History of Fentanyl in Timeline
Fentanyl is a potent synthetic opioid analgesic, significantly stronger than morphine and heroin. Clinically, it manages severe pain, particularly in cancer patients and post-surgery. It also acts as a sedative. Fentanyl acts by activating μ-opioid receptors. Overdose can occur rapidly from small quantities, depending on the method of delivery. Fentanyl is sold under various brand names, including Actiq, Duragesic, and Sublimaze.
1959: Fentanyl Synthesis
In 1959, Fentanyl was first synthesized by Paul Janssen.
1959: First Synthesis by Paul Janssen
In 1959, Fentanyl was first synthesized in Belgium by Paul Janssen under the label of his relatively newly formed Janssen Pharmaceutica.
1964: Patent of the Original Synthesis
In 1964, the original synthesis as patented by Paul Janssen involves the synthesis of benzylfentanyl from N-Benzyl-4-Piperidone.
1968: Fentanyl Citrate Enters Medical Use
In 1968, Fentanyl citrate entered medical use as a general anaesthetic, manufactured by McNeil Laboratories under the brand name Sublimaze.
1968: Approval for Medical Use
In 1968, Fentanyl was approved for medical use in the United States.
1971: Fentanyl Classified in the UK
In 1971, fentanyl is classified as a controlled Class A drug under the Misuse of Drugs Act in the UK.
1998: Introduction of Actiq
In 1998, a flavored lollipop of fentanyl citrate mixed with inert fillers was introduced under the brand name Actiq, becoming the first quick-acting formation of fentanyl for use with chronic breakthrough pain.
1999: Fatal Pediatric Cases Report
In a report published in JAMA Pediatrics, 37.5% of all fatal pediatric cases between 1999 and 2021 were related to fentanyl; most of the deaths were among adolescents (89.6%) and children aged 0 to 4 years (6.6%).
2002: Moscow Theater Hostage Crisis
In 2002, Russian Spetsnaz security forces used a fentanyl analogue, suspected to be carfentanil and remifentanil, to incapacitate people in the Moscow theater hostage crisis. Many hostages died from the gas.
February 2004: Janssen Pharmaceutica Recalls Duragesic Patches
In February 2004, Janssen Pharmaceutica Products recalled one lot of Duragesic fentanyl patches due to seal breaches that might have allowed medication leakage.
March 2004: Initiation of Class II Recalls
In March 2004, a series of class II recalls was initiated following an initial recall in February of the same year.
2004: Experiment on Patient-Controlled Transdermal System
In a 2004 experiment with 189 patients experiencing post-operative pain, a fentanyl patient-controlled transdermal system (PCTS) was tested, showing superiority to a placebo but with 25% of patients withdrawing due to inadequate pain relief.
2006: Outbreak of Overdose Deaths
In 2006, illegally manufactured, non-pharmaceutical fentanyl often mixed with cocaine or heroin caused an outbreak of overdose deaths in the United States and Canada, heavily concentrated in the cities of Dayton, Ohio; Chicago, Illinois; Detroit, Michigan; and Philadelphia, Pennsylvania.
2006: FDA Investigates Respiratory Deaths
In 2006, the United States Food and Drug Administration (FDA) began investigating several respiratory deaths related to fentanyl.
February 2008: ALZA Corporation Recalls Duragesic Patches
In February 2008, ALZA Corporation recalled their 25 μg/h Duragesic patches due to concerns about small cuts in the gel reservoir, potentially exposing patients or health care providers to the fentanyl gel.
September 2008: UK Doctors Warned of Fentanyl Risks
In September 2008, doctors in the United Kingdom were warned of the risks associated with fentanyl.
2009: FDA Approval of Onsolis
In 2009, the US Food and Drug Administration (FDA) approved Onsolis (fentanyl buccal soluble film), a fentanyl drug in a new dosage form for cancer pain management in opioid-tolerant subjects.
2011: Increase in Synthetic Opioid Overdose Deaths
From 2011 to 2021, deaths from prescription opioids remained stable, while synthetic opioid (primarily fentanyl) deaths increased from 2,600 to 70,601.
April 2012: FDA Reports Deaths and Illnesses in Children
In April 2012, the FDA reported that twelve young children had died and twelve more had become seriously ill from separate accidental exposures to fentanyl skin patches.
2012: Commercial Availability of Recuvyra for Dogs
In 2012, a highly concentrated transdermal fentanyl solution, Recuvyra, became commercially available for dogs only. It is FDA-approved to provide four days of analgesia after a single application before surgery.
June 2013: CDC Health Advisory on Acetylfentanyl Overdoses
In June 2013, the CDC issued a health advisory alerting emergency departments about 14 overdose deaths in Rhode Island among intravenous drug users, linked to acetylfentanyl, a synthetic opioid analog of fentanyl.
July 2014: MHRA Issues Warning on Fentanyl Patches
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.
2014: Fentanyl Reports Increase
In 2014, The United States National Forensic Laboratory estimates fentanyl reports by federal, state, and local forensic laboratories increased to 4,697 reports.
