Meprobamate

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. If symptoms (such as redness or irritation) develop, immediately transport the victim to a hospital.

Meprobamate preparations generally should be stored in tight containers at a temperature less than 40 °C, preferably at 15-30 °C. However, USP states that the tablets can be stored in well-closed containers. The fixed-combination tablets of meprobamate and aspirin should be stored in tight, light-resistant containers at 20-25 °C and protected from moisture.

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with 60-70% ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with 60-70% ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

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.

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

Meprobamate crosses the placenta; the maternal blood meprobamate levels approximate those of the fetus. Meprobamate is excreted in breast milk and should not be given to lactating mothers. An epidemiologic study of the use of meprobamate in pregnancy (1,870 offspring) did not reveal any increased evidence of fetal demise or abnormalities when these children were studied until 4 years of age.

Meprobamate is distributed into the milk of lactating women in a concentration 2-4 times that in plasma.

Excretion of meprobamate may be incr to point of net tubular secretion by addn of furosemide to saline diuresis. This resulted in excretion of 35% of admin dose of meprobamate over 4 hr period.

Although animal studies indicated that meprobamate shortened the half-life of warfarin, subsequent human studies have shown the meprobamate does not have any clinically important effect on warfarin-induced hypoprothrombinemia.

Although imipramine enhances the CNS effects of meprobamate in animals, no clinically important effect of this interaction has been documented in humans.

Additive CNS depression may occur when meprobamate is administered concomitantly with other CNS depressants, including alcohol. If meprobamate is used concomitantly with other depressant drugs, including alcohol, caution should be used to avoid overdosage.

For more Interactions (Complete) data for MEPROBAMATE (6 total), please visit the HSDB record page.

Rates of serum enzyme elevations during meprobamate therapy have not been reported. While instances of clinically apparent liver injury due to meprobamate have been mentioned in review articles, no cases with specific information on clinical features have appeared in the published literature. Thus, meprobamate may be capable of causing clinically apparent liver injury, but it must be rare. Meprobamate is metabolized in the liver via the cytochrome P450 system and has major potential for drug-drug interactions. Meprobamate can exacerbate symptoms of porphyria. Serious allergic reactions to meprobamate have been reported including Stevens Johnson syndrome. In cases of meprobamate overdose, the cause of death has been respiratory suppression and not liver failure, although liver histology was not well defined.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 60(SRC), determined from a log Kow of 0.70(2) and a regression-derived equation(3), indicates that meprobamate is expected to have high mobility in soil(SRC). Volatilization of meprobamate from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.8X10-10 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Meprobamate is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.0X10-3 mm Hg at 25 °C(SRC), determined from a fragment constant method(5). Meprobamate has been classified as non-biodegradable(6).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 60(SRC), determined from a log Kow of 0.70(2) and a regression-derived equation(3), indicates that meprobamate is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 1.8X10-10 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 3(SRC), from its log Kow(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Meprobamate has been classified as non-biodegradable(7).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), meprobamate, which has an estimated vapor pressure of 3.0X10-3 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase meprobamate is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 20 hours(SRC), calculated from its rate constant of 1.9X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Meprobamate does not contain chromophores that absorb at wavelengths >290 nm(4) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

EXPERIMENTAL: Meprobamate is excreted in /human/ breast milk and should not be given to lactating mothers.

EXPERIMENTAL: Meprobamate is distributed into the milk of lactating women in a concentration 2-4 times that in plasma.

The Koc of meprobamate is estimated as 60(SRC), using a log Kow of 0.70(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that meprobamate is expected to have high mobility in soil.

/SIGNS AND SYMPTOMS/ Sudden withdrawal of the drug after prolonged and excessive use may precipitate recurrence of pre-existing symptoms such as anxiety, anorexia, insomnia, or withdrawal reactions such as vomiting, ataxia, tremors, muscle twitching, confusional states, hallucinosis, and rarely, convulsive seizures. Such seizures are more likely to occur in persons with central nervous system damage or pre-existent or latent convulsive disorders. Onset of withdrawal symptoms occurs usually within 12 to 48 hours after discontinuation of meprobamate; symptoms usually cease within the next 12 to 48 hours.

