History of Fentanyl in Timeline

Fentanyl is a powerful synthetic opioid analgesic, significantly more potent than heroin and morphine. Clinically, it's used for severe pain management, particularly for cancer patients and post-operative care, and as a sedative. Fentanyl acts by activating μ-opioid receptors in the brain. However, its high potency makes it prone to causing overdoses, as even small amounts can be lethal. It is sold under various brand names, including Actiq, Duragesic, and Sublimaze.

1959: Fentanyl first synthesized

In 1959, Fentanyl was first synthesized by Paul Janssen.

1959: Fentanyl synthesized by Paul Janssen

In 1959, Fentanyl was first synthesized in Belgium by Paul Janssen under the label of Janssen Pharmaceutica. It was developed by screening chemicals similar to pethidine (Demerol).

1964: Synthesis as patented by Paul Janssen

In 1964, the original synthesis as patented by Paul Janssen involves the synthesis of benzylfentanyl from N-benzyl-4-Piperidone. The resulting benzylfentanyl is used as feedstock to norfentanyl.

1968: Fentanyl approved for medical use in the United States

In 1968, Fentanyl was approved for medical use in the United States. Fentanyl citrate also entered medical use as a general anaesthetic.

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.

1971: Fentanyl classified as controlled drug in the UK

In 1971, fentanyl is classified as a controlled Class A drug under the Misuse of Drugs Act in the UK.

1978: Siegfried method described

In 1978, the Siegfried method, was initially described and later published on The Hive. This method involves the initial synthesis of N-phenethyl-4-piperidone (NPP).

1998: Introduction of Actiq fentanyl lollipop

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: Pediatric fatalities related to Fentanyl

A report published in JAMA Pediatrics, indicates that pediatric cases between 1999 and 2021 were related to fentanyl. Most of the deaths were among adolescents.

2002: Moscow Theater Hostage Crisis

In 2002, Russian Spetsnaz security forces are suspected to have used a fentanyl analogue, or derivative (suspected to be carfentanil and remifentanil), to rapidly incapacitate people in the Moscow theater hostage crisis. The siege was ended, but many hostages died from the gas after their health was severely taxed during the days long siege.

February 2004: Janssen Pharmaceutica Recalls Duragesic Patches

In February 2004, Janssen Pharmaceutica Products recalled one lot, and later, additional lots of fentanyl (brand name: Duragesic) patches because of seal breaches that might have allowed the medication to leak from the patch.

March 2004: Class II Recalls Initiated for Duragesic Patches

In March 2004, a series of class II recalls was initiated for Duragesic patches due to seal breaches.

2004: Experiment of patient-controlled transdermal system

In a 2004 experiment involving 189 patients with moderate to severe postoperative pain, 25% of patients withdrew due to inadequate analgesia. However, the PCTS method proved superior to the placebo.

2006: Outbreak of overdose deaths due to fentanyl

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 underestimated duration of action of Fentanyl.

February 2008: ALZA Corporation Recalls Duragesic Patches

In February 2008, the ALZA Corporation recalled their 25 μg/h Duragesic patches due to a concern that small cuts in the gel reservoir could result in accidental exposure of patients or health care providers to the fentanyl gel.

September 2008: Doctors warned of risks of fentanyl

In September 2008, doctors in the United Kingdom were warned of the risks associated with fentanyl.

2009: FDA approves 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 deaths in the US

From 2011 to 2021, deaths from prescription opioids remained stable, while synthetic opioid deaths (primarily fentanyl) increased from 2,600 to 70,601 per year.

April 2012: FDA reports children deaths and illnesses from fentanyl skin patches

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 (50 mg/mL) transdermal solution, brand name Recuvyra, became commercially available for dogs only. It is approved by the Food and Drug Administration to provide four days of analgesia after a single application before surgery and is also approved in Europe.

June 2013: CDC Issues Health Advisory on Acetylfentanyl Overdoses

In June 2013, the United States Centers for Disease Control and Prevention (CDC) issued a health advisory to emergency departments alerting to 14 overdose deaths among intravenous drug users in Rhode Island. These deaths were associated with acetylfentanyl, a synthetic opioid analog of fentanyl that has never been licensed for medical use.