September 2015: Fentanyl Overdose Deaths in Canada
Since September 2015, death from fentanyl overdose continues to be a public health issue of national concern in Canada.
October 2015: CDC Issues Initial HAN Advisory
In October 2015, the U.S. Centers for Disease Control (CDC) issued an initial HAN Advisory regarding fentanyl misuse and fatal overdose.
2015: Fentanyl Overdoses Begin in Canada
Beginning in 2015, Canada experienced several fentanyl overdoses, with authorities suspecting the drug was imported from Asia and pressed into pseudo-OxyContin tablets. Fentanyl traces were also found in other recreational drugs.
2015: Global Healthcare Usage
In 2015, 1,600 kilograms (3,500 pounds) of Fentanyl were used in healthcare globally.
2015: Annual Aggregate Manufacturing Quota
In 2015, the annual aggregate manufacturing quota for fentanyl was 2,300,000 kg.
November 2016: DEA uncovers fentanyl pill operation in Utah
In November 2016, the DEA uncovered an operation in Cottonwood Heights, Utah, manufacturing counterfeit oxycodone and Xanax pills using fentanyl sourced from China. Approximately 70,000 oxycodone pills and 25,000 Xanax pills were seized, with estimates suggesting millions more could have been distributed.
2016: Fentanyl Overdose Deaths in British Columbia
In 2016, deaths from fentanyl overdoses in the province of British Columbia averaged two persons per day.
2016: Annual Aggregate Manufacturing Quota
In 2016, the annual aggregate manufacturing quota for fentanyl was 2,300,000 kg.
April 2017: Increase in Overdose-Related Deaths in British Columbia
In April 2017, the death rate in British Columbia increased by more than 100% with 368 overdose-related deaths between January and April 2017.
2017: Study on Fentanyl Lozenges for Children
A 2017 study suggested the efficacy of fentanyl lozenges in children as young as five, weighing as little as 13 kg.
2017: Most Widely Used Synthetic Opioid
As of 2017, Fentanyl was the most widely used synthetic opioid in medicine.
2017: Medical Toxicology Report on Fentanyl Overdose Risk
In 2017, The American College of Medical Toxicology and the American Academy of Clinical Toxicology issued a joint report asserting the risk of fentanyl overdose via incidental transdermal exposure is very low.
2017: Increase in Fentanyl-Related Deaths in the US
In 2017, fentanyl and fentanyl analogs caused over 29,000 deaths in the US, a large increase over the previous four years.
2017: Fentanyl Discovered in Illicit Australian Markets
In 2017, fentanyl was discovered for sale in illicit markets in Australia, marking its presence in the region.
February 2018: DEA Classifies Illicit Fentanyl Analogs
In February 2018, the U.S. Drug Enforcement Administration indicated that illicit fentanyl analogs have no medically valid use, and thus applied a "Schedule I" classification to them.
July 2018: CDC Issues HAN Alert on Rising Deaths
In July 2018, the CDC issued a HAN Alert warning of rising numbers of deaths due to fentanyl abuse and mixing with non-opioids.
August 2018: Nebraska Executes Prisoner with Fentanyl
In August 2018, Nebraska became the first American state to use fentanyl to execute a prisoner, Carey Dean Moore, using a four-drug lethal injection that included fentanyl citrate. This caused concern and protests due to the untested drug cocktail.
2018: Dark Web Drug Suppliers Ban Fentanyl
In 2018, The Guardian reported that many major drug suppliers on the dark web have voluntarily banned the trafficking of fentanyl.
2018: Fentanyl Discovered in New Zealand
In 2018, fentanyl was discovered in illicit markets in New Zealand, leading experts to call for wider availability of naloxone.
2018: Fentanyl Overdose Dominance
Since 2018, Fentanyl has been responsible for most drug overdose deaths in the United States, overtaking heroin.
February 2019: Record Fentanyl Seizure at Nogales Border
In February 2019, U.S. Customs and Border Protection in Nogales, Arizona, seized a record amount of fentanyl: 254 pounds (115 kg), with an estimated value of US$3.5 million, hidden in a truck transporting cucumbers.
May 2019: Record Number of Drug Overdose Deaths
From May 2019 to May 2020, 81,230 drug overdose deaths occurred, the largest number for a 12-month interval ever recorded for the U.S.
May 2019: China Regulates Fentanyl-Type Drugs
In May 2019, China regulated the entire class of fentanyl-type drugs and two fentanyl precursors, though it remained a primary source of fentanyl in the United States.
2019: Prescription Statistics in the US
In 2019, Fentanyl was the 278th most commonly prescribed medication in the United States, with more than a million prescriptions.
2019: Surge in Overdose Deaths Due to Fentanyl
Since 2019, overdose deaths due to fentanyl and other illegally imported opioids have been surging, becoming a major cause of death in all U.S. states.
March 2020: Increase in Overdose Deaths
From March 2020 to May 2020, there was a concerning acceleration of the increase in drug overdose deaths, coinciding with the implementation of widespread mitigation measures for the COVID-19 pandemic.
