药品名称

通用名称：甲琥胺（锡朗丁）
英文名：Methsuximide(Mesuximide,Celontin,Petinutin)
性状：白色或灰白色结晶性粉末；无臭或有微臭。微溶于水（1：350）、易溶于乙醇（1：3）、氯仿（1：1）、乙醚（1：2）。
生产厂家：Pfizer 辉瑞
作用机制

与琥胺类似，但对癫痫小发作的作用较弱。
药动学

口服易吸收，起效和维持时间类似苯琥胺。半衰期仅为1.2-1.6h，但其在肝脏经N-去甲基代谢后的产物抗癫痫的活性几乎与原药相等，且半衰期达28-36h。
注意事项

不良反应与苯琥胺相同，但毒性较大。主要有恶心、呕吐、乏力、嗜睡等，还有皮疹、粒细胞降低、肝、肾功能损害。
适应症

用于治疗癫痫小发作和复杂性部分发作。因其毒性较大而疗效较低，主要用于对其他抗癫痫药物疗效不显著者。
用法用量

口服：成人，开始剂量300mg/d，分次服用，以后每周增加300mg，直至最高剂量1.2g/d。
任何疑问,请遵医嘱!
规格

胶囊剂：300mg。

英文药名: Celontin (Methsuximide Capsules)

中文药名: 甲琥胺胶囊

生产厂家: Pfizer

CELONTIN (methsuximide)

CELONTIN (methsuximide) elevates the seizure threshold in the cortex and basal ganglia and reduces synaptic response to low frequency repetitive stimulation. The paroxysmal spike and wave pattern of the EEG, common in petit mal seizure, is suppressed.

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.

Limited studies indicate that the drug is metabolized via N-demethylation to N-demethylmethsuximide (NDM). Profound CNS depression following methsuximide overdose has been attributed to this metabolite, and it is probable that the anticonvulsant effects of the drug are due to NDM. In one study, which measured methsuximide and NDM levels simultaneously in plasma of patients who were receiving methsuximide chronically, the concentration of NDM was 700 times greater than the concentration of methsuximide. On the basis of this study, a tentative therapeutic plasma level of 10 to 40 µg/mL of NDM has been proposed.

Less than 1% of a dose of methsuximide is excreted unchanged in the urine, although a number of as yet unidentified metabolites are excreted in urine.
 
Only available
with prescription

INDICATIONS AND CLINICAL USAGE

CELONTIN (methsuximide) is used for the control of absence (petit mal) seizures refractory to other drugs.

CONTRAINDICATIONS

Methsuximide should not be used in patients with a history of hypersensitivity to succinimides, methsuximide or any component of this medication.
 
PRECAUTIONS
 
General

Proceed slowly when increasing or decreasing dosage, as well as when adding or eliminating other medication. Abrupt withdrawal of anticonvulsant medications may precipitate petit mal status.

Methsuximide, when used alone in mixed types of epilepsy, may increase the frequency of grand mal seizures in some patients.

Hematopoietic Effect

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. Patients should be instructed to promptly contact their physician if they develop signs and/or symptoms suggesting an infection (eg. Sore throat, fever); blood counts should be considered at that point.

Hepatic/Renal Impairment

It has been reported that succinimides, including methsuximide, have produced morphological and functional changes in animal liver. For this reason, administer methsuximide 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.

Autoimmune Disorders

Cases of systemic lupus erythematosus have been reported with the use of methsuximide. The physician should be alerted to this possibility.

Psychiatric

It is recommended that the physician withdraw the drug slowly on the appearance of unusual depression, aggression, or other behavioral alterations.

Information to be Provided to the Patient

Methsuximide may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a motor vehicle or other such activity requiring alertness; therefore the patient should be cautioned accordingly.

Patients taking methsuximide should be advised of the importance of adhering strictly to the prescribed dosage regimen.

Patients should be instructed to promptly contact their physician if they develop signs and/or symptoms (e.g., sore throat, fever) suggesting an infection.

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).

Lamotrigine: Methsuximide may lower the serum concentrations of lamotrigine. When methsuximide is used in combination with lamotrigine, adjustment of the lamotrigine dose may be necessary when methsuximide is started or stopped.

Pregnancy: Recent reports indicate an association between the use of anticonvulsant drugs and an elevated incidence of birth defects in children born to epileptic women taking such medications during pregnancy. The incidence of congenital malformations in the general population is regarded to be approximately 2%; in children of treated epileptic women this incidence may be increased 2- to 3-fold. The increase is largely due to specific defects, e.g., congenital malformations of the heart, and cleft lip and/or palate. Nevertheless, the great majority of mothers receiving anticonvulsant medications deliver normal infants.

