Do Formulation and Dose of Long-Term Opioid Therapy Contribute to Risk of Adverse Events among Older Adults?

Abstract

BACKGROUND: Chronic non-cancer pain (CNCP) is highly prevalent in older adults and long-term opioid therapy (LTOT) has been used to manage chronic pain. However, the safety of LTOT among older adults with CNCP is not well-established and there is a need to identify therapyrelated risk factors of opioid-related adverse events among older adults. OBJECTIVE: To evaluate the relationship between opioid dose and formulation and the risk of opioid-related adverse events among Medicare-eligible older adults on LTOT. DESIGN: Nested case-control study. PARTICIPANTS: Older Medicare beneficiaries (N=35,189) who received > 3 opioid prescriptions with a total dayssupply of >45 days within a 90-day period for CNCP between 2012 and 2016. MAIN MEASURES: This study utilized Medicare 5% medical and prescription claims data. Outcome measures included opioid-induced respiratory depression (OIRD), opioid overdose, all-cause mortality, and a composite outcome, defined as the first occurrence of any of the previous three events. Key independent variables were opioid formulation and opioid dose (measured in morphine milligram equivalents (MME)) prescribed during LTOT. KEY RESULTS: Seventy-four OIRD, 133 overdose, 982 all-cause mortality, and 1122 composite outcome events were observed during follow-up. In unadjusted analyses, the use of combination opioids (OR: 4.52 [95%CI: 1.51-13.47]) was significantly associated with OIRD compared to short-acting (SA) opioids. In adjusted analyses, opioidrelated adverse events were significantly associated with the use of LA (overdose OR: 13.00 [95%CI: 1.30-130.16] and combination opioids (overdose OR: 6.27 [95%CI: 1.91-20.55]; mortality OR: 2.75 [95%CI: 1.87-4.04]; composite OR: 2.82 [95%CI: 2.01-3.96]) when compared to SA opioids. When compared to an average dose of less than 20 MME, outcomes were significantly associated with doses of 20-50 MME (mortality OR

Comparative Study of Opioid Initiation With Tramadol, Short-acting Hydrocodone, or Short-acting Oxycodone on Opioid-related Adverse Outcomes Among Chronic Noncancer Pain Patients

“…43 Likewise, the literature is consistent on elevated risks of opioidrelated adverse outcomes when prescribing long-acting opioids, which accounted for 40% of the high-dose other opioid categories in our study. 43,52,53 Our study reported higher risks of opioid-related adverse outcomes for the combination of opioids with and without tramadol, although the estimates had higher magnitudes for nontramadol combination. These findings suggest that more caution is needed when coprescribing more than 1 opioid, and strategies such as opioid rotation, which is shown to help with pain control in cancer patients, 54 may be evaluated for chronic noncancer pain.…”

“…In a study conducted using Medicare data on individuals with long-term opioid therapy, combination opioid therapy had a 5-fold increase in the odds of opioid overdose compared with short-acting opioids. 52 In comparison to no opioid therapy, a combination of short-acting and long-acting was associated with a 384% increase in the hazard of overdose, whereas shortacting only had a 69% higher hazard of overdose. 43 Likewise, the literature is consistent on elevated risks of opioidrelated adverse outcomes when prescribing long-acting opioids, which accounted for 40% of the high-dose other opioid categories in our study.…”

“…The highest risks of opioid overdoses and opioid use disorders were observed when persons combined opioids leading to high doses or used high-dose opioids that did not include one of the 3 target opioids. In a study conducted using Medicare data on individuals with long-term opioid therapy, combination opioid therapy had a 5-fold increase in the odds of opioid overdose compared with short-acting opioids 52. In comparison to no opioid therapy, a combination of short-acting and long-acting was associated with a 384% increase in the hazard of overdose, whereas short-acting only had a 69% higher hazard of overdose 43.…”

Predictors of older adults' chronic pain in the context of opioid adverse drug events

“…Comorbid factors such as history of opioid-induced respiratory depression, renal insufficiency, or mental illness predict increased risk of death with opioid use, as does low income (Salkar et al, 2021). Opioid dose greater than 20 milliequivalents of morphine sulfate, or a long-acting opioid, or a combination short/long-acting opioid all predict increased risk of death in older adults (Salkar et al, 2021).…”

“…Comorbid factors such as history of opioid-induced respiratory depression, renal insufficiency, or mental illness predict increased risk of death with opioid use, as does low income (Salkar et al, 2021). Opioid dose greater than 20 milliequivalents of morphine sulfate, or a long-acting opioid, or a combination short/long-acting opioid all predict increased risk of death in older adults (Salkar et al, 2021). Medicare part D beneficiaries with a history of chronic pain, fibromyalgia, and/or fatigue who filled an opioid prescription had 5.65 times greater odds of filling a high-dose (greater than 120 milliequivalents of morphine sulfate) opioid prescription (Maciejewski et al, 2021).…”