Carisoprodol

260.33

260.33

201-118-7

8192

756671|172124

DTXSID8024733

Crystals

M - Musculo-skeletal system

2924199090

90.6

2.1

Carisoprodol is a white powder. (NTP, 1992)

1.1±0.1 g/cm3

92-93 °C

160-170 °C @ Press: 2 Torr

209.9±24.0 °C

1.466

H2O: <0.1 g/100 mL at 19.5 ºC

2-8°C

3.01X10-4 mm Hg at 25 deg C (est)

LD50 in mice, rats (mg/kg): 2340, 1320 orally; 980, 450 i.p. (Berger)

Slightly bitter taste

15.06(Strongest acidic)

Henry's Law constant = 7.14X10-10 atm-cu m/mol at 25 °C (est)

15.06 (Strongest acidic)

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

Stable in dilute acids and alkalies|Hydroxyl radical reaction rate constant = 3.42X10-11 cu cm/molec-sec at 25 °C (est)

Insoluble in water.

Carbamates

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.

NONH for all modes of transport

22

36

FB3325000

Xn

STABLE IN DIL ACIDS & ALKALIES.

P301 + P312 + P330

H302

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.

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).

Flash point data for this chemical are not available, but it it probably combustible. (NTP, 1992)

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P264, P270, P301+P312, P330, and P501|Aggregated GHS information provided by 42 companies from 1 notifications to the ECHA C&L Inventory.

Fires involving this compound should be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)

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. STORAGE PRECAUTIONS: You should store this material in a refrigerator. (NTP, 1992)

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.

Wipe up spillage or collect spillage using a high- efficiency vacuum cleaner. Avoid breathing dust. Place spillage in appropriately labeled container for disposal. Wash spill site.

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.

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).

**LD50 values** The LD50 values of carisoprodol for rats are 450 mg/kg for intravenous (IV) and intraperitoneal injection, and 1,320 mg/kg for gavage dosing. In mice, the LD50 values are 165 mg/kg for intravenous injection, 980 mg/kg for intraperitoneal injection, and 2,340 mg/kg for gavage dosing. The LD50 value for rabbits given carisoprodol by intravenous injection is 124 mg/kg. **Overdose** An overdose of carisoprodol leads to CNS depression, and in severe cases, induction of a coma. Shock, depression of respiratory function, seizures and death have also been reported in rare cases. Several symptoms may be associated with carisoprodol overdose, such as horizontal and vertical nystagmus, blurred vision, mydriasis, mild tachycardia and hypotension, respiratory depression, euphoria, CNS stimulation, muscular incoordination, and/or rigidity, confusion, headache, hallucinations, and dystonic reactions. Alcohol or other CNS depressants or psychotropic agents can exert additive effects on carisoprodol even when one of the agents has been ingested at the normal, therapeutic dose. Fatal accidental and non-accidental overdoses have both been reported with carisoprodol ingestion alone or ingestion of carisoprodol in combination with alcohol or psychotropic drugs. **A note on dependence and withdrawal** In the postmarketing reports after carisoprodol use, cases of dependence, withdrawal, and abuse have been reported with long-term use. The majority of dependence and withdrawal cases, as well as abuse, have occurred in patients with a history of addiction or who have used this drug in combination with other drugs having abuse potential. However, multiple post-marketing adverse event reports have been made of carisodopril-associated abuse when used without other drugs possessing abuse potential. Withdrawal symptoms have been observed and reported following sudden abrupt cessation after long-term carisodoprol use. To reduce the chance of carisodopril dependence, withdrawal, or abuse, carisodopril should be used with caution in addiction-prone patients and in patients taking other CNS depressants including alcohol. This drug should not be taken for longer than 2 to 3 weeks for symptomatic relief of acute musculoskeletal discomfort. **Use in pregnancy** This drug has been classified as Pregnancy Category C. There are no clinical trial data on the use of carisoprodol during human pregnancy. Animal studies show that carisoprodol crosses the placenta and leads to adverse effects on fetal growth and postnatal survival. In postmarketing reports, the main metabolite, _meprobamate_, has not demonstrated a consistent association between maternal use and an increased risk for specific congenital malformations. **Use in nursing** Limited data in humans demonstrate that this is found excreted in breast milk and may reach concentrations in breast milk of 2-4 times the maternal plasma concentrations. It is therefore advisable to exercise caution when this drug is used during breastfeeding.