Data are more extensive with respect to phenytoin and phenobarbital, but these drugs are also the most commonly prescribed anticonvulsants. Some reports indicate a possible similar association with the use of other anticonvulsants, including trimethadione and paramethadione. However, the possibility also exists that other factors, e.g., genetic predisposition or the epileptic condition itself may contribute to or may be mainly responsible for the higher incidence of birth defects.

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 risk to both the mother and the unborn child. With regard to drugs given for minor seizures, the risk of discontinuing medications prior to or during pregnancy should be weighed against the risk of congenital defects in the particular case and with the particular family history.

Epileptic women of childbearing age should be encouraged to seek professional counsel and should report the onset of pregnancy promptly to their physician. Where the necessity for continued use of the antiepileptic medication is in doubt, appropriate consultation might be indicated.

The preceding considerations should be borne in mind and methsuximide should be used in women of childbearing potential only when the expected benefits to the patients warrant the possible risk to a fetus.

Lactation: Methsuximide is excreted in human breast milk. Because the effects of methsuximide on the nursing infant are unknown, caution should be exercised when methsuximide is administered to a nursing mother. Methsuximide should be used in nursing mothers only if the benefits clearly outweigh the risks.

Occupational Hazards: Methsuximide may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a motor vehicle or other such activities requiring alertness; therefore, caution the patient accordingly.

ADVICE TO THE PHARMACIST AND PATIENT: Since methsuximide has a relatively low melting temperature (51.1 °C), storage conditions which may promote high temperatures (closed cars, delivery vans, or storage near steam pipes) should be avoided. Do not dispense or use capsules that are not full or in which contents have melted. Effectiveness may be reduced. Protect from excessive heat (40.0 °C).

ADVERSE REACTIONS
 
Body as a Whole: Abdominal pain, fever, headache and systemic lupus erythematosus (see PRECAUTIONS, Autoimmune Disorders).

Digestive System: Anorexia, constipation, diarrhea, epigastric pain, nausea, vomiting.

Hemic and Lymphatic System: Eosinophilia, leukopenia, monocytosis, pancytopenia with or without bone marrow suppression (see PRECAUTIONS, Hematopoietic Effect).

Metabolism and Nutrition: Porphyria, weight loss.

Nervous System: Aggression, ataxia, auditory hallucinations, depression, dizziness, drowsiness, insomnia, irritability, nervousness, psychosis.

Drowsiness, ataxia, and dizziness have been the most frequent adverse effects noted.

Psychological abnormalities have included confusion, instability, mental slowness, depression, hypochondriacal behavior, and aggression. There have been rare reports of psychosis, suicidal behavior and auditory hallucinations (see PRECAUTIONS, Psychiatric).

Respiratory System: Hiccups

Skin/Appendages: Rash, Stevens-Johnson syndrome, urticaria. ,

Special Senses: Blurred vision, photophobia.

Urogenital: Microscopic hematuria, proteinuria.

Miscellaneous: Periorbital edema, hyperemia.

SYMPTOMS AND TREATMENT OF 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 mcg/mL have caused toxicity, and coma has been seen at levels of 150 mcg/mL. (see ACTION AND CLINICAL PHARMACOLOGY)

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.

DOSAGE AND ADMINISTRATION 
 
Optimal dosage (that which is just sufficient to control seizures without causing disturbing side effects) must be determined by trial and should be individualized according to the needs of each patient. A suggested schedule is 300 mg daily for the first week. If required, the daily dosage may be increased at weekly intervals by 300 mg/day for the 3 weeks following to a daily dosage of 1200 mg.

Capsule Composition

Each yellow capsule with orange cap contains: methsuximide 300 mg. Nonmedicinal ingredients: cornstarch; capsule shell: D&C Yellow No. 10, FD&C Red No. 3, FD&C Yellow No. 6 and gelatin. Energy: 1.57 kJ (0.38 kcal). Gluten-, lactose-, paraben-, sodium-, sulfite- and tartrazine-free.

Stability and Storage Recommendation

Store CELONTIN (methsuximide) between 15 and 30°C. Protect from light, moisture and excessive heat.

AVAILABILITY OF DOSAGE FORMS
 
CELONTIN (methsuximide) capsules are available in the dosage strength of 300 mg per capsule.
Each capsule with yellow body and orange cap, is imprinted with "Parke-Davis".
Available in bottles of 100.

PHARMACOLOGY
 
Drug Substance

Proper Name: Methsuximide

Chemical Name: (±)-1,3-dimethyl-3-phenylpyrrolidine-2,5-dione

Empirical Formula: C12H13NO2

Molecular Weight: 203.24

Melting Range: 50o to 56oC