Incidence of Naloxone Redosing in the Age of the New Opioid Epidemic

Klebacher, Ronald; Harris, Matthew; Ariyaprakai, Navin; Tagore, Ammundeep; Robbins, Vince; Dudley, Larissa S; Bauter, Robert; Koneru, Susmith; Hill, Ryan; Wasserman, Eric; Shanes, Andrew; Merlin, Mark A.

doi:10.1080/10903127.2017.1335818

Cited by 42 publications

(27 citation statements)

References 15 publications

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“…Routine toxicological detection of FAs is difficult, and clandestine laboratories can easily modify fentanyl and its derivatives. Expanded access to addiction treatment and ready availability of naloxone to treat acute opioid overdoses are needed (Frank and Pollack, 2017;Klebacher et al, 2017;Samet and Kertesz, 2018;Thomson et al, 2017;CDC, 2018). Multifaceted fentanyl outbreak identification, prevention, harm reduction, and expanded treatment strategies that consider social, economic, and other contributing factors are needed to address the opioid and illicit drug crisis (Dasgupta et al, 2018;CDC, 2018).…”

Section: Discussionmentioning

confidence: 99%

Fentanyl and fentanyl-analog involvement in drug-related deaths

Dai

Abate

Smith

et al. 2019

Drug and Alcohol Dependence

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Background: To describe and analyze the involvement of fentanyl and fentanyl analogs (FAs) in drug-related deaths in West Virginia (WV), United States. Methods: Retrospective analyses of all WV drug-related deaths from 2005-2017 were performed, including comparisons of demographic and toxicological characteristics among total deaths, deaths in which fentanyl/FAs were present, deaths in which they were absent, heroinrelated deaths, and prescription opioid-related deaths. Results: Most of the 8813 drug-related deaths were overdoses, with about 11% resulting from transportation/other injuries in which drugs were contributors. Prescription opioid presence (without fentanyl) decreased by 75% from 2005-14 to 2015-17 (3,545 deaths to 859 deaths, respectively), while fentanyl involvement in the deaths increased by 122% between these periods (487 to 1082 deaths). Ten FAs were identified (427 instances) after 2015. Alprazolam and ethanol were among the top five most frequently identified substances across years. Fentanyl, heroin and cocaine replaced oxycodone, diazepam and hydrocodone in the top five beginning in 2015. Few decedents had a prescription for fentanyl after 2015, with fewer prescriptions also present for other controlled substances identified.

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Section: Discussionmentioning

confidence: 99%

Fentanyl and fentanyl-analog involvement in drug-related deaths

Dai

Abate

Smith

et al. 2019

Drug and Alcohol Dependence

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“…In a retrospective study of 2166 patients treated by paramedics in New Jersey from 2014 to 2016 for a suspected opioid overdose, 91% experienced complete resolution of symptoms with a single dose of naloxone using an INND and 9% needed a second dose, generally by the intravenous route. 12 Training is needed to understand how to assemble and use the INND, and even with training, there is a 45% failure rate in its use by the public. 13 A portion of the naloxone solution delivered using the device may be lost dripping down the nasopharynx or externally from the nose because of the introduction of a 1-mL solution into each naris.…”

Section: Discussionmentioning

confidence: 99%

“…Of these events, 83% reported that 2 or more doses of naloxone using the INND per suspected fentanyl overdose were used before the person responded. In a retrospective study of 2166 patients treated by paramedics in New Jersey from 2014 to 2016 for a suspected opioid overdose, 91% experienced complete resolution of symptoms with a single dose of naloxone using an INND and 9% needed a second dose, generally by the intravenous route …”

Section: Discussionmentioning

confidence: 99%

Comparison of the Pharmacokinetic Properties of Naloxone Following the Use of FDA‐Approved Intranasal and Intramuscular Devices Versus a Common Improvised Nasal Naloxone Device

