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Fentanyl - Wikipedia, the free encyclopedia

Fentanyl
From Wikipedia, the free encyclopedia

Fentanyl (also known as fentanil, brand names


Sublimaze,[3] Actiq, Durogesic, Duragesic, Fentora,
Matrifen, Haldid, Onsolis,[4] Instanyl,[5] Abstral,[6]
Lazanda[7] and others[8] ) is a potent, synthetic opioid
analgesic with a rapid onset and short duration of
action.[9] It is a strong agonist at the -opioid receptors.
Historically, it has been used to treat breakthrough pain
and is commonly used in pre-procedures as a pain
reliever as well as an anesthetic in combination with a
benzodiazepine.

Fentanyl

Fentanyl is approximately 80 to 100 times more potent


than morphine and roughly 40 to 50 times more potent
than pharmaceutical grade (100% pure) heroin.[10][11]
Fentanyl was first synthesized by Paul Janssen in
1960[12] following the medical inception of pethidine
several years earlier. Janssen developed fentanyl by
assaying analogues of the structurally related drug
pethidine for opioid activity.[13] The widespread use of
fentanyl triggered the production of fentanyl citrate (the
salt formed by combining fentanyl and citric acid in a 1:1
stoichiometry),[14] which entered the clinical practice as
a general anaesthetic under the trade name Sublimaze in
the 1960s. Following this, many other fentanyl analogues
were developed and introduced into medical practice,
including sufentanil, alfentanil, remifentanil, and
lofentanil.
In the mid-1990s, fentanyl was first introduced for
widespread palliative use with the clinical introduction of
the Duragesic patch, followed in the next decade by the
introduction of the first quick-acting prescription
formulations of fentanyl for personal use, the Actiq
lollipop and Fentora buccal tablets. Through the delivery
method of transdermal patches, as of 2012 fentanyl was
the most widely used synthetic opioid in clinical practice,
with several new delivery methods now available,
including a sublingual spray for cancer patients.[15][16]
In 2013 1700 kilograms were used globally.[17]

Systematic (IUPAC) name


N-(1-(2-phenylethyl)-4-piperidinyl)-N-phenylpropanamide

Clinical data
Trade names

Actiq, Duragesic, Fentora,


Sublimaze and others

AHFS/Drugs.com monograph
Pregnancy
category

AU:

Legal status

AU:

C
US: C (Risk not ruled out)
Controlled (S8)
UK: Class A
US: Schedule II
(Prescription only)

Dependence
liability
Routes of
administration

Very high
TD, IM, IV, oral transmucosal,
sublingual, buccal

Pharmacokinetic data
Bioavailability

92% (transdermal)
89% (intranasal)
50% (buccal)
33% (ingestion)

Protein binding

8085%

Metabolism

hepatic, primarily by CYP3A4

Biological halfhttps://en.wikipedia.org/wiki/Fentanyl

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Fentanyl and its derivatives are used recreationally.


Deaths have resulted from both recreational and
improper medical use.[18]

Contents
1 Medical uses
1.1 Patches
1.2 Lozenges
1.3 Other
2 Veterinary use
3 Adverse effects
4 Storage and disposal
4.1 Overdoses and fatalities
5 Analogues
6 Mechanism of action
7 History
8 Recreational use
9 Military use
9.1 Analgesic
9.2 As a poison
10 See also
11 References
12 External links

life

(IV)= 10-20 mins (T1/2 )


2-4 hours (T1/2 )
Intranasal = 6.5 mins
Transdermal = 2027 h[1]

Excretion

60% Urinary (metabolites, <10%


unchanged drug)[2]
Identifiers

CAS Registry
Number
ATC code

437-38-7

PubChem

CID: 3345

IUPHAR/BPS

1626

DrugBank

DB00813

ChemSpider

3228

UNII

UF599785JZ

KEGG

D00320

ChEBI

CHEBI:119915

ChEMBL

CHEMBL596

N01AH01 N02AB03

Chemical data
Formula

C22H28N2O

Molecular mass 336.471 g/mol

Medical uses

SMILES
InChI

Physical data

Intravenous fentanyl is often used for anesthesia and


Melting point
87.5 C (189.5 F)
analgesia. During anaesthesia it is often used along with
a hypnotic agent like propofol. Fentanyl may be included
(what is this?) (verify)
in a solution along with local anesthetic for neuraxial
administration (epidural or intrathecal/spinal). It is also administered in combination with a benzodiazepine,
such as midazolam, to produce procedural sedation for endoscopy, cardiac catheterization, oral surgery,
etc., and is often used in the management of chronic pain including cancer pain.
In children intranasal fentanyl is useful for the treatment of moderate and severe pain and is well
tolerated.[19]

