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Synthetic opioids have disrupted conventional wisdom for treating opioid overdose
Phil Skolnick1, Jordan Paavola1, Christian Heidbreder1
1Indivior, Inc., N, Chesterfield, VA 23235, United States.
Drug and Alcohol Dependence Reports
|September 12, 2024
Summary
Synthetic opioid overdoses require faster-acting reversal agents. Intranasal nalmefene shows greater effectiveness than naloxone in preventing cardiac arrest, challenging traditional overdose treatment strategies.
Area of Science:
- Pharmacology
- Toxicology
- Emergency Medicine
Background:
- Synthetic opioids cause over 90% of North American overdose deaths, with increasing concern for their spread in Europe.
- Traditional opioid overdose reversal strategies using naloxone may be less effective due to the rapid respiratory depression caused by synthetic opioids.
- Intravenous naloxone administration, while effective, is often not feasible for first responders.
Purpose of the Study:
- To evaluate the effectiveness of different naloxone formulations and administration routes for synthetic opioid overdose reversal.
- To compare the efficacy of intranasal nalmefene with intranasal naloxone in a translational model of opioid overdose.
Main Methods:
- Utilized a translational mechanistic model of opioid overdose developed by the FDA's Division of Applied Regulatory Science.
- Assessed the impact of various naloxone doses and administration timings (intramuscular, intranasal, sequential, simultaneous) on preventing cardiac arrest.
- Compared the effectiveness of intranasal nalmefene against intranasal naloxone in the overdose model.
Main Results:
- Standard naloxone tools (2 mg IM, 4 mg IN) showed unacceptable mortality rates in synthetic opioid (fentanyl, carfentanil) overdose models.
- Sequential administration of intranasal naloxone did not improve outcomes compared to a single dose, indicating absorption limitations.
- Intranasal nalmefene demonstrated significant reductions in cardiac arrest incidence compared to intranasal naloxone; four doses of intranasal naloxone were needed to approach the efficacy of a single intranasal nalmefene dose.
Conclusions:
- Current naloxone-based strategies may be insufficient for rapidly reversing synthetic opioid-induced respiratory depression.
- Intranasal nalmefene presents a more effective alternative for reversing synthetic opioid overdoses due to faster absorption and higher receptor affinity.
- These findings suggest a need to reconsider conventional opioid overdose treatment protocols in light of the synthetic opioid crisis.
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