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.

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.

Carisoprodol (CARI) was evaluated for reproductive toxicity in CD-1 (Swiss) mice using the Reproductive Assessment by Continuous Breeding Protocol (RACB). After a 2 wk dose- range-finding study, dose levels for the Task 2 Continuous cohabitation phase were set at 0, 300, 750, & 1500 mg/kg/day, in corn oil gavage. When the high dose killed 2/20 (10%) of males & 4/20 (20%) of females after <1 wk exposure, the high dose level was reduced to 1200 mg/kg/day. During 14 wks of cohabitation in Task 2, with daily dosing of CARI, there was no effect on the ability of the F0 animals to produce litters. However, the proportion of pups born alive, & absolute & adjusted live pup weight, were decreased in the high-dose group compared to the controls. Evaluation of the control & 1200 mg/kg/day dose groups in the Task 3 crossover mating trail (to identify the affected sex) found no effect of CARI on any measure of reproductive function. At F0 necropsy of controls & 1200 mg/kg/d groups, there was no effect of 1200 mg/kg/day CARI on sperm concn, motility, or morphology. Relative right epididymis weight was significantly increased over the control group for high-dose males. Additionally, high-dose males exhibited increased relative liver weight, whereas high-dose females exhibited decreased absolute but not relative kidney/adrenal weight, compared to the controls. There was no effect of CARI on F0 estrous cyclicity. No treatment-related histopathology in the kidney, liver, or reproductive organs was observed in either males or females exposed to 1200 mg/kg/day CARI. Indications of generalized toxicity in the F0 animals included tranquilization, primarily in the high-dose group during the first wks of Task 2, & reduced body weight in high-dose females during Tasks 2 & 3. Mortality (non-gavage related) for the F0 generation was 1/40 (2%), 0/20 (0%), 1/20 (5%), & 9/20 (45%) for males, & 3/40 (7.5%), 1/20 (5%), 1/20 (5%), & 4/20 (20%) for females in the control through high-dose groups. Task 4, a trial to determine the fertility & reproductive competence of the second generation (F1 animals), was conducted with the final offspring of all groups. There was no effect of CARI on indices of mating, pregnancy or fertility, the proportion of pups born alive, the sex ratio of live pups, unadjusted live pup weight, or average number of days to litter. The number of pups/litter (females & the sexes combined) was reduced in the high dose group. Adjusted live pup weight was significantly decreased in the mid- & high-dose groups. At F1 necropsy, there was no effect of treatment on the relative weight of any male or female reproductive organs; spermatid head count was significantly reduced at all levels of CARI. Relative liver weight was significantly increased for females at 300 mg/kg/day & for both males & females at both 750 & 1200 mg/kg/day. There were no treatment-related histopathological changes. Indications of generalized toxicity in the F1 generation included decreased survival of the pups through postnatal day 21 at 750 mg/kg/day CARI (females & sexes combined), 1200 mg/kg/day (sexes combined), & decreased body weight for males at doses of 750 &/or 1200 mg/kg/day, & for females at all dose groups. Only a few animals exhibited transient tranquilization during Task 4. In summary, despite indications of generalized toxicity, only minimal effects of CARI on the reproductive processes were observed in the F0 generation and their offspring at the doses used in this study.

Because carisoprodol is metabolized by the liver and excreted by the kidneys, the drug should be used with caution in patients with impaired hepatic or renal function. Patients should be warned that carisoprodol may impair ability to perform hazardous activities requiring mental alertness or physical coordination such as operating machinery or driving a motor vehicle.|Carisoprodol should be used with caution in patients with reduced CYP2C19 activity. Published studies indicate that patients who are poor CYP2C19 metabolizers have a 4-fold increase in exposure to carisoprodol, and concomitant 50% reduced exposure to meprobamate compared to normal CYP2C19 metabolizers. The prevalence of poor metabolizers in Caucasians and African Americans is approximately 3-5% and in Asians is approximately 15-20%.|Carisoprodol is contraindicated in patients with acute intermittent porphyria and in patients who have previously demonstrated allergic or idiosyncratic reactions to carisoprodol or related compounds such as meprobamate, mebutamate, or tybamate.|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.

