Tramadol (Trade Name: Ultram®)

Tramadol Introduction:

Tramadol was approved for marketing as a noncontrolled analgesic in 1995 under the trade name of Ultram®. Although the company initially claimed that this substance produced only very weak narcotic effects, recent data demonstrates that opioid activity is the overriding contributor to the drug’s pharmacological activity. Because of inadequate product labeling and lack of established abuse potential, many physicians felt this drug was perfectly safe to prescribe to recovering narcotic addicts and to known narcotic abusers. As a consequence, a large number of reports of abuse and dependence have been received.

Licit Tramadol Uses:

Tramadol is approved for the treatment of moderate to moderately severe pain in adults. Although FDA has still not recommended the scheduling of this substance in the Controlled Substances Act (CSA), a requirement necessary for DEA to place a substance under control, they have required the company to inform physicians about recent abuse data and to include new information under the "Drug Abuse and Dependence" section in the approved labeling. The labeling now contains the following language:

"Ultram® has a potential to cause psychic and physical dependence of the morphine-type (μ-opioid). The drug is associated with craving, drug-seeking behavior and tolerance development. Cases of abuse and dependence on Ultram® have been reported. Ultram® should not be used in opioid-dependent patients. Ultram® can reinitiate physical dependence in patients that have been previously dependent or chronically using other opioids. In patients with a tendency to drug abuse, a history of drug dependence, or are chronically using opioids, treatment with Ultram® is not recommended."

Tramadol Chemistry/Pharmacology:

Tramadol is a centrally acting synthetic opioid. Opioid activity is due to both the parent compound and the more active O-desmethylated metabolite. Apart from analgesia, tramadol may produce a number of symptoms including dizziness, somnolence, nausea, and constipation similar to other opioids.

Tramadol is well absorbed orally. It can be administered in 50 to 100 mg doses as needed for pain relief every 4 to 6 hours, not to exceed 400 mg/day. Seizures have been reported in patients receiving recommended doses but are more likely in high doses associated with abuse of this medication.

Poison Control data (2002 AAPCC Annual Report) indicates that there were 2,400 exposures of tramadol reported to poison control centers. Of those, 108 resulted in a major medical outcome and 8 resulted in death.

Illicit Uses:

Tramadol is abused for its opiate effects. The Drug Abuse Warning Network (DAWN) is a database which provides data on drug related episodes reported by hospital emergency rooms. In 2002, there were 1,714 episodes for tramadol and a total of 7,890 episodes from 1998 through 2002. DAWN medical examiners reported that tramadol was involved in 95 drug-related deaths in 2002 and a total of 382 deaths from 1998 through 2002.

The National Forensic Laboratory System (NFLIS) and System to Retrieve Drug Evidence (STRIDE) are both DEA databases that collect scientifically verified data on analyzed samples in state/local and DEA forensic laboratories, respectively. In 2003, there were 267 exhibits of tramadol in NFLIS and 2 exhibits in STRIDE. These relatively small numbers are most probably a reflection of the uncontrolled status of tramadol in the U.S.

Tramadol User Population:

The current pattern of tramadol abuse in the US involves street drug addicts, chronic pain patients, and health professionals. The lack of control and lack of urine toxicology screen for this medication have probably contributed significantly to the availability of this drug.
Illicit distribution:
Like other legal pharmaceuticals with abuse potential, diversion of this medication occurs in a number of ways including prescription fraud. As an uncontrolled substance, there are no CSA regulations regarding manufacturing, distribution, or prescription of this medication.
Control status:
Tramadol is not controlled under the CSA but is under review for possible control.

Tramadol