American College of Medical Toxicology and the American Academy of Clinical Toxicology position statement: nalmefene should not replace naloxone as the primary opioid antidote at this time.

BACKGROUND: Nalmefene is a potent opioid antagonist that has recently been reintroduced in the United States to treat known or suspected opioid overdose. NALMEFENE CLINICAL TRIAL DATA: The injection formulation, which had been withdrawn in 2008, was reintroduced in 2022, and in 2023 the United States Food and Drug Administration approved a new intranasal formulation of nalmefene. Because nalmefene had been previously approved for use in 1995 via injection, the new intranasal formulation did not require new clinical data as it was approved under an Abbreviated New Drug Application. Inherent to this abbreviated approval process, intranasal nalmefene was not studied in patients currently suffering opioid overdose. NALOXONE AND NALMEFENE: Nalmefene also has unique characteristics compared with naloxone, the current standard opioid antidote. Nalmefene has a higher affinity for opioid receptors and a longer duration of action than naloxone. Comparative effectiveness data regarding naloxone and nalmefene are sparse, and it is unclear if the inherent properties of nalmefene are beneficial in opioid overdose. We have decades of experience using naloxone safely and effectively as the primary opioid antidote, even in cases of fentanyl and fentanyl analog overdoses. There is, however, evidence to suggest nalmefene may result in more prolonged and severe opioid withdrawal than naloxone, which could be harmful to patients. POSITION: As nalmefene is untested in the current clinical environment of synthetic opioid overdoses and has the potential to cause harm via prolonged withdrawal, it is the opinion of the American College of Medical Toxicology and the American Academy of Clinical Toxicology that nalmefene should not replace naloxone as the primary opioid antidote at this time. RECOMMENDATIONS: We recommend additional clinical studies of nalmefene, administered via all approved routes, be conducted in a comparative fashion with naloxone, and that safety and effectiveness outcomes be evaluated before nalmefene is recommended as a primary opioid antidote.

2023 American Heart Association focused update on the management of patients with cardiac arrest or life-threatening toxicity due to poisoning: an update to the American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care

In this focused update, the American Heart Association provides updated guidance for resuscitation of patients with cardiac arrest, respiratory arrest, and refractory shock due to poisoning. Based on structured evidence reviews, guidelines are provided for the treatment of critical poisoning from benzodiazepines, ß-adrenergic receptor antagonists (also known as ß-blockers), L-type calcium channel antagonists (commonly called calcium channel blockers), cocaine, cyanide, digoxin and related cardiac glycosides, local anesthetics, methemoglobinemia, opioids, organophosphates and carbamates, sodium channel antagonists (also called sodium channel blockers), and sympathomimetics. Recommendations are also provided for the use of venoarterial extracorporeal membrane oxygenation. These guidelines discuss the role of atropine, benzodiazepines, calcium, digoxin-specific immune antibody fragments, electrical pacing, flumazenil, glucagon, hemodialysis, hydroxocobalamin, hyperbaric oxygen, insulin, intravenous lipid emulsion, lidocaine, methylene blue, naloxone, pralidoxime, sodium bicarbonate, sodium nitrite, sodium thiosulfate, vasodilators, and vasopressors for the management of specific critical poisonings.

2023 American Heart Association Focused Update on the Management of Patients With Cardiac Arrest or Life-Threatening Toxicity Due to Poisoning: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.

In this focused update, the American Heart Association provides updated guidance for resuscitation of patients with cardiac arrest, respiratory arrest, and refractory shock due to poisoning. Based on structured evidence reviews, guidelines are provided for the treatment of critical poisoning from benzodiazepines, ß-adrenergic receptor antagonists (also known as ß-blockers), L-type calcium channel antagonists (commonly called calcium channel blockers), cocaine, cyanide, digoxin and related cardiac glycosides, local anesthetics, methemoglobinemia, opioids, organophosphates and carbamates, sodium channel antagonists (also called sodium channel blockers), and sympathomimetics. Recommendations are also provided for the use of venoarterial extracorporeal membrane oxygenation. These guidelines discuss the role of atropine, benzodiazepines, calcium, digoxin-specific immune antibody fragments, electrical pacing, flumazenil, glucagon, hemodialysis, hydroxocobalamin, hyperbaric oxygen, insulin, intravenous lipid emulsion, lidocaine, methylene blue, naloxone, pralidoxime, sodium bicarbonate, sodium nitrite, sodium thiosulfate, vasodilators, and vasopressors for the management of specific critical poisonings.

