(1-Methylethyl)carbaminsäure-2-(((aminocarbonyl)-oxy)methyl)-2-methylpentylester

DEA NFLIS-Drug Category -> Depressants and Tranquilizers

DEA Schedule IV Controlled Substance -> Depressants

Pharmaceuticals -> Synthetic Cannabinoids or Psychoactive Compounds

Pharmaceuticals

2.1

2.01

less than 1 mg/mL at 67.1 °F (NTP, 1992)

slightly soluble

Soluble in most common organic solvents; practically insoluble in vegetable oils

In water, 30 mg/100 mL at 25 °C; 140 mg/100 mL water at 50 °C

7.92e-01 g/L

Breast Feeding; Lactation; Milk, Human; Muscle Relaxants, Central

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Pharmaceuticals

198 to 199 °F (NTP, 1992)

92 °C

92 - 93 °C

Carisoprodol is a white powder. (NTP, 1992)

Solid

172.2 Ų [M+Na]+ [CCS Type: DT; Buffer gas: N2; Ionization: ESI+; Dataset: TOXCAST; Source Identifier: DTXSID8024733]

149.1 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

167.96 Ų [M+Na]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

Warning

H302 (100%): 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 43 reports by companies from 1 notifications to the ECHA C&L Inventory.

SYMPTOMS: The most common symptoms of exposure to this chemical are drowsiness and hives. Other symptoms may include nausea, vomiting, epigastric distress, vertigo, ataxia, tremors, agitation, irritability, headache, insomnia, fainting, hiccups, visual disturbances, asthma, fever, hypotension, excitement and paralysis. (NTP, 1992)

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

This is notice that the Drug Enforcement Administration (DEA) will hold a hearing with respect to the proposed placement of carisoprodol in schedule IV of the Controlled Substances Act (21 U.S.C. 801, et seq.). The control of carisoprodol was initially proposed in a Notice of Proposed Rulemaking published in the Federal Register on November 17, 2009 (74 FR 59108).

CARISOPRODOL is a carbamate ester. Carbamates are chemically similar to, but more reactive than amides. Like amides they form polymers such as polyurethane resins. Carbamates are incompatible with strong acids and bases, and especially incompatible with strong reducing agents such as hydrides. Flammable gaseous hydrogen is produced by the combination of active metals or nitrides with carbamates. Strongly oxidizing acids, peroxides, and hydroperoxides are incompatible with carbamates.

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. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

Carisoprodol tablets should be stored in well-closed containers at a temperature less than 40 °C, preferably at 15-30 °C.

Store in tight container as defined in the USP-NF. This material should be handled and stored per label instructions to ensure product integrity.

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, you should dampen the solid spill material with alcohol, then transfer the dampened material to a suitable container. Use absorbent paper dampened with alcohol 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 alcohol followed by washing with a strong soap and water solution. Do not reenter the contaminate area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

Engineering controls such as exhaust ventilation are recommended.

This material is assumed to be combustible. As with all dry powders, it is advisable to ground mechanical equipment in contact with dry material to dissipate the potential buildup of static electricity.

As a general rule, when handling USP Reference Standards, avoid all contact and inhalation of dust, mists, and/or vapors associated with the material. Wash thoroughly after handling.

SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a permitted wastewater treatment facility is acceptable only after review by the governing authority and assurance that "pass through" violations will not occur. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must be evaluated in accordance with EPA 40 CFR Part 261, specifically Subpart B, in order to determine the appropriate local, state and federal requirements for disposal.

For more Preventive Measures (Complete) data for CARISOPRODOL (7 total), please visit the HSDB record page.

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)

Use a NIOSH-approved respirator, if it is determined to be necessary by an industrial hygiene survey involving air monitoring. In the event that a respirator is not required, an approved dust mask should be used.

Wear approved respiratory protection, chemically compatible gloves, and protective clothing.

