CARISOPRODOL

July 2008 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. There were about 9.88 million prescriptions for carisoprodol prescribed in 2006 (IMS Health^™).

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 recemic 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 2004 National Survey on Drug Use and Health (NSUDH) data, the nonmedical 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 (1.1%), and LibriumÒ (0.4%). 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 System to Retrieve Information from Drug Evidence (STRIDE), a federal database for the seized drugs samples analyzed by DEA forensic laboratories, there were 60, 57, 58 and 54 carisoprodol cases involving seizure of 101, 117, 99 and 79 drug records in 2003, 2004, 2005 and 2006, respectively. According to the National Forensic Laboratory Information System (NFLIS), since 2000, carisoprodol has been consistently listed in the top 25 most frequent drugs identified by the state and local forensic laboratories. In 2006, a total of 3,354 analyzed items were recorded in NFLIS. Louisiana (651 items) and Texas (998 items) accounted for about a half of these items. Toxic Exposure Surveillance System (TESS) reported an increase of 25% in carisoprodol exposures from 6,656 in 2000 to 8,337 in 2005. Reports by Florida Medical Examiners indicate that carisoprodol/meprobamate related deaths in Florida increased by 51% from 208 in 2003 to 314 in 2005 and surpassed opioids such as heroin, fentanyl, hydromorphone, and tramadol.

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

Comments and additional information are welcomed by the Drug and Chemical Evaluation Section, FAX 202-307-1263 or telephone 202-307-7183.