Epidemiology of severe buprenorphine exposures reported to the U.S. Poison Centers

Rege, Saumitra V.; Ngo, Duc Anh; Ait-Daoud, Nassima; Holstege, Christopher P.

doi:10.1016/j.drugalcdep.2019.05.015

Cited by 7 publications

(10 citation statements)

References 60 publications

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“…Severe buprenorphine exposures including those resulting in life threatening symptoms or death reported to US poison centers increased 67% from 2011 to 2016. 8 F I G U R E 2 Buprenorphine use (mg / person) reported to the Drug Enforcement Administration by state or territory (A) or US Census division (B). n t test P < .05 vs New England; t t test P < .05 vs the U.S.…”

Section: Key Pointsmentioning

confidence: 99%

Rise and regional disparities in buprenorphine utilization in the United States

Azar

Cruz-Mullane

Podd

et al. 2020

Pharmacoepidemiology and Drug

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Purpose Buprenorphine is an opioid partial agonist used to treat opioid use disorder. While several policy changes have attempted to increase buprenorphine availability, access remains well below optimal levels. This study characterized how buprenorphine utilization in the United States has changed over time and whether there are regional disparities in distribution of the medication. Methods The amount of buprenorphine distributed from 2007 to 2017 was obtained from the Drug Enforcement Administration's Automated Reports and Consolidated Ordering System. Data were expressed as the percent change and milligrams per person in each state. The formulations and cost for prescriptions covered by Medicaid (2008 to 2018) were also examined. Results Buprenorphine distributed to pharmacies increased about 7‐fold (476.8 to 3179.9 kg) while the quantities distributed to hospitals grew 5‐fold (18.6 to 97.6 kg) nationally from 2007 to 2017. Buprenorphine distribution per person was almost 20‐fold higher in Vermont (40.4 mg/person) relative to South Dakota (2.1 mg/person). There was a strong association between the number of physicians authorized to prescribe buprenorphine and distribution per state (r[49] = +0.94, P < .0005). The buprenorphine/naloxone sublingual film (Suboxone) was the predominant formulation (92.6% of 0.31 million Medicaid prescriptions) in 2008 but accounted for less than three‐fifth (57.3% of 6.56 million prescriptions) in 2018. Conclusions Although buprenorphine availability has substantially increased over the last decade, distribution was very nonhomogeneous across the United States.

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Section: Key Pointsmentioning

confidence: 99%

Rise and regional disparities in buprenorphine utilization in the United States

Azar

Cruz-Mullane

Podd

et al. 2020

Pharmacoepidemiology and Drug

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“…This is ineffective if used clinically, as "weak" opioids are considered less likely to lead to addiction and adverse side effects, while this can be seen as untrue for buprenorphine. Reducing diversion may require developing new misuse-deterrent formulations of buprenorphine (112). More work needs to be done in determining drug interactions with buprenorphine that are the result of some interaction or inhibition with metabolizing enzymes like CYP3A4 and CYP2C8.…”

Section: Resultsmentioning

confidence: 99%

“…before the US), they quickly had cases of asphyxic deaths from misuse or concomitant drug ingestion of psychotropic drugs like benzodiazepines and neuroleptics (17,111). The Drug Abuse Warning Network stated that emergency department visits associated with buprenorphine have grown, with a significant amount resulting from nonmedical use (112). Benzodiazepine prescription was associated with increased risk of opioid overdose, mortality, and, in those using buprenorphine, decreased discontinuation of buprenorphine (101).…”

Section: Misuse Potentialmentioning

confidence: 99%

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An Examination of the Complex Pharmacological Properties of the Non-Selective Opioid Receptor Modulator Buprenorphine

Pande¹,

Piper²

2020

Preprint

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Buprenorphine, an analogue of thebaine, is a Schedule III opioid in the United States used for opioid-use disorder and as an analgesic. Research has shown drugs like buprenorphine have a complicated pharmacology with characteristics that challenge traditional definitions of terms like agonist, antagonist, and efficacy. Buprenorphine has a high affinity for the mu (MOR), delta (DOR), kappa (KOR), and intermediate for the nociceptin opioid receptors (NOR). Buprenorphine is generally described as a partial MOR agonist with limited activity and decreased response at the mu-receptor relative to full agonists. In opioid naïve patients, the drug’s analgesic efficacy is equivalent to a full MOR agonist, despite decreased receptor occupancy and the “ceiling effect” produced from larger doses. Some argue buprenorphine’s effects depend on the endpoint measured, as it functions as a partial agonist for respiratory depression, but a full-agonist for pain. Buprenorphine’s active metabolite, norbuprenorphine, attenuates buprenorphine's analgesic effects due to NOR binding and respiratory depressant effects. The method of administration impacts efficacy and tolerance when administered for analgesia. There have been eleven-thousand reports involving buprenorphine and minors (age < 19) to US poison control centers, the preponderance (89.2%) with children. The consequences of prenatal buprenorphine exposure in experimental animals and humans should continue to be carefully evaluated. In conclusion, buprenorphine’s characterization as only a partial mu-agonist is an oversimplification. Contemporary research shows the traditional explanation of the pharmacology of buprenorphine does not take into account changes to receptor theory, pharmacological terminology, route of administration, and biologically active major metabolites.

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“…Severe buprenorphine exposures including those resulting in life threatening symptoms or death reported to US poison centers increased 67% from 2011 to 2016. 8 The US . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.…”

mentioning

confidence: 99%

Rise and Regional Disparities in Buprenorphine Utilization in the United States

Pashmineh

Cruz-Mullane

Podd

et al. 2019

Preprint

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Aims: Buprenorphine is an opioid partial-agonist used to treat Opioid Use Disorders (OUD). While several state and federal policy changes have attempted to increase buprenorphine availability, access remains well below optimal levels. This study characterized how buprenorphine utilization in the United States has changed over time and whether there are regional disparities in distribution. Measurements: Buprenorphine weights distributed from 2007 to 2017 were obtained from the Drug Enforcement Administration. Data was expressed as the percent change and as the mg per person in each state. Separately, the formulations for prescriptions covered by Medicaid (2008 to 2018) were examined. Findings: Buprenorphine distributed to pharmacies increased about seven-fold (476.8 to 3,179.9 kg) while the quantities distributed to hospitals grew five-fold (18.6 to 97.6 kg) nationally from 2007 to 2017. Buprenorphine distribution per person was almost 20-fold higher in Vermont (40.4 mg/person) relative to South Dakota (2.1 mg/person). There was a strong association between the number of waivered physicians per 100K population and distribution per state (r(49) = +0.76, p < .0005). The buprenorphine/naloxone sublingual film (Suboxone) was the predominant formulation (92.6% of 0.31 million Medicaid prescriptions) in 2008 but this accounted for less than three-fifths (57.3% of 6.56 million prescriptions) in 2018. Conclusions: Although buprenorphine availability has substantially increased over the last decade, distribution was very non-homogenous across the US.

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Epidemiology of severe buprenorphine exposures reported to the U.S. Poison Centers

Cited by 7 publications

References 60 publications

Rise and regional disparities in buprenorphine utilization in the United States

Rise and regional disparities in buprenorphine utilization in the United States

An Examination of the Complex Pharmacological Properties of the Non-Selective Opioid Receptor Modulator Buprenorphine

Rise and Regional Disparities in Buprenorphine Utilization in the United States

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