Life-Saving Naloxone: Review of Currently Approved Products
In 2015, the Centers for Disease Control and Prevention (CDC) reported that 44 people die from prescription opioid-related toxicity in the United States every day.1 This figure equates to almost 2 deaths every hour. Moreover, 83% of these opioid deaths were unintentional, or at least unanticipated.2 From 2013 to 2014, the CDC also noted a 14% increase in age-adjusted drug overdose deaths.3 An age-adjusted death rate was calculated by applying age-specific death rates to the US standard population age distribution.3
With acute and chronic pain management issues touching almost all aspects of healthcare, opioid medications are prescribed frequently to help manage these patients. Physicians who prescribe opioids maintain an important role and are tasked with opioid safety initiatives that include monitoring, which involves risk-mitigation strategies to help combat the rising death toll associated with unintentional opioid-induced respiratory depression.
To help prevent accidental drug overdoses, the Food and Drug Administration has approved a number of new naloxone-containing products. Naloxone is a non-scheduled opioid antagonist that has been proven to rapidly reverse life-threatening respiratory depression and other opioid depressant effects.4 Naloxone (in any formulation) is not intended to replace emergency medical care. It works by displacing opioid agonists at the mu receptor-binding site in the central nervous system.4 There are currently three different naloxone products available to providers and patients, and this overview examines the attributes and pitfalls of each formulation.
Handheld Auto Injector
In April of 2014, the FDA approved a handheld auto-injector with unique technology that includes auditory stepwise instructions for naloxone delivery.5 This new product, Evzio, is approved for in-home use to reverse opioid-induced respiratory depression. Each injection delivers a dose of 0.4 mg, up to 0.4 mL.6
The product is designed with ease of use in mind for patients, their caregivers or acquaintances, and providers to enable an intramuscular (IM) injection with little or no training. While the majority of patients will receive a dose from a caregiver or healthcare professional, there have been documented cases of patients self-injecting with naloxone.
The auto-injector features an electronic voice system that directs the administrator, as well as red and green light activation, which is helpful for patients with poor eyesight or hearing. In addition, the auto-injector does not require manipulation of a vial or syringe, which might otherwise be difficult for anyone with poor dexterity or in a panicked state of mind.
The needle inside the auto-injector is engaged only after consistent pressure is placed on a 3-second timer, and immediately retracts after injection. This feature minimizes and virtually eliminates the risk of an accidental needle stick. Another benefit to the public is that certain states bar emergency medical technicians (EMTs) from giving injections in the field; the auto-injector is a feasible solution that may be carried and legally used by those individuals.7
The most obvious drawback of the auto-injector is price, which has been at least in part attributable to the advanced technology. The most recent average wholesale price (AWP) for the auto-injector is $4500 per kit.8 Each kit includes a trainer and 2 naloxone auto-injectors. The trainer does not contain naloxone and is needleless for teaching and training purposes. Patient assistance programs and coupons for reimbursement are available from the manufacturer, Kaléo Pharma. The product coverage has expanded since its approval and is now covered by all private insurance payers and Medicaid in most states.
Narcan, which has been available for many years as an injectable, recently has been rebranded as a nasal spray by Adapt Pharma and was approved by the FDA in November 2015.9 It is available as a prefilled, single-dose nasal spray. It is approved for in-home use for the reversal of opioid overdose. Each unit contains and delivers 4 mg, up to 0.1 mL of naloxone HCl. Narcan is dispensed as a kit containing 2 units.10 No assembly is required prior to administration. As intranasal (IN) administration does not require a needle, there is no risk of a needle stick with this formulation.
Although Narcan nasal spray arguably may require more dexterity than Evzio, it is still more user-friendly than a vial and syringe. Prior medical training is not required in order to administer Narcan nasal spray. Nevertheless, there is a NARCAN Now smartphone app that provides access to training and safety information. Per these instructions, administration is relatively simple and straightforward—although use of just an app would require familiarity in advance. Review on such a platform would not be conducive to use in an emergency situation. (Patients and caregivers should be advised by the pharmacist to review the app or instruction when they first fill the prescription.) The instructions are fairly straightforward, and similar to other intranasal devices. According to the manufacturer, “First, peel back the package and remove the device, second place the tip of the nozzle in either nostril until your fingers touch the bottom of the patient’s nose, and finally press the plunger firmly to release the dose into the patient’s nose.”10
More information about this product, including directions, an instructional video on how to use it, and information on how purchase it, are available on Adapt Pharma’s website. The most recent AWP for each individual Narcan nasal spray is $150 per kit.10 Each kit is dispensed as previously stated with 2 prepared nasal spray devices; however, no trainer is included.
The premise for both the nasal spray and the auto-injector in dispensing 2 units is to allow caregivers or healthcare professionals to give a second dose after 3 to 5 minutes if help has not arrived and the patient becomes or remains unresponsive.6,8