In July 2014, Kaleo launched Evzio®, a 1-mg/mL naloxone hydrochloride auto-injector. This drug and device combination product has an electronic audio system that voices step-by-step instructions on how to administer an intramuscular or subcutaneous tissue injection. A carton contains two 0.4-mg/0.4 mL auto-injectors and a reusable trainer device.14 Adapt Pharma has acquired the right to use the brand name for naloxone, Narcan®, for its naloxone nasal spray, which has received FDA approval for safety and efficacy.11,14
Clinicians have not widely adopted the co-prescription of naloxone with opioids or the distribution of naloxone kits and education to laypersons in the past for fear of legal ramifications. As of July 2016, there were 46 states with a naloxone access law. Prescribers have immunity from criminal action for prescribing, dispensing, or distributing naloxone to a layperson in 32 states and immunity from civil liability in 36 states. In 41 states, third-party individuals who may have the ability to respond quickly to an overdose are authorized to prescribe naloxone, and 40 states have legalized standing orders for naloxone to pharmacies and community-based naloxone dispensing programs. Laypersons are protected by Good Samaritan laws from criminal liability in 32 states and from civil liability in 40 states. In 14 states, there is no criminal liability if someone is discovered to be in possession of naloxone.15
As legal restrictions have decreased, financial restrictions have increased.14,16 A carton of Kaleo auto-injectors has been priced at four times the invoice price of a box of same-strength 2-mL naloxone syringes. Also, the cost of Amphastar Pharmaceuticals’ 10-pack container of 2-mL naloxone syringes has increased by 60%, whereas the price of Hospira’s 10-pack container of 1-mL vials (0.4 mg/mL) is half the Amphastar price. A 2-mL naloxone syringe that fits an atomizer for intranasal administration is priced at $50.14 Kits containing a single intramuscular dose of naloxone have cost the health department of Baltimore, Maryland, $40 each.16
As legislation expands, so does FDA approval of naloxone, and because research supports the use of naloxone for at-risk patients undergoing pain management with opioids, there is a push to allow over-the-counter (OTC) access to naloxone with brief education or written instructions.12 To make naloxone even more accessible, Dr. Karen Mahoney in 2016 released the FDA opioid action plan initiative to identify ways to aid manufacturers in acquiring approval for an OTC version of naloxone.17 A consumer-friendly Drug Fact Label (DFL) is required. The FDA has developed a DFL model with simple icons that correspond to the label directions; these provide consumers with the information needed to use naloxone safely.
As of December 2016, press releases by two popular US pharmacies, Walgreens and CVS, had announced the OTC distribution of naloxone in 24 and 30 states, respectively.18,19 The term OTC as used in the press releases is misleading, however. An individual wishing to purchase naloxone does not need a prescription in hand from a prescriber, but the participating pharmacies do, through a standing order or collaborative practice agreement.20
Naloxone use in the community
For more than 30 years, paramedics have used naloxone to reverse respiratory depression resulting from opioid overdose. It has proved to be effective and safe in the field.21,22 Opioid overdose and naloxone distribution (OEND) programs were first established in 1996, and their numbers have increased dramatically since then, with approximately 140 organizations known to provide naloxone kits to individuals at 644 sites in the United States in 2014.21,22 Evidence shows that laypersons who observe an overdose and have received appropriate education can and do use naloxone to reverse the effects of opioid overdoses.21
In one OEND program, the Baltimore Student Harm Reduction Coalition, it was found that the distribution of naloxone, together with training in intramuscular administration and the recognition of overdose risk factors and signs, successfully increased self-efficacy for overdose prevention and response. This self-efficacy persisted at 8 to 12 months after the completion of training.21 In a literature review, McDonald and Strang evaluated the association between take-home naloxone programs and overdose survival.22 The association was found to be strong, with a successful overdose reversal rate of 96.3% in 2336 cases in which take-home naloxone was administered.