Approximately 60%.

Carisoprodol's production and use as a medication(1) may result in its release to the environment through various waste streams(SRC).

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 rate constant for the vapor-phase reaction of carisoprodol with photochemically-produced hydroxyl radicals has been estimated as 3.4X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 11 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Carisoprodol may undergo hydrolysis in the environment due to the presence of functional groups that hydrolyze under environmental conditions(3). However, estimated rate constants would suggest that hydrolysis is not environmentally relevant(SRC). A base-catalyzed second-order hydrolysis rate constant of 7.1X10-5 L/mole-sec(SRC) was estimated using a structure estimation method(2); this corresponds to half-lives of 3,000 and 300 years at pH values of 7 and 8, respectively(2). Carisoprodol does not contain chromophores that absorb at wavelengths >290 nm(3), and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 17 was calculated in fish for carisoprodol(SRC), using an estimated log Kow of 2.36(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).

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.

The Henry's Law constant for carisoprodol is estimated as 7.14X10-10 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that carisoprodol is expected to be essentially nonvolatile from water surfaces(2). Carisoprodol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.0X10-4 mm Hg(SRC), determined from a fragment constant method(3).

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. ...

NIOSH (NOES Survey 1981-1983) has statistically estimated that 2,431 workers (1,194 of these were female) were potentially exposed to carisoprodol in the US(1). Occupational exposure to carisoprodol may occur through inhalation and dermal contact with this compound at workplaces where carisoprodol is produced or used. Monitoring data indicate that the general population may be exposed to carisoprodol via dermal contact with contaminated water or soils irrigated with contaminated treatment plant effluent. Limited exposure will occur via ingestion of medications containing carisoprodol, a muscle relaxant(SRC).

Carisoprodol is indicated for the relief of discomfort related to acute, painful musculoskeletal conditions. **Important limitations of use**: • Should only be used for acute treatment periods up to two or three weeks • Adequate evidence of effectiveness for more prolonged use has not been established • Not recommended in pediatric patients less than 16 years of age|FDA Label

Carisoprodol is a centrally acting muscle relaxant that has been in use for more than fifty years without significant evidence for causing hepatic injury.

Autonomic Agents: Muscle Relaxants, Central

Muscle Relaxants, Central|Carisoprodol is used as an adjunct to rest, physical therapy, analgesics, and other measures for the relief of discomfort associated with acute, painful musculoskeletal conditions. /Included in US product label/

Occasionally, patients may have allergic or idiosyncratic reactions to carisoprodol. In patients who have not received carisoprodol previously, these reactions are usually evident by the time of the fourth dose of the drug. Idiosyncratic reactions may be characterized by extreme weakness, transient quadriplegia, dizziness, ataxia, temporary loss of vision, diplopia, mydriasis, dysarthria, agitation, euphoria, confusion, and disorientation. These symptoms usually subside within several hours; however, symptomatic and supportive therapy, including hospitalization, may be necessary in some patients. Rash, erythema multiforme, pruritus, urticaria, eosinophilia, and fixed drug eruption have occurred in patients receiving carisoprodol who previously had similar reactions to meprobamate. Severe allergic reactions have been characterized by asthmatic episodes, fever, weakness, dizziness, angioedema, smarting eyes, hypotension, and anaphylactic shock.|The most frequent adverse effects of carisoprodol are drowsiness and dizziness. Other adverse CNS effects include vertigo, ataxia, tremor, agitation, irritability, headache, depressive reactions, syncope, and insomnia.|Because carisoprodol is metabolized by the liver and excreted by the kidneys, the drug should be used with caution in patients with impaired hepatic or renal function. Patients should be warned that carisoprodol may impair ability to perform hazardous activities requiring mental alertness or physical coordination such as operating machinery or driving a motor vehicle.|Adverse GI effects of carisoprodol include nausea, vomiting, hiccups, increased bowel activity, and epigastric distress. Adverse cardiovascular effects include tachycardia, postural hypotension, and facial flushing. Although a causal relationship to carisoprodol has not been established, leukopenia and pancytopenia have occurred rarely in patients receiving carisoprodol along with other drugs.|For more Drug Warnings (Complete) data for CARISOPRODOL (13 total), please visit the HSDB record page.

