Naloxone should remain the appropriate antidote to treat opioid overdose

Mégarbane, Bruno; Chevillard, L; Vodovar, Dominique

doi:10.1186/s13054-020-2835-5

Cited by 4 publications

(4 citation statements)

References 9 publications

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“…Additionally, patients who received buprenorphine had more “complete responses” with less recurrence of respiratory depression than patients who received naloxone. There are several concerns with this study though, as described by Mégarbane et al ( 2020 ), including the mild opioid poisoning (i.e., Glasgow Coma Scores of 13–15 and respiratory rate of 10–16 breaths/min) of these patients and the high doses of naloxone. It is also important to consider that buprenorphine may be less effective at reducing high efficacy μ-opioid agonist effects in people who have developed tolerance and/or physical dependence on opioids.…”

Section: Recent Advances In Overdose Treatments and Technologiesmentioning

confidence: 89%

Treatment of opioid overdose: current approaches and recent advances

Britch

Walsh

2022

Psychopharmacology

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Background The USA has recently entered the third decade of the opioid epidemic. Opioid overdose deaths reached a new record of over 74,000 in a 12-month period ending April 2021. Naloxone is the primary opioid overdose reversal agent, but concern has been raised that naloxone is not efficacious against the pervasive illicit high potency opioids (i.e., fentanyl and fentanyl analogs). Methods This narrative review provides a brief overview of naloxone, including its history and pharmacology, and the evidence regarding naloxone efficacy against fentanyl and fentanyl analogs. We also highlight current advances in overdose treatments and technologies that have been tested in humans. Results and conclusions The argument that naloxone is not efficacious against fentanyl and fentanyl analogs rests on case studies, retrospective analyses of community outbreaks, pharmacokinetics, and pharmacodynamics. No well-controlled studies have been conducted to test this argument, and the current literature provides limited evidence to suggest that naloxone is ineffective against fentanyl or fentanyl analog overdose. Rather a central concern for treating fentanyl/fentanyl analog overdose is the rapidity of overdose onset and the narrow window for treatment. It is also difficult to determine if other non-opioid substances are contributing to a drug overdose, for which naloxone is not an effective treatment. Alternative pharmacological approaches that are currently being studied in humans include other opioid receptor antagonists (e.g., nalmefene), respiratory stimulants, and buprenorphine. None of these approaches target polysubstance overdose and only one novel approach (a wearable naloxone delivery device) would address the narrow treatment window.

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Section: Recent Advances In Overdose Treatments and Technologiesmentioning

confidence: 89%

Treatment of opioid overdose: current approaches and recent advances

Britch

Walsh

2022

Psychopharmacology

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“…Similarly, in terms of buprenorphine toxicity, drug-drug interactions and intravenous buprenorphine administration are currently the two most recognized circumstances that impair the buprenorphine-related ceiling effect (Mégarbane et al 2020). Various mechanisms have been proposed to explain the respiratory depression resulting from the concomitant use of buprenorphine and sedatives, including pharmacokinetic interaction, reversal of down regulation of opioid receptors, and possible malfunction of key transporter proteins in the blood-brain barrier.…”

Section: Buprenorphine Toxicitymentioning

confidence: 99%

Buprenorphine, Polydrug Use and Deaths

Ojanperä

Mariottini

Kriikku

2022

Handbook of Substance Misuse and Addictions

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Buprenorphine is an opioid analgesic and a medication used for opioid agonist treatment.Being a partial mu-opioid receptor agonist, it has a greater margin of safety compared to full agonists. Despite the relative safety of buprenorphine, the concomitant use of central nervous system depressant drugs is associated with an increased risk of respiratory depression, intoxication and death. Injection of buprenorphine and polydrug use are major mortality risk factors. Clonazepam, alprazolam, diazepam, pregabalin and alcohol are particularly often associated with fatal poisonings. An established user does not favour buprenorphine because of its euphoric effect, but the drug is rather used to manage opioid withdrawal symptoms, while concomitant sedative-hypnotic or illicit drugs may be taken to obtain or augment the opioid high. Perceived underdosing of buprenorphine in opioid agonist treatment is one reason for polydrug use. Prevention measures include encouraging safer consumption habits such as avoiding injection, as well as efforts to reduce concomitant use of alcohol, sedative-hypnotic drugs, and illicit drugs among buprenorphine users.

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“…The previous notion that buprenorphine is toxic only in specific situations has given way to more recent epidemiological data on more significant harms of this drug. Drug–drug interactions, especially with concomitant sedative‐hypnotic drugs, and intravenous buprenorphine administration are currently the two most recognized circumstances that impair the buprenorphine‐related ceiling effect 10 . The issue of buprenorphine abuse has been raised in many contexts, especially in Finland, 8 Sweden, 11 Australia, 12 and the United States 13 .…”

Section: Introductionmentioning

confidence: 99%

“…Drug-drug interactions, especially with concomitant sedative-hypnotic drugs, and intravenous buprenorphine administration are currently the two most recognized circumstances that impair the buprenorphine-related ceiling effect. 10 The issue of buprenorphine abuse has been raised in many contexts, especially in Finland, 8 Sweden, 11 Australia, 12 and the United States. 13 Buprenorphine is commonly associated with polydrug use, as demonstrated for instance by studies on vulnerable populations in the United States 14 or buprenorphine deaths in Finland.…”

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confidence: 99%

Investigation of buprenorphine‐related deaths using urinary metabolite concentrations

Mariottini

Kriikku

Ojanperä

2022

Drug Testing and Analysis

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Quantitative analysis of postmortem urine, instead of blood, for buprenorphine and metabolites may provide additional evidence for the diagnosis of fatal buprenorphine poisoning. In this study, 247 autopsy urine samples, previously testing positive for buprenorphine or norbuprenorphine, were quantitatively reanalysed with a recently developed liquid chromatography–tandem mass spectrometry (LC‐MS/MS) method for unconjugated buprenorphine (BUP), norbuprenorphine (NBUP), naloxone (NAL), and their respective conjugated metabolites, buprenorphine glucuronide (BUPG), norbuprenorphine glucuronide (NBUPG), and naloxone glucuronide (NALG). The cases were divided, according to medical examiners' decision, to buprenorphine poisonings and other causes of death. The groups were compared for urinary concentrations and metabolite concentration ratios of the six analytes. All median concentrations were higher in the buprenorphine poisoning group. The median concentration of BUPG was significantly higher and the median metabolite ratios NBUP/BUP, NBUPG/BUPG, and NBUPtotal/BUPtotal were significantly lower in poisonings than in other causes of death. Naloxone‐related concentrations and ratios were not significantly different between the groups.

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Naloxone should remain the appropriate antidote to treat opioid overdose

Cited by 4 publications

References 9 publications

Treatment of opioid overdose: current approaches and recent advances

Treatment of opioid overdose: current approaches and recent advances

Buprenorphine, Polydrug Use and Deaths

Investigation of buprenorphine‐related deaths using urinary metabolite concentrations

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