July 2014: MHRA issues warning about transdermal 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, particularly in children.

2014: Increase in fentanyl reports by forensic labs

In 2014, the United States National Forensic Laboratory estimated 4,697 fentanyl reports by federal, state, and local forensic laboratories.

September 2015: Fentanyl deaths as a public health issue 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 to prevent fentanyl misuse and fatal overdose.

2015: Fentanyl Overdoses Begin in Canada

Beginning in 2015, Canada experienced a rise in fentanyl overdoses. Authorities suspected that organized crime groups were importing the drug from Asia to the western coast in powder form, pressing it into pseudo-OxyContin tablets. Traces of fentanyl were also found in other recreational drugs, including cocaine, MDMA, and heroin.

2015: Global healthcare use of fentanyl

In 2015, 1,600 kilograms (3,500 pounds) of fentanyl were used in healthcare globally.

2015: Annual aggregate manufacturing quota for fentanyl

In 2015, the annual aggregate manufacturing quota for fentanyl was 2,300,000 kg.

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 for fentanyl

In 2016, the annual aggregate manufacturing quota for fentanyl was 2,300,000 kg.

April 2017: Increase in fentanyl-related deaths in British Columbia

Between January and April 2017, the death rate increased by more than 100% with 368 overdose-related deaths in British Columbia.

2017: Efficacy of fentanyl lozenges in children

A 2017 study suggested the efficacy of fentanyl lozenges in children as young as five, weighing as little as 13 kg, for pain treatment.

2017: Fentanyl becomes the most widely used synthetic opioid in medicine

As of 2017, fentanyl was the most widely used synthetic opioid in medicine.

2017: Fentanyl-related deaths in the US

In 2017, fentanyl and fentanyl analogs caused over 29,000 deaths in the US, which was a large increase over the previous four years.

2017: Fentanyl Discovered in Illicit Markets in Australia

In 2017, fentanyl was discovered for sale in illicit markets in Australia.

February 2018: DEA classifies illicit fentanyl analogs as Schedule I

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 fentanyl deaths

In July 2018, the CDC issued a subsequent HAN Alert, warning of rising numbers of deaths due to fentanyl abuse and mixing with non-opioids.

August 2018: Nebraska Uses Fentanyl in Execution

In August 2018, Nebraska became the first American state to use fentanyl to execute a prisoner. Carey Dean Moore was executed at the Nebraska State Penitentiary using a lethal injection that included fentanyl citrate, raising concerns about the use of an untested drug cocktail.

2018: Dark web drug suppliers ban fentanyl trafficking

A 2018 report indicated that many major drug suppliers on the dark web have voluntarily banned the trafficking of fentanyl.

2018: Allegations of Hindered Cooperation Between Canada and China

In 2018, Global News reported allegations that diplomatic tensions between Canada and China hindered cooperation to seize imports, with Beijing being accused of inaction regarding fentanyl.

2018: Fentanyl Discovered in Illicit Markets in New Zealand

In 2018, fentanyl was discovered for sale in illicit markets in New Zealand, prompting calls for wider availability of naloxone from New Zealand experts.

2018: Fentanyl overtakes heroin as leading cause of overdose deaths in the US

Since 2018, fentanyl has constituted the majority of all drug overdose deaths in the United States, overtaking heroin.

February 2019: Record Fentanyl Seizure in Nogales, Arizona

On February 2019, U.S. Customs and Border Protection in Nogales, Arizona, seized a record amount of fentanyl, totaling 254 pounds (115 kg) with an estimated value of US$3.5 million. The fentanyl was concealed in a compartment under a false floor of a truck transporting cucumbers.

May 2019: China classifies fentanyl as controlled narcotic

Effective from 1 May 2019, China officially classified all forms of fentanyl as controlled narcotics.

May 2019: Drug overdose deaths in the United States

From May 2019 to May 2020, 81,230 drug overdose deaths occurred during the 12 months, the largest number of drug overdoses 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 in an effort to combat the flow of the drug. Nevertheless, it remains the principal origin of fentanyl in the United States.