Prescription Drug Shortages: Pediatric Emergency and Critical Care Medications.

OBJECTIVES: Drug shortages have been increasing over the past 2 decades. There are limited data on drug shortages and their effect on pediatric emergency and critical care. Our objective was to describe pediatric emergency and critical care drug shortages. METHODS: Drug shortage data from January 2001 to December 2015 were obtained from the University of Utah Drug Information Services. Shortages were reviewed, identifying agents used in pediatric emergency and critical care. Shortage data were analyzed for the type of drug, formulation, shortage reason, duration, marketing status (generic vs brand name), or if it was a pediatric-friendly formulation, used for a high-acuity condition, or a single-source product. The availability of a substitute was also described. RESULTS: Of 1883 products on shortage, 779 were used in pediatric emergency or critical care. The annual number of shortages decreased from 2001 to 2004, but then increased, reaching a high in 2011. The median duration for resolved shortages was 7.6 months (interquartile range, 3.0-17.6 months). The most common category affected was infectious disease drugs. High-acuity agents were involved in 27% of shortages and in 11% of pediatric-friendly formulations. An alternative agent was available for 95% of drugs, yet 43% of alternatives were also affected at some time during the study period. The most common reported reason for a shortage was manufacturing problems. CONCLUSIONS: From 2001 to 2015, drug shortages affected a substantial number of agents used in pediatric emergency and critical care. This has had implications to the medications available for use and may impact patient outcomes. Providers must be aware of current shortages and implement mitigation strategies to optimize patient care.

The role of take-home naloxone in the epidemic of opioid overdose involving illicitly manufactured fentanyl and its analogs.

INTRODUCTION: There has been an exponential increase in overdose fatalities as illicitly manufactured fentanyl and its analogs (IMF) are becoming more prevalent in the illicit drug supply. In response, overdose education and naloxone distribution (OEND) programs have been implemented throughout the United States as a harm reduction strategy. However, there are increasing reports that higher naloxone doses or repeat administration might be required for overdose victims involving IMF. AREAS COVERED: In this article, we provide a comprehensive review of the epidemiology, public health impact, and pharmacologic properties of IMF. The pharmacokinetic properties of currently available take-home naloxone (THN) kits, the role of THN as a harm reduction strategy and available data on its clinical use are discussed. Implications of occupational IMF exposure for first responders are also described. EXPERT OPINION: THN administration by a bystander is an effective harm reduction intervention. However, there is growing evidence that higher dose or multiple administrations of naloxone are required to fully reverse IMF related toxicity. Recently, the US Food and Drug Administration approved THN kits with a concentrated naloxone dose that produce high bioavailability. However, limited presence of OEND programs and cost of these new devices impede their accessibility to the general public.

Prescription Drug Shortages: Implications for Ambulatory Pediatrics.

OBJECTIVE: To describe contemporary drug shortages affecting general ambulatory pediatrics. STUDY DESIGN: Data from January 2001 to December 2015 were obtained from the University of Utah Drug Information Service. Two pediatricians reviewed drug shortages and identified agents used in ambulatory pediatrics. Shortage data were analyzed by the type of drug, formulation, reason for shortage, duration, marketing status, if a pediatric friendly-formulation was available, or if it was a single-source product. The availability of an alternative, and whether that alternative was affected by a shortage, also was noted. RESULTS: Of 1883 products in shortage during the study period, 314 were determined to be used in ambulatory pediatrics. The annual number of new pediatric shortages decreased initially but then increased to a high of 38 in 2011. Of the 314 pediatric shortages, 3.8% were unresolved at the end of the study. The median duration of resolved shortages was 7.6 months. The longest shortage was for ciprofloxacin 500-mg tablets. The most common class involved was infectious disease drugs. Pediatric-friendly dosage forms were affected in 19.1% of shortages. An alternative agent was available for 86% drugs; however, 29% of these also were affected. The most common reason for shortage was manufacturing problems. CONCLUSIONS: Drug shortages affected a substantial number of agents used in general ambulatory pediatrics. Shortages for single-source products are a concern if a suitable alternative is unavailable. Providers working in the ambulatory setting must be aware of current shortages and implement mitigation strategies to optimize patient care.