsant drugs should not be discontinued in patients in whom the drug is administered to prevent major seizures because of the strong possibility of precipitating status epilepticus with attendant hypoxia and threat to life. In individual cases where the severity and frequency of the seizure disorder are such that the removal of medication does not pose a serious threat to the patient, discontinuation of the drug may be considered prior to and during pregnancy, although it cannot be said with any confidence that even minor seizures do not pose some hazard to the developing embryo or fetus. The prescribing physician will wish to weigh these considerations in treating or counseling epileptic women of childbearing potential. Pregnancy To provide information regarding the effects of in utero exposure to Celontin, physicians are advised to recommend that pregnant patients taking Celontin enroll in the (NAAED) Pregnancy Registry. This can be done by calling the...
Overdosage
OVERDOSAGE Acute overdoses may produce nausea, vomiting, and CNS depression including coma with respiratory depression. Methsuximide poisoning may follow a biphasic course. Following an initial comatose state, patients have awakened and then relapsed into a coma within 24 hours. It is believed that an active metabolite of methsuximide, N-desmethylmethsuximide, is responsible for this biphasic profile. It is important to follow plasma levels of N-desmethylmethsuximide in methsuximide poisonings. Levels greater than 40 µg/mL have caused toxicity, and coma has been seen at levels of 150 µg/mL. Treatment 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.
How Supplied
HOW SUPPLIED N 0071-0525-24 (P-D 525)–Celontin Capsules, #1 capsule each containing 300 mg methsuximide; bottles of 100. Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) [see USP Controlled Room Temperature]. Protect from light and moisture. Protect from excessive heat 40°C (104°F).
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.