Laffont 2024: nalmefene vs naloxone nasal spray in a computer model

What they tested

The researchers used a published computer model that predicts breathing suppression and cardiac arrest from opioids. They first reproduced its original results for a 2 mg naloxone injection into a muscle, then extended it to simulate a 4 mg naloxone hydrochloride nasal spray and a 3 mg nalmefene hydrochloride nasal spray, both FDA-approved for opioid overdose.

They simulated overdoses of fentanyl and carfentanil in 2,000 virtual patients, with and without the nasal sprays, in chronic opioid users and in opioid-naive people, who don't normally use opioids.

What they found

In simulated fentanyl and carfentanil overdoses in chronic opioid users, nalmefene nasal spray produced a substantially greater reduction in cardiac arrest than naloxone nasal spray. After a 1.63 mg fentanyl dose that caused cardiac arrest in 52.1% of virtual patients, nalmefene cut the rate to 2.2% and naloxone to 19.2%.

Nalmefene also produced large reductions in cardiac arrest in simulated opioid-naive people. Across the dosing scenarios, four doses of naloxone spray given at once were needed to approach the effect of a single dose of nalmefene.

Limits

• These are computer predictions in virtual patients, not observations of real overdoses.
• Indivior, which now sells the nalmefene spray (Opvee), funded the study, and 3 of its 5 authors are Indivior employees.
• The model measures cardiac arrest only. The authors note that nalmefene's longer action could make precipitated withdrawal more severe and longer in people dependent on opioids, which the model doesn't weigh.

What it means if you're considering naltrexone

Nalmefene is a close relative of naltrexone. In the US it's sold as an overdose-reversal spray, and in Europe as a tablet to cut drinking. This study predicts the spray prevents more cardiac arrests than naloxone after a fentanyl overdose, but the prediction comes from a model, in a study its maker paid for.