Ethotoin

204.22518

204.23

201-665-1

760074

DTXSID6023020

Stout prisms from water.

N - Nervous system

2933210000

52.90000

0.87730

Solid

1.197 g/cm1.197 g/cm3

94 °C

342.72°C (rough estimate)

1.555

2.38e+00 g/L

Store below 40 deg C (104 deg F), preferably between 15 and 30 deg C (59 and 86 deg F), unless otherwise specified by manufacturer. Store in a tight container. /Ethotoin/

5.5X10-8 mm Hg at 25 deg C (est)

Henry's Law constant = 3.7X10-10 atm0cu m/mol at 25 °C (est)

Hydroxyl radical reaction rate constant = 1.4X10-11 cu cm/molec-sec at 25 °C (est)

22

Ethotoin darkens on exposure to light or extreme heat.

P264, P270, P301+P312, P330, P501

H302

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.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl ethotoin, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Badalian LO, et al; Zh Nevropatol Psikhiatr Im S S Korsakova 93 (1): 90-3 (1993). Epilepsy and pregnancy, a review.|Strasnick B, Jacobson JT; J Am Acad Audiol 6 (1): 28-38 (1995). Teratogenic hearing loss /is reviewed/.|Maternal factors, medications and drug exposure in congenital limb reduction defects.[Foster UG, Baird PA; Environ Health Perspect 101 (Suppl 3): 269-74 (1993)]|Markova IV; Farmakol Toksikol 53 (4): 82-6 (1990). The undesirable action of drugs on the embryo, fetus and newborn infant.|For more Special Reports (Complete) data for ETHOTOIN (9 total), please visit the HSDB record page.

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P264, P270, P301+P312, P330, and P501|Aggregated GHS information provided by 43 companies from 1 notifications to the ECHA C&L Inventory.

Symptoms of overdose include drowsiness, loss of or impaired muscle coordination, nausea, visual disturbance, and, at very high doses, coma.

Risk of hepatotoxicity from a single toxic dose or prolonged use of acetaminophen may be increased and therapeutic efficacy may be decreased in patients regularly taking other hepatic enzyme-inducing agents such as phenytoin. /Hydantoin anticonvulsants/|Concurrent use of alcohol or CNS depression-producing medications with hydantoin anticonvulsants may enhance CNS depression. Chronic use of alcohol may decrease serum concentrations and effectiveness of hydantoins; concurrent use of hydantoin anticonvulsants with acute alcohol intake may increase serum hydantoin concentrations. /Hydantoin anticonvulsants/|Concurrent use of amiodarone with phenytoin and possibly with other hydantoin anticonvulsants may increase plasma concentrations of the hydantoin, resulting in increased effects and/or toxicity. /Hydantoin anticonvulsants/|Concurrent use with coumarin- or indandione-derivative anticoagulants, chloramphenicol, cimetidine, disulfiram, influenza virus vaccine, isoniazid, methylphenidate, phenylbutazone, ranitidine, salicylates, or sulfonamide may increase serum concentrations of hydantoin anticonvulsants because of decreased metabolism, thereby increasing the hydantoins' effects and/or toxicity. /Hydantoin anticonvulsants/|For more Interactions (Complete) data for ETHOTOIN (22 total), please visit the HSDB record page.

LD50 Mouse sc 1060 mg/kg|LD50 Mouse ip 923 mg/kg|LD50 Rat sc 1000 mg/kg|LD50 Rat ip 625 mg/kg|LD50 Rat oral 1500 mg/kg

Following equal doses of phenytoin, total plasma phenytoin concentrations are lower in chronic uremic patients than in non-uremic patients which suggests an altered metabolic disposition of the drug in patients with uremia. /Phenytoin/

While data specific to ethotoin were not located(SRC, 2007), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2).

Ethotoin is distributed into milk. Because of the potential for serious adverse reactions from ethotoin in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.

For the control of tonic-clonic (grand mal) and complex partial (psychomotor) seizures.

