Epinephrine nasal spray effective, tolerable with nasal congestion
Click Here to Manage Email Alerts
Key takeaways:
- Fears of pain or misuse may cause delays in autoinjector use during anaphylaxis.
- Patients experienced higher concentrations of epinephrine with nasal spray during congestion.
Patients with nasal congestion experienced enhanced absorption of epinephrine when it was administered via nasal spray compared with intramuscular administration, according to a study published in Annals of Allergy, Asthma & Immunology.
This treatment also was well tolerated with no clinical impact on heart rate or blood pressure, David A. Dworaczyk, PhD, advisor and consultant for Bryn Pharma, and colleagues wrote.
Although epinephrine is the standard treatment when anaphylaxis strikes, many patients and caregivers may hesitate to administer it via autoinjector because they are afraid of the pain of the shot or of using it incorrectly, the researchers said.
These hesitations can increase the risks for hospitalizations or fatal outcomes, the researchers continued, making alternative forms of administration such as nasal spray more attractive alternatives.
Considering the question of whether nasal congestion due to allergic rhinitis or anaphylaxis itself could affect how well epinephrine nasal spray is absorbed, the researchers conducted a phase 1, open-label, partial crossover study.
The study included 50 healthy, nonsmoking adults aged 19 to 65 years who had a history of seasonal allergies for at least 2 years. These subjects were divided into two cohorts.
The first cohort (mean age, 38.7 years; 46% women; 62% white) received a single dose of NDS1C (Bryn Pharma) epinephrine nasal spray administered as two consecutive sprays of 6.6 mg each delivered in opposite nostrils within 10 seconds of each other.
The second cohort (mean age, 39.3 years; 52% women; 60% white) received a single dose of NDS1C also administered as two consecutive sprays of 6.6 mg each within 10 seconds of each other but delivered in the same nostril.
Subjects received NDS1C 30 minutes after receiving a nasal allergen challenge delivered into a single nostril during period 1.
During periods 2 and 3, subjects received 0.3 mg of epinephrine delivered by an autoinjector and 0.5 mg of epinephrine delivered by a manual syringe, respectively. Period 4 included NDS1C. There were no nasal allergen challenges in periods 2, 3 or 4.
Subjects experienced a higher extent and peak exposures of epinephrine as well as faster times to reach maximum concentration (Tmax) with NDS1C after nasal allergen challenges compared with autoinjector, manual syringe and NDSC1 without nasal allergen challenges.
Specifically, maximum observed plasma concentrations (Cmax) included 458 pg/mL for NDS1C with nasal allergen challenge, 279 pg/mL for autoinjector, 364.2 pg/mL for manual syringe and 270.1 pg/mL for NDS1C with no nasal allergen challenge in the first cohort.
In the second cohort, Cmax findings included 463.3 pg/mL for NDS1C with nasal allergen challenge, 228.2 pg/mL for autoinjector, 322.3 pg/mL for manual syringe and 250.8 pg/mL for NDSC1 with no nasal allergen challenge.
Median Tmax results included 15 minutes for NDS1C with nasal allergen challenge, 21 minutes with autoinjector, 45 minutes with manual syringe and 25 minutes with NDSC1 with no nasal allergen challenge in the first cohort.
In the second cohort, median Tmax results included 18 minutes for NDSC1 with nasal allergen challenge, 20 minutes with autoinjector, 45 minutes with manual syringe and 20 minutes with NDSC1 with no nasal allergen challenge.
The researchers also said that NDSC1 achieved equivalent plasma concentrations as quickly as the autoinjector and manual syringe, based on the similar proportions of subjects who reached specific concentration thresholds of 50 pg/mL, 100 pg/mL and 200 pg/mL at 10 to 60 minutes after the dose across treatments.
Regardless of plasma concentrations, heart rates after doses were relatively stable and similar to values before doses, the researchers said. Changes from baseline heart rate compared with time-adjusted plasma epinephrine concentrations included R2 values of 0.0396 in the first cohort and 0.0141 in the second cohort.
Differences in maximum positive effect levels (Emax) least square mean (LSM) for changes in heart rate from baseline were not significant across all the comparisons between means of administration, the researchers continued.
Systolic and diastolic blood pressure values after dosing remained stable and similar to their values before dosing, the researchers added, again regardless of concentrations of plasma epinephrine.
R2 values for changes in systolic and diastolic blood pressure from baseline compared with time-matched baseline-adjusted plasma concentrations of epinephrine were 0.0227 or less for all comparisons as well.
Among the few significant differences in Emax LSM values for change from baseline systolic and diastolic blood pressure between NDSC1 and the autoinjector and manual syringe, the researchers said, the greatest difference was just 8.2 mmHg in systolic blood pressure and 5.7 mmHg for diastolic blood pressure.
Overall, the researchers said, none of the modes of administration had any clinical impact on heart rate or blood pressure.
Further, none of the patients experienced any serious adverse events or discontinued participation due to adverse events. The most common adverse events with NDSC1 were mild nausea (median onset, 41 minutes; median duration, 109 minutes) and mild headache (median onset, 106 minutes; median duration, < 1 minute).
Percentages of patients in the first cohort who experienced treatment-emergent adverse events after NDSC1 included 54% with a nasal allergen challenge 64% without a nasal allergen challenge. In the second cohort, these percentages included 44% with a nasal allergen challenge and 48% without a nasal allergen challenge.
The researchers classified 93% of the treatment-emergent adverse events as mild and 7% as moderate. Also, they said that 80% of the treatment-emergent adverse events were likely or probably related to the treatment. All adverse events resolved without any sequelae.
These findings should reassure health care providers and patients that nasal congestion will not impede NDSC1’s ability to deliver sufficient and tolerable concentrations of epinephrine during anaphylaxis, the researchers said, adding that absorption is even enhanced with congestion.
Perspective
Back to Top
During an allergic reaction, many patients will have typical nasal allergy symptoms, eg, nasal congestion, runny nose and sneezing. Therefore, there could be changes in the absorption of the epinephrine if given intranasally during an allergic reaction as compared with if given without nasal symptoms.
One could hypothesize that increased mucous in the nasal passages (during an allergic reaction or nasal allergen challenge) could decrease the absorption of epinephrine into the bloodstream. On the other hand, the leaky blood vessels could allow for quicker or increased absorption.
In this case, it appears that the latter is happening, and the epinephrine is getting absorbed more efficiently when there is localized inflammation in the nose. This may be surprising at first glance to some. However, similar data have been shown with another intranasal epinephrine device, so this is consistent with what is out there.
As a clinician who cares for patients at risk for anaphylaxis, I would love to see continued research with any noninjectable epinephrine, so that we can get closer to having approved, alternative forms of epinephrine for our patients.
Perspective
Back to Top
These findings are significant and surprising because one may assume that uptake of medicine is reduced when there is nasal congestion, as absorption may be less. This study actually showed the opposite — that uptake is enhanced, and similar pharmacokinetics were achieved.
It important to test nasal spray during periods of congestion because congestion is a common feature of anaphylaxis and a common comorbidity in those who have anaphylaxis, so we would want to make sure this nasal spray had similar absorption in this population and reached the same pharmacokinetics.
The next step in this research should be observing how well the spray works in real-world scenarios in those with congestion and those without. It is impossible to do a double-blind randomized study in those who have anaphylaxis due to ethical reasons, but real-world observational data would be helpful in how effective it is in an anaphylaxis situation.
Collapse
Read more about
Click Here to Manage Email Alerts