Nonprescription availability of the opioid antagonist naloxone

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Nonprescription availability of the opioid antagonist naloxone Am J Health-Syst Pharm. 2018; 75: e389-92 Allison Landers, Pharm.D., BCPS, WakeMed, Raleigh, NC. Address correspondence to Dr. Landers ([email protected]). This article will be published in a future issue of AJHP. Keywords: Comprehensive Addiction and Recovery Act, naloxone, opioid abuse Copyright © 2018, American Society of Health-System Pharmacists, Inc. All rights reserved. 1079-2082/18/0000-e389. DOI 10.2146/ajhp170560

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n the last 15 years in the United States, annual fatal overdoses involving opioids have increased by 200%.1 Almost 50,000 Americans died of a drug overdose in 2014, with the drugs involved including prescription pain killers and heroin.1 As a result, opioid overdose prevention has been added to the Centers for Disease Control and Prevention’s list of top 5 public health challenges.2 Opioids, including heroin, oxycodone, hydrocodone, fentanyl, hydromorphone, and morphine, can affect the central nervous system, causing respiratory depression, heart failure, stroke, and, eventually, death. Individuals at greater risk for opioid overdose include those using injectable opioids, taking large doses, resuming use after detoxification, combining opioids with other medications, or prone to accidental ingestion.3 Naloxone is an opioid antagonist that can reverse the effects of opioid drugs, including respiratory depression. In the absence of opioids, naloxone has no pharmacologic activity. Naloxone

can induce temporary withdrawal symptoms, which are generally not life-threatening.3 Lawmakers across the country are taking notice and creating legislation to help battle this epidemic. The Comprehensive Addiction and Recovery Act (CARA), enacted in July 2016, authorizes grants to help states stop deaths from opioid overdoses.4 CARA provisions address 3 focus areas that are seen as a good starting point for decreasing fatal overdoses from opioids: primary prevention, increased access to effective treatments, and increased distribution of naloxone.5 The law authorizes states to develop standing orders for pharmacies to dispense naloxone, to implement best practices that include issuing a prescription for naloxone when opioids are prescribed, to develop training for healthcare professionals, and to provide education to laypeople who may use naloxone administration kits.4 The CARA naloxone provisions are significant because they have the potential to save thousands of lives by providing funding for pharmacies and pharmacists to provide the reversal agent naloxone in communities. Nielsen and Hout6 reported, “The increased role of prescription opioid medication in overdose fatalities, combined with the desire to expand the geographic reach of take-home naloxone initiatives has brought into sharp focus the opportunity for community pharmacy to become an important outlet and harm reduction partner in responding to concerns around opioid-related mortality.” McDonald and Strang7 found a strong association between overdose survival rates and programs involving takehome naloxone kits. Economic impact. Funding for naloxone kits is a major hurdle and one that CARA provisions can help

overcome. In 2015 only 70,000 kits were distributed by community-based programs, but data showed that close to 600,000 kits were needed.8 Prices of naloxone have continued to increase after almost doubling in 2014 alone.5 In 2015, the Food and Drug Administration (FDA) approved a nasal version of naloxone. At the time of writing, the 2-dose nasal spray kit cost around $140, and the injection kit cost up to $2,500.9,10 The question still remains on how to cover the cost of these kits in a retail pharmacy setting and whether insurance would cover part of the cost in certain situations. Medicare and Medicaid now cover intranasal naloxone, and most private insurers are also providing coverage.11 The take-home nasal spray kits can still be considered cost-effective because of the money saved from the decrease in fatal overdoses resulting from their use.7 State-level impact. Most states have laws in effect regarding funding for education and treatment programs, as well as regulations that allow either nonprescription access to naloxone or prescriber authority to write prescriptions to patients and family members. Illinois enacted the Heroin Crisis Act in 2015, and in 2016 New Hampshire passed Bradley’s Bill, which strengthened those states’ prescription monitoring programs and increased overdose prevention measures by providing increased access to treatment.12 Over 40 states have enacted “Good Samaritan” laws that offer immunity from civil or criminal actions to witnesses who try to help overdose victims.8 These laws provide immunity against prosecution for most low-level possession charges but not for higher-level charges like manufacturing, trafficking, and distribution.5 CARA provisions include funding grants to states to be used to imple-

