American Society of Consultant Pharmacists
View all recommendations from this societyReleased June 8, 2022
Don’t prescribe tramadol for older adults without due consideration of the potential risks and harms related to serotonergic excess, seizures, falls and drug-drug interactions.
The utilization of tramadol, a weak and mixed centrally acting opioid analgesic, has increased steadily over the past decade, a trend influenced by perceived safety advantages over opioid medications like morphine, oxycodone, and hydrocodone. However, a recent national study reported that older adults account for 33% of tramadol-associated emergency department visits and half of subsequent hospitalizations, suggesting that greater scrutiny of tramadol’s safety in this population is warranted.
Tramadol’s adverse effects such as sedation, and the potential for serotonin syndrome and hyponatremia are well recognized by clinicians, however tramadol-induced seizures and hypoglycemia are particularly harmful for older adults and may further elevate risk of falls and fractures.
The risk of tramadol’s clinically relevant adverse effects is heightened among patients with decreased renal function.
By way of brief review, the opioid receptor-mediated analgesic effects are mainly attributed to the active metabolite M1 (O-desmethyltramadol), whereas the inhibition of the neurotransmitter reuptake is caused by the parent drug. The metabolic conversion to the M1 metabolite is mediated primarily through CYP2D6 enzyme, which exhibits substantial genetic variability, consequently the pharmacological effect of tramadol is affected by drug-drug and drug-gene interactions.
Knowledge of this genetic variability to tramadol’s analgesic response and potential for drug-drug interactions may help optimize pain control and prevent emergence of adverse effects.
These items are provided solely for informational purposes and are not intended as a substitute for consultation with a medical professional. Patients with any specific questions about the items on this list or their individual situation should consult their physician.
How The List Was Created
(1–5)
A deprescribing task force led by chair (Manju T. Beier, Pharm D, BCGP, FASCP) was created by ASCP in November 2018. Members comprised of pharmacists practicing in academia, community and long-term care settings. The chair also invited pharmacists from international countries (Canada and Australia) where deprescribing initiatives have a strong focus and literature base. The collective experience and knowledge represent a focus on medication management, medication selection and reconciliation, and monitoring for drug-drug interactions (DDIs). The emphasis is on older adults no matter where they reside in step with ASCP’s mission.
Definition wise, deprescribing is a stepwise reduction of unnecessary or potentially inappropriate medications in concert with patient and family goals and wishes. We recognize that even with the best of intentions, many older adults are left on unnecessary and potentially dangerous or duplicative medications that might precipitate adverse events and other negative outcomes.
The task force prioritized formulation of the Choosing Wisely (CW) List, since the goals of CW intersect and overlap with deprescribing initiatives. The list was created to address general medication regimen review statements, and more importantly to address the paucity of statements that address DDIs with several incriminating medication therapeutic classes prescribed for older adults. After a review of published CW statements on www.choosingwisely.org and also a review of CW statements published by international countries, it was decided by consensus to have a strong emphasis on DDIs.
After several virtual meetings, the CW workgroup was divided into subgroups to formulate DDIs that have a strong evidence base in the literature and those that focus on CNS therapeutic classes, anticholinergic burden, heightened bleeding risk, and other pivotal pharmacokinetic and pharmacodynamic DDIs. For each statement the group formulated a rationale that was evidence-based accompanied with several recent, pertinent references. The compiled list (after several virtual meetings and email discussion) was further reduced to top ten statements with the strongest evidence base and practice trends on medication management in older adults.
The top five list was selected by consensus for initial submission.
Attached is a recently published guest editorial in ASCP’s journal that highlights the emphasis on DDIs.
Beier MT. Vigilance of Drug-Drug Interactions to Mitigate ADRs: Front and Center for Pharmacists (Guest Editorial). Sr Care Pharm 2020; 35:336-7.
(6–10)
A deprescribing task force led by chair (Manju T. Beier, Pharm D, BCGP, FASCP) was created by ASCP in November 2018. Members comprised of pharmacists practicing in academia, community and long-term care settings. The chair also invited pharmacists from international countries (Canada and Australia) where deprescribing initiatives have a strong focus and literature base. The collective experience and knowledge represent a focus on medication management, medication selection and reconciliation, and monitoring for drug-drug interactions (DDIs). The emphasis for all our statements is on older adults no matter where they reside in step with ASCP’s mission. Our first 5 CW statements were published in May 2021.
As previously addressed, the rationale for the new 2022 list (statements 6–10) includes one medication review statement in older adults with limited life expectancy, and three statements emphasizing the adverse combination of CNS medications that have a strong evidence base in the literature including tramadol’s potential for greater harm than benefit for pain relief, especially in older adults. We had previously highlighted pharmacodynamic DDIs for heightened bleeding risk, and this time our statement addresses the complexity of pharmacokinetic DDIs with Direct Oral Anticoagulants (DOACs).
Sources
Bush DM. The DAWN Report: Emergency Department Visits for Drug Misuse or Abuse Involving the Pain Medication Tramadol. (2015). Substance Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and Quality. Rockville, MD.
Fournier JP, Azoulay L, Yin H, Montastruc JL, Suissa S. Tramadol use and the risk of hospitalization for hypoglycemia in patients with noncancer pain. JAMA Intern Med 2015;175(2):186-93.
Bigal LM, Bibeau K, Dunbar S. Tramadol Prescription over a 4-Year Period in the USA. Curr Pain Headache Rep 2019;23(10):76.
Hamilton WG, Gargiulo JM, Parks NL. Using pharmacogenetics to structure individual pain management protocols in total knee arthroplasty. Bone Joint J 2020;102-B(6_Supple_A):73-78.
Robertson SS, Mouksassi MS, Varin F. Population pharmacokinetic/pharmacodynamic modeling of o-desmethyl tramadol in young and elderly healthy volunteers. Drugs Aging 2019;36(8):747-758.
Owsiany MT, Hawley CE, Triantafylidis LK, Paik JM. Opioid management in older adults with chronic kidney disease: a review. Am J Med 2019;132(12):1386-1393.
Wei J, Lane NE, Bolster MB, et al. Association of tramadol use with risk of hip fracture. J Bone Miner Res. 2020;35(4):631-640.
Musich S, Wang SS, Schaeffer JA, Slindee L, Kraemer S, Yeh CS. Safety events associated with tramadol use among older adults with osteoarthritis. Population Health Management. 2021;24(1):122-132.
