1. Aschenbrenner, Diane S. MS, RN


* U.S. deaths from opioid overdose are on the rise. Heroin and other illegal opioids are being adulterated with the potent opioid fentanyl, significantly increasing the risk of sudden, lethal overdose. Highly potent fentanyl analogs, such as the large-animal sedative carfentanil, are also being mixed with heroin.


* Naloxone is an antidote to opioid overdose. Despite new preparations of naloxone designed for use by nonmedical bystanders, the drug is not being sufficiently prescribed or used. The increasing cost of naloxone products may be contributing to poor usage.



Article Content

Opioid abuse and deaths from opioid overdose are increasing dramatically in the United States. According to the Centers for Disease Control and Prevention (CDC), opioids (including prescription opioids and heroin) were responsible for the deaths of more than 33,000 Americans in 2015, and opioid overdoses have quadrupled since 1999.1 This month's Drug Watch explores the role the opioid fentanyl plays in these deaths and offers suggestions to help mitigate this crisis.

Table 1 - Click to enlarge in new window States with the Highest Rate of Opioid Overdose Deaths in 2015

Fentanyl. All opioids, whether produced and distributed legally or illegally, work in a similar manner: they bind to opioid receptors in the brain and throughout the body to reduce the perception of pain. Also known as narcotics, opioids produce mood changes such as euphoria and can induce respiratory depression or respiratory arrest. Fentanyl, a synthetic opiate, is much more potent than other opioids. A drug's potency is determined by the number of milligrams needed for the drug to achieve its desired effect. More potent drugs need fewer milligrams per dose to achieve this effect, while less potent drugs require more milligrams per dose to do so. Potency is not the same as efficacy, which is how well a drug achieves its intended effect. Morphine and fentanyl have similar efficacies-they both relieve pain. Yet fentanyl is 50 to 100 times more potent than morphine2 and 50 times more potent than the illegal opioid heroin.3


Prescription fentanyl is used to induce anesthesia and to treat severe pain, typically severe chronic cancer pain. When used to treat severe chronic pain, fentanyl is dispensed in the form of transdermal patches (Duragesic, Ionsys) or lozenges (Actiq). Unlike morphine, which is water soluble, fentanyl is fat soluble, meaning that if it is injected into the bloodstream, it rapidly crosses the blood-brain barrier and enters the brain. Fentanyl's high potency and rapid action contribute to its therapeutic effect as well as to the risk of addiction to the drug.


A different form of fentanyl is made illegally. This form is mixed with heroin and/or cocaine to boost the drugs' euphoric effects. A person purchasing heroin or cocaine may or may not realize that fentanyl has been added. Illegal fentanyl can also be purchased as a single entity in powdered form.


Fentanyl-related overdose deaths. When fentanyl is mixed with heroin, its high potency contributes to the increasing number of opioid overdoses. According to Rudd and colleagues, overdose deaths involving "synthetic opioids other than methadone," which includes fentanyl, increased by 72% between 2014 and 2015.4


Additionally, fentanyl analogs, such as carfentanil, acetyl fentanyl, butyrfentanyl, and others, are also being mixed into heroin. Carfentanil is an extremely potent fentanyl analog introduced into veterinary medicine in 1974. It's designed for use with large animals (such as elephants and moose) and is not approved for use in humans. It is 100 times more potent than fentanyl and approximately 10,000 times more potent than morphine.5, 6 Acetyl fentanyl is about 15 times more potent than morphine, and butyrfentanyl is about 30 times more potent than morphine.6


Fentanyl and fentanyl analogs have been found in heroin seized by law enforcement. The Drug Enforcement Administration's National Forensic Laboratory Information System (NFLIS) collects data from laboratories across the country that perform forensic analyses of illegal drugs seized in law enforcement cases. According to NFLIS data, the number of drug submissions testing positive for acetyl fentanyl increased from 463 in 2014 to 1,870 in 2015.5


One reason U.S. fentanyl/heroin deaths have risen so dramatically is that heroin use has increased. New users include women, the privately insured, and people with higher incomes.7 According to the CDC, heroin use among young adults ages 18 to 25 more than doubled in the past decade.7 And those who abuse heroin are likely to abuse other drugs. The CDC states that people who abuse prescription opioids are 40 times more likely to be addicted to heroin, compared with those who abuse alcohol, who are only two times as likely to be addicted to heroin.7 Prescription opioid abuse appears to be a gateway to heroin abuse.