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COMMENTARY ment new programs or enhance existing ones. States with the most need— for example, West Virginia, which has the highest per capita rate of overdose in the country—would be given preference when applying for grants.13 This means more people, both laypersons and healthcare professionals, will benefit from access to treatment programs, education, and naloxone kits. Several states already allow pharmacists to dispense naloxone without a prescription, including Connecticut, Idaho, New Mexico, North Dakota, and Oregon.14 Ethical considerations. Ethical concerns regarding the distribution of naloxone rescue kits to opioid drug addicts have arisen. Some critics believe that practice may encourage opioid drug use (because people will know they have easy access to a reversal agent) and that current users may engage in heavier opioid use and take more risks, knowing they have a safety net.13 Another ethical issue pertains to how pharmacists should go about targeting patients in their practice who would benefit from a reversal kit. Some of the recommended target groups include anyone with a methadone prescription, patients receiving high-dose opioids, patients who have previously experienced an overdose, and patients receiving high-risk medications in addition to an opioid.6 Some pharmacists may have concerns about singling out those patients for fear of offending them or causing them to be stigmatized. Although CARA was approved by Congress by a wide margin, showing broad support for the law, there is still some opposition to provisions of the law regarding the availability of naloxone without a patient-specific prescription. Proponents’ arguments. Proponents of making naloxone available without a prescription believe that more people will be able to gain access to a medication that can help reverse opioid overdoses and that “any attempt at resuscitation is better than no attempt.”15 Addicted individuals may

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not be willing to go to a physician to get a prescription for a naloxone kit because of either cost concerns or reluctance to admit their addiction to opioid drugs. It may be more acceptable to be able to go to a local pharmacy or community outreach center, where they can get the kits at low or no cost. Some community programs are currently in place across the country in areas where intravenous use of drugs like heroin is prevalent. It has been suggested that users of opioids are not being reached by these community programs because they live in outlying areas.16 “In multiple states in the USA, models of pharmacy based naloxone distribution have leveraged the capacity of pharmacies and the skills of pharmacists to expand access to naloxone beyond those who are reached by community-based organizations.”16 Use of naloxone kits is relatively easy and requires little instruction. One intramuscular naloxone product has a recording that talks the user through the process, which is similar to using an epinephrine device in a severe allergic reaction. Some studies have shown that overdose mortality rates dramatically decreased in areas where take-home naloxone kits were available.7 Being able to administer the kits at home could allow for faster reversal of an overdose, which could be the difference between life and death. Global and national organizations support increased access to naloxone. The World Health Organization, American Medical Association, and American Public Health Association all advocate layperson access to naloxone as part of a strategy to reduce deaths due to opioid overdoses.16 Having the support of these organizations will help to implement programs, not just in America but worldwide. Physician support is extremely important, because access to naloxone kits often starts with a physician willing to provide a standing order to make it legal to dispense the kits. Proponents also believe there are minimal adverse effects of naloxone

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use, with the greatest risk being symptoms of opioid withdrawal, which include nausea, vomiting, sweating, and diarrhea in mild cases. Research indicates a lower likelihood of severe withdrawal symptoms and less agitation with intranasal versus intramuscular naloxone administration, with no difference in reversal rates.8 The intranasal form may be more acceptable to users due to some people’s anxiety and fear over using a needle. Hospital personnel have used naloxone for over 40 years, and it has been found to have a good safety profile. Opponents’ arguments. One of opponents’ main arguments against nonprescription access to naloxone is their belief that it will promote an increase in use of opioids because users will feel like they have a safety net in an overdose situation.13 Another concern is that people may be less likely to call 911 if they feel they can handle the situation by themselves. Oftentimes patients need a second dose of naloxone because its half-life is shorter than the half-life of many prescription opioids, which means that they can go back into respiratory depression after the first dose. Opponents have also raised concerns about naloxone use leading to opioid withdrawal. Administering naloxone can result in abrupt development of withdrawal symptoms. In severe cases this can lead to seizures, cardiac arrest, and pulmonary edema. Estimates of these serious complications are between 0.3% and 1.6%.8 The average person would not be able to adequately take care of a person with severe symptoms of withdrawal without professional medical attention. Another argument is that community-based programs that provide education to addicts can be effective and safer than making naloxone more readily available to opioid-addicted individuals and their families. A recent study indicated that participants in an opioid overdose prevention program “did not differ in opioid use, overdose rate, or response to a witnessed overdose” from those


