Effect of Intranasal vs Intramuscular Naloxone on Opioid Overdose

Dietze, Paul; Jauncey, Marianne; Salmon, Allison M.; Mohebbi, Mohammadreza; Latimer, Julie; Beek, Ingrid van; McGrath, Colette; Kerr, Debra

doi:10.1001/jamanetworkopen.2019.14977

Cited by 41 publications

(33 citation statements)

References 36 publications

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“… 9 Despite the advantages of intranasal naloxone and its endorsement in current guidelines, 7 a recent clinical trial conducted in a supervised injection facility demonstrated greater efficacy of intramuscular naloxone over intranasal when the 2 medications were provided at equal doses in the same concentration. 10 …”

Section: Discussionmentioning

confidence: 99%

Naloxone Use by Emergency Medical Services During the COVID-19 Pandemic: A National Survey

Cone

Bogucki

Burns

et al. 2020

Journal of Addiction Medicine

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Objectives: The COVID-19 epidemic in the United States has hit in the midst of the opioid overdose crisis. Emergency medical services (EMS) clinicians may limit their use of intranasal naloxone due to concerns of novel coronavirus infection. We sought to determine changes in overdose events and naloxone administration practices by EMS clinicians. Methods: Between April 29, 2020 and May 15, 2020, we surveyed directors of EMS fellowship programs across the US about how overdose events and naloxone administration practices had changed in their catchment areas since March 2020. Results: Based on 60 respondents across all regions of the country, one fifth of surveyed communities have experienced an increase in opioid overdoses and events during which naloxone was administered, and 40% have experienced a decrease. The findings varied by region of the country. Eighteen percent of respondents have discouraged or prohibited the use of intranasal naloxone with 10% encouraging the use of intramuscular naloxone. Conclusions: These findings may provide insight into changes in opioid overdose mortality during this time and assist in future disaster planning.

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Section: Discussionmentioning

confidence: 99%

Naloxone Use by Emergency Medical Services During the COVID-19 Pandemic: A National Survey

Cone

Bogucki

Burns

et al. 2020

Journal of Addiction Medicine

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“…The comparator dose of 0.8 mg intramuscularly was also used in a recent clinical trial of overdoses in an Australian safe injection Open access facility. 9 An advisory committee to the the US Food and Drug Administration has advised that a dose above 0.4 mg is the most appropriate comparator. 25 The WHO recommends intramuscular doses not to exceed 0.8 mg as the first dose in community overdose.…”

Section: Route Of Administration Concentration and Dosementioning

confidence: 99%

“…Open access are needed to deliver a therapeutic dose. Despite these shortcomings, epidemiological studies 5 and a few clinical trials [6][7][8][9] have shown promising results of such improvised IN naloxone. The WHO pointed out the low evidence behind many nasal sprays used in naloxone programmes and called for clinical trials on this crucial issue.…”

mentioning

confidence: 99%

“…Previous trials in patients have shown nasal spray to be inferior to intramuscular (IM) naloxone. [6][7][8][9] This is not surprising as these studies used dilute formulations of IN naloxone such as 0.4 mg/2 mL, 8 0.8 mg/1 mL 9 or 2 mg/1 mL. 6 7 Because of limitations in the nasal mucosal uptake, such doses are expected to provide far less systemic exposure than the commonly administered intramuscular dose of 0.8 mg.…”

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confidence: 99%

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NTNU intranasal naloxone trial (NINA-1) study protocol for a double-blind, double-dummy, non-inferiority randomised controlled trial comparing intranasal 1.4 mg to intramuscular 0.8 mg naloxone for prehospital use