/SIGNS AND SYMPTOMS/ Physical dependence, psychological dependence, and abuse have occurred. When chronic intoxication from prolonged use occurs, it usually involves ingestion of greater than recommended doses and is manifested by ataxia, slurred speech, and vertigo. Therefore, careful supervision of dose and amounts prescribed is advised, as well as avoidance of prolonged administration, especially for alcoholics and other patients with a known propensity for taking excessive quantities of drugs.

/SIGNS AND SYMPTOMS/ Tolerance and psychologic and physical dependence may occur following prolonged use of high doses of meprobamate. Daily ingestion of 3.2 g of meprobamate for weeks or months has produced physical dependence and withdrawal symptoms when the drug was suddenly discontinued. Because of the drug's potential for inducing dependence, prolonged administration of meprobamate is not recommended.

/SIGNS AND SYMPTOMS/ Symptoms of meprobamate dependence are similar to those of barbiturate dependence or chronic alcoholism and may include drowsiness, ataxia, slurred speech, and vertigo. Sudden discontinuance of the drug in physically dependent patients may produce severe withdrawal symptoms within 12-48 hours including anxiety, anorexia, insomnia, vomiting, ataxia, tremors, muscle twitching, confusion, hallucinations, and seizures clinically indistinguishable from generalized tonic-clinic (grand mal) seizures. Seizures are most likely to occur in patients ingesting large amounts of the drug or patients who have CNS damage or a history of seizure disorders. Some fatalities have occurred following abrupt withdrawal of meprobamate. Withdrawal symptoms usually cease within 12-48 hours they appear.

For more Human Toxicity Excerpts (Complete) data for MEPROBAMATE (18 total), please visit the HSDB record page.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Meprobamate

vNo-DILI-concern

0

No match

DOI:10.1016/j.drudis.2016.02.015

An estimated BCF of 3 was calculated in fish for meprobamate(SRC), using a log Kow of 0.70(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Henry's Law constant for meprobamate is estimated as 1.8X10-10 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that meprobamate is expected to be essentially nonvolatile from water surfaces(2). Meprobamate is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.0X10-3 mm Hg(SRC), determined from a fragment constant method(3).

Schedule IV shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. Depressants. Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation which contains any quantity of the following substances, including its salts, isomers, and salts of isomers whenever the existence of such salts, isomers, and salts of isomers is possible within the specific chemical designation: Meprobamate (DEA Code Number: 2820) is included on this list.

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

Medicine (antianxiety agent)

THERAP CAT: Anxiolytic

Meprobamate is rapidly absorbed after oral administration and has a duration of 3 - 4 hr. Its primary clinical use is for daytime sedation in anxious patients, but it is occasionally administered orally as part of a regimen of bedrest and physical rehabilitation for painful musculoskeletal conditions.

Meprobamate is an anxiolytic agent which has anticonvulsant, myorelaxant, and sedative properties, but it does not directly interfere with the GABA-receptor complex ... This carbamate derivative has been used for the management of anxiety disorders and tension states but has been superseded by benzodiazepines.

For more Uses (Complete) data for MEPROBAMATE (6 total), please visit the HSDB record page.

/Meprobamate is/ prepared by reaction of 2-methyl-2-propyl-1,3-propanediol with excess phosgene and ammonium hydroxide.

Preparation: ... Berger, Ludwig, US 2724720 (1955 to Carter Prod.)

Oral: Tablets 200 mg Meprobamate Tablets (Watson); 400 mg Meprobamate Tablets (Watson). NOTE: Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name.

Oral: Tablets: 200 mg with Aspirin 325 mg, Equagesic (C-IV; scored) (Leitner). /Meprobamate combinations/

1,3-Propanediol, 2-methyl-2-propyl-, 1,3-dicarbamate: ACTIVE

This is a controlled substance (depressant): 21CFR1308.14