Prescription opioids can be abused either by the person who was given the prescription or by those who illegally obtain access to opioids prescribed to someone else. Prescription opioid overdose contributes to twice as many opioid deaths nationwide as heroin overdose.8 However, prescription fentanyl is not a major source of these deaths. The CDC states that the most common prescription opioids involved in overdose deaths are methadone (Dolophine and others), oxycodone (OxyContin and others), and hydrocodone (Vicodin [hydrocodone plus acetaminophen] and others).9 Some people addicted to these prescription opioids may resort to buying them illegally. They may purchase fake pills that contain fentanyl instead of the desired drug.5 Many deaths from prescription opioid overdose involve the combination of an opioid with a benzodiazepine prescribed for anxiety, sedation, or seizure prevention-such as alprazolam (Xanax), diazepam (Valium, Diastat), or lorazepam (Ativan).


Characteristics of fentanyl overdose. Fentanyl overdose can occur within seconds to minutes of exposure to the drug. Respiratory depression and respiratory arrest occur with overdose. Death can follow if the victim doesn't swiftly receive the opioid antagonist naloxone (Narcan and others), an antidote to opioid overdose; sometimes more than one dose of the antidote is needed. Those who take heroin that has been mixed with fentanyl and do not die likely have a strong tolerance to opioids.6 Because fentanyl can be absorbed through the skin or inhaled as aerosolized particles, it can also cause respiratory depression in first responders (and police dogs) who come into contact with it when administering aid to someone who has overdosed on heroin mixed with fentanyl.


Around the country, states are reporting dramatic increases in fentanyl-related deaths. For example, death rates related to fentanyl use increased 250% from 2010-2012 to 2013-2014 in Florida, and 526% from 2013 to 2014 in Ohio.2 Two-thirds of the investigated opioid overdose deaths in Massachusetts between 2014 and 2016 involved fentanyl (almost all of which was illicitly made), reflecting an increase in fentanyl involvement in opioid deaths from 32% in 2013-2014 to 74% in the first half of 2016.10


Reversing the effects of opioids. Treatment for fentanyl or other opioid overdose is naloxone. This antidote works by attaching to opioid receptors and blocking opioid attachment, thus preventing opioid action. The drug is highly competitive for these receptor sites, which results in naloxone replacing most of the opioid and quickly reversing respiratory depression secondary to overdose. Naloxone's onset of action is extremely rapid, within one to two minutes. Because naloxone's duration is shorter than the duration of most opioids, more than one dose is often needed to fully correct opioid-induced respiratory depression.


Naloxone is available in vials for intravenous or subcutaneous injection administered by health care providers; in an auto-injector device for single, fixed-dose injections administered by the patient or bystander without medical training (sold under the trade name Evzio); and as the Narcan nasal spray formulation, which can be administered by bystanders or first responders.


