Children Show Greater Epinephrine Exposure with Neffy Than Adults

A study found children had slightly greater epinephrine exposures with neffy 1 and 2 mg than what had been previously reported in adults. Additionally, pediatric patients achieved mean maximum concentration levels, showcasing the efficacy of neffy.1

“…it is important to note that this is the first [Good Clinical Practice] pediatric epinephrine study conducted for the purpose of regulatory approval,” wrote investigators, led by David M. Fleischer, MD, from Children's Hospital Colorado, University of Colorado School of Medicine. “The comparison of pediatric data with comparable data in adults provides the necessary scientific rationale to conclude that pediatric doses of neffy have a comparable [pharmacokinetic] profile relative to epinephrine injection.”

Epinephrine is the first-line treatment for severe allergic reactions, yet research shows this type of adrenaline is underused in anaphylaxis cases. A recent study found only 8% of children with ≥ Grade II anaphylactic reactions received it.2

Investigators pointed to uncertainty among healthcare professionals in recognizing and treating anaphylaxis, although patient hesitancy toward injections may also play a role. Avoiding epinephrine increases the risk of complications, but fortunately for patients scared of needles, epinephrine nasal spray offers an alternative treatment option.

This past March, the US Food and Drug Administration (FDA) approved epinephrine nasal spray 1 mg (neffy) for the treatment of type 1 allergic reactions, including anaphylaxis, in patients aged ≥ 4 years who weighed 15 – 29 kg.3 This decision followed a historic FDA approval of epinephrine nasal spray 2 mg (neffy) in adults and children who weighed ≥ 30 kg. ARS Pharmaceuticals stated in their press release that the new 1 mg formulation is expected by May 2025.

Although neffy is already approved, investigators conducted a phase 1, multicenter, single-dose study to characterize neffy’s pharmacokinetic and pharmacodynamic profiles in children and compare these profiles with adults.1 The study included 42 children dosed with 1 or 2 mg of neffy, based on weight.

The sample included patients aged 4 – 17 years; 21 weighed between 15 – 29 Kg and received neffy 1 mg, while 21 weighed ≥ 30 kg and received neffy 2 mg. Investigators also examined 42 healthy adults aged 22 – 54, dosed with neffy 2 mg during another study, as the comparator.

The study found neffy 1 mg resulted in a slightly lower mean maximum concentration than neffy 2 mg (651 vs 690 pg/mL). Children on both doses had greater concentrations of neffy compared with adults (481 pg/mL); however, the difference was nonsignificant (P < .05).1

Furthermore, children on neffy 1 mg achieved median Tmax values faster than children on neffy 2 mg (20 vs 29.5 minutes).

Unlike adults who experienced a post-dose increase in systolic blood pressure, the systolic blood pressure in children had a significantly lower increase. Investigators observed a transient decrease in systolic blood pressure, occurring at 5 minutes for the 1 mg dose and 10 minutes for the 2 mg dose.

Additionally, children had minimal differences in diastolic blood pressure. Children had a similar heart rate effect from neffy as adults.

“Interestingly, despite the increased absorption observed in pediatric patients relative to adults, pediatric patients demonstrated less pronounced [pharmacodynamic] responses, particularly [systolic blood pressure],” investigators wrote.1

The study demonstrated a good safety profile of neffy, despite 52.4% on neffy 1 mg and 66.7% of neffy 2 mg experiencing adverse events. Common adverse events included nasal congestion, upper respiratory tract congestion, dry throat, nasal dryness, paresthesia, rhinorrhea, sneezing, rhinalgia, epistaxis, fatigue, and jitters. The study reported no serious adverse events.

Although the study supports the effectiveness of neffy for pediatric anaphylaxis, investigators noted the limitations of pediatric pharmacokinetic trials. For instance, these trials often include small sample sizes due to the requirement of multiple blood draws. The trials also lack a control arm.

“Overall, when administered to pediatric subjects, neffy demonstrated comparable-to-greater absorption relative to adults, with increase in [systolic blood pressure] and [heart rate] that suggest that these pediatric doses activate relevant adrenergic receptors,” investigators concluded.1 “The difference in [pharmacodynamic] responses to epinephrine can be largely attributed to normal, age-related differences in physiology. By bridging the data with adult data from over 700 subjects, it appears that pediatric doses of neffy perform as expected.”

References

1. Fleischer DM, Li HH, Talreja N, Lockey RF, Kaliner MA, Wainford RD, Greenhawt MJ, Casale TB, Lowenthal R, Tanimoto S. Pharmacokinetics and pharmacodynamics of neffy, epinephrine nasal spray, in pediatric allergy patients. J Allergy Clin Immunol Pract. 2025 Mar 20:S2213-2198(25)00269-7. doi: 10.1016/j.jaip.2025.03.019. Epub ahead of print. PMID: 40120808.

2. Derman, C. Many Patients with Anaphylaxis Do Not Receive First-Line Adrenaline Treatment. HCPLive. March 26, 2025. https://www.hcplive.com/view/many-patients-anaphylaxis-do-not-receive-first-line-adrenaline-treatment. Accessed March 26, 2025.

3. Campbell, P. FDA Approves 1 mg neffy Nasal Spray for Pediatric Anaphylaxis. HCPLive. March 6, 2025. https://www.hcplive.com/view/fda-approves-1-mg-neffy-nasal-spray-for-pediatric-anaphylaxis. Accessed March 26, 2025.