US Pharm. 2019;44(3):6-9.

Opioid misuse and overdose continue to be a major public health crisis. Today Americans have a greater chance of dying from a drug overdose than from a motor vehicle accident.1 On average, 130 Americans die each day from an opioid overdose, which includes prescription opioids and illegal opioids such as heroin and illicitly manufactured fentanyl.2 Since 2000, the death rate attributed to opioid overdose increased by 200%.3 From 1999 to 2017, almost 400,000 people died from an opioid overdose, with more than 200,000 deaths attributed to prescription opioids in this time period.2,4 The most common medications involved in prescription-opioid overdose deaths include methadone, oxycodone, and hydrocodone.4 In addition, life expectancy in the United States has continued to decrease; a child born in 2017 is now expected to live to be age 78.6 years.5 This decline, in part, can be attributed to increasing deaths from drug overdose.6

As the number of opioid deaths continues to rise, it is important for pharmacists to consider ways to help with reducing the overdose risk while also maintaining access to prescription painkillers when required by patients. According to an American Society of Health System Pharmacists statement published in 2014, “Pharmacists have the unique knowledge, skills, and responsibilities for assuming an important role in substance abuse prevention, education, and assistance. Pharmacists, as health care providers, should be actively involved in reducing the negative effects that substance abuse has on society, health systems, and the pharmacy profession.”7

The Substance Abuse and Mental Health Services Administration provides five strategies to help prevent overdose deaths, and pharmacists are in a unique position to play a vital role in each of these (Table 1).8 Community pharmacies dispense close to 250 million prescription opioids each year.9 In addition to screening for opioid misuse using state Prescription Drug Monitoring Programs and discussing opioid-related risks with patients, pharmacists are in a position to identify patients who may be at risk for overdose and promote the use of the lifesaving drug naloxone.   


Naloxone is a pure opioid antagonist developed in the 1960s and approved by the FDA in 1971 for the reversal of acute opioid intoxication. Unlike its predecessors, naloxone is a highly competitive mu-opioid receptor antagonist that readily reverses the central and peripheral effects of both exogenous and endogenous opioids, rapidly reversing respiratory depression with fewer side effects. In the absence of opioids, it is devoid of any pharmacologic activity.10,11 Naloxone’s safety and efficacy profile has resulted in its acceptance as the preferred agent for opioid-toxicity reversal.

Naloxone is considered relatively safe when administered appropriately; however, opioid withdrawal symptoms may occur in patients who have become physically dependent. Upon rapid reversal, patients may experience body aches, diarrhea, tachycardia, vomiting, dysphoria, nervousness, and agitation. Although these symptoms are unpleasant, they are not life-threatening and are typically of little clinical consequence.10,11 In very rare instances, severe side effects of opioid withdrawal include pulmonary edema, cardiac arrhythmias, profound hypertension or hypotension and cardiac arrest.11

Naloxone can be administered through several different routes, including IM, SC, and intranasal. It is also available as an IV formulation to be administered by medical personnel. The efficacy of naloxone is not dependent on its route of administration; however, the onset of action ranges from 30 seconds to 6 minutes; IV administration produces a more rapid effect compared with IM and intranasal routes, but a slower onset of action may result in fewer withdrawal symptoms. Naloxone’s duration of action varies between 20 and 90 minutes and is not only dependent on the route of administration but also on the type and dose of opioid involved.10,11

Available Products

As of January 2017, there are 11 FDA-approved naloxone products manufactured by six different companies. One product, the Carpuject Luer Lock Glass Syringe, is not recommended for distribution to laypersons owing to its complex assembly process, which has resulted in several reports of failed assembly in the field during overdose emergencies.12

Intranasal: The intranasal formulation is the most common form used by naloxone-distribution programs. Prior to November 2015, there were no FDA-approved intranasal formulations. The prefilled syringes intended for IV use were administered intranasally with an atomizer. In November 2015, the FDA approved an intranasal product containing 4 mg of naloxone per dose that requires no assembly. It is sprayed into one nostril with the patient lying on his or her back. The dose can be repeated if needed.13

IM: Naloxone is available for IM injection as a kit with two single-use 1-mL vials and two 3-mL syringes for IM use.12 Many patients may not feel comfortable drawing up the dose or handling a syringe. Injectable naloxone is also available as a prefilled autoinjector device, similar to an epinephrine pen. It has an automated voice instruction system that guides the user through the administration of the product. The autoinjector also comes with a training pen.14