May 2020: Increase in Overdose Deaths
From March 2020 to May 2020, there was a concerning acceleration of the increase in drug overdose deaths, coinciding with the implementation of widespread mitigation measures for the COVID-19 pandemic.
May 2020: Record Number of Drug Overdose Deaths
From May 2019 to May 2020, 81,230 drug overdose deaths occurred, the largest number for a 12-month interval ever recorded for the U.S.
December 2020: CDC Issues HAN Advisory on Overdose Deaths
In December 2020, the CDC issued a HAN Advisory regarding increases in drug overdose deaths across the United States, primarily driven by illicitly manufactured fentanyl.
2020: Journal of Medical Toxicology Article
A 2020 article from the Journal of Medical Toxicology stated that "the consensus of the scientific community remains that illness from unintentional exposures is extremely unlikely, because opioids are not efficiently absorbed through the skin and are unlikely to be carried in the air."
2020: Survey of First Responders in New York
A 2020 survey of first responders in New York found that 80% believed “briefly touching fentanyl could be deadly.”
2020: British Columbia Reports High Fentanyl Death Toll
In 2020, British Columbia reported 1,716 deaths related to fentanyl, contributing to rising deaths across Canada.
2020: Increase in Fentanyl Reports
In 2020, The United States National Forensic Laboratory estimates fentanyl reports by federal, state, and local forensic laboratories increased to 117,045 reports.
2020: Fentanyl Tablet Price Comparison
In 2020, the 800 mcg fentanyl tablet was 6.75 times more expensive than the lozenge in the United States. Additionally, a 2020 report valued a 100-microgram transdermal patch between AU$75 and AU$450 on illicit markets.
2020: Myanmar Confiscates "Methyl Fentanyl" and Precursors
In 2020, the Myanmar military and police confiscated 990 gallons of "methyl fentanyl" and precursors for the illicit synthesis of the drug.
October 2021: Continued Rise in British Columbia Fentanyl Deaths
From January to October 2021, British Columbia reported 1,782 deaths related to fentanyl, prompting Health Canada to expedite the review of naloxone's prescription-only status to combat overdoses.
2021: Concerns About Physical Fears Over Fentanyl
A 2021 paper expressed concern that these physical fears over fentanyl may inhibit effective emergency response to overdoses by causing responding officers to spend additional time on unnecessary precautions and that the media coverage could also perpetuate a wider social stigma that people who use drugs are dangerous to be around.
2021: Gupta Method Predominant Synthesis Route
For the first half of 2021, the U.S. Drug Enforcement Administration found the Gupta method was the predominant synthesis route in their samples of seized fentanyl.
2021: Fentanyl Overdoses Percentage Remains Stable
From 2021 to 2024, the overall percentage of overdoses involving fentanyl has remained stable between 70% and 80%.
2021: Fentanyl Overdose Deaths
In 2021, Fentanyl caused over 71,238 drug overdose deaths in the United States.
2021: Expansion of Synthetic Drug Market in Burma
In 2021, the United Nations Office on Drugs and Crime reported a further drop in opium poppy cultivation in Burma, as the region's synthetic drug market continued to expand and diversify, including fentanyl derivatives.
2021: Reduced Manufacturing Quota
In 2021, the annual aggregate manufacturing quota was significantly reduced to 731,452 kg, a nearly 68.2% decrease from the previous manufacturing quota.
2022: China Halts Drug Trafficking Cooperation with the United States
Following Nancy Pelosi's visit to Taiwan in 2022, China halted cooperation with the United States on combatting drug trafficking, impacting efforts to address the fentanyl crisis.
2022: Fentanyl Synthesis using Continuous Flow
In 2022, Braga and coworkers described a synthesis of fentanyl involving continuous flow that uses reagents similar to the ones described for the Gupta procedure.
April 2023: Teva Pharmaceuticals Recalls Fentanyl Buccal Tablets
In April 2023, Teva Pharmaceuticals USA recalled 13 lots of their Fentanyl Buccal Tablets CII due to missing safety information sheets.
2023: Cost of Injectable Fentanyl Solution
As of 2023, the average cost for an injectable fentanyl solution (50 mcg/mL) is around US$17 for a supply of 20 milliliters, depending on the pharmacy.
2023: California Police Union Director Charged with Importing Synthetic Opioids
In 2023, a California police union director was charged with importing synthetic opioids, including fentanyl and tapentadol, disguised as chocolate.
2023: Record Overdose Deaths
In 2023, overdose deaths in the U.S. and Canada again reached record numbers. According to a 2023 report from the United Nations Office on Drugs and Crime (UNODC), the increased numbers of deaths are not related to an increased number of users but to the lethal effects of fentanyl itself.
2024: Fentanyl-Involved Overdoses Stable
In 2024, while overdoses involving fentanyl in the United States have decreased, the overall percentage of overdoses involving fentanyl has remained stable between 70% and 80% from 2021-2024.