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

Carisoprodol is metabolized in the liver by CYP2C19 to form meprobamate. Co-administration of CYP2C19 inhibitors, such as omeprazole or fluvoxamine, with carisoprodol could result in increased exposure of carisoprodol and decreased exposure of meprobamate. Co-administration of CYP2C19 inducers, such as rifampin or St. John's Wort, with carisoprodol could result in decreased exposure of carisoprodol and increased exposure of meprobamate. Low dose aspirin also showed an induction effect on CYP2C19. The full pharmacological impact of these potential alterations of exposures in terms of either efficacy or safety of carisoprodol is unknown.

Neither carisoprodol nor tramadol is a controlled substance at the federal level. However, evidence indicates that these medications may have abuse potential, particularly in patients with a history of substance abuse. We report three cases in which a combination of carisoprodol and tramadol was used illicitly to obtain psychotropic effects. Carisoprodol or tramadol should be prescribed with caution for patients at risk for substance abuse, and extreme caution should be used when prescribing both drugs simultaneously for any patient.

There have been no adequate prospective studies demonstrating the rates of aminotransferase elevations on carisoprodol therapy or convincing case reports of clinically apparent liver injury due to carisoprodol. Thus, the hepatotoxic potential of this medication is low. It has been increasingly reported as a substance of abuse, taken in higher than recommended doses.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 610(SRC), determined from a structure estimation method(2), indicates that carisoprodol is expected to have moderate mobility in soil(SRC). Volatilization of carisoprodol from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 7.14X10-10 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Carisoprodol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.01X10-4 mm Hg at 25 °C(SRC), determined from a fragment constant method(4). Biodegradation data were not available(SRC, 2010).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 610(SRC), determined from a structure estimation method(2), indicates that carisoprodol is 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 7.14X10-10 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 17(SRC), from an estimated log Kow of 2.36(6) and a regression-derived equation(7), suggests that the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data were not available(SRC, 2010).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), carisoprodol, which has an estimated vapor pressure of 3.01X10-4 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase carisoprodol 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 11 hours(SRC), calculated from its rate constant of 3.4X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase carisoprodol may be removed from the air by wet or dry deposition(SRC). Carisoprodol 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).

The most common adverse drug reactions of carisoprodol include drowsiness, headache, and dizziness. According to the product labeling, up to 17% of patients experienced sedation after receiving carisoprodol compared to 6% of patients who were administered a placebo. This adverse drug reaction can impair the mental and physical capabilities required to perform potentially hazardous work, such as driving or working with heavy machinery. Post-marketing reports have indicated motor vehicle accidents linked to carisoprodol usage. The potential for misuse, abuse, physical dependence, and withdrawal is apparent if carisoprodol is used indiscriminately. In March 2007, Norwegian medical regulatory authorities reviewed carisoprodol, leading the Committee for Medicinal Products for Human Use and the European Medicines Agency. They concluded that the benefits of carisoprodol no longer outweigh their associated risks. Consequently, all marketing authorizations for carisoprodol were suspended throughout Europe. Another potentially significant reported adverse effect is seizures. In Indonesia, in September 2017, close to 100 people suffered seizures with at least 1 fatality when PCC, standing for "paracetamol-caffeine-carisoprodol," was mixed into student's drinks.

The drug distributes into milk in concentrations 2-4 times higher than concurrent maternal plasma concentrations.

The objective of this study was to quantify the excretion of carisoprodol and meprobamate in human milk and estimate the dose received by breast-fed infants. The concentrations of carisoprodol and meprobamate were measured in breast milk on 4 consecutive days at steady-state conditions in one woman using carisoprodol 2100 mg/d. The average milk concentrations were 0.9 microg/mL for carisoprodol and 11.6 ug/mL for meprobamate. Based on the milk concentrations measured, the absolute dose ingested by an exclusively breast-fed infant could be estimated at 1.9 mg/kg per day, and the relative dose would be 4.1% of the weight-adjusted maternal dose. ...

Signs and Symptoms of Overdose

Carisoprodol is a central nervous system depressant that acts as a sedative and skeletal muscle relaxant. Rather than acting directly on skeletal muscle, carisoprodol interrupts neuronal communication within the reticular formation and spinal cord, resulting in sedation and alteration in pain perception. Its exact mechanism of action is not yet known.