Anticonvulsants|Hydantoin anticonvulsants are indicated in the suppression and control of tonic-clonic (grand mal) and simple or complex partial (psychomotor or temporal lobe) seizures. Ethotoin may be administered as a second-line agent when seizures have not been adequately controlled by the primary anticonvulsants and before proceeding to more toxic anticonvulsants. /Hydantoin anticonvulsants; Included in US product labeling./|Hydantoin anticonvulsants are not indicated in the treatment of absence (petit mal) seizures, or as first-line treatment of febrile, hypoglycemic, or other metabolic seizures. When tonic-clonic (grand mal) seizures coexist with absence seizures, combined therapy may be necessary. /Hydantoin anticonvulsants; NOT included in US product label/|Ethotoin may be substituted for phenytoin without loss of seizure control for improvement of gum hyperplasia, or other side effects, during anticonvulsant therapy. Ethotoin doses are usually 4 to 6 times greater than those of phenytoin. /NOT included in US product label/

Ethotoin is contraindicated in patients with hepatic abnormalities or hematologic disorders.|Although the etiologic role of ethotoin has not been definitely established, blood dyscrasias have been reported in patients receiving the drug, and clinicians should be alert to the possibility of their occurrence. Patients should be advised to report immediately any sign or symptom indicative of hematologic toxicity (e.g., sore throat, fever, malaise, petechiae, easy bruising, epistaxis). Complete blood cell counts should be performed before and at monthly intervals for several months after initiation of ethotoin therapy. The drug should be discontinued if marked depression of blood cell count occurs.|Liver function tests should be performed in patients receiving ethotoin if there is clinical evidence of possible hepatic dysfunction. If signs of hepatotoxicity occur during ethotoin therapy, the drug should be discontinued.|Ataxia and gingival hyperplasia have been reported only rarely during ethotoin therapy and usually only in patients receiving an additional hydantoin derivative. When ethotoin has replaced other hydantoin-derivative anticonvulsants, both of these reactions have subsided in some patients.|For more Drug Warnings (Complete) data for ETHOTOIN (16 total), please visit the HSDB record page.

Ethotoin is a hydantoin derivative and anticonvulsant. Ethotoin exerts an antiepileptic effect without causing general central nervous system depression. The mechanism of action is probably very similar to that of phenytoin. The latter drug appears to stabilize rather than to raise the normal seizure threshold, and to prevent the spread of seizure activity rather than to abolish the primary focus of seizure discharges.

A class of drugs that inhibit the activation of VOLTAGE-GATED SODIUM CHANNELS. (See all compounds classified as Voltage-Gated Sodium Channel Blockers.)|Drugs used to prevent SEIZURES or reduce their severity. (See all compounds classified as Anticonvulsants.)

Fairly rapidly absorbed, however, the extent of oral absorption is not known.|Ethotoin is fairly rapidly absorbed from the GI tract following oral administration; the extent of absorption is not known.|Therapeutic serum concentrations range from 15 to 50 ug/mL (74 to 245 umol/L) for ethotoin.|Ethotoin and phenytoin are distributed into breast milk...|Limited data suggest that ethotoin and, to a lesser degree, 5-phenylhydantoin (the N-deethylated metabolite) may exhibit nonlinear pharmacokinetics following oral administration of single 500-, 1000-, and 1500-mg doses of ethotoin. The degree of nonlinearity may increase following oral administration of multiple doses (with a dosing interval of 4-6 hours) of ethotoin when compared with single doses, probably secondary to accumulation of the drug in plasma.|For more Absorption, Distribution and Excretion (Complete) data for ETHOTOIN (9 total), please visit the HSDB record page.

Hepatic. The drug exhibits saturable metabolism with respect to the formation of N-deethyl and p-hydroxyl-ethotoin, the major metabolites.|Ethotoin is metabolized by the liver to p-hydroxylated and m-hydoxylated derivatives following N-deethylation; these metabolites are conjugated with glucuronic acid. The N-deethylated metabolite may also be metabolized to 2-phenylhydantoic acid. Ethotoin appears to exhibit saturable metabolism with respect to the formation of the p-hydroxylated and N-deethylated metabolites.|The rate of hepatic biotransformation is increased in younger children, in pregnant women, in women during menses, and in patients with acute trauma; rate decreases with advancing age. /Hydantoin anticonvulsants/|The urinary excretion pattern of ethotoin and five metabolites were examined in three patients receiving continuous treatment with ethotoin at two dose levels, in order to investigate the mechanism behind the dose-dependent kinetics of this anticonvulsant drug. The results suggest a partial saturation in the dealkylation process at high dose levels in three patients. A rough approximation of the Michaelis-Menten constants for different enzymatic processes was attempted. On the basis of the results obtained, the p-hydroxylation may be a saturable process. The dose-dependent kinetics of ethotoin in man seem to be explicable by the existence of partly saturable enzymatic pathways.