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who received both education and a naloxone kit.13 Money used toward the kits could be used for more programs to provide education and counseling, opponents contend. Some people are not opposed to the idea of having naloxone available but are concerned about the route of administration. Intramuscular has been the preferred route and the most studied. Kits that contain a compounded version of naloxone that can be given intranasally have been available. Concerns over that product’s bioavailability, the ability to give it to someone in a horizontal position, and the potential for compromised nasal membranes and obstruction are some of the issues surrounding intranasal use of naloxone.17 Some of these concerns may be alleviated by the intranasal form approved last year by FDA, which is specifically formulated for the intranasal route. Healthcare services perspective. Not all healthcare professionals are in agreement with regard to the distribution of naloxone kits. Legal issues arise from how it will be handled in each state. Some states allow standing orders, where physicians can make a document that permits another person, in many cases a pharmacist, to be able to “acquire, dispense, or administer medication without a person-specific prescription.”4 Forty states have implemented this approach in the form of collaborative agreements.18 CARA provisions will help provide funding to states wanting to set up these types of orders. Small focus groups have been convened to discuss the issue of naloxone distribution. Pharmacists included in these groups expressed high levels of support when they had provider support in the form of standing orders.6 The main concerns for pharmacists are the issue of reimbursement, which CARA grants should alleviate partially, and the ability to have the appropriate amount of time to counsel patients receiving the kits. Costs include not just the naloxone kit but time spent by pharmacists to counsel

the patients receiving the kits. It is imperative that people receiving the kit get adequate education about how to use the naloxone appropriately. This includes information on how to recognize an overdose, how to use the naloxone dispensing device, and the need to call emergency services even with proper naloxone administration. Initial training programs were up to 8 hours, but research has shown that brief training can be just as effective.6 Although this training can be done effectively in around 5–10 minutes, it is sometimes hard for the pharmacist to fit it into a busy schedule. CARA provisions will also help keep and expand the use of naloxone by emergency medical personnel. Emergency service workers have saved countless lives by responding to opioid overdose emergencies and being able to administer naloxone in suspected opioid overdoses. Even if doses of naloxone have been given by a family member or other overdose witness, the patient still needs continued medical attention and monitoring. First responders who carry naloxone have the potential to cut the delivery time from around 10 minutes to about 5 minutes, potentially reducing the mortality and morbidity following an opioid overdose.5 Conclusion. The opioid epidemic has been spiraling out of control in recent years, and the grants authorized in the CARA can help states continue to battle the opioid addiction epidemic. Although education and distribution of naloxone kits will not save every overdose, they are steps in the right direction. It is important to note that naloxone does not treat addiction but may give someone the opportunity for a second chance to seek help after an overdose.

Disclosures The author has declared no potential conflicts of interest.

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COMMENTARY overdose deaths. J Urban Health. 2016; 93:117-30. 17. Strang J, McDonald R, Tas B, Day E. Clinical provision of improvised nasal naloxone without experimental testing and without regulatory approval: imaginative shortcut or dangerous bypass of essential safety procedures? Addiction. 2016; 111:574-82. 18. Gupta R, Shah ND, Ross JS. The rising price of naloxone—risks to efforts to stem overdose deaths. N Engl J Med. 2016; 375:2213-5.

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