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Naloxone: A Lifesaving Antidote in the Epidemic of Opioid Substance

Monday, May 16, 2016   (0 Comments)
Posted by: Elizabeth Maynard
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Jennifer Nguyen, PharmD Candidate 2017
Jasica Truong, PharmD Candidate 2018

Jennifer Andres, PharmD, BCPS
Temple University School of Pharmacy


Opioid substance abuse has evolved into an epidemic and public health issue in the United States. More people have died from opioid overdose in 2014 than any previous year recorded. In 2014, over 47,000 deaths occurred from drug overdose in the US, 61% of which are opioid and heroin related.1 The leading cause of accidental death in Pennsylvania is now opioid and heroin overdose, surpassing motor vehicle accidents.2 This is due to the increased amount of opioid prescriptions written, expansion of opioid indications, and marketing by pharmaceutical companies. For example, 207 million prescriptions were written for opioids in 2013 compared to only 76 million prescriptions written in 1999.3 From the doctor’s office, to the pharmacy and to the streets, there are enough opioid painkiller prescriptions written for every American adult to have one bottle of pills.4 Without action, opioid substance abuse will continue to grow at the stake of millions of lives.

Naloxone is an FDA approved, lifesaving antidote which reverses fatal respiratory depression caused by opioid overdose. In Pennsylvania, naloxone is permitted to be purchased by anyone to allow for immediate assistance if an overdose occurs. Information for self-training and instructional materials on using naloxone properly is publicly available online.5 As a pure opioid antagonist, Naloxone competes for and displaces opioids from opioid receptor sites, including the mu, kappa, and sigma located in the CNS. It displays no opioid agonistic effects in the body. Naloxone is indicated for suspected or known acute opioid overdose by completely or partially reversing opioid depression effects such as respiratory depression, sedation, and hypotension, induced by natural and synthetic opioids and certain mixed agonist-antagonist analgesics.6 Refer to Table 1 for information regarding the availability of naloxone products.

The duration of action of naloxone may be shorter than some opiates, requiring repeated doses of administration highlighted in Table 1.6,7,8,9 No data has shown tolerance or physical/psychological dependence to naloxone. However, individuals with physical dependence to opioids may have acute withdrawal symptoms within minutes of naloxone administration. These withdrawal symptoms include non-life-threatening symptoms of anxiety, piloerection, rhinorrhea, nausea, vomiting or diarrhea.  Symptoms typically subside in about 2 hours. Individuals who have overdosed on partial agonists or mixed agonist/antagonists often require higher doses of naloxone due to the slower rate of binding and dissociation from opioid receptor. Precautions should be taken if using naloxone in individuals who have pre-existing cardiovascular effects, over age 65 or take opioid medications for painful illnesses. Naloxone has not been studied in individuals with renal or hepatic issues. Naloxone can cross the placenta but it is unknown if naloxone is excreted into breast milk.8 Under serious circumstances that may endanger a victim, it is best to weigh the risks versus benefits of administering naloxone.

    Although naloxone brings hope to the future, many individuals and healthcare professionals may be hesitant to using naloxone due to cost and liability.9 Coverage for naloxone varies by state and insurance plan. Coverage is limited for individuals seeking to purchase naloxone outside of a medical setting, such as a pharmacy.10 In Pennsylvania, Evzio® is covered by certain medical assistance plans with prior authorization while generic naloxone is covered without the need of prior authorization.2 Health care professionals are permitted to prescribe and dispense naloxone without liability of giving naloxone to individuals that are believed to be suffering from opioid overdose. In Pennsylvania, the ‘Good Samaritan’ provision of Act 139 encourages those who witness an overdose to call for help and remain with the individual until emergency medical personnel arrives without being held liable for being present, witnessing and reporting an overdose.2,5

In addition to the availability of naloxone, there are many strategies that can be implemented to halt the progression of this growing epidemic. In order to be successful in the management of opioid misuse, protection of patients with legitimate uses for opioids must be kept in mind. Providers should educate patients on the proper use of opioids and discourage the sharing of such agents. On the state and federal level, the creation of prescription drug monitoring programs (PDMP) to assess appropriate use of opioids may improve issues with drug diversion and misuse. PDMPs are a great tool in accessing legitimate medical use of a controlled substance, identification of drug abuse/diversion, and identifying persons addicted to prescription drugs to facilitate in treatment. Additionally, post-marketing data on the long-term impact of extended release/long acting opioids should be required to obtain better evidence on the serious risks of misuse/abuse of these agents.4, 11, 12

