CARISOPRODOL

June 2009 DEA/OD/ODE

Carisoprodol is a prescription drug marketed since 1959. It is a centrally acting muscle relaxant. The diversion and abuse of carisoprodol have increased in the last decade.

Carisoprodol is used as an adjunct to rest, physical therapy and other measures for relief of acute, painful musculoskeletal conditions. It is available in tablets containing either 350 mg carisoprodol or 200 mg carisoprodol in combination with 325 mg aspirin and 16 mg codeine phosphate. The standard dosage for adults is 350 mg three times daily and at bed-time. Use in patients under age 12 is not recommended. According to IMS Health^™, there were approximately 10.58 million prescriptions for carisoprodol dispensed in 2008.

Carisoprodol is N-isopropyl-2-methyl-2-propyl-1,3-propanediol dicarbamate and is both structurally and pharmacologically related to meprobamate, a schedule IV substance. It is present as a racemic mixture. Carisoprodol does not directly affect skeletal muscle in man. Skeletal muscle relaxant action of carisoprodol may be related to its sedative properties. Recent animal studies conducted under the directive of the National Institute on Drug Abuse (NIDA) indicate that subjective effects of carisoprodol may be similar to other central nervous system depressants such as meprobamate, pentobarbital and chlordiazepoxide and it possesses rewarding effects. These data suggest that carisoprodol has abuse liability.

The onset of action of carisoprodol is rapid and effects last 4 to 6 hours. It is metabolized in the liver and excreted through kidney. The major metabolic pathway of carisoprodol involves its conversion to meprobamate, a drug with substantial barbiturate-like biological actions. Adverse reactions may include central nervous system related effects such as drowsiness, dizziness, vertigo, ataxia, tremor, agitation, irritability, head ache, depressive reactions, syncope and insomnia. Carisoprodol may also adversely affect cardiovascular (tachycardia, postural hypotension and facial flushing), gastrointestinal (nausea, vomiting, hiccup and epigastric distress), and hematologic systems. It may cause idiosyncratic symptoms including extreme weakness, transient quadriplegia, ataxia, difficulty in speech, temporary loss of vision, double vision, dilated pupils, agitation, euphoria, confusion, and disorientation. Carisoprodol overdose has resulted in stupor, coma, shock, respiratory depression and death.

Carisoprodol abuse has escalated in the last decade in the United States. According to 2007 National Survey on Drug Use and Health (NSDUH) data, non-medical use by U.S. population aged 12 and older of SomaÒ (1.1%) was similar to or greater than other commonly abused schedule IV controlled drugs such as KlonopinÒ (1.5%), and LibriumÒ (0.3%). With prolonged abuse at high dosage, carisoprodol can lead to tolerance, dependence and withdrawal symptoms in humans.

According to the Diversion Drug Trends, published by the Drug Enforcement Administration (DEA) on the trends in the diversion of controlled and noncontrolled pharmaceuticals, carisoprodol continues to be one of the most commonly diverted drugs. Diversion and abuse of carisoprodol is prevalent throughout the country. Street prices for Soma ranged from $1 to $5 per tablet. Diversion methods include doctor shopping for the purpose of obtaining multiple prescriptions and forging prescriptions.

According to the National Forensic Laboratory Information System (NFLIS), carisoprodol has been consistently listed in the top 25 most frequently identified drugs by the state and local forensic laboratories since 2000. NFLIS data indicate that DEA laboratories identified 99 drug items as carisoprodol in 2007 and 51 in 2008. In 2008, a total of 3,450 items were seized and submitted to state and local laboratories for analysis, a slight decline from 4,307 in 2007. Texas, Louisiana, and Florida accounted for approximately half of the carisoprodol items seized in 2008, according to NFLIS.

The American Association of Poison Control Centers reported 8,821 case mentions and 3,605 single exposures of carisoprodol poisonings in 2007. Medical Examiners Commission Reports released by the Florida Department of Law Enforcement (FDLE) indicate that carisoprodol/meprobamate related deaths in Florida increased by 100% from 208 in 2003 to 415 in 2008, surpassing opioids such as heroin, fentanyl, and hydromorphone.

Carisoprodol is not controlled under the federal Controlled Substances Act of 1970. It is currently scheduled under state law in Alabama, Arizona, Arkansas, Florida, Georgia, Hawaii, Indiana, Kentucky, Louisiana, Massachusetts, Minnesota, Nevada, New Mexico, Oklahoma, Oregon, Texas, and West Virginia.

Comments and additional information are welcomed by the Drug and Chemical Evaluation Section, Fax 202-353-1263, telephone 202-307-7183, or Email ODE@usdoj.gov.