Patches
Fentanyl transdermal patch (Durogesic/Duragesic/Matrifen) is used in chronic pain management. The
patches work by slowly releasing fentanyl through the skin into the bloodstream over 48 to 72 hours,
allowing for long-lasting pain management.[20] Dosage is based on the size of the patch, since, in general,
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the transdermal absorption rate is constant at a constant skin temperature.[20] Rate of absorption is
dependent on a number of factors. Body temperature, skin type, amount of body fat, and placement of the
patch can have major effects. The different delivery systems used by
different makers will also affect individual rates of absorption.
Under normal circumstances, the patch will reach its full effect
within 12 to 24 hours; thus, fentanyl patches are often prescribed
with a fast-acting opiate (such as morphine or oxycodone) to handle
breakthrough pain.[20]
In palliative care, transdermal fentanyl has a definite, but limited,
role for:
people already stabilized on other opioids who have persistent
swallowing problem and cannot tolerate other parenteral
routes such as subcutaneous administration.
people with moderate to severe renal failure.
troublesome side effects of oral morphine, hydromorphone, or
oxycodone.

A Fentanyl patch, from Israel.

Lozenges
Fentanyl lozenges (Actiq) are a solid formulation of fentanyl citrate on a stick in the form of a lollipop that
dissolves slowly in the mouth for transmucosal absorption. These lozenges are intended for opioid-tolerant
individuals and are effective in treating breakthrough cancer pain.[21] It has also been used for
breakthrough pain for patients with nonmalignant (not cancer related) pain, but this application is
controversial.[22] The unit is a berry-flavored lozenge on a stick swabbed on the mucosal surfaces inside
the mouth inside of the cheeks, under and on the tongue and gums to release the fentanyl quickly into
the system. It is most effective when the lozenge is consumed within 15 minutes. About 25% of the drug is
absorbed through the oral mucosa, resulting in a fast onset of action, and the rest is swallowed and
absorbed in the small intestine, acting more slowly. The lozenge is less effective and acts more slowly if
swallowed as a whole, as despite good absorbance from the small intestine there is extensive first-pass
metabolism, leading to an oral bioavailability of about 33% as opposed to 50% when used correctly (25%
via the mouth mucosa and 25% via the gut).[21]
However, most people find that it takes 1015 minutes to use all of one lozenge, and those with a dry mouth
cannot use this route. In addition, medical personnel are unable to document how much of a lozenge has
been used by a person, making drug records inaccurate.

Other
A wide range of fentanyl preparations is available, including buccal tablets or patches, nasal sprays,
inhalers, and active transdermal patches (heat or electrical). Some preparations such as nasal sprays and
inhalers may result in a rapid response, but the fast onset of high blood levels may compromise safety. In
addition, the expense of some of these appliances may greatly reduce their cost-effectiveness. In children it
is unclear if intranasal fentanyl is as good as or same as morphine.[23]
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Fentanyl is sometimes given intrathecally as part of spinal anesthesia or epidurally for epidural anesthesia
and analgesia. Because of fentanyl's high lipid solubility, its effects are more localized than morphine, and
some clinicians prefer to use morphine to get a wider spread of analgesia.

Veterinary use
Fentanyl (in injectable formulation) is commonly used for analgesia and as a component of balanced
sedation and general anesthesia in small animal patients. Its potency and short duration of action make it
particularly useful in critically ill patients. In addition, it tends to cause less vomiting and regurgitation than
do other pure-opioid agonists (morphine, hydromorphone) when given as a continuous infusion postoperatively. As with other pure opioids, fentanyl can be associated with dysphoria in both dogs and cats.
Transdermal fentanyl has also been used for many years in dogs and cats for post-operative analgesia.
Most commonly this has been accomplished by off-label use of fentanyl patches manufactured for use in
humans with chronic malignant pain. In 2012 a highly concentrated (50 mg/ml) transdermal solution, trade
name Recuvyra, has become commercially available for use in dogs only. It is FDA approved to provide
four days of analgesia (again in dogs only) after a single application prior to surgery. It is not approved for
multiple doses or use in other species.[24] The drug is also approved in Europe.[25]

Adverse effects
Fentanyl's most common side-effects (more than 10% of patients) include diarrhea, nausea, constipation,
dry mouth, somnolence, confusion, asthenia (weakness), and 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), dyspnea (shortness of
breath), hypoventilation, apnea, and urinary retention. Fentanyl use has also been associated with
aphasia.[3]
Despite being a more potent analgesic, fentanyl tends to induce less nausea, as well as less histaminemediated itching, in relation to morphine.[26]
Fentanyl may produce more prolonged respiratory depression than other opioid
analgesics.[27][28][29][30][31][32][33] 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.[34] The FDA reported in April 2012 that young children had died or
become seriously ill from accidental exposure to a fentanyl skin patch.[35]
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.
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Fentanyl has a therapeutic index of 270.[36]