Symptoms of overdose include drowsiness, giddiness, nausea, indigestion, or rash. Other adverse effects attributed to therapeutic use of carisoprodol include dizziness, irritability, insomnia, diplopia, temporary loss of vision, ataxia, weakness, headache, and dysarthria. Non-CNS adverse effects include gastrointestinal complaints, tachycardia, and postural hypotension. Patients sensitive to sulfites or tartrazine may experience wheezing, allergic rashes including erythema multiforme, or anaphylaxis after using some preparations of carisoprodol which contain such additives

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical.[Available from: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=78-44-4]

Carisoprodol was detected in three wastewater treatment plant effluents associated with facilities involved in the manufacture of pharmaceuticals in New York; 35-38 samples were collected from each plant between 2004 and 2009. The maximum concentrations of carisoprodol were 1.2 (15% detection); 3 ug/L (100% detection) and 0.2 ug/L (7.7% detection) in the three New York sample, respectively; the latter receives 20% of its discharge from a pharmaceutical formulation facility. It was detected in 43% of samples (maximum concentration = 0.8 ug/L) from twenty-three plants across the US that were analyzed once between 2004 and 2009 as part of a National Survey; more than half of these plants receive hospital discharge. Detection limit = 0.011 ug/L(1).

Carisoprodol was detected in agricultural irrigation runoff from fields in the Calleguas Creek watershed in coastal Ventura County, southern California. Strawberry and onion fields were treated with disinfected tertiary recycled water over two growing seasons, from July 1999 through August 2000. The wastewater treatment plant does receive discharge from one hospital. Carisoprodol was reported present at 680 mg/L in runoff, <10-63 ng/L in wastewater treatment plant effluent, and 0.30 ng/L in effluent-dominated stream water. Method detection limits were 302 ng/L in water extracts and 80 ug/g in suspended particle extracts(1).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of carisoprodol can be estimated to be 610(SRC). According to a classification scheme(2), this estimated Koc value suggests that carisoprodol is expected to have moderate mobility in soil.

/SIGNS AND SYMPTOMS/ Carisoprodol overdosage produces symptoms which are similar to those of meprobamate overdosage and may include stupor, coma, shock, respiratory depression, and, very rarely, death.

/SIGNS AND SYMPTOMS/ In the post-marketing experience with carisoprodol, cases of dependence, withdrawal, and abuse have been reported with prolonged use. Most cases of dependence, withdrawal, and abuse occurred in patients who have had a history of addiction or who used carisoprodol in combination with other drugs with abuse potential. However, there have been post-marketing adverse event reports of Carisoprodol-associated abuse when used without other drugs with abuse potential. Withdrawal symptoms have been reported following abrupt cessation after prolonged use. To reduce the chance of carisoprodol dependence, withdrawal, or abuse, carisoprodol should be used with caution in addiction-prone patients and in patients taking other CNS depressants including alcohol, and Carisoprodol should not be used more than two to three weeks for the relief of acute musculoskeletal discomfort. Carisoprodol, and one of its metabolites, meprobamate (a controlled substance), may cause dependence

/SIGNS AND SYMPTOMS/ Overdosage of carisoprodol commonly produces CNS depression. Death, coma, respiratory depression, hypotension, seizures, delirium, hallucinations, dystonic reactions, nystagmus, blurred vision, mydriasis, euphoria, muscular incoordination, rigidity, and/or headache have been reported with Carisoprodol overdosage. Many of the carisoprodol overdoses have occurred in the setting of multiple drug overdoses (including drugs of abuse, illegal drugs, and alcohol). The effects of an overdose of carisoprodol and other CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants) can be additive even when one of the drugs has been taken in the recommended dosage. Fatal accidental and non-accidental overdoses of carisoprodol have been reported alone or in combination with CNS depressants

/SIGNS AND SYMPTOMS/ Daily ingestion of very large doses of carisoprodol (100 mg/kg for an unspecified number of days) has produced mild withdrawal symptoms such as abdominal cramps, insomnia, chilliness, headache, and nausea when the drug was abruptly discontinued. Psychological dependence has been reported rarely with prolonged administration of usual adult doses, and the drug should be used with caution in patients who have histories of drug abuse.

