Fentanyl, also known as fentanil, is an opioid which is used as a pain medication and together with other medications for anesthesia. It has a rapid onset and effects generally last less than an hour or two. Fentanyl is avaliable in a number of forms including by injection, as a skin patch, and to be absorbed through the tissues inside the mouth.

Common side effects include nausea, constipation, sleepiness, and confusion. Serious side effects may include a decreased effort to breathe (respiratory depression), serotonin syndrome, low blood pressure, or addiction. Fentanyl works in part by activating μ-opioid receptors. It is about 75 times stronger than morphine for a given amount. Some fentanyl analogues may be as much as 10,000 times stronger than morphine.

Fentanyl was first made by Paul Janssen in 1960 and approved for medical use in the United States in 1968. It was developed by testing chemicals similar in structure to pethidine (meperidine) for opioid activity. In 2015, 1,600 kilograms (3,500 lb) were used globally. As of 2017, fentanyl was the most widely used synthetic opioid in medicine.

Fentanyl patches are on the World Health Organization’s List of Essential Medicines, the most effective and safe medicines needed in a health system. The wholesale cost in the developing world as of 2015 is between 0.08 and 0.81 USD per 100 micrograms vial. In the United States this amount costs about 0.40 USD as of 2017. Fentanyl is also made illegally and used as a recreational drug often mixed with heroin or cocaine. In 2016 an more than 20,000 deaths occurred in the United States due to overdoses of fentanyl and its analogues.

Adverse effects
Fentanyl’s most common side effects (more than 10% of patients) include diarrhoea, nausea, constipation, dry mouth, somnolence, confusion, asthenia (weakness), sweating, and less frequently (3 to 10 % of patients) abdominal pain, headache, fatigue, anorexia and weight loss, dizziness, nervousness, hallucinations, anxiety, depression, flu-like symptoms, dyspepsia (indigestion), dyspnoea (shortness of breath), hypoventilation, apnoea, and urinary retention. Fentanyl use has also been associated with aphasia.

Despite being a more potent analgesic, fentanyl tends to induce less nausea, as well as less histamine-mediated itching, than morphine.

Fentanyl may produce more prolonged respiratory depression than other opioid analgesics. In 2006 the U.S. Food and Drug Administration (FDA) began investigating several respiratory deaths, but doctors in the United Kingdom were not warned of the risks with fentanyl until September 2008. The FDA reported in April 2012 that twelve young children had died and twelve more made seriously ill from separate accidental exposures to fentanyl skin patches.

The precise reason for sudden respiratory depression is unclear, but there are several hypotheses:

Saturation of the body fat compartment in patients with rapid and profound body fat loss (patients with cancer, cardiac or infection-induced cachexia can lose 80 % of their body fat).
Early carbon dioxide retention causing cutaneous vasodilatation (releasing more fentanyl), together with acidosis, which reduces protein binding of fentanyl, releasing yet more fentanyl.
Reduced sedation, losing a useful early warning sign of opioid toxicity and resulting in levels closer to respiratory-depressant levels.
Fentanyl has a therapeutic index of 270.


US yearly overdose deaths, and some of the drugs involved. Among the more than 64,000 deaths estimated in 2016, the sharpest increase occurred among deaths related to fentanyl and fentanyl analogs (synthetic opioids in the chart) with over 20,000 deaths.
See also: Opioid overdose
In July 2014, the Medicines and Healthcare Products Regulatory Agency (MHRA) of the UK issued a warning about the potential for life-threatening harm from accidental exposure to transdermal fentanyl patches, particularly in children, and advised that they should be folded, with the adhesive side in, before being discarded. The patches should be kept away from children, who are most at risk from fentanyl overdose.

Death from fentanyl overdose was declared a public health crisis in Canada in September 2015, and it continues to be a significant public health issue. In 2016, deaths from fatal fentanyl overdoses in British Columbia, Canada, averaged two persons per day. In 2017 the death rate rose over 100% with 368 overdose related deaths in British Columbia between January and April 2017.

Medical examiners concluded that musician Prince died on April 21, 2016, from an accidental fentanyl overdose. Fentanyl was among many substances identified in counterfeit pills recovered from his home, especially some that were mislabeled as Watson 385, a combination of hydrocodone and paracetamol.

In the US Fentanyl caused 20,100 deaths in 2016, a rise of 540% over the past 3 years.

Fentanyl was first synthesized by Paul Janssen under the label of his relatively newly formed Janssen Pharmaceutica in 1959. The widespread use of fentanyl triggered the production of fentanyl citrate (the salt formed by combining fentanyl and citric acid in a 1:1 stoichiometric ratio), which entered medical use as a general anaesthetic under the trade name Sublimaze in the 1960s.

In the mid-1990s, Janssen Pharmaceutica developed and introduced into clinical trials the Duragesic patch, which is a formation of an inert alcohol gel infused with select fentanyl doses, which are worn to provide constant administration of the opioid over a period of 48 to 72 hours. After a set of successful clinical trials, Duragesic fentanyl patches were introduced into medical practice.

Following the patch, a flavoured lollipop of fentanyl citrate mixed with inert fillers was introduced under the brand name of Actiq, becoming the first quick-acting formation of fentanyl for use with chronic breakthrough pain. Fentanyl has been developed into an effervescent tab for buccal absorption much like the Actiq lollipop, followed by a buccal spray device for fast-acting relief and other delivery methods currently in development.

A fentanyl product has been approved by the US Food and Drug Administration (FDA) for breakthrough cancer pain called Onsolis. It uses a medication delivery technology called BEMA (fentanyl buccal soluble film) on a small disc placed in the mouth. Unlike many other fentanyl products, the drug cannot be abused by crushing and inhaling.

Fentanyl has a US DEA ACSCN of 9801 and a 2013 annual aggregate manufacturing quota of 2,108.75 kg, unchanged from the prior year.