Storage and disposal


Fentanyl is one of a small number of drugs that may be especially harmful, and in some cases fatal, with
just one dose, if used by someone other than the person for whom the drug was prescribed.[37] All fentanyl
medicine should be kept in a secure location such as a locked cabinet that is out of childrens sight and
reach.
When they cannot be disposed of through a drug take-back program, flushing is recommended for fentanyl
medicines because it is the fastest and surest way to remove these potent medicines from the home so they
cannot harm children, pets, and others not intended to use them.[37][38]
Fentanyl patches should be flushed down the toilet as soon as they are removed from the body, and unused
fentanyl patches should be flushed as soon as they are no longer needed. Detailed "Instructions for Use",
with complete information on how to apply, use, and dispose of fentanyl patches, are available on the FDA
website.[39]

Overdoses and fatalities


In 2009, the former guitarist for the band Wilco, Jay Bennett, died in his sleep of an overdose of the drug
via Duragesic time-release patches prescribed for him.[40] In 2010, band Slipknot's bassist Paul Gray
overdosed and died after using a mixture of fentanyl and morphine, for which there was no evidence of a
prescription.[41] An inquest jury found by a majority verdict of 3-2 that an overdose of fentanyl was
responsible for the death by misadventure of Anita Chan Lai-ling, 69, who died on October 17, 2007, after
she was given an overdose of fentanyl.[42] On June 27, 2005, Laurence Harvey's daughter Domino Harvey
was found unconscious in her bathtub, and the Los Angeles County Coroner's office determined that she
had overdosed on fentanyl.[43] In 2009 27-year-old Hayley Fisher, a midwife at King Edward Memorial
Hospital for Women in Australia, died after injecting herself with fentanyl.[44]
In July 2014, the Medicines and Healthcare Products Regulatory Agency (MHRA) issued a warning about
the potential for life-threatening harm from accidental exposure to transdermal fentanyl patches,
particularly in children,[45] 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.[46]

Analogues
Structural analogs of fentanyl include:
Alfentanil (trade name Alfenta), an ultra-short-acting (five- to 10-minute) analgesic.
Sufentanil (trade name Sufenta), a potent analgesic (five to 10 times more potent than fentanyl) for
use in specific surgeries and surgery in heavily opioid-tolerant/opioid-dependent patients. Its binding
affinity is high enough to theoretically break through a buprenorphine blockade to offer pain relief
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from acute trauma in patients taking high-dose buprenorphine.


Remifentanil (trade name Ultiva), currently the shortest-acting opioid, has the benefit of rapid offset,
even after prolonged infusions.
Carfentanil (trade name Wildnil) is an analogue of fentanyl with an analgesic potency 10,000 times
that of morphine and is used in veterinary practice to immobilize certain large animals such as
elephants.
Lofentanil is an analogue of fentanyl with a potency slightly greater than that of carfentanil.
3-Methylfentanyl (thought to be the active constituent of Kolokol-1, a chemical weapon)
3-Methylthiofentanyl
Acetyl--methylfentanyl
-Methylfentanyl (see below)
-Methylthiofentanyl
-Hydroxy-3-methylfentanyl
-Hydroxyfentanyl
p-Flurorofentanyl
Thiofentanyl
Acetylfentanyl
Butyrfentanyl
Furanyl-fentanyl
The tropane analog of fentanyl was prepared (2 isomers).
Acryloyl analog of fentanyl 2x potency/duration of regular fentanyl (Egyptian scientist).

Mechanism of action
Fentanyl provides some of the effects typical of other opioids through its agonism of the opioid receptors.
Its strong potency in relation to that of morphine is largely due to its high lipophilicity, per the MeyerOverton correlation. Because of this, it can more easily penetrate the CNS.[26]

History
Fentanyl was first synthesized by Paul Janssen under the label of his relatively newly formed Janssen
Pharmaceutica in 1959.[47] In the 1960s, fentanyl was introduced as an intravenous anesthetic under the
trade name of Sublimaze. 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 the medical practice.
Following the patch, a flavored 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. More recently, 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.

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A fentanyl product has been approved by the US Food and Drug Administration (FDA) for breakthrough
cancer pain called Onsolis. It uses a drug 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 2108.75
kilos, unchanged from the prior year.

