Drugs and Chemicals of Concern

FENTANYL

(Trade Names: Actiq®, Fentora™, Duragesic®)

October 2009 DEA/OD/ODE

Introduction:

Fentanyl is a potent synthetic opioid. It was introduced into medical practice as an intravenous anesthetic under the trade name of Sublimaze in the 1960s.

Licit Uses:

The clinical use of fentanyl has been steadily increasing over the years. For example, fentanyl prescriptions jumped from about 2.59 million in 2000 to 7.64 million in 2008 (IMS Health™). Fentanyl pharmaceuticals are currently available in the dosage forms of oral transmucosal lozenges, commonly referred to as the fentanyl "lollipops" (Actiq®), effervescent buccal tablets (Fentora™), transdermal patches (Duragesic®), and injectable formulations. Oral transmucosal lozenges and effervescent buccal tablets are used for the management of breakthrough cancer pain in patients who are already receiving opioid medication for their underlying persistent pain. Transdermal patches are used in the management of chronic pain in patients who require continuous opioid analgesia for pain. Fentanyl citrate injections are administered intravenously, intramuscularly, spinally or epidurally for potent analgesia and anesthesia. Fentanyl is frequently used in anesthetic practice for patients undergoing heart surgery or for patients with poor heart function. Because of a recent concern about deaths and overdoses resulting from fentanyl transdermal patches (Duragesic® and generic version), on July 15, 2005, the Food and Drug Administration issued safety warnings and reiterated the importance of strict adherence to the guidelines for the proper use of these products.

Chemistry and Pharmacology:

Fentanyl is 100 times more potent than morphine as an analgesic. It is a mu opioid receptor agonist with high lipid solubility and a rapid onset and short duration of effects. Fentanyl rapidly crosses the blood-brain barrier. It is similar to other mu opioid receptor agonists (like morphine or oxycodone) in its pharmacological effects and produces analgesia, sedation, respiratory depression, nausea, and vomiting. Fentanyl appears to produce muscle rigidity with greater frequency than other opioids. Unlike some mu opioid receptor agonists, fentanyl does not cause histamine release and has minimal depressant effects on the heart.

Illicit Uses:

Fentanyl is abused for its intense euphoric effects. Fentanyl can serve as a direct substitute for heroin in opioid dependent individuals. However, fentanyl is a very dangerous substitute for heroin because it is much more potent than heroin and results in frequent overdoses that can lead to respiratory depression and death.

Fentanyl patches are abused by removing the gel contents from the patches and then injecting or ingesting these contents. Patches have also been frozen, cut into pieces and placed under the tongue or in the cheek cavity for drug absorption through the oral mucosa. Used patches are attractive to abusers as a large percentage of fentanyl remains in these patches even after a 3-day use. Fentanyl oral transmucosal lozenges and fentanyl injectables are also diverted and abused.

Abuse of fentanyl initially appeared in mid-1970s and has increased in recent years. There have been reports of deaths associated with abuse of fentanyl products.

Illicit Distribution:

Fentanyl is diverted via pharmacy theft, fraudulent prescriptions, and illicit distribution by patients and registrants (physicians and pharmacists). Theft has also been identified at nursing homes and other long-term care facilities. According to the National Forensic Laboratory Information System, 1,938 fentanyl items/exhibits were submitted to state and local forensic laboratories for analysis in 2006, 897 items/exhibits were submitted in 2007, and 512 items/exhibits were submitted in 2008. From January to June 2009, 230 fentanyl exhibits were identified by the state and local laboratories. DEA laboratories identified 249 fentanyl drug exhibits in 2006, 42 exhibits in 2007 and 53 exhibits in 2008. In the first six months of 2009, federal officials seized 17 drug exhibits identified by DEA forensic laboratories as fentanyl.

Clandestine Manufacture:

From April 2005 – March 2007, an outbreak of fentanyl overdoses and deaths occurred. The Centers for Disease Control and Prevention (CDC)/Drug Enforcement Administration surveillance system reported 1,013 confirmed nonpharmaceutical fentanyl-related deaths. Most of these deaths occurred in Delaware, Illinois, Maryland, Michigan, Missouri, New Jersey, and Pennsylvania. Consequently, DEA immediately undertook the development of regulations to control the precursor chemicals used by the clandestine laboratories to illicitly manufacture fentanyl. In 2007, DEA published an Interim Final Rule to designate N-phenethyl-4-piperidone (NPP) as a List 1 chemical. After the control of NPP, the number of fentanyl-related deaths continually declined. NPP is the precursor to 4-anilino-N-phenethyl-4-piperidone (ANPP). DEA is now in the process of designating ANPP as a schedule II immediate precursor.

Control Status:

Fentanyl is a schedule II substance under the Controlled Substances Act. Indiana enacted legislation to add certain fentanyl derivatives to schedule I of state law.

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.