FDA Approves Iloprost Injection for Treatment of Severe Frostbite

Credit: US Food and Drug Administration

The US Food and Drug Administration (FDA) has approved iloprost injection (Aurlumyn) to treat severe frostbite in adults to reduce the risk of finger or toe amputation.

Announced on February 14, 2023, approval was primarily granted based on an open-label, controlled trial that randomized 47 adults with severe frostbite, in which patients treated with a prostacyclin (iloprost) alone experienced a significantly lower risk of amputation.

Iloprost injection previously received Priority Review and Orphan Drug designations for this indication by the FDA. This approval was awarded to Eicos Sciences Inc.

“This approval provides patients with the first-ever treatment option for severe frostbite,” said Norman Stockbridge, MD, PhD, the director of the division of cardiology and nephrology in the FDA Center for Drug Evaluation and Research. “Having this new option provides physicians with a tool that will help prevent the life-changing amputation of one’s frostbitten fingers or toes.”

Frostbite can occur in multiple stages, from a mild condition without a requirement for medical intervention and no permanent skin damage to a severe stage when both skin and underlying tissue are frozen and blood flow stops. Amputation can occur if a patient reaches the severe frostbite stage.

Many alternatives have been proposed for frostbite treatment, ranging from low-molecular-weight heparin to prostacyclin analogues. An active ingredient in the approved medication, iloprost is a vasodilator that prevents blood from clotting. Its efficacy in treating severe frostbite was established in the controlled trial that occurred between 1996 and 2008.

Severe frostbite was defined as ≥1 digit with frostbite stage 3 (lesion extending past the proximal phalanx) or stage 4 (lesion extending proximal to the metacarpal or metatarsal joint). Directly after a mountain rescue, the population matching the study criteria received rapid rewarming of the frostbite-affected areas plus 250 mg of aspirin and intravenous administration of 400 mg of buflomedil.

For the trial, the 47 patients (mean age, 33.1 years; 44 men) underwent randomization to receive 1 of 3 treatment regimens for 8 days. The first group received intravenous iloprost for 6 hours daily up to 8 days, while Groups 2 and 3 received other medications unapproved for frostbite, given with iloprost or without iloprost, respectively. Efficacy endpoints included a bone scan obtained 7 days are initial frostbite, to predict the need for amputation of ≥1 finger or toe.

On day 7, results showed the bone scan finding predictive of amputation need was identified in 0% (0 of 16) patients receiving iloprost alone, compared to 19% (3 of 16) patients in Group 2 and 60% (9 of 15) patients in Group 3. The findings also showed the presence of the bone scan abnormality was significantly lower in the two groups receiving iloprost.

Further follow-up information revealed whether a patient subsequently underwent ≥1 finger or toe amputation. These results showed the need for amputation remained consistent with the bone scan findings. Safety data revealed the most common side effects of iloprost injection included headache, flushing, heart palpitations, fast heart rate, nausea, vomiting, dizziness, and hypotension.

Guidance from the Centers for Disease Control and Prevention (CDC) recommends those experiencing signs of frostbite or hypothermia seek immediate medical care.

References

1. _{Commissioner O of the. FDA approves first medication to treat severe frostbite. U.S. Food and Drug Administration. February 14, 2024. Accessed February 14, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-medication-treat-severe-frostbite.}
2. _{Cauchy E, Cheguillaume B, Chetaille E. A controlled trial of a prostacyclin and rt-PA in the treatment of severe frostbite. N Engl J Med. 2011;364(2):189-190. doi:10.1056/NEJMc1000538}
3. _{Hypothermia|Winter weather. Centers for Disease Control and Prevention. November 2, 2023. Accessed February 14, 2024. https://www.cdc.gov/disasters/winter/staysafe/hypothermia.html.}