Opioid tolerance and clinically recognized opioid poisoning among patients prescribed extended-release long-acting opioids.
Adult
Aged
Analgesics, Opioid
/ administration & dosage
Delayed-Action Preparations
/ administration & dosage
Dose-Response Relationship, Drug
Drug Labeling
/ standards
Drug Overdose
/ epidemiology
Drug Prescriptions
/ standards
Drug Tolerance
Female
Humans
Male
Middle Aged
Pain
/ diagnosis
Pain Management
/ methods
Pain Measurement
/ standards
Practice Patterns, Physicians'
/ standards
Risk Assessment
/ standards
Time Factors
extended-release long-acting opioids
opioid poisoning
opioid tolerance
pharmacoepidemiology
Journal
Pharmacoepidemiology and drug safety
ISSN: 1099-1557
Titre abrégé: Pharmacoepidemiol Drug Saf
Pays: England
ID NLM: 9208369
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
26
09
2017
revised:
30
03
2018
accepted:
07
05
2018
pubmed:
12
6
2018
medline:
25
2
2020
entrez:
12
6
2018
Statut:
ppublish
Résumé
In recognition of potential for increased overdose risk, drug labels for extended-release and long-acting (ER/LA) opioids emphasize the need for established opioid tolerance prior to initiating high dosages. Describe the proportion of patients with opioid tolerance prior to initiation of 90 morphine milligram equivalents (MME) ER/LA opioids and examine subsequent risk of opioid poisoning. We used Truven Health Analytics' MarketScan Databases (2006-2015) to identify patients initiating ER/LA opioids ≥90 MME. We examined prescription histories and describe the proportion of initiators with opioid tolerance (defined as ≥7 days of 60 MME in the prior 14 days). We adjusted for age, sex, year of initiation, and baseline comorbidities using inverse probability of treatment weighted Cox proportional hazards models. We estimated adjusted hazard ratios and 95% confidence intervals for the effect of opioid tolerance on the risk of clinically recognized opioid poisoning (based on diagnosis codes) in specific periods (0-7, 8-30, 31-90, and 91-365 days) following initiation. Among 372 038 initiators, 38% did not meet opioid tolerance criteria. The proportion of nontolerant initiators was highest among those initiating methadone (44%) and fentanyl (42%). Nontolerant patients were 37% more likely to be diagnosed with opioid poisoning (adjusted hazard ratios = 1.37 [1.07, 1.76]) in the week following ER/LA initiation. Over one-third of patients initiating ≥90 MME ER/LA opioids did not have evidence of opioid tolerance. The 7 days following high dose ER/LA initiation may represent a high-risk period for clinically diagnosed opioid poisoning in patients who do not have prior opioid tolerance.
Sections du résumé
BACKGROUND
In recognition of potential for increased overdose risk, drug labels for extended-release and long-acting (ER/LA) opioids emphasize the need for established opioid tolerance prior to initiating high dosages.
OBJECTIVES
Describe the proportion of patients with opioid tolerance prior to initiation of 90 morphine milligram equivalents (MME) ER/LA opioids and examine subsequent risk of opioid poisoning.
METHODS
We used Truven Health Analytics' MarketScan Databases (2006-2015) to identify patients initiating ER/LA opioids ≥90 MME. We examined prescription histories and describe the proportion of initiators with opioid tolerance (defined as ≥7 days of 60 MME in the prior 14 days). We adjusted for age, sex, year of initiation, and baseline comorbidities using inverse probability of treatment weighted Cox proportional hazards models. We estimated adjusted hazard ratios and 95% confidence intervals for the effect of opioid tolerance on the risk of clinically recognized opioid poisoning (based on diagnosis codes) in specific periods (0-7, 8-30, 31-90, and 91-365 days) following initiation.
RESULTS
Among 372 038 initiators, 38% did not meet opioid tolerance criteria. The proportion of nontolerant initiators was highest among those initiating methadone (44%) and fentanyl (42%). Nontolerant patients were 37% more likely to be diagnosed with opioid poisoning (adjusted hazard ratios = 1.37 [1.07, 1.76]) in the week following ER/LA initiation.
CONCLUSIONS
Over one-third of patients initiating ≥90 MME ER/LA opioids did not have evidence of opioid tolerance. The 7 days following high dose ER/LA initiation may represent a high-risk period for clinically diagnosed opioid poisoning in patients who do not have prior opioid tolerance.
Substances chimiques
Analgesics, Opioid
0
Delayed-Action Preparations
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
39-47Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR001111
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG050733
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA191454
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL118255
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG023178
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2018 John Wiley & Sons, Ltd.