Krieter

Chiang

Gyaw

et al. 2019

The Journal of Clinical Pharma

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For more than a decade, first responders and the general public have been able to treat suspected opioid overdoses using an improvised nasal naloxone device (INND) constructed from a prefilled syringe containing 2 mg of naloxone (1 mg/mL) attached to a mucosal atomization device. In recent years, the U.S. Food and Drug Administration (FDA)-approved Ezvio, an autoinjector that delivers 2 mg by intramuscular injection and Narcan nasal spray (2-and 4-mg strengths; 0.1 mL/dose) for the emergency treatment of a known or suspected opioid overdose. The present study was conducted to compare the pharmacokinetics of naloxone using the FDA-approved devices (each administered once) and either 1 or 2 administrations using the INND. When naloxone was administered twice using the improvised device, the doses were separated by 2 minutes. The highest maximum plasma concentration was achieved using the 4-mg FDA-approved spray. The highest exposures at 5 minutes postdose, based on AUC values, were after administration with the autoinjector and the 4-mg FDA-approved spray; at 10, 15, and 20 minutes postdose, the latter yielded the greatest exposure. Even after 2 administrations, the INND failed to achieve naloxone plasma levels comparable to the FDA-approved devices at any time. The ease of use and higher plasma concentrations achieved using the 4-mg FDA-approved spray, compared with the INND, should be considered when deciding which naloxone device to use.

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“…Delivery of naloxone by the nasal route has been recognized by the medical community and public officials as an effective way to reverse opioid overdoses (Ryan and Dunne, 2018). However, the short half-life of naloxone and the increased incidence of overdoses linked to synthetic opioids with a longer duration of action may require more than one dose to be administered to prevent renarcotization (Klebacher et al, 2017). Therefore, the addition of a longer-acting opioid antagonist to the naloxone formulation was initially hypothesized as a means to increase the time to obtain proper medical attention.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic Interaction between Naloxone and Naltrexone Following Intranasal Administration to Healthy Subjects

et al. 2019

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Naloxone (17-allyl-4,5a-epoxy-3,14-dihydroxymorphinan-6-one HCl), a m-opioid receptor antagonist, is administered intranasally to reverse an opioid overdose but its short half-life may necessitate subsequent doses. The addition of naltrexone [17-(cyclopropylmethyl)-4,5a-epoxy-3,14-dihydroxymorphinan-6-one], another m-receptor antagonist, which has a reported half-life of 3 1/2 hours, may extend the available time to receive medical treatment. In a phase 1 pharmacokinetic study, healthy adults were administered naloxone and naltrexone intranasally, separately and in combination. When administered with naloxone, the C max value of naltrexone decreased 62% and the area under the concentration-time curve from time zero to infinity (AUC 0-inf) decreased 38% compared with when it was given separately; lower concentrations of naltrexone were observed as early as 5 minutes postdose. In contrast, the C max and AUC 0-inf values of naloxone decreased only 18% and 16%, respectively, when given with naltrexone. This apparent interaction was investigated further to determine if naloxone and naltrexone shared a transporter. Neither compound was a substrate for organic cation transporter (OCT) 1, OCT2, OCT3, OCTN1, or OCTN2. There was no evidence of the involvement of a transmembrane transporter when they were tested separately or in combination at concentrations of 10 and 500 mM using Madin-Darby canine kidney II cell monolayers at pH 7.4. The efflux ratios of naloxone and naltrexone increased to six or greater when the apical solution was pH 5.5, the approximate pH of the nasal cavity; there was no apparent interaction when the two were coincubated. The importance of understanding how opioid antagonists are absorbed by the nasal epithelium is magnified by the rise in overdose deaths attributed to long-lived synthetic opioids and the realization that better strategies are needed to treat opioid overdoses.

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Incidence of Naloxone Redosing in the Age of the New Opioid Epidemic

Cited by 42 publications

References 15 publications

Fentanyl and fentanyl-analog involvement in drug-related deaths

Fentanyl and fentanyl-analog involvement in drug-related deaths

Comparison of the Pharmacokinetic Properties of Naloxone Following the Use of FDA‐Approved Intranasal and Intramuscular Devices Versus a Common Improvised Nasal Naloxone Device

Pharmacokinetic Interaction between Naloxone and Naltrexone Following Intranasal Administration to Healthy Subjects

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