A Swedish Powder Wants to End the Second Naloxone Dose

The scene that worries paramedics is not the first dose of naloxone. It is the third.

Standard rescue kits carry two nasal sprays. In an increasing share of fentanyl-involved overdoses, that is not enough. A bystander administers one spray, waits, administers the second, and the person still is not breathing when EMS arrives. This is the problem the Swedish pharmaceutical company Orexo is trying to sell an answer to, and on Sept. 29 it moved one step closer to the American market.

Orexo announced it had completed the resubmission of its New Drug Application for IZIPRY, a high-dose naloxone nasal powder, to the U.S. Food and Drug Administration. The FDA had issued a Complete Response Letter in July 2024 asking for an additional human factors study and technical data from commercially scaled manufacturing — a rejection Orexo's chief executive called unexpected, since the company had submitted pilot-scale manufacturing data it believed was sufficient.

The resubmission, per the company, contains the documentation needed to close both gaps. The FDA is expected to notify Orexo within weeks whether it accepts the filing and what the review timeline will be.

Why the Dose Matters

IZIPRY is not a new molecule. It is naloxone delivered as a powder rather than a liquid spray, using Orexo's AmorphOX platform. Powder formulations of the drug have shown faster absorption and higher plasma concentrations than intramuscular injection, and in an earlier clinical study an Orexo development formulation produced more rapid absorption and higher bioavailability than the market-leading nasal rescue product at an equivalent dose.

The stability claim is a practical one: a powder does not degrade the way a liquid does, and Orexo says the product holds from sub-zero temperatures to above room temperature without losing efficacy. Patents on the formulation run to 2039.

The rationale for a high-dose product rests on real-world data. Studies of bystander and EMS response have documented rising use of multiple naloxone administrations, and a 2019 paper in Substance Abuse Treatment, Prevention, and Policy made the case for higher doses in what its authors called the synthetic opioid era. In May 2026 the Drug Enforcement Administration issued a public safety advisory noting that fentanyl combined with emerging synthetic opioids may require several doses of naloxone to reverse.

CEO Nikolaj Sørensen called the filing a milestone. "The opioid crisis continues to have devastating consequences across communities in the U.S., and we remain committed to bringing this innovative rescue medication to patients, caregivers and healthcare professionals in need," he said.

What Approval Would and Would Not Change

A high-dose rescue product is not a substitute for what already exists. Naloxone remains available over the counter, and most of the country's opioid addiction treatment infrastructure depends on the four-milligram sprays already in distribution. A powder that reduces repeat dosing would add an option at the point of reversal. It would not change why the person overdosed, and the medications that do — buprenorphine or methadone started in an emergency department — depend on a system that is often not ready to provide them.

Orexo is also funding a second rescue product through a partnership with BARDA, the biomedical arm of the Department of Health and Human Services, aimed at overdoses caused by adulterated drug supplies. That program received an additional $3 million from the agency earlier in September.

The company has no U.S. commercialization partner announced. If the FDA accepts the resubmission, the next news will be a review date — and, on this product's record, another round of waiting.