2019: Fentanyl prescription rates 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 in the U.S.

Overdose deaths by fentanyl and other illegally imported opioids were surging in the U.S. since 2019 and are presently a major cause of death in all U.S. states.

March 2020: Increase in drug 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 drug overdose deaths

May 2020: Drug overdose deaths in the United States

From May 2019 to May 2020, 81,230 drug overdose deaths occurred during the 12 months, the largest number of drug overdoses 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 warning of substantial increases in drug overdose deaths across the United States, primarily driven by rapid increases in overdose deaths involving illicitly manufactured fentanyl.

2020: 1,716 Fentanyl Deaths Reported in British Columbia

In 2020, British Columbia reported 1,716 deaths related to fentanyl overdoses, contributing to the rising death toll across the country.

2020: Fentanyl Cost Analysis

In 2020, the 800 mcg tablet of Fentanyl was 6.75 times more expensive than the lozenge in the United States. In a 2020 report by the Australian Institute of Criminology, a 100-microgram transdermal patch was valued from between AU$75 and AU$450 on illicit markets.

2020: Confiscation of Methyl Fentanyl in Myanmar

In 2020, the Myanmar military and police confiscated 990 gallons of "methyl fentanyl" [sic], as well as precursors for the illicit synthesis of the drug.

2020: Sharp increase in fentanyl reports by forensic labs

In 2020, the United States National Forensic Laboratory estimated 117,045 fentanyl reports by federal, state, and local forensic laboratories, a sharp increase from 2014.

October 2021: 1,782 Fentanyl Deaths Reported in British Columbia

From January to October 2021, British Columbia reported 1,782 deaths related to fentanyl overdoses, contributing to the rising death toll across the country.

2021: Pediatric fatalities related to Fentanyl

A report published in JAMA Pediatrics, indicates that pediatric cases between 1999 and 2021 were related to fentanyl. Most of the deaths were among adolescents.

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: Percentage of overdoses involving fentanyl

From 2021-2024, the overall percentage of overdoses involving fentanyl has remained stable between 70% and 80%.

2021: Over 71,000 deaths caused by fentanyl and its analogues

In 2021, fentanyl and its analogues were responsible for over 71,238 drug overdose deaths in the United States.

2021: UNODC Reports Drop in Opium Poppy Cultivation 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 continues to expand and diversify.

2021: Reduction in fentanyl manufacturing quota

In 2021, the annual aggregate manufacturing quota for fentanyl was 731,452 kg, a nearly 68.2% decrease from previous years.

2022: Direct Fentanyl Shipments from China Stopped

According to the national archives and the DEA, direct fentanyl shipments from China have stopped since 2022. The majority of illicit fentanyl and analogues now entering the U.S. from Mexico are final products in form of "tablets" and adulterated heroin from previously synthesized fentanyl.

2022: China Halted Cooperation with the United States on Combatting Drug Trafficking

Following Nancy Pelosi's visit to Taiwan in 2022, China halted cooperation with the United States on combatting drug trafficking.

2022: Synthesis of fentanyl involving 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 USA 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 on how to properly administer their product. The corporation issued a consumer recall report and stressed the importance of safety in the use and administration of opioid therapeutics.

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 U.S. and Canada

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: Bilateral Talks on Fentanyl Resumed

In 2024, bilateral talks on fentanyl resumed in San Francisco when then U.S. President Joe Biden and Chinese President Xi Jinping met.

2024: Overdoses in the U.S. involving fentanyl decreased

While overdoses involving fentanyl in the United States have decreased in 2024, the overall percentage of overdoses involving fentanyl has remained stable between 70% and 80% from 2021-2024.

January 2025: President Trump's Tariffs on Mexico

In January 2025, President Trump said that tariffs on Mexico were intended to reduce the U.S. trade deficit and force the country to secure its border with the U.S. against fentanyl smuggling and illegal immigration.

February 2025: US president Trump imposed a 10% tariff on Chinese imports

In February 2025, US president Trump imposed a 10% tariff on Chinese imports, claiming the move as a way "to pressure China into taking action on fentanyl".