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.

The clinical use of fentanyl has increased during the past decade. For example, fentanyl prescriptions increased from about 0.5 million in 1994 to 7.04 million in 2006 (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.

Fentanyl is 100 times more potent than morphine as an analgesic. It is a µ 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 µ 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 µ opioid receptor agonists, fentanyl does not cause histamine release and has minimal depressant effects on the heart.

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 which results in frequent overdoses that can lead to respiratory depression and death.

Fentanyl patches are abused by removing the liquid 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.

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. Fentanyl oral transmucosal lozenges (Actiq®) are typically sold illicitly (street names: "Perc-O-Pop" or "Lollipop") at $20 to $25 per unit or $450 per carton (contains 24 units) while transdermal patches (Duragesic®) are sold at prices ranging from $10 to $100 per patch depending upon the dose of the unit and geographical area. According to the National Forensic Laboratory Information System, state and local cases involving fentanyl expressed as a percent of the total of all drug cases increased by 18-fold from 0.0078 percent in 2001 (37 cases) to 0.144 percent in 2006 (1,472 cases involving 1,643 drug items).

During the last year, the distribution of clandestinely manufactured fentanyl has caused an unprecedented outbreak of hundreds of suspected fentanyl-related overdoses and over 972 confirmed and 162 suspected fentanyl-related deaths among the heroin user population. Most of these deaths have occurred in Delaware, Illinois, Maryland, Michigan, Missouri, New Jersey, and Pennsylvania. DEA has immediately undertaken the development of regulations to control the precursor chemicals used by the clandestine laboratories to illicitly manufacture fentanyl. Recently, one of the precursors was designated as a List 1 chemical. DEA is now in the process of designating a second chemical as a schedule II immediate precursor.

Fentanyl is a schedule II substance under the federal Controlled Substances Act of 1970.

Comments and additional information are welcomed by the Drug and Chemical Evaluation Section, FAX 202-353-1263 or telephone 202-307-7183.