Naloxone Expansion: Blocking the Effect of Opioids

EVIDENCE OF CONCERN

The number of deaths from drug overdoses has increased 5-fold since 1980. By 2008, poisoning deaths, of which nearly 90% were drug overdoses, became the leading cause of injury death in the United States. And by 2009, deaths from drug overdoses for the first time outnumbered deaths due to motor vehicle crashes. Unfortunately, this trend has continued¹ (Figure 1).

By 2014, drug overdose was considered the leading cause of accidental death across the nation, with 47,055 lethal drug overdoses. With 18,893 overdose deaths related to prescription pain relievers and 10,574 overdose deaths related to heroin, clearly opioid addiction is driving this epidemic.²

In 2010, the data show that the rates for deaths due to opioid analgesics began to level off and then began to fall in 2011. However, the data show that the rates for deaths due to heroin began to increase around that time. The trends follow an inverse relationship³ (Figure 2).

The rate of deaths due to opioid analgesics compared with the rates of deaths due to heroin raises many questions regarding the reasons behind this inverse relationship. One could speculate that this trend was because of the implementation of risk minimization approaches to reduce abuse, which may include any of the following:⁴

• Risk management strategies, including risk evaluation and mitigation strategies for opioids
• Prescription monitoring programs
• Use of abuse-deterrent formulations of opioids

RISK REDUCTION STRATEGY

With the growing epidemic of accidental and preventable deaths due to overdoses of prescription drugs and illicit opioids, access to naloxone is being expanded. With this expansion, lay people have access to naloxone products and can administer them to reverse opioid overdose.⁵

STATE REGULATIONS

As of August 2016, 46 jurisdictions have laws that address access to naloxone. The laws vary from state to state in regard to liability protection, third-party prescribing, and standing order allowances. The 5 jurisdictions that do not have any laws that address access to naloxone are Kansas, Missouri, Arizona, Wyoming, and Montana⁶ (Figure 3, adapted from reference 6). To learn about the laws regarding access to naloxone in a state, refer to the Prescription Drug Abuse Policy System website.

WHO IS AT RISK?

The first step in providing access to naloxone products is knowing who is at risk of an opioid overdose. People at greater risk include those who take a high-dose prescription opioid; those with lung, kidney, or liver disease; those who are mixing opioids with other drugs; those using opioids recreationally; and those with bipolar disease or schizophrenia.

NALOXONE PRODUCTS

There are several naloxone products available, and they differ in the formulation, ease of administration, potential for risks, convenience, and cost. Depending on patients’ preference, pharmacists can help them decide which option is best. Naloxone is available in a vial for injection, in a prefilled syringe, in a prefilled autoinjection (Evzio), and as a prepackaged nasal spray (Narcan).⁷

Naloxone is available in the following formulations⁸ :

1. Injectable products (vial for injection and prefilled syringe for injection)

• Administered intravenously, intramuscularly, or subcutaneously, depending on the product

2. Prefilled syringe with luer-lock adaptor and a mucosal atomization device [MAD])

• Naloxone with a MAD is administered intranasally.

The advantage of the products listed above is that they are inexpensive. The cash costs for each product are below:

• Naloxone HCl, 0.4 mg/mL vial: cash cost ~$17/each
• Naloxone HCl, 2 mg/2 mL prefilled syringe with needle attached: cash cost ~$40/each
• Naloxone HCl, 2 mg/2 mL prefilled syringe without needle attached: cash cost ~$40/each
• MAD device: cash cost ~$5

The disadvantages of the injectable products are that they require training and proper use. In addition, there is a risk of needle sticks.

2.) Evzio (prefilled auto-injection device)⁹

• Available in 2 mg/0.4 mL and 0.4 mg/0.4 mL
• Administered intramuscularly or subcutaneously

The advantages of Evzio are that it is convenient and provides intelligent voice guidance. Therefore, it is easy to use/administer.

