Fentanyl is a powerful synthetic opioid significantly more potent than both heroin and morphine. It is primarily prescribed for pain management, particularly for cancer patients and post-surgical recovery, due to its analgesic properties. Fentanyl's potency makes it fast-acting and increases the risk of overdose even with small amounts. It functions by activating μ-opioid receptors. Brand names for fentanyl include Actiq, Duragesic, and Sublimaze.
1959: Fentanyl First Synthesized
In 1959, Paul Janssen successfully synthesized fentanyl for the first time.
1959: Paul Janssen First Synthesizes Fentanyl
In 1959, Paul Janssen, a scientist working at Janssen Pharmaceutica in Belgium, achieved the first successful synthesis of fentanyl. This breakthrough came about as he explored chemical compounds structurally similar to pethidine (meperidine) in search of opioid activity.
1964: Paul Janssen Patents Original Fentanyl Synthesis
In 1964, Paul Janssen secured a patent for his groundbreaking method of synthesizing fentanyl. This process involved creating benzylfentanyl from N-Benzyl-4-Piperidone, which then served as the precursor to norfentanyl. Ultimately, norfentanyl reacted with phenethyl chloride to produce fentanyl.
1968: Fentanyl Citrate Introduced as General Anesthetic
Fentanyl citrate, created by combining fentanyl with citric acid in a 1:1 ratio, was introduced into the medical field in 1968 as a general anesthetic. This marked a significant step in fentanyl's medical journey, as it was marketed under the brand name Sublimaze by McNeil Laboratories.
1968: Fentanyl Approved for Medical Use in the US
The United States granted approval for the medical use of fentanyl in 1968.
1971: UK Classifies Fentanyl as Class A Drug
In 1971, under the UK's Misuse of Drugs Act, fentanyl was categorized as a controlled Class A drug, acknowledging its high potential for abuse and associated harms. This classification reflects the strict regulations placed on fentanyl's production, possession, and distribution within the UK.
1998: Actiq: First Quick-Acting Fentanyl Formulation for Breakthrough Pain
In 1998, a groundbreaking fentanyl formulation, Actiq, was launched. This innovative medication, a flavored lollipop containing fentanyl citrate combined with inert fillers, became the first fast-acting fentanyl option specifically designed to manage chronic breakthrough pain.
1999: Start of Study on Pediatric Overdose Deaths
A study was initiated in 1999 to analyze pediatric overdose fatalities.
2002: Suspected Use of Fentanyl Analogue in Moscow Theater Hostage Crisis
Russian Spetsnaz forces are suspected of using a fentanyl analogue, potentially carfentanil or remifentanil, during the 2002 Moscow theater hostage crisis. While the siege ended, numerous hostages died from the gas's effects.
February 2004: Janssen Pharmaceutica Products Recalls Fentanyl Patches
In February 2004, Janssen Pharmaceutica Products issued a recall for a batch of their fentanyl patches (Duragesic) due to seal defects that could have resulted in medication leakage.
March 2004: Series of Class II Recalls for Fentanyl Patches
Following the initial recall, a series of Class II recalls for fentanyl patches were initiated in March 2004 to address the ongoing concerns.
2004: Experiment on Fentanyl Patient-Controlled Transdermal System (PCTS)
In 2004, an experiment was conducted involving 189 patients to assess the effectiveness of a fentanyl PCTS in managing postoperative pain. While 25% of participants withdrew due to insufficient pain relief, the PCTS demonstrated better results compared to a placebo, as indicated by lower pain scores and the absence of notable respiratory depression.
2006: FDA Investigates Fentanyl-Related Respiratory Deaths
The United States Food and Drug Administration (FDA) launched investigations into several deaths attributed to respiratory complications potentially linked to fentanyl use in 2006.
2006: Outbreak of Fentanyl-Laced Heroin and Cocaine Overdoses
In 2006, a wave of overdose deaths swept through the United States and Canada, largely concentrated in cities such as Dayton, Ohio; Chicago, Illinois; Detroit, Michigan; and Philadelphia, Pennsylvania. This crisis was attributed to the emergence of illicitly manufactured, non-pharmaceutical fentanyl, often found mixed with heroin or cocaine, increasing the potency and risk of these drugs.
February 2008: ALZA Corporation Recalls 25 μg/h Duragesic Patches
ALZA Corporation issued a recall for their 25 μg/h Duragesic patches in February 2008 over concerns about potential cuts in the gel reservoir.
September 2008: UK Doctors Warned About Fentanyl Risks
It was not until September 2008 that medical professionals in the United Kingdom were cautioned about the potential hazards linked to fentanyl use.