Naloxone Access

Community-based and public health organizations have established overdose education and naloxone distribution programs to help prevent opioid-overdose fatalities by providing prevention services to laypersons who might witness an overdose. This program was started in Chicago in the late 1990s and has expanded to more than 130 programs throughout the U.S.15

Acknowledging the benefit and success of such programs in reducing fatal overdoses, there have been a number of initiatives to allow for the distribution of naloxone beyond the traditional prescription. All 50 states and the District of Columbia have passed legislation increasing naloxone access.16 These new laws extend access to laypersons by expanding who can receive naloxone beyond those directly at risk of an overdose; by allowing for the distribution of naloxone beyond pharmacists; and by simplifying the process of obtaining naloxone.17 In addition, as of December 2018, 46 states and the District of Columbia have passed an overdose Good Samaritan law, providing protection from arrest or prosecution for persons who report an overdose in good faith.16

Emerging Role of the Pharmacist

Community pharmacists are the most widely accessible healthcare professionals, with more than 90% of Americans living within 5 miles of a community pharmacy.18 Because of this, pharmacists can have a significant impact on reducing the number of fatal overdoses resulting from misuse or abuse of prescription opioids. In 2017, there were almost 58 opioid prescriptions written for every 100 persons. More than 17% of people had at least one opioid prescription filled, with an average of 3.4 opioid prescriptions dispensed per patient.4 The number of deaths involving prescription opioids was five times higher in 2017 than in 1999. In 2017 alone, there were 47,600 overdose deaths associated with prescription-opioid analgesics, accounting for almost 68% of all drug overdose deaths.19

Many pharmacy organizations have advocated for the role of the pharmacist in the opioid crisis. The CDC has also recognized the pharmacist’s importance in communicating with both patients and prescribers to mitigate the risks associated with opioid misuse.20 To maximize pharmacists’ efforts, all 50 states and the District of Columbia have expanded pharmacists’ legal abilities to furnish naloxone. More than half of states allow the dispensing of naloxone pursuant to a standing order. Other states have provided pharmacists with prescriptive authority through a collaborative-practice agreement to initiate prescriptions for naloxone, and a few states allow for the dispensing of naloxone without a prescription.21,22

Naloxone education and the offer of a naloxone kit should be provided to all patients who are at a greater risk for experiencing an opioid overdose (Table 2). Pharmacists should also encourage patients to educate family members, caregivers, and friends about naloxone use. When educating patients about the risk of overdose, it is important to choose language that is appropriate and relatable. The terms overdose and overdose risk have a negative connotation; instead it is suggested that terms such as accidental overdose and opioid-medication safety be used. When providing naloxone, patients should be instructed on how to (1) administer naloxone; (2) seek emergency medical care by calling 911 and following the dispatcher’s instructions for resuscitative measures; (3) assemble naloxone for administration based on the product dispensed; and (4) explain to others how to respond to a potential overdose.23


The opioid epidemic continues to be a public health crisis. Many people die each year from opioid overdoses. Naloxone, a lifesaving medication that is underutilized, can be used safely and effectively to reduce such outcomes. Pharmacists are essential members of the healthcare team who can have a significant impact by engaging patients and their caregivers, family, and friends in the prevention and treatment of opioid overdoses by providing education and access to naloxone.

Patient Information

What is an opioid emergency or overdose?

When a person takes too much of an opioid, this can cause his or her breathing to slow or even stop. This can happen if the prescription medicine for pain is not taken as directed or is misused.

Who is at risk for having an opioid overdose?

There are some factors that can increase the risk of an opioid overdose. These include having a history of drug misuse or substance use disorder; having a history of a mental disorder; mixing opioids with other medicines, illegal drugs, or alcohol; taking high doses of opioids; or having a history of lung problems or sleep apnea.

What are signs of an opioid overdose?

If someone is experiencing an opioid overdose, he or she will begin to have slow or shallow breathing; the lips and fingernails will turn blue or gray; the skin will become moist and pale; and the pupils will become extremely small. He or she will have a slow heartbeat and/or low blood pressure and will be unresponsive.

 What do I do in case of an overdose?

You should call 911 immediately. You should administer naloxone if available and try to keep the person awake and breathing. You should lay the person on his or her side to prevent choking and stay with the person until help arrives.

What is naloxone?