The disadvantages of Evzio are that the voice guidance is available only in English and therefore may not be as helpful for those who do not speak the language. Evzio is also very expensive. The cash cost for a 2-pack of Evzio (0.4 mg/0.4 mL) is about $4200.

3.) Narcan Nasal Spray (prefilled, needle-free device)¹⁰

• Available in 2 mg and 4 mg of naloxone hydrochloride in 0.1 mL
• Administered intranasally

The advantages of Narcan Nasal Spray are that it is convenient, is easy to use/administer, and does not require much assembly.

The disadvantage of the product is its cost. The cash cost of a 2-pack of Narcan Nasal Spray (4 mg/0.1 mL) is about $150.

Naloxone has about a 30-to-90-minute duration, which is much shorter than that of many opioids. Thus, opioid overdoses may recur. Because of the difference in duration of action between most opioids and naloxone, it is critical that the caregiver call 911 and seek emergency care after the first dose of naloxone is administered. This is because the individual must be monitored for several hours.

When counseling caregivers, it is important to discuss the possibility of naloxone causing withdrawal symptoms from the opioid medicine. These include sweating, a runny nose, body aches, shivering/trembling, irritability, diarrhea, and nausea/vomiting.^8-10

Dr. Anyssa Garza received her doctor of pharmacy degree from the University of Texas at Austin before becoming the director of pharmacy for a Central Texas Department of Aging and Disability facility. She now serves as the vice president of content and patient education programs at Digital Pharmacist. In this role, she provides patients with medication information and medical knowledge that can contribute significantly to the quality of care they receive and improve their quality of life and health outcomes. Her work focuses on educating patients and providing them with the resources they need to navigate the health system and their health care issues. She also is an adjunct assistant professor at the University of Texas at Austin College of Pharmacy​​​​​​​.

References

• Addressing prescription drug abuse in the United States: current activities and future opportunities. US Department of Health and Human Services website. http://cdc.gov/drugoverdose/pdf/hhs_prescription_drug_abuse_report_09.2013.pdf. Published September 2013. Accessed May 3, 2017.
• Opioid addiction 2016 facts & figures. American Society of Addiction Medicine website. http://asam.org/docs/default-source/advocacy/opioid-addiction-disease-facts-figures.pdf. Accessed May 3, 2017.
• Drug-poisoning deaths involving heroin: United States, 2000—2013. National Center for Health Statistics website. http://cdc.gov/nchs/data/databriefs/db190.pdf. Published March 2015. Accessed May 3, 2017.
• Hahn KL. Strategies to prevent opioid misuse, abuse and diversion that may also reduce the associated costs. Am Health Drug Benefits. 2011;4(2):107-114.
• Kim D, Irwin KS, Khoshnood K. Expanded access to naloxone: options for critical response to the epidemic of opioid overdose mortality. Am J Public Health. 2009;99(3):402—407. doi: 10.2105/AJPH.2008.136937.
• Naloxone overdose prevention laws. Prescription Drug Abuse Policy System website. http://lawatlas.org/datasets/laws-regulating-administration-of-naloxone. Accessed May 3, 2017.
• Opioid overdose reversal with naloxone (Narcan, Evzio). National Institute of Drug Abuse website. http://drugabuse.gov/related-topics/opioid-overdose-reversal-naloxone-narcan-evzio. Revised September 2016. Accessed May 3, 2017.
• Micromedex Solutions [prescribing information]. Truven Health Analytics, Inc; 2017. http:// micromedexsolutions.com. Accessed May 7, 2017.
• Evzio [prescribing information]. Richmond, VA: Kaleo, Inc; 2014. http://accessdata.fda.gov/drugsatfda_docs/label/2014/205787Orig1s000lbl.pdf. Accessed July 6, 2017.
• Narcan [prescribing information]. Radnor, PA: Adapt Pharma, Inc; 2017. http://accessdata.fda.gov/drugsatfda_docs/label/2015/208411lbl.pdf. Accessed July 6, 2017.