2009: FDA Approves Onsolis, a New Fentanyl Dosage Form
In 2009, the U.S. Food and Drug Administration (FDA) granted approval for Onsolis, a novel fentanyl drug delivery system designed for managing cancer pain in opioid-tolerant individuals. This system utilizes BEMA (BioErodible MucoAdhesive) technology, involving a small, dissolvable polymer film placed on the inner cheek lining, delivering various doses of fentanyl.
2011: Start of the Rise in Synthetic Opioid Deaths
The year 2011 marked the beginning of a period characterized by a consistent rise in deaths attributed to synthetic opioids.
April 2012: FDA Report on Accidental Fentanyl Patch Exposure in Children
In April 2012, the FDA released a report revealing that accidental exposure to fentanyl skin patches had resulted in fatalities and severe health complications among children, with twelve deaths and twelve cases of serious illness reported.
2012: Recuvyra, a Transdermal Fentanyl Solution for Dogs, Becomes Available
In 2012, a highly concentrated transdermal fentanyl solution called Recuvyra (50 mg/mL) was introduced to the market specifically for use in dogs. This FDA-approved solution aimed to provide pain relief for up to four days after a single application before surgery.
June 2013: CDC Issues Health Advisory on Acetylfentanyl Overdoses
In June 2013, the U.S. Centers for Disease Control and Prevention (CDC) issued a health advisory specifically addressing the dangers of acetylfentanyl, a synthetic fentanyl analog that had never been approved for medical use. This advisory, directed at emergency departments, was prompted by 14 overdose deaths in Rhode Island linked to acetylfentanyl use among intravenous drug users.
July 2014: MHRA Issues Warning About Accidental Fentanyl Patch Exposure
The UK's Medicines and Healthcare products Regulatory Agency (MHRA) issued a warning in July 2014 concerning the potential dangers of unintentional exposure to transdermal fentanyl patches, especially for children. The agency recommended specific disposal instructions, advising that the patches should be folded with the adhesive side inward before discarding.
2014: Increase in Fentanyl Reports by Forensic Laboratories
The United States National Forensic Laboratory reported 4,697 instances of fentanyl in 2014.
September 2015: Fentanyl Overdose Deaths Become a Public Health Concern in Canada
Canada began grappling with fentanyl overdose deaths as a pressing public health concern in September 2015.
October 2015: CDC Issues Initial Health Alert on Fentanyl Misuse
In October 2015, recognizing the growing threat of fentanyl, the U.S. Centers for Disease Control (CDC) issued its first Health Alert Network Advisory (HAN) regarding fentanyl misuse and the risk of fatal overdose.
2015: Beginning of Canada's Fentanyl Crisis
Canada started experiencing a surge in fentanyl overdoses in 2015. Authorities suspected organized crime groups were importing the drug from Asia.
2015: High Annual Aggregate Manufacturing Quota for Fentanyl
In 2015 and 2016, the annual aggregate manufacturing quota for fentanyl, as determined by the U.S. Drug Enforcement Administration (DEA), was set at a significantly high level of 2,300,000 kg, indicating the large-scale production and demand for this powerful opioid during those years.
2015: Global Fentanyl Use in Healthcare
In 2015, the global healthcare sector utilized 1,600 kilograms (3,500 pounds) of fentanyl.
November 2016: Large-Scale Counterfeit Pill Operation Uncovered in Utah
In November 2016, the DEA uncovered a significant illegal operation in Cottonwood Heights, Utah, where counterfeit oxycodone and Xanax pills were being manufactured. The operation was producing these counterfeit pills using fentanyl, highlighting the growing trend of fentanyl being used in counterfeit pills.
2016: High Annual Aggregate Manufacturing Quota for Fentanyl
In 2015 and 2016, the annual aggregate manufacturing quota for fentanyl, as determined by the U.S. Drug Enforcement Administration (DEA), was set at a significantly high level of 2,300,000 kg, indicating the large-scale production and demand for this powerful opioid during those years.
2016: High Rate of Fentanyl Overdose Deaths in British Columbia
In 2016, the province of British Columbia faced an alarming rate of fentanyl overdose deaths, averaging two fatalities per day.
April 2017: Significant Increase in Fentanyl Overdose Deaths in British Columbia
British Columbia experienced a dramatic surge in overdose-related deaths, with 368 fatalities recorded between January and April 2017, representing a more than 100% increase compared to the previous year.
2017: Joint Report on Fentanyl Overdose Risk via Transdermal Exposure
In 2017, a joint report by the American College of Medical Toxicology and the American Academy of Clinical Toxicology asserted that the likelihood of fentanyl overdose through unintentional skin contact is minimal. The report explained that it would require 200 minutes of inhaling fentanyl at its highest airborne concentration to achieve a therapeutic dose, but not a potentially lethal one.
2017: Fentanyl-Related Deaths in the US
In 2017, the United States witnessed a significant surge in fatalities attributed to fentanyl and its analogs, with over 29,000 deaths recorded, marking a substantial increase compared to the preceding four years.
