Pharmaceuticals -> Used in SwitzerlandPharmaceuticals -> Antiepileptics
LogP（分配係数）
log Kow = 0.380.10.23
臭い
CHARACTERISTIC ODOR
Color/Form
Crystals from acetone and etherWHITE TO OFF-WHITE CRYSTALLINE POWDER OR WAXY SOLID
溶解度
Freely soluble in waterVERY SLIGHTLY SOL IN SOLVENT HEXANE1.01e+02 g/Lエタノール：100mg/mL190g/L(25℃)
Human Drugs
Breast FeedingLactationMilk, HumanAnticonvulsantsFDA approved drugs -> Active ingredientPharmaceuticalsAntiseizure medicines
Decomposition
When heated to decomposition it emits toxic fumes of /nitrogen oxide/.
融点
64 - 65 °C64.5 °C51 °C
Physical Description
Solid
Stability/Shelf Life
Commercially available capsules have an expiration date of 5 years and the oral solution has an expiration date of 4 years following the date of manufacture.Stable in light, air, and heat at 37 °C
Collision Cross Section
123.52 Ų [M+H-H2O]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]
WarningH302 (95.7%): Harmful if swallowed [Warning Acute toxicity, oral]P264, P270, P301+P317, P330, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 46 reports by companies from 4 notifications to the ECHA C&L Inventory.
規制情報
Ethosuximide: Does not have an individual approval but may be used under an appropriate group standard
その他の安全情報
IMAP assessments - 2,5-Pyrrolidinedione, 3-ethyl-3-methyl-: Environment tier I assessment
FDA 要件
The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl ethosuximide, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.
Special Reports
Review with 11 ref on absorption, distribution, excretion, placental transfer, & protein binding.[CHANG T ET ALANTIEPILEPTIC DRUGS 417 (1972)]
Hazard Classes and Categories
Acute Tox. 4 (95.7%)
保管条件
Ethosuximide capsules should be stored in tight containers at a temperature less than 30 °C, preferably between 15-30 °C. Ethosuximide oral solution should be stored in tight, light-resistant containers at a temperature less than 30 °C, preferably between 15-30 °Cfreezing should be avoided.
処分方法
SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.
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. Hemodialysis may be useful to treat ethosuximide overdose. Forced diuresis and exchange transfusions are ineffective. (L1712)
相互作用
... It is thus assumed that the probable mechanism of action of ethosuximide consists in lowering calcium transport since the inhibitors of calcium transport sodium nitroprusside and verapamil intensify the blocking effect of ethosuximide on smooth muscle contractile activity.
Ethosuximide is an anticonvulsant drug that is used in minor forms of epilepsy.
一般的な説明
Ethosuximide is considered the prototypical anticonvulsantneeded for treating patients with absence seizures.Ethosuximide and the N-dealkylated active metabolite ofmethsuximide work by blocking the lowthresholdT-type calcium channels, thereby reducing thehyperexcitability of thalamic neurons that is specifically associatedwith absence seizure.
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/
For more Interactions (Complete) data for ETHOSUXIMIDE (8 total), please visit the HSDB record page.
健康影響
May cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease.
Hepatotoxicity
Prospective studies suggest that chronic ethosuximide therapy is not accompanied by significant elevations in serum aminotransferase levels, but can increase gamma glutamyltranspeptidase levels. Clinically apparent hepatotoxicity from ethosuximide is very rare with few case reports published despite use of this agent for half a century. Futhermore, the liver injury in reported cases was usually mild and asymptomatic and a part of a generalized hypersensitivity syndrome with fever, rash, facial edema, lymphadenopathy, and eosinophilia or atypical lymphocytosis. The usual latency to onset of the hypersensitivity syndrome is 2 to 8 weeks. The typical serum enzyme elevations are a mixed-cholestatic-hepatocellular pattern and reported cases have not been jaundiced. While the product labeling for ethosuximide warns of hepatic dysfunction and recommends periodic monitoring of liver tests, clinically apparent liver injury with jaundice from ethosuximide is rare.
