Safety Events Associated with Tramadol Use Among Older Adults with Osteoarthritis

Abstract

Tramadol is a low-level opioid increasingly recommended to treat moderate-to-severe acute and chronic pain. Although characterized as having fewer opioid-related adverse events, the longer term safety of tramadol use among older adults has not been thoroughly documented. Thus, the primary objective was to examine the risk of safety events associated with chronic tramadol use compared to other chronic opioid use or no opioids among older adults with osteoarthritis. Safety events considered included: ‡3 emergency room (ER) visits, falls/hip fractures, cardiovascular (CVD) hospitalization, composite safety event hospitalization, and all-cause mortality. The study population included older adults ages ‡65 years diagnosed with osteoarthritis and classified into new or continuing tramadol use, new or continuing other opioid use, or nonuse. Inclusion criteria included: 6-month pre period and up to 33 months post period. Tramadol, other opioid, and no opioid users were 1:1 propensity-matched providing study populations of 25,899 within each category; 72% were new chronic opioid users. Multiple logistic regression or Cox proportional hazard ratios were used to document risk. Generally, tramadol users had fewer adverse event risks compared to other opioid users but higher risks than nonusers. New users of tramadol or other opioids had higher risks than continuing users. Tramadol use was associated with increased risk of multiple ER utilizations, falls/fractures, CVD hospitalizations, safety event hospitalizations, and mortality (new users only) compared to nonuse. Thus, although tramadol use may be appropriately recommended within a pain management strategy for older adults with osteoarthritis, careful monitoring for adverse safety events is warranted.

A harm reduction model to assess the impact of new treatments for pain over standard of care among patients with osteoarthritis

“…These findings, consistent with the substantial evidence of clinical and economic burden of standard of care therapies for treatment of OA, [11][12][13]24 suggest several takeaways and possible areas for further research. Patients initiated on NSAIDs and opioids as part of their OA treatments may experience severe and costly negative health outcomes, particularly in the presence of comorbid conditions in an elderly population, such as cardiovascular disease, hypertension, and kidney disease.…”

“…These negative clinical outcomes include an increased risk of opioid use disorder (OUD), constipation, fatigue, falls, fractures, and nausea, which have all been shown to result in significant humanistic and economic burden. [11][12][13] Given the clinical and economic burden associated with existing pain treatments for OA, there are new drug treatments currently in development that are anticipated to be alternatives to existing treatments. For example, on the short-term horizon, 2 anti-nerve growth factor antibodies, tanezumab and fasinumab, are in active development.…”

Future projections of opioid use and cost in patients with chronic osteoarthritis pain in Spain

“…Other side-effects related to opioid use could add even more burden to the NHS. 43,44 Particularly worrisome is the excess mortality associated with opioid use as described in the scientific literature, [45][46][47][48] mainly with strong opioids, which has also been observed in Spanish OA patients receiving strong opioids in the OPIOIDS study. 31,33 (A) (B) We used a real-world approach to project the future opioid burden for OA, based on recent opioid dispensing trends by the AEMPS, anticipated growth in the OA population and the opioid utilization rates observed in the real-world OPIOIDS study.…”

Chronic exposure to tramadol induces cardiac inflammation and endothelial dysfunction in mice

“…Despite its effectiveness in managing moderate to severe pain, tramadol has been associated with several tissues damage 10 , 12 , 13 . Additionally, chronic use of tramadol was linked to increased hospitalizations due to CVD 34 . Due to the paucity of data describing its actions on the cardiovascular system, we sought to investigate the effect of chronic tramadol treatment on mice heart and aorta.…”

“…On the other hand, Solomon and colleagues have reported increased risk for cardiovascular events in arthritis patients taking opioid 32 . Recently, Musich and co-workers demonstrated that 15% of chronic tramadol users had been hospitalized for cardiovascular diseases 34 . Since there is limited literature specifically describing the effects of tramadol on the heart and blood vessels, therefore, it is imperative to characterize the effect of tramadol on the cardiovascular system and the signaling pathways involved.…”