Recreational use
Illicit use of pharmaceutical fentanyl and its analogues first appeared in the
mid-1970s in the medical community and continues in the present. United
States authorities classify fentanyl as a narcotic and an opioid. To date,
more than 12 different analogues of fentanyl have been produced
clandestinely and identified in the U.S. drug traffic. The biological effects of
the fentanyl analogues are similar to those of heroin, with the exception that
many users report a noticeably less euphoric "high" associated with the drug
and stronger sedative and analgesic effects.
Fentanyl analogues may be hundreds of times more potent than street
heroin, and tends to produce significantly more respiratory depression,
making it somewhat more dangerous than heroin to users. Fentanyl is used
orally, smoked, snorted, or injected. Fentanyl is sometimes sold as heroin,
often leading to overdoses. Many fentanyl overdoses are initially classified
as heroin overdoses.[49] In Estonia, due to its high rate of recreational use,
fentanyl causes more deaths nationwide than traffic accidents.[50]

Fentanyl powder seized by a


Lake County Deputy Sheriff
in Painesville, Ohio, where
a male subject had been
discovered unresponsive and
struggling to breathe. [48]

Fentanyl is sometimes sold on the black market in the form of transdermal fentanyl patches such as
Duragesic, diverted from legitimate medical supplies. The patches may be cut up and eaten, or the gel from
inside the patch smoked.
Another dosage form of fentanyl that has appeared on the streets is the Actiq fentanyl lollipops, which are
sold under the street name of "percopop". The pharmacy retail price ranges from US$15 to US$50 per unit
(based on strength of lozenge), with the black market cost anywhere from US$20 to US$80 per unit,
depending on the strength.
Non-medical use of fentanyl by individuals without opiate tolerance can be very dangerous and has resulted
in numerous deaths.[51] Even those with opiate tolerances are at high risk for overdoses. Once the fentanyl
is in the user's system, it is extremely difficult to stop its course because of the nature of absorption. Illicitly
synthesized fentanyl powder has also appeared on the United States market. Because of the extremely high
strength of pure fentanyl powder, it is very difficult to dilute appropriately, and often the resulting mixture
may be far too strong and, therefore, very dangerous.
Some heroin dealers mix fentanyl powder with heroin to increase potency or compensate for low-quality
heroin. In 2006, illegally manufactured, non-pharmaceutical fentanyl often mixed with cocaine or heroin
caused an outbreak of overdose deaths in the United States, heavily concentrated in the cities of Dayton,

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(Ohio), Chicago, Detroit, and Philadelphia,[52] as well as Baltimore, Pittsburgh, St. Louis, Milwaukee, and
Camden (New Jersey).[53] Little Rock and Dallas[54] were also affected. The mixture of fentanyl and
heroin is known as "magic" or "the bomb", among other names, on the street.[55]
Several large quantities of illicitly produced fentanyl have been seized by U.S. law enforcement agencies. In
June 2006, 945 grams of 83%-pure fentanyl powder was seized by Border Patrol agents in California from
a vehicle that had entered from Mexico.[56] Mexico is the source of much of the illicit fentanyl for sale in
the U.S. However, in April 2006, there was one domestic fentanyl lab discovered by law enforcement in
Azusa, California. The lab was a source of counterfeit 80-mg OxyContin tablets containing fentanyl instead
of oxycodone, as well as bulk fentanyl and other drugs.[57][58]
The "China White" form of fentanyl refers to any of a number of clandestinely produced analogues,
especially -methylfentanyl (AMF).[59] This Department of Justice document lists "China White" as a
synonym for a number of fentanyl analogues, including 3-methylfentanyl and -methylfentanyl,[60] which
today are classified as Schedule I drugs in the United States.[61] Part of the motivation for AMF is that,
despite the extra difficulty from a synthetic standpoint, the resultant drug is relatively more resistant to
metabolic degradation. This results in a drug with an increased duration.[62]
In June 2013, the United States' Centers for Disease Control and Prevention (CDC) issued a health
advisory[63] to emergency departments alerting to 14 overdose deaths among intravenous drug users in
Rhode Island associated with acetylfentanyl, a novel, injected, non-prescription synthetic opioid analog of
fentanyl.

Military use
Analgesic
The Danish Army uses the fentanyl stick in military operations as a painkiller. The war documentary
Armadillo (2010) features an interview with a Danish medic who tells of using fentanyl on a severely
wounded soldier in Afghanistan.
The United States Air Force Pararescue and Swedish armed forces combat medics utilize lollipops with
fentanyl.[64]

As a poison
It is alleged that Mossad agents used "levofentanyl" in their 1997 attempt to kill Hamas leader Khalid
Mishal.[65] However, since fentanyl is achiral (i.e., has no "levo-" form), the substance was probably
fentanyl itself, a fentanyl analogue, or another opioid. However, it could have been a non-opioid sedative or
unknown drug.

See also
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3-Methylbutyrfentanyl
3-Methylfentanyl
4-Fluorofentanyl
-Methylfentanyl
Acetylfentanyl
Butyrfentanyl
Furanylfentanyl
List of Fentanyl analogues

References
1. Janssen Pharmaceuticals (Duragesic) (http://www.duragesic.com/)
2. Hess R, Stiebler G, Herz A (June 1972). "Pharmacokinetics of fentanyl in man and the rabbit". Eur. J. Clin.
Pharmacol. 4 (3): 13741. doi:10.1007/BF00561135 (https://dx.doi.org/10.1007%2FBF00561135).
PMID 4655287 (https://www.ncbi.nlm.nih.gov/pubmed/4655287).
3. "fentanyl" (http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?
fuseaction=Search.SearchAction&SearchTerm=fentanyl&SearchType=BasicSearch). Drugs@FDA: FDA
Approved Drug Products. U.S. Food and Drug Administration.
4. "Introducing Onsolis" (http://www.onsolis.com). Onsolis.com. Retrieved 2010-07-28.
5. "EPAR summary for the public: Instanyl" (http://www.ema.europa.eu/docs/en_GB/document_library/EPAR__Summary_for_the_public/human/000959/WC500033142.pdf) (PDF). European Medicines Agency. Retrieved
2010-07-28.
6. "Abstral: Prescribing Information" (http://newdrugreview.com/index.php/analgesic-drugs/abstral-fentanyl).
Retrieved 2011-01-07.
7. "Lazanda (fentanyl nasal spray) CII" (http://www.lazanda.com/). Lazanda.com. Retrieved 2012-05-14.
8. "Fentanyl" (http://www.drugs.com/international/fentanyl.html). International Drug Names. Drugs.com.
9. "WCPI Focus on Pain Series: The Three Faces of Fentanyl" (http://aspi.wisc.edu/wpi/focus/spring96.htm).
Aspi.wisc.edu. Retrieved 2010-07-28.
10. "FENTANYL : Incapacitating Agent"
(http://www.cdc.gov/niosh/ershdb/EmergencyResponseCard_29750022.html). CDC. Retrieved 2014-09-18.
11. Mutschler, Ernst; Schfer-Korting, Monika (2001). Arzneimittelwirkungen (in German) (8 ed.). Stuttgart:
Wissenschaftliche Verlagsgesellschaft. p. 286. ISBN 3-8047-1763-2.
12. Stanley TH (April 1992). "The history and development of the fentanyl series". J Pain Symptom Manage 7 (3
Suppl): S37. doi:10.1016/0885-3924(92)90047-L (https://dx.doi.org/10.1016%2F0885-3924%2892%2990047L). PMID 1517629 (https://www.ncbi.nlm.nih.gov/pubmed/1517629).
13. Black J (March 2005). "A personal perspective on Dr. Paul Janssen"
(http://www.pauljanssenaward.com/janssen/A_Personal_Perspective.pdf#zoom=100) (PDF). J. Med. Chem. 48 (6):
16878. doi:10.1021/jm040195b (https://dx.doi.org/10.1021%2Fjm040195b). PMID 15771410
(https://www.ncbi.nlm.nih.gov/pubmed/15771410).
14. "DailyMed: About DailyMed" (http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=10055).
Dailymed.nlm.nih.gov. Retrieved 2010-07-28.
15. "Subsys (fentanyl sublingual spray)" (http://www.centerwatch.com/drug-information/fda-approveddrugs/drug/1179/subsys-fentanyl-sublingual-spray).
16. "Long Term Safety and Efficacy Study of Fentanyl Sublingual Spray for the Treatment of Breakthrough Cancer
Pain - Full Text View" (http://clinicaltrials.gov/ct2/show/NCT00538863). ClinicalTrials.gov. Retrieved
2010-07-28.
17. Narcotic Drugs 2014 (https://www.incb.org/documents/Narcotic-Drugs/TechnicalPublications/2014/Narcotic_Drugs_Report_2014.pdf) (PDF). INTERNATIONAL NARCOTICS CONTROL
BOARD. 2015. p. 21. ISBN 9789210481571.
18. Parry WH, Martorano F, Cotton EK (January 1976). "Management of life-threatening asthma with intravenous
isoproterenol infusions". Am. J. Dis. Child. 130 (1): 3942. doi:10.1001/archpedi.1976.02120020041006

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9/13

12/7/2015

19.

20.
21.
22.
23.

24.
25.
26.
27.

28.

29.

30.

31.

32.

33.

34.

35.

Fentanyl - Wikipedia, the free encyclopedia

isoproterenol infusions". Am. J. Dis. Child. 130 (1): 3942. doi:10.1001/archpedi.1976.02120020041006


(https://dx.doi.org/10.1001%2Farchpedi.1976.02120020041006). PMID 2007
(https://www.ncbi.nlm.nih.gov/pubmed/2007).
Murphy A, O'Sullivan R, Wakai A, Grant TS, Barrett MJ, Cronin J et al. (Oct 10, 2014). "Intranasal fentanyl for
the management of acute pain in children". The Cochrane database of systematic reviews 10: CD009942.
doi:10.1002/14651858.CD009942.pub2 (https://dx.doi.org/10.1002%2F14651858.CD009942.pub2).
PMID 25300594 (https://www.ncbi.nlm.nih.gov/pubmed/25300594).
Jasek, W, ed. (2007). Austria-Codex (in German) (62nd ed.). Vienna: sterreichischer Apothekerverlag.
pp. 2621f. ISBN 978-3-85200-181-4.
Jasek, W, ed. (2007). Austria-Codex (in German) (62nd ed.). Vienna: sterreichischer Apothekerverlag. pp. 89
92. ISBN 978-3-85200-181-4.
O'Connor AB (2008). "Is actiq use in noncancer-related pain really "a recipe for success"?". Pain Medicine 9
(2): 25860; author reply 2615. doi:10.1111/j.1526-4637.2008.00413.x (https://dx.doi.org/10.1111%2Fj.15264637.2008.00413.x). PMID 18298711 (https://www.ncbi.nlm.nih.gov/pubmed/18298711).
Murphy A, O'Sullivan R, Wakai A, Grant TS, Barrett MJ, Cronin J et al. (10 October 2014). "Intranasal fentanyl
for the management of acute pain in children.". The Cochrane database of systematic reviews 10: CD009942.
doi:10.1002/14651858.CD009942.pub2 (https://dx.doi.org/10.1002%2F14651858.CD009942.pub2).
PMID 25300594 (https://www.ncbi.nlm.nih.gov/pubmed/25300594).
Original new animal drug application: Recuvyra
(http://www.fda.gov/downloads/AnimalVeterinary/Products/ApprovedAnimalDrugProducts/FOIADrugSummaries/
UCM314828.pdf)
European Medicines Agency: Recuvyra (http://www.ema.europa.eu/ema/index.jsp?
curl=pages/medicines/veterinary/medicines/002239/vet_med_000245.jsp&mid=WC0b01ac058008d7a8)
Stacey Mayes, PharmD MS, Marcus Ferrone, PharmD BCNSP, 2006.Fentanyl HCl Patient-Controlled
Iontophoretic Transdermal System for Pain: Pharmacology (http://www.medscape.com/viewarticle/549359_3) The
Annals of Pharmacotherapy
Smydo J (1979). "Delayed respiratory depression with fentanyl"
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2515983). Anesth Prog 26 (2): 478. PMC 2515983
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2515983). PMID 295585
(https://www.ncbi.nlm.nih.gov/pubmed/295585).
van Leeuwen L, Deen L, Helmers JH (August 1981). "A comparison of alfentanil and fentanyl in short operations
with special reference to their duration of action and postoperative respiratory depression". Anaesthesist 30 (8):
3979. PMID 6116461 (https://www.ncbi.nlm.nih.gov/pubmed/6116461).
Brown DL (November 1985). "Postoperative analgesia following thoracotomy. Danger of delayed respiratory
depression". Chest 88 (5): 77980. doi:10.1378/chest.88.5.779 (https://dx.doi.org/10.1378%2Fchest.88.5.779).
PMID 4053723 (https://www.ncbi.nlm.nih.gov/pubmed/4053723).
Blow HH, Linnemann M, Berg H, Lang-Jensen T, LaCour S, Jonsson T (August 1995). "Respiratory changes
during treatment of postoperative pain with high dose transdermal fentanyl". Acta Anaesthesiol Scand 39 (6):
8359. doi:10.1111/j.1399-6576.1995.tb04180.x (https://dx.doi.org/10.1111%2Fj.1399-6576.1995.tb04180.x).
PMID 7484044 (https://www.ncbi.nlm.nih.gov/pubmed/7484044).
Nilsson C, Rosberg B (June 1982). "Recurrence of respiratory depression following neurolept analgesia". Acta
Anaesthesiol Scand 26 (3): 2401. doi:10.1111/j.1399-6576.1982.tb01762.x
(https://dx.doi.org/10.1111%2Fj.1399-6576.1982.tb01762.x). PMID 7113633
(https://www.ncbi.nlm.nih.gov/pubmed/7113633).
McLoughlin R, McQuillan R (September 1997). "Transdermal fentanyl and respiratory depression". Palliat Med
11 (5): 419. doi:10.1177/026921639701100515 (https://dx.doi.org/10.1177%2F026921639701100515).
PMID 9472602 (https://www.ncbi.nlm.nih.gov/pubmed/9472602).
Regnard C, Pelham A (December 2003). "Severe respiratory depression and sedation with transdermal fentanyl:
four case studies". Palliat Med 17 (8): 7146. PMID 14694924
(https://www.ncbi.nlm.nih.gov/pubmed/14694924).
"Fentanyl patches: serious and fatal overdose from dosing errors, accidental exposure, and inappropriate use"
(http://www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/CON025631). Drug Safety Update 2
(2): 2. September 2008.
"Fentanyl Patch Can Be Deadly to Children" (http://www.drugs.com/fda-consumer/fentanyl-patch-can-be-deadly-

https://en.wikipedia.org/wiki/Fentanyl

10/13

12/7/2015

Fentanyl - Wikipedia, the free encyclopedia


35. "Fentanyl Patch Can Be Deadly to Children"
(http://www.drugs.com/fda-consumer/fentanyl-patch-can-be-deadlyto-children-214.html). FDA Consumer Information on drugs.com site. U.S. FDA(Drugs.com). April 19, 2012.
Retrieved July 30, 2013.
36. Stanley, Theodore Henry; Petty, William Clayton (1983-03-31). New Anesthetic Agents, Devices, and Monitoring
Techniques (http://books.google.com/?
id=msYvkdGM6F0C&pg=PA122&lpg=PA122&dq=fentanyl+%22therapeutic+index%22+-narrow+-carfentanil).
Springer. ISBN 978-90-247-2796-4. Retrieved 20 October 2007.
37. "Disposal of Unused Medicines: What You Should Know"
(http://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/EnsuringSafeUseofMedicine
/SafeDisposalofMedicines/ucm186187.htm). U.S. Food and Drug Administration. Retrieved 2013-09-10.
38. "Medicines Recommended for Disposal by Flushing"
(http://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/EnsuringSafeUseofMedicine
/SafeDisposalofMedicines/ucm186187.htm#MEDICINES). U.S. Food and Drug Administration. Retrieved
2013-09-10.
39. "Medication Guide and Instructions for Use Duragesic (fentanyl) Transdermal System"
(http://www.fda.gov/downloads/Drugs/DrugSafety/UCM088584.pdf) (PDF). U.S. Food and Drug Administration.
Retrieved 2013-09-10.
40. "Coroner: Painkiller killed ex-Wilco member" (http://www.chicagobreakingnews.com/2009/06/coroner-painkillerkilled-ex-wilco-member.html). Chicago Tribune. 2009-06-23. Retrieved 2010-08-20.
41. "Slipknot bassist Paul Gray died of morphine overdose"
(http://news.bbc.co.uk/1/hi/entertainment_and_arts/10372085.stm). BBC News. 2010-06-21. Retrieved
2010-07-28.
42. "Painkiller death was misadventure" (http://www.scmp.com/article/732255/painkiller-death-was-misadventure).
2010-12-03. Retrieved 2014-11-16.
43. http://www.utsandiego.com/uniontrib/20051014/news_1c14harvey.html
44. http://www.abc.net.au/news/2013-09-12/coroner-calls-for-stricter-access-to-pain-medication/4953786
45. Fentanyl patches warning (http://www.pharmaceutical-journal.com/news-and-analysis/notice-board/fentanylpatches-warning/20066029.article)
46. MHRA warns about fentanyl patches after children exposed (http://www.pharmaceutical-journal.com/news-andanalysis/news-in-brief/mhra-warns-about-fentanyl-patches-after-children-exposed/20065930.article)
47. Lopez-Munoz, Francisco; Alamo, Cecilio (2009). "The Consolidation of Neuroleptic Therapy: Janssen, the
Discovery of Haloperidol and Its Introduction into Clinical Practice". Brain Research Bulletin 79 (2): 130141.
doi:10.1016/j.brainresbull.2009.01.005 (https://dx.doi.org/10.1016%2Fj.brainresbull.2009.01.005).
PMID 19186209 (https://www.ncbi.nlm.nih.gov/pubmed/19186209).
48. "DEA Microgram Bulletin, June 2006"
(http://www.usdoj.gov/dea/programs/forensicsci/microgram/mg0606/mg0606.html). US Drug Enforcement
Administration, Office of Forensic Sciences Washington, D.C. 20537. June 2006. Retrieved 22 June 2009.
49. Boddiger, D. (2006, August 12).Fentanyl-laced street drugs "kill hundreds"
(http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2806%2969181-2/fulltext). The Lancet.
Retrieved June 15, 2010.
50. "Synthetic drug fentanyl causes overdose boom in Estonia" (http://www.bbc.co.uk/news/world-europe-17524945).
BBC News. 30 March 2012.
51. http://www.deadiversion.usdoj.gov/drugs_concern/fentanyl.htm
52. "CDC Nonpharmaceutical Fentanyl-Related Deaths - Multiple States, April 2005-March 2007"
(http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5729a1.htm). Cdc.gov. Retrieved 2010-07-28.
53. Press Release by the Chicago Police Department
(http://www.chicagopolice.org/MailingList/PressAttachment/releaseheroinhomicide.pdf) Police report about a
death linked to heroin/fentanyl mixture August 24, 2006
54. "SMU student's death blamed on rare drug"
(http://www.dallasnews.com/sharedcontent/dws/dn/latestnews/stories/122106dnmetsmudrug.2b395050.html).
Dallasnews.com. 2006-12-20. Retrieved 2010-07-28.
55. Fentanyl probe nets 3 suspects (http://www.detnews.com/apps/pbcs.dll/article?
AID=/20060623/METRO/606230339/1003) by Norman Sinclair and Ronald J. Hansen, The Detroit News, June
23, 2006. Retrieved June 25, 2006.
56. Intelligence alert: High purity fentanyl seized near Westmoreland, California

https://en.wikipedia.org/wiki/Fentanyl

11/13

12/7/2015

Fentanyl - Wikipedia, the free encyclopedia

56. Intelligence alert: High purity fentanyl seized near Westmoreland, California
(http://www.usdoj.gov/dea/programs/forensicsci/microgram/mg0606/mg0606.html), DEA Microgram, June 2006
57. Intelligence alert: Large fentanyl / MDA / TMA laboratory in Azuza, California - possibly the "OC-80" tablet
source (http://www.usdoj.gov/dea/programs/forensicsci/microgram/mg0406/mg0406.html), DEA Microgram, April
2006.
58. Intelligence alert: Oxycontin mimic tablets (containing fentanyl) near Atlantic, Iowa
(http://www.usdoj.gov/dea/programs/forensicsci/microgram/mg0106/mg0106.html), DEA Microgram, January
2006.
59. List of Schedule I Drugs, U.S. Department of Justice.
(http://www.deadiversion.usdoj.gov/schedules/listby_sched/sched1.htm)
60. Behind the Identification of China White
(http://www.erowid.org/archive/rhodium/chemistry/china.white.identification.html) Analytical Chemistry, 53(12),
1379A-1386A (1981)
61. List of Schedule I Drugs, U.S. Department of Justice.
(http://www.deadiversion.usdoj.gov/schedules/listby_sched/sched1.htm)
62. Van Bever WF, Niemegeers CJ, Janssen PA (October 1974). "Synthetic analgesics. Synthesis and pharmacology of
the diastereoisomers of N-(3-methyl-1-(2-phenylethyl)-4-piperidyl)-N-phenylpropanamide and N-(3-methyl-1-(1methyl-2-phenylethyl)-4-piperidyl)-N-phenylpropanamide". J. Med. Chem. 17 (10): 104751.
doi:10.1021/jm00256a003 (https://dx.doi.org/10.1021%2Fjm00256a003). PMID 4420811
(https://www.ncbi.nlm.nih.gov/pubmed/4420811).
63. CDC Health Alert Network (June 20, 2013). "Recommendations for Laboratory Testing for Acetyl Fentanyl and
Patient Evaluation and Treatment for Overdose with Synthetic Opioids"
(http://emergency.cdc.gov/HAN/han00350.asp). Centers for Disease Control and Prevention. Retrieved June 20,
2013.
64. Shachtman, Noah (September 10, 2009). "Airborne EMTs Shave Seconds to Save Lives in Afghanistan"
(http://www.wired.com/dangerroom/2009/09/airborne_emts_in_astan/). Danger Room. Wired.com. Retrieved
July 1, 2010.
65. McGeough, Paul (2009) Kill Khalid - The Failed Mossad Assassination of Khalid Mishal and the Rise of Hamas.
Quartet Books. ISBN 978-0-7043-7157-6. Page 184.

External links
National Institute of Health (NIH) Medline Plus: Fentanyl Buccal (Transmucosal)
(http://www.nlm.nih.gov/medlineplus/druginfo/meds/a605043.html)
RxList: Fentanyl (http://www.rxlist.com/cgi/generic/fentanyl.htm)
US DEA information: fentanyl (http://www.usdoj.gov/dea/concern/fentanyl.html)
08/16/2007 News Release: Cephalon Announces Positive Results from a Pivotal Study of FENTORA
in Opioid-tolerant Patients with Non-cancer Breakthrough Pain
(http://www.cephalon.com/newsroom/news_reader.aspx?ID=1041238)
BBC news report on Russian siege story (http://news.bbc.co.uk/1/hi/world/europe/2377563.stm)
Fentanyl: Emergency Response Database
(http://www.cdc.gov/niosh/ershdb/EmergencyResponseCard_29750022.html). National Institute for
Occupational Safety and Health.
U.S. National Library of Medicine: Drug Information Portal - Fentanyl
(http://druginfo.nlm.nih.gov/drugportal/dpdirect.jsp?name=Fentanyl)
Retrieved from "https://en.wikipedia.org/w/index.php?title=Fentanyl&oldid=670439819"
Categories: General anesthetics Synthetic opioids Piperidines Anilides Propionamides
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