PMID- 37394178 OWN - NLM STAT- MEDLINE DCOM- 20231025 LR - 20231025 IS - 2213-2201 (Electronic) VI - 11 IP - 10 DP - 2023 Oct TI - Fast Acting, Dry Powder, Needle-Free, Intranasal Epinephrine Spray: A Promising Future Treatment for Anaphylaxis. PG - 3047-3054 LID - S2213-2198(23)00709-2 [pii] LID - 10.1016/j.jaip.2023.06.044 [doi] AB - BACKGROUND: Epinephrine intramuscular (IM) autoinjector is a life-saving drug for the emergency treatment of immediate-type allergic reactions (type I). Nevertheless, it is sometimes applied incorrectly or underused because of short shelf life, high costs, fear of use, or inconvenience of carrying. FMXIN002, a nasal powder spray of epinephrine, was developed as a needle-free alternative. OBJECTIVE: To compare epinephrine pharmacokinetics, pharmacodynamics, and safety after the administration of the FMXIN002 nasal spray versus autoinjector. METHODS: An open-label trial was performed in 12 adults with seasonal allergic rhinitis without asthma. Epinephrine pharmacokinetics, pharmacodynamics, and safety were compared between FMXIN002 (1.6 mg and 3.2 mg) administered intranasally with/without a nasal allergen challenge and IM (0.3 mg) EpiPen. RESULTS: FMXIN002 3.2 mg, administered after a nasal allergen challenge, displayed a shorter Tmax than EpiPen (median: 2.5 minutes vs 9.0 minutes, statistically nonsignificant [NS]) and a significantly shorter time when the measured analyte concentration is 100 pg/mL during the absorption phase pg/mL (median: 1.0 minutes vs 3.0 minutes for FMXIN002, P < .02). Moreover, FMXIN002 3.2 mg administered after the challenge test has resulted in a doubling of the maximal measured plasma analyte concentration over the sampling period (1110 vs 551 pg/mL, NS); area under the curve from 0 to 8 hours was 56% higher (672 vs 431 hours pg/mL, compared with EpiPen, NS). Pharmacodynamic response was comparable at all treatments. FMXIN002 was well tolerated, and treatment-emergent adverse events (AEs) were mild, local, and resolved spontaneously. No AEs were reported after the administration of EpiPen in our study. FMXIN002 was stable for 2 years at room temperature conditions. However, variability in the pharmacokinetics (expressed in coefficient of variation) is high. Having a prior nasal allergen challenge results in a substantial increase and speed of absorption. CONCLUSIONS: Intranasal absorption of dry powder epinephrine is faster than EpiPen offering a clinical advantage in the short therapeutic window for the treatment of anaphylaxis. The FMXIN002 product offers a needle-free, pocket-size, safe, user-friendly, and stable alternative to epinephrine autoinjectors. CI - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Tal, Yuval AU - Tal Y AD - Allergy and Clinical Immunology Unit, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. FAU - Ribak, Yaarit AU - Ribak Y AD - Allergy and Clinical Immunology Unit, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. FAU - Rubin, Limor AU - Rubin L AD - Allergy and Clinical Immunology Unit, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. FAU - Talmon, Aviv AU - Talmon A AD - Allergy and Clinical Immunology Unit, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. FAU - Shamriz, Oded AU - Shamriz O AD - Allergy and Clinical Immunology Unit, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. Electronic address: oded.shamriz@mail.huji.ac.il. FAU - Hershko, Alon Y AU - Hershko AY AD - Allergy and Clinical Immunology Unit, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. FAU - Blotnick, Simcha AU - Blotnick S AD - Clinical Pharmacology Unit, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. FAU - Bouhajib, Mohammed AU - Bouhajib M AD - Pharma Medica Research Inc, Bioanalytical services, Mississauga, ON, Canada. FAU - Krayz, Galia Temtsin AU - Krayz GT AD - Formulex Pharma Innovation Ltd, Pharmaceutical development and manufacturing, Nes Ziona, Israel. FAU - Abrutzky, Carolina AU - Abrutzky C AD - Nasus Pharma, Tel Aviv, Israel. FAU - Megiddo, Dalia AU - Megiddo D AD - Nasus Pharma, Tel Aviv, Israel. FAU - Lapidot, Tair AU - Lapidot T AD - Nasus Pharma, Tel Aviv, Israel. Electronic address: tair@nasuspharma.com. FAU - Caraco, Yoseph AU - Caraco Y AD - Clinical Pharmacology Unit, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. LA - eng SI - ClinicalTrials.gov/NCT04696822 PT - Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230630 PL - United States TA - J Allergy Clin Immunol Pract JT - The journal of allergy and clinical immunology. In practice JID - 101597220 RN - 0 (Allergens) RN - YKH834O4BH (Epinephrine) RN - 0 (Powders) SB - IM MH - Adult MH - Humans MH - Administration, Intranasal MH - Allergens/therapeutic use MH - *Anaphylaxis/drug therapy MH - Epinephrine/therapeutic use MH - Powders/therapeutic use OTO - NOTNLM OT - Anaphylaxis OT - Bioavailability OT - Epinephrine OT - Intranasal OT - Powder OT - Spray EDAT- 2023/07/03 00:41 MHDA- 2023/10/23 00:42 CRDT- 2023/07/02 19:28 PHST- 2022/11/23 00:00 [received] PHST- 2023/06/13 00:00 [revised] PHST- 2023/06/19 00:00 [accepted] PHST- 2023/10/23 00:42 [medline] PHST- 2023/07/03 00:41 [pubmed] PHST- 2023/07/02 19:28 [entrez] AID - S2213-2198(23)00709-2 [pii] AID - 10.1016/j.jaip.2023.06.044 [doi] PST - ppublish SO - J Allergy Clin Immunol Pract. 2023 Oct;11(10):3047-3054. doi: 10.1016/j.jaip.2023.06.044. Epub 2023 Jun 30.