有害作用
The overall incidence of adverse effects associated with ethosuximide therapy is lower compared to most other anti-seizure medications (ASMs). Gastrointestinal adverse effects (eg, nausea, vomiting, diarrhea, anorexia) are common initially and often diminish within 2 weeks. Other common adverse effects include drowsiness, lethargy, insomnia, and hiccups. Headache may occur in 14% of children taking ethosuximide.
暴露経路
Bioavailability following oral administration is 93%.
Milk Concentrations
...The breast milk concentrations of ES were similar to those in maternal serum (milk/serum: 0.86 +/- 0.08, n = 12) and the nursed infants maintained serum levels between 15 and 40 micrograms/mL. ...... Concentrations of ethosuximide in breast milk may approach 94% of plasma concentrations.A total of 10 epileptic mothers treated with ethosuximide (ES) as well as their 13 newborns were included in this study. ... The breast milk concentrations of ES were similar to those in maternal serum (milk/serum: 0.86 +/- 0.08, n = 12) and the nursed infants maintained serum levels between 15 and 40 ug/mL. ...
毒性の概要
Signs and Symptoms of OverdoseBinds to T-type voltage sensitive calcium channels. Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1G gives rise to T-type calcium currents. T-type calcium channels belong to the "low-voltage activated (LVA)" group and are strongly blocked by mibefradil. A particularity of this type of channels is an opening at quite negative potentials and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes.
Signs and Symptoms
Acute overdoses may produce nausea, vomiting, and CNS depression including coma with respiratory depression.
Human Toxicity Excerpts
/HUMAN EXPOSURE STUDIES/ A total of 10 epileptic mothers treated with ethosuximide (ES) as well as their 13 newborns were included in this study. At birth fetal/maternal serum concentration ratios were 0.97 +/- 0.02 (n = 7) and ES half-lives in three neonates were 32, 37 and 38 hr. The breast milk concentrations of ES were similar to those in maternal serum (milk/serum: 0.86 +/- 0.08, n = 12) and the nursed infants maintained serum levels between 15 and 40 ug/mL. Two major malformations (bilateral clefting, hare-lip) were observed in two neonates whose mothers received either ES/PB or ES/PMD comedication. The number of minor anomalies was higher in the ES group (6.2, n = 12) than in the pair-matched control group of infants born to non-epileptic mothers (2.1, n = 10). Neonatal behaviour complications occurred in seven infants, two of them were severely affected./HUMAN EXPOSURE STUDIES/ The use of ethosuximide has been reported in 163 pregnancies. Due to the lack of specific information on the observed malformations, mutiple drug therapies, and differences in study methodology, conclusions linking the use of ethosuximide with congenital defects are difficult. Spontaneous hemorrhage in the neonate following in utero exposure to ethosuximide has been reported. Abnormalities identified with ethosuximide use in 10 pregnancies include: patent ductus arteriosus (eight cases)cleft lip and/or palate (seven cases)mongoloid faces, short neck, altered palmar crease and accessory nipple (one case)hydrocephalus (one case)./SIGNS AND SYMPTOMS/ Acute overdoses may produce nausea, vomiting, and CNS deppression including coma with respiratory depression. A relationship between ethosuximide toxicity and plasma levels has not been established./SIGNS AND SYMPTOMS/ The use of ethosuximide has also been associated with blood dyscrasias including leukopenia, eosinophilia, agranulocytosis, pancytopenia, (with or without bone marrow depression) and aplastic anemia which have sometimes resulted in fatalities.For more Human Toxicity Excerpts (Complete) data for ETHOSUXIMIDE (13 total), please visit the HSDB record page.
Carcinogen Classification
No indication of carcinogenicity to humans (not listed by IARC).
Drug Induced Liver Injury
Drug Induced Liver Injury Rank (DILIrank 2.0)EthosuximideAmbiguous-DILI-concern3Warnings & precautionsDOI:10.1016/j.drudis.2016.02.015
