METHADONE 
(Trade Names: Methadose®, Dolophine®; Street Names: Fizzies, Amidone, Chocolate Chip Cookies)

October 2009 DEA/OD/ODE

Methadone, a pharmaceutical opioid, is currently marketed as oral concentrate (10 mg/ml), oral solution (5 and 10 mg/5ml), tablet (5, 10, and 40 mg), injectable (10mg/ml) and powder (50, 100, and 500 mg/bottle for prescription compounding).

Recently, there have been increasing concerns about the marked escalation of diversion and abuse of methadone and its adverse health consequences. According to the National Center for Health Statistics (NCHS) Health E-Stats publication, poisoning deaths increased 66% from 19,741 in 1999 to 32,691 in 2005. During the same time period, methadone deaths increased 468% to 4,462 (14% of all poisonings). In November 2006, the Food and Drug Administration (FDA) issued a public health advisory stating that methadone use in pain control may result in life-threatening cardiac and respiratory changes and deaths. FDA further advised that methadone doses for pain should be carefully selected, slowly titrated and carefully monitored by the prescribing physician. As of January 1, 2008, manufacturers of 40 mg methadone hydrochloride dispersible tablets have voluntarily agreed to restrict distribution of this formulation to only those facilities authorized for detoxification and maintenance treatment of opioid addiction, and hospitals. The 40 mg product is not FDA approved for use in the management of pain.

Methadone has been used for over forty years primarily as a detoxification and maintenance treatment of opioid addiction. In recent years, methadone is also being increasingly prescribed for relief of moderate to severe pain. The prescriptions for methadone products have nearly doubled in the past five years, from 2.2 million in 2003 to 4.2 million in 2008 (IMS Health™). Aggregate production quota for methadone products, as established by DEA for legitimate national need, increased from 12,705 kg in 2001 to 25,000 kg in 2008. Methadone products, when used for treatment of narcotic addition in detoxification or maintenance programs, shall be dispensed only by pharmacies approved by appropriate regulatory authorities. When used as analgesics, they may be dispensed by any licensed pharmacy.

Methadone, [3-heptanone, 6-(dimethyl-amino)-4,4-diphenyl-, hydrochloride] is a synthetic drug with mu-opioid receptor agonist activity. Pharmacological and toxic effects, abuse and dependence liabilities of methadone are qualitatively similar to those of other Schedule II opioid analgesics such as morphine and oxycodone. Analgesic activity of racemic methadone is entirely due to its l-isomer, 8 to 50 times more potent than d-isomer. d-isomer lacks significant respiratory depressant action and addiction liability, but possesses antitussive activity. The analgesic effect of 8 to 10 mg of methadone is almost equivalent to that of 10 mg of morphine. With respect to total analgesic effects, methadone given orally is one-half as effective as its intramuscular administration. Pain relief from a dose of methadone lasts about 4 to 8 hours, but the drug may stay in the body for 8 to 59 hours.

Methadone binds strongly to proteins in various tissues, including the brain. Upon discontinuation of its administration, low concentrations of methadone are maintained in the body because of the slow release of methadone from tissue binding sites. Notable features of methadone are its efficacy by the oral route, its prolonged duration of action in suppressing withdrawal symptoms in physically dependent individuals and its tendency to produce persistent effects with repeated administration. Acute overdose of methadone, similar to morphine, can produce severe respiratory depression, somnolence, coma, skeletal muscle flaccidity, cool clammy skin, constricted pupils, reduction in blood pressure and heart rate, pulmonary edema and death. Pure opioid antagonists such as naloxone are specific antidotes against respiratory depression from methadone overdose.

Methadone has abuse potential and may produce psychic and physical dependence and tolerance. Methadone abuse has escalated markedly in recent years in the United States. According to the 2008 National Survey on Drug Use and Health, about 1.8 million persons age 12 and older reported that they used methadone for non-medical purposes at least once in their lifetime. The American Association for Poison Control Centers reported 5,025 case mentions, 2,364 single exposures, and 27 deaths associated with methadone in 2007.

DEA field offices reported that the street prices for methadone ranged from $2 to $30 per tablet and $10 to $40 per diskette in 2005. A majority of diversion involves tablets.

DEA forensic laboratories reported an increase of methadone seized exhibits from 121 in 2004 to 172 in 2008. According to the National Forensic Laboratory Information System (NFLIS), methadone exhibits submitted to state and local laboratories increased 69% from 4,872 exhibits in 2004 to 8,240 exhibits in 2008. From January to June 2009, DEA laboratories identified 64 drug items/exhibits as methadone and state and local laboratories identified 4,093 items/exhibits.

Methadone is in Schedule II of the Controlled Substances Act.

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.