Workers' Comp

Ask The Pharmacist: Emerging Opioid Overdose Reversal Medications

October 4, 2023

Spencer Sherman, Pharm.D.

Clinical Pharmacist, Pharmacy Solutions

What are the different types of opioid overdose reversal agents, and how do they compare?

Opioids continue to represent a decreasing portion of overall workers’ comp scripts, with favorable trends being seen in markers such as dose and duration of use. Despite declines, it remains essential to promote risk management strategies such as overdose rescue medications.

Often when opioids are prescribed, health care providers also recommend that patients have rescue medications on hand. By doing this, providers are not implying there will be a potential overdose or misuse of the prescribed opioids by the patient. In actuality they are advocating for a proactive safety plan, recognizing that unintentional misuse can occasionally occur. A helpful analogy is to compare a rescue medication to a fire extinguisher: having one doesn’t imply an imminent fire threat but serves as a precautionary measure, with the hope that it remains unused.

The most recognized opioid reversal agent Narcan, and its generic equivalent naloxone, recently gained approval for over-the-counter distribution. The nasal spray has been a first-line agent for individuals at risk of opioid overdose by reversing the toxic effects of opioid analgesics (i.e., respiratory depression, drop in blood pressure, sedation). The Food and Drug Administration (FDA) approved Narcan nasal spray for the emergency treatment of known or suspected opioid overdose in 2015, and the life-saving drug gained momentum through expanded access in several areas including medical, law enforcement, government, and community efforts.

New opioid overdose reversal medications are emerging, including Kloxxado. A survey revealed that 34% of overdoses required multiple Narcan doses. In response to this, Hikma Pharmaceuticals USA Inc. developed Kloxxado with double the naloxone content to potentially reduce the need for successive doses. While Narcan provides 4 mg of naloxone per device with two spray devices per package, Kloxxado offers 8 mg in one device. Due to its increased potency, Kloxxado may be particularly effective against overdoses involving potent illicit drugs or higher opioid doses. However, Kloxxado won’t be available over-the-counter, while equally effective Narcan will be.

In May 2023, the FDA approved Opvee, another nasal spray designed to counteract opioid overdoses. While both Narcan and Kloxxado utilize naloxone, Opvee contains nalmefene, a drug introduced in the 1990s as an injection that was discontinued due to limited sales. Initial information suggests that nalmefene remains in the system longer than naloxone. Opvee’s longer-lasting effect may reduce the number of doses needed when addressing overdoses from longer-lasting opioids like fentanyl.

With the FDA’s approval of Narcan for over-the-counter use and its endorsements of other opioid overdose reversal medications, the FDA demonstrates its commitment to "undertake impactful, creative actions to prevent drug overdoses and reduce deaths.” As these developments continue, consumers can expect the arrival of naloxone on retail shelves in the upcoming months and they should also anticipate the approval of more alternative options in the months and years ahead.

This information is meant to serve as a general overview, and any specific questions or concerns should be more fully reviewed with your health care professional such as the prescribing doctor or dispensing pharmacist.

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