For more Human Toxicity Excerpts (Complete) data for CARISOPRODOL (15 total), please visit the HSDB record page.

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

This is notice that the Drug Enforcement Administration (DEA) will hold a hearing with respect to the proposed placement of carisoprodol in schedule IV of the Controlled Substances Act (21 U.S.C. 801, et seq.). The control of carisoprodol was initially proposed in a Notice of Proposed Rulemaking published in the Federal Register on November 17, 2009 (74 FR 59108).

M - Musculo-skeletal system

QM - Musculo-skeletal system

Carisoprodol is a centrally acting skeletal muscle relaxant that does not act directly on skeletal muscle but acts directly on the central nervous system (CNS). This drug relieves the painful effects of muscle spasm. A metabolite of carisoprodol, _meprobamate_, possesses both anxiolytic and sedative properties. Clinical studies have shown that this drug causes impairment of psychomotor performance in neuropsychological tests.

The mechanism of action of carisoprodol in relieving discomfort associated with acute painful musculoskeletal conditions has not been confirmed. In studies using animal models, the muscle relaxation that is induced by carisoprodol is associated with a change in the interneuronal activity of the spinal cord and of the descending reticular formation, located in the brain. The abuse potential of this drug is attributed to its ability to alter GABAA function. This drug has been shown to modulate a variety of GABAA receptor subunits. GABAA receptor modulation can lead to anxiolysis due to inhibitory effects on neurotransmission.

Carisoprodol is a CNS depressant which has sedative and skeletal muscle relaxant effects. The precise mechanism of action of the drug is not known. The skeletal muscle relaxant effects of orally administered carisoprodol are minimal and are probably related to its sedative effect. The drug does not directly relax skeletal muscle and, unlike neuromuscular blocking agents, does not depress neuronal conduction, neuromuscular transmission, or muscle excitability. In animals, carisoprodol appears to modify central perception of pain without abolishing peripheral pain reflexes and to have slight antipyretic activity, but these effects have not been demonstrated in clinical studies.

Carisoprodol is an increasingly abused, centrally-acting muscle relaxant. Despite the prevalence of carisoprodol abuse, its mechanism of action remains unclear. Its sedative effects, which contribute to its therapeutic and recreational use, are generally attributed to the actions of its primary metabolite, meprobamate, at GABA(A) receptors (GABA(A)R). Meprobamate is a controlled substance at the federal level; ironically, carisoprodol is not currently classified as such. Using behavioral and molecular pharmacological approaches, we recently demonstrated carisoprodol, itself, is capable of modulating GABA(A)R function in a manner similar to central nervous system depressants. Its functional similarities with this highly addictive class of drugs may contribute to the abuse potential of carisoprodol. The site of action of carisoprodol has not been identified; based on our studies, interaction with benzodiazepine or barbiturate sites is unlikely. ...

The terminal half-life is approximately 2 hours.

Carisoprodol is eliminated by both renal and non-renal routes with a terminal elimination half-life of approximately 2 hours. The half-life of meprobamate is approximately 10 hours.

The plasma half-life of carisoprodol is approximately 8 hours.

The main pathway of carisoprodol is liver metabolism is by the cytochrome enzyme CYP2C19 to form meprobamate. This enzyme exhibits genetic polymorphism, which may affect the metabolism of this drug.

The major pathway of carisoprodol metabolism is via the liver by cytochrome enzyme CYP2C19 to form meprobamate. This enzyme exhibits genetic polymorphism.

Carisoprodol is metabolized in the liver; animal studies indicate the drug may induce liver microsomal enzymes. Animal studies also indicate that the drug is excreted in urine, principally as hydroxycarisoprodol and hydroxymeprobamate, and to a lesser extent as meprobamate; trace amounts of carisoprodol are excreted unchanged in urine. The drug may be removed by hemodialysis or peritoneal dialysis.