Naloxone is a medication that blocks the effects of opioids. It is used to reverse the overdose. It only works if opioids are causing the effect. It will not work if other drugs or alcohol are the cause. It takes about 2 to 5 minutes to begin to work and will stop the effects of opioids for a short time.

How do I give naloxone?

Naloxone is available as a nose spray or as an injection into a muscle.

What are the side effects of naloxone?

Naloxone is generally safe when used as directed. Some people may experience signs and symptoms of opioid withdrawal if they have become opioid dependent. These include body aches, fever, sweating, runny nose, weakness, irritability, nervousness, diarrhea, nausea or vomiting, abdominal cramps, and increased heart rate. These symptoms are not life-threatening.

Will naloxone work even if someone has used it before?

Yes, naloxone will work even if the person has used it before. It is not possible to develop tolerance to naloxone.

Where can I go for more information?

Visit to learn about the risks of opioid abuse and overdose. If you believe you, or someone you know, may be struggling with addiction, tell a healthcare provider and ask for guidance, or call the Substance Abuse and Mental Health Services Administrations National Helpline at 1-800-662-HELP.


1. National Safety Council Injury Facts. Odds of dying. Accessed February 6, 2019.
2. CDC. Opioid overdose. Understanding the epidemic. Published December 19, 2018. Accessed February 6, 2019.
3. Rudd RA, Aleshire N, Zibbell JE, Gladden RM. Increases in drug and opioid overdose deaths—United States, 2000-2014. MMWR Morb Mortal Wkly Rep. 2016;64(50-51):1378-1382.
4. CDC. Opioid overdose. Prescription opioid data. Published December 21, 2018. Accessed January 2, 2019.
5. CDC. National Center for Health Statistics. Data Briefs. Number 328: November 2018. Published November 29, 2018. Accessed February 6, 2019.
6. Dyer O. US life expectancy falls for third year in a row. BMJ. 2018;363:k5118.
7. ASHP statement on the pharmacist’s role in substance abuse prevention, education, and assistance. Am J Health Syst Pharm. 2014;71(3):243-246.
8. SAMHSA Publications. Opioid overdose prevention toolkit. Accessed February 6, 2019.
9. Volkow ND, McLellan AT. Opioid abuse in chronic pain—misconceptions and mitigation strategies. N Engl J Med. 2016;374:1253-1263.
10. Kim HK, Nelson LS. Reducing the harm of opioid overdose with the safe use of naloxone: a pharmacologic review. Expert Opin Drug Saf. 2015;14(7):1137-1146.
11. Rzasa Lynn R, Galinkin J. Naloxone dosage for opioid reversal: current evidence and clinical implications. Ther Adv Drug Saf. 2018;9(1):63-88.
12. Prescribe to Prevent. Formulations. Accessed February 6, 2019.
13. Brown T. FDA approves Narcan nasal spray to treat opioid overdose. Medscape. Accessed February 6, 2019.
14. Evzio (naloxone hydrochloride injection) prescribing information. Richmond, VA: Kaléo. October 2016:25.
15. Wheeler E, Jones TS, Gilbert MK, Davidson PJ; CDC. Opioid overdose prevention programs providing naloxone to laypersons - United States, 2014. MMWR Morb Mortal Wkly Rep. 2015;64(23):631-635.
16. Network for Public Health Law. Legal interventions to reduce overdose mortality: naloxone access and overdose Good Samaritan laws. Accessed February 21, 2019.
17. Substance Abuse and Mental Health Services Administration. Preventing the consequences of opioid overdose: understanding naloxone access laws. Accessed February 9, 2019.
18. National Association of Chain Drug Stores. Pharmacy. The face of neighborhood health care in America. Accessed February 9, 2019.
19. CDC. Opioid Overdose. Drug overdose deaths. Published December 21, 2018. Accessed January 31, 2019.
20. CDC. Pharmacists: on the front lines. Accessed February 9, 2019.
21. National Alliance of State Pharmacy Associations. Naloxone access in community pharmacies. Accessed February 9, 2019.
22. Davis C, Carr D. State legal innovations to encourage naloxone dispensing. J Am Pharm Assoc. 2017;57(2):S180-S184.
23. Prescribe to Prevent. Prescribe naloxone, save a life. Accessed February 9, 2019.
24. U.S. Department of Health & Human Services. HHS recommends prescribing or co-prescribing naloxone to patients at high risk for an opioid overdose. Published December 19, 2018. Accessed February 9, 2019.

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