Because of the dramatic increase in opioid-related deaths from both prescription abuse and abuse of illegal drugs that may be adulterated with fentanyl, national and state agencies have taken action to improve access to naloxone to help save lives. National agencies have promoted the development of new naloxone formulations and products that can be used by the lay public, and have offered grants to states for purchase of naloxone products and training for bystander use. The CDC has recommended that health care providers prescribe naloxone to their patients who receive prescription opioids, especially if they are also prescribed benzodiazepines.8 Many states have passed laws to allow third-party prescriptions of naloxone (prescriptions to family members of individuals prescribed opioids) and to eliminate the risk of civil or criminal charges against those who provide emergency assistance during an overdose. Additionally, states and community groups are offering naloxone kits and education programs to the public and to emergency medical service (EMS) providers. Yet, despite this increased attention to the need for naloxone, prescriptions and purchase of the antidote did not increase substantially from 2009 to 2015.8 The stigmatization of opioid use may be one factor; another could be the lack of knowledge about naloxone among both health care providers and opioid users. However, a major contributing factor may be naloxone's rising cost. Lack of competition contributes to this rising cost. Although a year ago there were three manufacturers with Food and Drug Administration approval for marketing the 0.4 mg/mL dose injections of naloxone, most were sold by Hospira, which increased the price by 129% between 2012 and 2016.8 Newer formulations are even more expensive-last year, Narcan nasal spray cost $150 for two doses; a two-dose Evzio package that cost $690 in 2014 cost $4,500 two years later.8


What nurses can do. Nurses and NPs should ensure that patients who are prescribed opioids, especially those who are also prescribed benzodiazepines, receive a prescription for naloxone. The patient, as well as the patient's family and/or partner, should be taught how to recognize respiratory depression and drug overdose, and how to administer naloxone. Nurses should confirm that the patient can afford to purchase naloxone, as cost may be important when choosing a delivery route for this product. Patients who are known or suspected to abuse prescription opioids should also be warned that adulterated pills containing fentanyl are being sold and about the risk of overdose from an opioid with this added ingredient. Nurses who work with those addicted to intravenous opioids such as heroin should also provide information about the risks involved when fentanyl is mixed in. These patients should also be given access to naloxone. Nurses should become familiar with the options for naloxone treatment kits and education available in their community, usually through the local health department. Nurses should know that more than one dose of naloxone will likely be necessary, especially if the person overdoses on fentanyl. Nurses should educate patients on safe storage of opioids, so they cannot be accessed by others. Finally, nurses should write or provide testimony to local, state, and federal politicians and government agencies to encourage the availability of affordable naloxone to local health departments, EMS providers, and loved ones of those who abuse opioids.


For more information on opioid overdose, nurses are encouraged to explore the CDC website on this topic at




1. Centers for Disease Control and Prevention. Drug overdose death data. 2016. [Context Link]


2. Peterson AB, et al Increases in fentanyl-related overdose deaths-Florida and Ohio, 2013-2015 MMWR Morb Mortal Wkly Rep 2016 65 33 844-9 [Context Link]


3. Tomassoni AJ, et al Multiple fentanyl overdoses-New Haven, Connecticut, June 23, 2016 MMWR Morb Mortal Wkly Rep 2017 66 4 107-11 [Context Link]


4. Rudd RA, et al Increases in drug and opioid-involved overdose deaths-United States, 2010-2015 MMWR Morb Mortal Wkly Rep 2016 65 5051 1445-52 [Context Link]


5. Centers for Disease Control and Prevention, Health Alert Network. Influx of fentanyl-laced counterfeit pills and toxic fentanyl-related compounds further increases risk of fentanyl-related overdose and fatalities. Atlanta; 2016 Aug 25. Emergency preparedness and response; [Context Link]


6. Compton WM. Research on the use and misuse of fentanyl and other synthetic opioids. Testimony before the House Committee on Energy and Commerce, Subcommittee on Oversight and Investigations. Washington, DC; 2017 Jun 30. [Context Link]


7. Centers for Disease Control and Prevention. Vital signs. Today's heroin epidemic. 2015. [Context Link]


8. Gupta R, et al The rising price of naloxone-risks to efforts to stem overdose deaths N Engl J Med 2016 375 23 2213-5 [Context Link]


9. Centers for Disease Control and Prevention. Prescription opioid overdose data 2017. [Context Link]


10. Somerville NJ, et al Characteristics of fentanyl overdose-Massachusetts, 2014-2016 MMWR Morb Mortal Wkly Rep 2017 66 14 382-6 [Context Link]