2017: Fentanyl Enters Illicit Drug Markets in Australia
Fentanyl was discovered being sold illegally in Australia in 2017.
2017: Study Suggests Efficacy of Fentanyl Lozenges in Children
A 2017 study indicated that fentanyl lozenges could effectively manage pain in children as young as five years old, weighing a minimum of 13 kg.
2017: Fentanyl as the Most Widely Used Synthetic Opioid
By 2017, fentanyl emerged as the most prevalent synthetic opioid employed in medical treatments.
February 2018: DEA Classifies Illicit Fentanyl Analogs as Schedule I
In February 2018, the U.S. Drug Enforcement Administration (DEA) took a decisive step to address the proliferation of illicit fentanyl analogs, declaring that these substances lacked any legitimate medical purpose and classified them as Schedule I drugs. This action underscored the DEA's concern about the public health threat posed by these potent and uncontrolled fentanyl variations.
July 2018: CDC Issues Second Health Alert on Rising Fentanyl Deaths
In July 2018, due to the escalating number of deaths linked to fentanyl abuse and its combination with non-opioids, the CDC issued another HAN Alert. This alert further emphasized the dangers and growing prevalence of fentanyl in the drug supply.
August 2018: Nebraska First U.S. State to Use Fentanyl in Execution
Nebraska marked a controversial milestone in August 2018 by becoming the first U.S. state to carry out an execution using fentanyl. Carey Dean Moore was executed with a lethal injection that included fentanyl citrate.
2018: Dark Web Drug Suppliers Ban Fentanyl Trafficking
In 2018, a report by The Guardian revealed a noteworthy development in the online drug trade: numerous prominent drug suppliers operating on the dark web voluntarily banned the sale and distribution of fentanyl. This self-imposed restriction demonstrated a growing awareness of the extreme risks associated with fentanyl within these illicit marketplaces.
2018: Fentanyl Detected in New Zealand's Illicit Drug Market
The presence of fentanyl in New Zealand's illicit drug market was confirmed in 2018, prompting calls for greater naloxone accessibility.
2018: Fentanyl Overtakes Heroin in Overdose Deaths
A significant shift occurred in 2018 when fentanyl surpassed heroin as the leading cause of drug overdose fatalities in the United States.
February 2019: Record Fentanyl Seizure at Arizona Border
On February 2, 2019, U.S. Customs and Border Protection made a record-breaking fentanyl seizure in Nogales, Arizona. They discovered 254 pounds (115 kg) of fentanyl concealed within a hidden compartment in a truck carrying cucumbers. This massive haul, estimated to be worth US$3.5 million, illustrated the scale of fentanyl trafficking across the U.S.-Mexico border.
May 2019: China Regulates Fentanyl-Type Drugs
In May 2019, China took a significant step by regulating all types of fentanyl-like drugs and two of their precursors.
May 2019: Start of 12-Month Period with Record-Breaking Overdose Deaths
May 2019 marked the start of a 12-month timeframe that would see the highest number of drug overdose deaths ever recorded in the United States. This period, culminating in May 2020, highlighted the escalating severity of the opioid crisis, driven largely by the prevalence of fentanyl.
2019: Fentanyl Prescription Rate in the US
In 2019, fentanyl secured its position as the 278th most frequently prescribed medication in the United States, with over a million prescriptions issued.
2019: Surge in Overdose Deaths from Illicitly Imported Opioids
Since 2019, there has been a dramatic increase in overdose deaths attributed to fentanyl and other illegally imported opioids, making it a leading cause of death across all U.S. states.
March 2020: Sharp Increase in Overdose Deaths Linked to Fentanyl and Methamphetamine
Between March 2020 and May 2020, the U.S. witnessed a dramatic surge in drug overdose deaths. This spike was largely attributed to the increased prevalence of illicitly manufactured fentanyl and methamphetamine within the drug supply.
May 2020: Peak Overdose Deaths During the COVID-19 Pandemic
By May 2020, the U.S. experienced its most substantial increase ever recorded in drug overdose deaths over a 12-month period, marking a peak during the initial wave of the COVID-19 pandemic. This surge was largely attributed to the spread of illicit fentanyl and methamphetamine within the drug supply.
December 2020: CDC Issues Third Health Alert on Increase in Overdose Deaths
In December 2020, the CDC issued a HAN Advisory to address the significant increase in drug overdose deaths across the U.S., primarily driven by illicitly manufactured fentanyl. The advisory highlighted the alarming acceleration of these deaths, particularly between March and May 2020, coinciding with the COVID-19 pandemic's onset.
2020: Significant Increase in Fentanyl Reports by Forensic Laboratories
The number of fentanyl reports received by federal, state, and local forensic laboratories in the United States saw a substantial rise to 117,045 in 2020, compared to 4,697 in 2014.