3 to 9 hours|At plasma concentrations less than about 8 ug/mL, ethotoin reportedly has an elimination half-life of 3-9 hours.|Ethotoin administration was 25 mg per kilogram in 5 patients. Ethotoin Tmax was 2 hours, with a T 1/2 of 5 hours. Saliva accurately represented the unbound fraction for ... /ethotoin/. Mean salivary levels (as percentage of total levels) were ... 54% for ethotoin.

The mechanism of action is probably very similar to that of phenytoin. The latter drug appears to stabilize rather than to raise the normal seizure threshold, and to prevent the spread of seizure activity rather than to abolish the primary focus of seizure discharges. Ethotoin inhibits nerve impulses in the motor cortex by lowering sodium ion influx, limiting tetanic stimulation.|The mechanism of action is not completely known, but it is thought to involve stabilization of neuronal membranes at the cell body, axon, and synapse and limitation of the spread of neuronal or seizure activity. ... Hydantoin anticonvulsants have an excitatory effect on the cerebellum, activating inhibitory pathways that extend to the cerebral cortex. This effect may also produce a reduction in seizure activity that is associated with an increased cerebellar Purkinje cell discharge. /Hydantoin anticonvulsants/

Since there is no specific antidote for overdose with hydantoin anticonvulsants, treatment is symptomatic and supportive and may include the following: ... Multiple oral doses of charcoal and cathartic may shorten the duration of symptoms. Supportive care - oxygen, vasopressors, and assisted ventilation may be necessary for CNS, respiratory, or cardiovascular depression. Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation. Following recovery, careful evaluation of blood-forming organs is advisable. /Hydantoin anticonvulsants/|Maintain an open airway and assist ventilation if necessary. Administer supplemental oxygen. Treat stupor and coma if they occur. Protect the patient from self-injury caused by ataxia. If seizures occur, consider an alternate diagnosis and treat with other usual anticonvulsants. If hypotension occurs with intravenous phenytoin administration, immediately stop the infusion and administer intravenous fluids and pressors if necessary. There are no specific antidotes. Decontamination: administer activated charcoal orally if conditions are appropriate. Gastric lavage is not necessary after small to moderate ingestions if activated charcoal can be given promptly. Elimination: Repeat-dose activated charcoal may enhance phenytoin elimination but is not necessary and may increase the risk of aspiration pneumonitis in drowsy patients. There is no role for diuresis, dialysis, or hemoperfusion.|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/SIGNS AND SYMPTOMS/ Clinical effects of overdose include ataxia (clumsiness or unsteadiness) or staggering walk, blurred or double vision, severe confusion, severe dizziness or drowsiness, dysarthria (stuttering) or slurred speech, hyperreflexia, nausea and vomiting, nystagmus (continuous, uncontrolled back-and-forth and/or rolling eye movements), tremor, and unusual tiredness or weakness. /Hydantoin anticonvulsants/|/OTHER TOXICITY INFORMATION/ The fetal hydantoin syndrome has been associated with the use of the more potent phenytoins. Only six reports describing the use of ethotoin during the first trimester have been located. Congenital malformations observed in two of these cases included cleft lip/plate and patent ductus arteriosus. No cause-and-effect relationship was established. Although the toxicity of ethotoin appears to be lower than the more potent phenytoin, the occurrence of congenital defects in two fetuses exposed to ethotoin suggests that a teratogenic potential may exist.|/OTHER TOXICITY INFORMATION/ Because acute attacks of porphyria may be precipitated by anticonvulsants, a therapeutic dilemma arises when seizures complicate hepatic porphyria. The list of unsafe agents includes barbiturates, primidone, phenytoin, mephenytoin, ethotoin, ethosuximide, methsuximide, phensuximide, and trimethadione. Agents are considered unsafe if they induce experimental porphyria in animals, and short trials in patients are unreliable for screening.

ethotoin

Peganone

Analyte: ethotoin; matrix: chemical identification; procedure: ultraviolet absorption spectrophotometry with comparison to standards|Analyte: ethotoin; matrix: chemical identification; procedure: retention time of the major peak of the liquid chromatogram with comparison to standards|Analyte: ethotoin; matrix: chemical purity; procedure: liquid chromatography with detection at 210 nm and comparison to standards|Analyte: ethotoin; matrix: pharmaceutical preparation (tablet); procedure: retention time of the major peak of the liquid chromatogram with comparison to standards (chemical identification)|Analyte: ethotoin; matrix: pharmaceutical preparation (tablet); procedure: liquid chromatography with detection at 254 nm and comparison to standards (chemical purity)

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