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.

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) (See all compounds classified as Muscle Relaxants, Central.)

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.|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. ...

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.

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 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. ...

Impurities: (2RS)-2-(hydroxymethyl)-2-methylpentyl (1-methylethyl)carbamate; 5-methyl-5-propyl-1,3-dioxan-2-one; 2-methyl-2-propylpropane-1,3-diol; meprobamate

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)

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. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

Emergency and Supportive Measures. Maintain an open airway and assist ventilation if necessary. Administer supplemental oxygen. Treat coma, hypothermia, hypotension, and pulmonary edema if they occur. Hypotension usually responds promptly to supine position and intravenous fluids. Monitor patients for at least 6 hours after ingestion, because delayed absorption may occur. /Skeletal muscle relaxants/|Decontamination. Adminster activated charcoal orally is conditions are appropriate. Gastric lavage is not necessary after small to moderate ingestions if activated charcoal can be given promptly. /Skeletal muscle relaxants/|Enhanced Elimination. Because of extensive tissue distribution, dialysiss and hemoperfusion are not very effective for most of the drugs in this group. ... /Skeletal muscle relaxants/|Basic life support measures should be instituted as dictated by the clinical presentation of the carisoprodol overdose. Induced emesis is not recommended due to the risk of CNS and respiratory depression, which may increase the risk of aspiration pneumonia. ... Circulatory support should be administered with volume infusion and vasopressor agents if needed. Seizures should be treated with intravenous benzodiazepines and the reoccurrence of seizures may be treated with phenobarbital. In cases of severe CNS depression, airway protective reflexes may be compromised and tracheal intubation should be considered for airway protection and respiratory support. ... Careful monitoring of urinary output is necessary and overhydration should be avoided. Observe for possible relapse due to incomplete gastric emptying and delayed absorption. For more information on the management of an overdose of carisoprodol, contact a Poison Control Center.|For more Antidote and Emergency Treatment (Complete) data for CARISOPRODOL (7 total), please visit the HSDB record page.

/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.

Carisoma

Carisoprodol|Soma|8192|Schedule IV - Substances in the DEA Schedule IV have a low potential for abuse relative to substances in Schedule III.|No

ESSENTIALLY 100% AS A MUSCLE RELAXANT

Oral: Tablets: 350 mg Soma (Medpointe); Vanadom (GM Pharmaceuticals). NOTE: Available from one or more manufacturer, distributor and/or repackager by generic (nonproprietary) name.

Carisoprodol is present as a racemic mixture. ... Other ingredients: alginic acid, magnesium stearate, potassium sorbate, starch, tribasic calcium phosphate

MASS SPECTRA OF NINE MEDICINAL CARBAMATES INCLUDING CARISOPRODOL WERE RECORDED & EXAMINED.|LIQUID CHROMATOGRAPHY DETERMINATION OF MUSCLE RELAXANT-ANALGESIC MIST USING NORMAL PHASE CHROMATOGRAPHY.|GAS CHROMATOGRAPHIC ANALYSIS OF DRUGS.

Analyte: carisoprodol; matrix: blood (serum); procedure: high performance liquid chromatography with ultraviolet detection at 190 nm|Analyte: carisoprodol; matrix: chemical identification; procedure: thin-layer chromatography with comparison to standards|Analyte: carisoprodol; matrix: chemical purity; procedure: dissolution in pyridine; addition of phenolphthalein indicator; titration with sodium methoxide titrant to a permanent pink endpoint; addition of sodium methoxide titrant; addition of alcohol and phenolphthalein indicator; titration of excess alkali with hydrochloric acid until the pink color disappears|Analyte: carisoprodol; matrix: pharmaceutical preparation (tablet); procedure: retention time of liquid chromatogram with comparison to standards (chemical identification)|For more Clinical Laboratory Methods (Complete) data for CARISOPRODOL (9 total), please visit the HSDB record page.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals