Detail:
Fentanyl, also spelled 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 available 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 US$0.08 and US$0.81 per 100 microgram vial. In the United States this amount costs about US$0.40 as of 2017. Fentanyl is also made illegally and used as a recreational drug often mixed with heroin or cocaine. In 2016, more than 20,000 deaths occurred in the United States due to overdoses of fentanyl and its analogues.
Intravenous and intrathecal:
Intravenous fentanyl is often used for anaesthesia and analgesia. During anaesthesia it is often used along with a hypnotic agent like propofol. It is also administered in combination with a benzodiazepine, such as midazolam, to produce sedation for procedures such as endoscopy, cardiac catheterization, and oral surgery, or in emergency rooms. It is often used in the management of chronic pain including cancer pain.
Fentanyl is sometimes given intrathecally as part of spinal anaesthesia or epidurally for epidural anaesthesia 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.
Patches:
A fentanyl transdermal patch with a release rate of 12 micrograms / hour, on a person's arm.
Fentanyl transdermal patches (Durogesic/Duragesic) are 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. Dosage is based on the size of the patch, since, in general, the transdermal absorption rate is constant at a constant skin temperature. 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 opioid (such as morphine or oxycodone) to handle breakthrough pain.
It is unclear if fentanyl gives long-term pain relief to people with neuropathic pain.
Storage and disposal:
The fentanyl patch is one of a small number of medications 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 medication was prescribed. Unused fentanyl patches should be kept in a secure location that is out of children’s sight and reach, such as a locked cabinet.
When patches cannot be disposed of through a medication take-back program, flushing is recommended for fentanyl patches because it is the fastest and surest way to remove them from the home so they cannot harm children, pets and others who were not intended to use them.
Intranasal:
The bioavailability of intranasal fentanyl is about 70–90%, but with some imprecision due to clotted nostrils, pharyngeal swallow and incorrect administration. For both emergency and palliative use, intranasal fentanyl is available in doses of 50, 100, and 200 µg. In emergency medicine, safe administration of intranasal fentanyl with a low rate of side effects and a promising pain reducing effect was demonstrated in a prospective observational study in about 900 out-of-hospital patients.
In children, intranasal fentanyl is useful for the treatment of moderate and severe pain and is well tolerated.
Sublingual:
Abstral dissolves quickly and is absorbed through the sublingual mucosa to provide rapid analgesia. Fentanyl is a highly lipophilic compound, which is well absorbed sublingually and generally well tolerated.Such forms are particularly useful for breakthrough cancer pain episodes, which are often rapid in onset, short in duration and severe in intensity.
Lozenges:
Package and example of fentanyl lollipop (brand: Actiq), 400 micrograms.
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. It has also been used for breakthrough pain for patients with nonmalignant (not cancer related) pain, but this application is controversial. The unit is a berry-flavoured 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 medication 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)
Adverse effects:
Fentanyl's most common side effects (more than 10% of patients) include diarrhea, 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), 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.
Overdose:
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.
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.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. American rapper Lil Peep also died of an accidental fentanyl overdose on November 15, 2017. On January 19, 2018, the medical examiner-coroner for the county of Los Angeles announced that Tom Petty died from an accidental drug overdose as a result of mixing medications that included fentanyl, acetyl fentanyl and despropionyl fentanyl (among others). He was reportedly treating "many serious ailments" that included a broken hip.
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