et al. 2020

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IntroductionIntranasal (IN) naloxone is widely used to treat opioid overdoses. The advantage of nasal administration compared with injection lies in its suitability for administration by lay people as it is needless. Approved formulations of nasal naloxone with bioavailability of approximately 50% have only undergone trials in healthy volunteers, while off-label nasal sprays with low bioavailability have been studied in patients. Randomised clinical trials are needed to investigate efficacy and safety of approved IN naloxone in patients suffering overdose. This study investigates whether the administration of 1.4 mg naloxone in 0.1 mL per dose is non-inferior to 0.8 mg intramuscular injection in patients treated for opioid overdose.Methods and analysisSponsor is the Norwegian University of Science and Technology. The study has been developed in collaboration with user representatives. The primary endpoint is the restoration of spontaneous respiration≥10 breaths/min based on a sample of 200 opioid overdose cases. Double-dummy design ensures blinding, which will be maintained until the database is locked.Ethics and disseminationThe study was approved by the Norwegian Medicines Agency and Regional Ethics Committees (REC: 2016/2000). It adheres to the Good Clinical Practice guidelines as set out by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use.Informed consent will be sought through a differentiated model. This allows for deferred consent after inclusion for patients who have regained the ability to consent. Patients who are unable to consent prior to discharge by emergency services are given written information and can withdraw at a later date in line with user recommendations. Metadata will be published in the Norwegian University of Science and Technology Open repository. Deidentified individual participant data will be made available to recipients conditional of data processor agreement being entered.Trial registration numbersEudraCT Registry (2016-004072-22) and Clinicaltrials.gov Registry (NCT03518021).

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“…Also, avoidance of the gastrointestinal tract and hepatic metabolic breakdown increases drug availability [15]. IN administration has been explored with drug formulation design for the treatment of conditions other than anaphylaxis, including pain (opioids), heroin overdose reversal (opioid antagonists), Alzheimer's disease, and seizures (benzodiazepines) [16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Intranasal epinephrine effects on epinephrine pharmacokinetics and heart rate in a nasal congestion canine model

et al. 2020

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Background: Histamine release and vasodilation during an allergic reaction can alter the pharmacokinetics of drugs administered via the intranasal (IN) route. The current study evaluated the effects of histamine-induced nasal congestion on epinephrine pharmacokinetics and heart rate changes after IN epinephrine. Methods: Dogs received 5% histamine or saline IN followed by 4 mg epinephrine IN. Nasal restriction pressure, epinephrine concentration, and heart rate were assessed. Maximum concentration (C max), area under plasma concentration-time curve from 1 to 90 min (AUC 1-90), and time to reach C max (T max) were measured. Clinical observations were documented. Results: In the 12 dogs in this study, nasal congestion occurred at 5-10 min after IN histamine administration versus no nasal congestion after IN saline. After administration of IN epinephrine, IN histamine-mediated nasal congestion was significantly reduced to baseline levels at 60, 80, and 100 min. There were no significant differences in C max and AUC 1-90 between histamine and saline groups after IN epinephrine delivery (3.5 vs 1.7 ng/mL, p = 0.06, and 117 vs 59 ng/ mL*minutes, p = 0.09, respectively). After receiving IN epinephrine, the histamine group had a significantly lower T max versus the saline group (6 vs 70 min, respectively; p = 0.02). Following IN epinephrine administration, the histamine group showed rapidly increased heart rate at 5 min, while there was a delayed increase in heart rate (occurring 30-60 min after administration) in the saline group. Clinical observations included salivation and emesis. Conclusion: IN histamine led to more rapid epinephrine absorption and immediately increased heart rate compared with IN saline. IN epinephrine decreased histamine-induced nasal congestion.

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Effect of Intranasal vs Intramuscular Naloxone on Opioid Overdose

Abstract: This randomized clinical trial compares 2 administration methods for the opioid antagonist naloxone in individuals served by a medically supervised drug-injecting facility in Australia.

Cited by 41 publications

References 36 publications

Naloxone Use by Emergency Medical Services During the COVID-19 Pandemic: A National Survey

Naloxone Use by Emergency Medical Services During the COVID-19 Pandemic: A National Survey

NTNU intranasal naloxone trial (NINA-1) study protocol for a double-blind, double-dummy, non-inferiority randomised controlled trial comparing intranasal 1.4 mg to intramuscular 0.8 mg naloxone for prehospital use

Intranasal epinephrine effects on epinephrine pharmacokinetics and heart rate in a nasal congestion canine model

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