Once identified, numerous therapies are available for the treatment of opioid addiction. Buprenorphine is a mixed opioid agonist-antagonist analgesic. Often co-formulated with naloxone, buprenorphine/naloxone (Suboxone®) is an option for opioid dependency, as naloxone serves as a barrier in the misuse of the drug.13 Methadone clinics are available for the maintenance and treatment of opioid addiction and for patients to manage opioid withdrawal symptoms under direct medical supervision.14 Naltrexone, a pure opioid antagonist, is another pharmacological approach used for the chronic management of physical dependence to morphine, heroin and other opioids.15 In addition to these pharmacological approaches, behavior therapy and support groups exist to further aid patients in the fight against addiction.13,14,15  

Naloxone should not be looked at as encouragement for opioid abuse, but rather as a positive outcome that allows patients a second chance to receive proper treatment for their opioid addiction. Without naloxone, many patients lose their battle to opioid addiction. Naloxone education is crucial in preventing victims from becoming another statistic in the public health epidemic.

Table 1. Administration and Cost of Naloxone (6,7,8,9)


Drug Name



Repeating Doses



Naloxone (generic)

0.4 mg/mL vials and syringes

1mg/mL syringes

0.4-2 mg IV, IM or subcut

May repeat dose every 2-3 minutes until up to a total of 10 mg

$17.40 per 1-mL vial


0.4 mg/0.4 mL prefilled auto-injector

0.4 mg IM or subcut

May repeat dose every 2-3 minutes until patient is responsive or arrival of emergency medical personnel

$375.00 per 1 auto-injector (supplied in packages of two)



4 mg/0.1 mL nasal spray

4 mg intranasally

May repeat dose every 2-3 minutes until patient is responsive or arrival of emergency medical personnel

$62.50 per 1 nasal spray device (supplied in cartons of two)



1.     Rudd RA, Aleshire NA, Zibbell JE, Gladden RM. Increases in Drug and Opioid Overdose Deaths - United States, 2000-2014. Centers for Disease Control and Prevention. January 1, 2016; 64: 1378-1382.

2.     Naloxone FAQs. PA Gov. Accessed March 3, 2016.

3.     Volkow N. America’s Addiction to Opioids: Heroin and Prescription Drug Abuse. National Institute on Drug Abuse. May 14, 2014. Accessed February 20, 2016.

4.     CDC Vital Signs: Opioid Painkiller Prescribing. Centers for Disease Control and Prevention Website. Updated July 2014. Accessed February 19, 2016.

5.     Standing Order DOH-002-2015: Naloxone Prescription for Overdose Prevention. Pennsylvania Department of Health. October 28, 2015.

6.     Naloxone Hydrochloride [package insert]. Lake Forest, IL: Hospira, Inc; September 2015.

7.     Evzio [package insert]. Richmond, VA: Kaleo, Inc: April 2014.

8.     Narcan [package insert]. Radnor, PA: Adapt Pharma, Inc: December 2015.

9.     Naloxone (Narcan) Nasal Spray for Opioid Overdose. The Medical Letter on Drugs and Therapeutics. January 4, 2016; 58 (1485): 1-3.

10. Seiler N, Horton K, Malcarney M. Medicaid Reimbursement for Take-home Naloxone: A Toolkit for Advocates. Accessed March 3, 2016.

11. Califf R, Woodcock J, Ostroff S. A Proactive Response to Prescription Opioid Abuse. The New England Journal of Medicine. 2016. Assessed February 7, 2016.

12. State Prescription Drug Monitoring Programs. U.S. Department of Justice Drug Enforcement Administration: Office of Diversion Control. Accessed March 20, 2016.

13. Suboxone [package insert]. Dublin, OH: Cardinal Health; March 2013.

14. Methadone Hydrochloride [package insert]. Canonsburg, PA: Mylan Institutional LLC; January 2013.

15. Naltrexone Hydrochloride [package insert]. Montvale, NJ: Barr Laboratories, Inc; January 2016.

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