Carisoprodol is a muscle relaxant analgesic, which has an active metabolite i.e. meprobamate. We conducted an open three-panel single-dose administration study with 15 healthy volunteers: five poor metabolizers of mephenytoin, five poor metabolizers of debrisoquine and five extensive metabolizers of both substrates. The aim was to investigate if the elimination of carisoprodol and meprobamate is dependent on the two metabolic polymorphisms of mephenytoin and debrisoquine. The subjects were given single oral doses of 700 mg carisoprodol and 400 mg meprobamate on separate occasions. The disposition of carisoprodol was clearly correlated to the mephenytoin hydroxylation phenotype. The mean serum clearance of carisoprodol was four times lower in poor metabolizers of mephenytoin than in extensive metabolizers, which confirms the hypothesis from our previous study that N-dealkylation of carisoprodol cosegregates with the mephenytoin hydroxylation polymorphism. However, mean serum clearance of meprobamate did not differ between the two groups. Also, polymorphic debrisoquine hydroxylation did not influence the elimination of carisoprodol or meprobamate. Poor metabolizers of mephenytoin thus have a lower capacity to metabolize carisoprodol and may therefore have an increased risk of developing concentration dependent side-effects such as drowsiness and hypotension, if treated with ordinary doses of carisoprodol.

Hepatic. Metabolized in the liver via the cytochrome P450 oxidase isozyme CYP2C19. Route of Elimination: Carisoprodol is eliminated by both renal and non-renal routes. Half Life: 8 hours

21925K482H

CARISOPRODOL

Physiologic Effects [PE] - Centrally-mediated Muscle Relaxation

Established Pharmacologic Class [EPC] - Muscle Relaxant

Carisoprodol is a Muscle Relaxant. The physiologic effect of carisoprodol is by means of Centrally-mediated Muscle Relaxation.

CARISOPRODOL

A heterogeneous group of drugs used to produce muscle relaxation, excepting the neuromuscular blocking agents. They have their primary clinical and therapeutic uses in the treatment of muscle spasm and immobility associated with strains, sprains, and injuries of the back and, to a lesser degree, injuries to the neck. They have been used also for the treatment of a variety of clinical conditions that have in common only the presence of skeletal muscle hyperactivity, for example, the muscle spasms that can occur in MULTIPLE SCLEROSIS. (From Smith and Reynard, Textbook of Pharmacology, 1991, p358)

The absolute bioavailability of carisoprodol has not yet been established. The mean time to peak plasma concentrations (Tmax) of this drug was about 1.5-2 hours in clinical studies. Co-administration of a fatty meal with carisoprodol (350 mg tablet) had no impact on carisoprodol pharmacokinetics.

Carisoprodol is eliminated by the kidneys as well as other routes. The half-life of meprobamate is approximately 10 hours.

0.93 to 1.3 L/kg, according to 4 different clinical studies.

Following an oral dose of carisoprodol, the oral clearance (Cl/F) was 39.52 ± 16.83 L/hour.

Carisoprodol crosses the placenta. The drug distributes into milk in concentrations 2-4 times higher than concurrent maternal plasma concentrations.

Plasma concentrations of carisoprodol required for sedative, skeletal muscle relaxant, or toxic effects are not known. One manufacturer reports that plasma concentrations of 4-7 ug/mL were attained in 4 hours following oral administration of 350 mg of carisoprodol to healthy adults. Following usual therapeutic dosages, the onset of action is usually within 30 minutes and the duration of action is 4-6 hours.

MEDICATION

Use (kg) in USA (2002): 89900

For the relief of discomfort associated with acute, painful, musculoskeletal conditions.

(1977) No Data

(1979) No Data

(1977) No Data

(1979) No Data

(1977) PROBABLY GREATER THAN 4.54X10+5 GRAMS

(1979) PROBABLY GREATER THAN 4.54X10+5 GRAMS

REACTION OF PHOSGENE WITH 2-METHYL-2-PROPYL-1,3-PROPANEDIOL IN THE PRESENCE OF DIMETHYLANILINE FOLLOWED BY REACTION WITH ISOPROPYLAMINE AND FINALLY WITH SODIUM CYANATE IN THE PRESENCE OF ANHYDROUS HYDROGEN CHLORIDE

BERGER, LUDWIG, US PATENT 2,937,119 (1960 TO CARTER PRODUCTS).