2020: Cost Disparity of Fentanyl Products and Illicit Market Prices
As of 2020, the price of an 800 mcg fentanyl tablet in the U.S. was 6.75 times higher than the lozenge form. Additionally, in Australia, a 100-microgram transdermal patch could cost between AU$75 and AU$450 on illicit markets.
2020: High Fentanyl-Related Deaths in British Columbia
In 2020, British Columbia reported a staggering 1,716 deaths linked to fentanyl, underscoring the ongoing crisis.
2020: Myanmar Military Confiscates "Methyl Fentanyl"
A significant event occurred in 2020 when the Myanmar military and police seized 990 gallons of "methyl fentanyl" along with precursors used in its illegal production.
2020: Journal of Medical Toxicology Article on Fentanyl Exposure
A 2020 article published in the Journal of Medical Toxicology emphasized the scientific consensus that accidental exposure to fentanyl, through touch or inhalation, poses an extremely low risk of intoxication or overdose. The article highlighted that opioids are not easily absorbed through the skin and are unlikely to be transmitted through the air.
2020: Survey of First Responders on Fentanyl Perceptions
A survey conducted in 2020 among first responders in New York revealed a concerning misconception: 80% of those surveyed believed that even momentary contact with fentanyl could have fatal consequences.
October 2021: Fentanyl Overdose Crisis in British Columbia
By October 2021, British Columbia had reported 1,782 deaths related to fentanyl overdoses, highlighting the severity of the crisis.
2021: End of Study on Pediatric Overdose Deaths and UNODC Report on Opioid Crisis
By the conclusion of a study in 2021 examining pediatric deaths from 1999 to 2021, it was revealed that 37.5% of these cases were linked to fentanyl. A concurrent report from the UNODC highlighted the ongoing opioid crisis in North America, emphasizing its severity due to an unparalleled number of overdose deaths.
2021: UN Identifies Shan State as Major Fentanyl Source
In 2021, the UN Office on Drugs and Crime identified Myanmar's Shan State as a significant production hub for fentanyl derivatives.
2021: Gupta Method Dominates Illicit Fentanyl Production
During the first half of 2021, the U.S. Drug Enforcement Administration (DEA) found that the Gupta method, a simplified approach to fentanyl synthesis, had become the most prevalent method used in the production of seized fentanyl samples. Unlike traditional methods, the Gupta method bypassed the direct use of 4-ANPP/NPP, generating these compounds only as transient intermediates or impurities.
2021: Significant Reduction in Fentanyl's Manufacturing Quota
By 2021, the DEA had significantly reduced the annual aggregate manufacturing quota for fentanyl to 731,452 kg. This represented a substantial decrease of nearly 68.2% compared to the 2015 and 2016 quotas, reflecting efforts to address the ongoing opioid epidemic and control the production of this powerful drug.
2021: Sharp Increase in Synthetic Opioid Deaths
By 2021, deaths attributed to synthetic opioids surged to a staggering 70,601, a significant increase from 2,600 overdoses in 2011, highlighting the escalating severity of the issue.
2021: Paper Highlights Concerns Over Exaggerated Fentanyl Fears
A 2021 research paper raised concerns that the widespread fear surrounding fentanyl, particularly the belief that even brief contact can be fatal, might hinder effective emergency responses to overdoses. The paper suggested that these unfounded fears could lead to delays in providing critical aid and reinforce negative stereotypes about individuals who use drugs.
2022: Direct Fentanyl Shipments from China to the U.S. Stop
According to the national archives and the DEA, shipments of fentanyl directly from China to the U.S. ceased in 2022.
2022: China Halts Drug Trafficking Cooperation with the U.S.
Following Nancy Pelosi's visit to Taiwan in 2022, China ceased its cooperation with the United States on combating drug trafficking.
2022: Continuous Flow Synthesis of Fentanyl
In 2022, Braga and his colleagues unveiled a novel method for synthesizing fentanyl utilizing continuous flow technology. This innovative approach employed reagents comparable to those used in the Gupta procedure, potentially offering a more efficient and scalable method for fentanyl production.
April 2023: Teva Pharmaceuticals Recalls Fentanyl Buccal Tablets
In April 2023, Teva Pharmaceuticals USA recalled 13 lots of their Fentanyl Buccal Tablets CII because they lacked the required safety information sheets.
June 2023: Record-High Overdose Deaths in US and Canada
Overdose fatalities reached unprecedented levels in the U.S. and Canada in June 2023.
2023: Average Cost of Injectable Fentanyl Solution
By 2023, the average price for a 20 milliliter supply of injectable fentanyl solution (50 mcg/mL) was approximately US$17, subject to pharmacy variations.
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, which were disguised as chocolate.