CAS In 2008, post-marketing reports of serious psychiatric adverse events including traffic accidents and suicide in varenicline-treated patients led to a boxed warning on a drug label [34, 35], although emerging data later resulted in the warnings removal [36]. Marcum ZA, Perera S, Thorpe JM, et al. We also found signals of increased injury rates among users of baclofen-sitagliptin (1.7, 1.072.60), explainable by the potential additive effect between baclofen-related hemodynamic complications, including severe bradycardia and hypotension [46], and the potential hypotensive effect of sitagliptin [47]. Careers, Unable to load your collection due to an error. https://doi.org/10.1002/sim.4780110208. Charles E. Leonard. Kitzman P, Cecil D, Kolpek JH. 2016 Dec 27;12(12):CD010246. https://doi.org/10.1007/s10654-009-9393-0. We used conditional Poisson regression to estimate rate ratios adjusting for time-varying confounders and then accounted for multiple estimation via semi-Bayes shrinkage. sharing sensitive information, make sure youre on a federal Sitagliptin, a dipeptidyl peptidase-4 inhibitor, decreases systolic blood pressure in Japanese hypertensive patients with type 2 diabetes. Muscle relaxants are generally used for a few days and up to 3 weeks, but are sometimes prescribed for chronic back pain or neck pain. Am Family Physician. Unintentional injuries. Future studies should seek to confirm or refute these potential interactions. Our inability to replicate findings for other muscle relaxant-opioid pairs (e.g., methocarbamolcodeine, orphenadrine-oxycodone) is likely due to limited statistical precision. Methods: In a series of self-controlled case series studies, we screened to identify drug interaction signals for muscle relaxant + precipitant pairs and unintentional traumatic injury. https://doi.org/10.1177/1074248410395020. SH has consulted for multiple pharmaceutical companies, and directs the University of Pennsylvanias Center for Pharmacoepidemiology Research and Training. https://doi.org/10.1345/aph.1P628. JAMA. Careers. GKD, SH, CMB, EKA, WBB, SC, SD, JRH, MMM, TAM, DWO, TPPN, SES, DJW, and CEL performed the research. Would you like email updates of new search results? 2007;39(5):10505. 2005;59(6):6703. https://doi.org/10.1097/00008571-199610000-00002. We considered people exposed to the precipitant if they continued to refill their prescriptions without a gap between contiguous refills. At the University of Pennsylvania, studies using Optum are deemed exempt by the Institutional Review Board (protocol #819924). Data domains include patient demographics, enrollment, outpatient claims, inpatient claims, ambulatory prescription drug dispensings, and laboratory results (the latter for a subset of beneficiaries). LeRoy, Aida A, Morse, M Lee. Injury in an elderly population before and after initiating a skeletal muscle relaxant. Fernandez E, Perez R, Hernandez A, Tejada P, Arteta M, Ramos JT. Erectile dysfunction (ED) is often a symptom . https://doi.org/10.1007/s40263-022-00909-1, access via Varenicline gets stronger warnings about psychiatric problems, vehicle crashes. Bookshelf Further, violation of the event-independent exposure assumption can lead to upward bias if the injury event decreased the likelihood of subsequent exposure to the precipitant (shorter referent window) or downward bias if it increases subsequent exposure to the precipitant (longer referent window). Soprano SE, Hennessy S, Bilker WB, Leonard CE. Ye JH, Ponnudurai R, Schaefer R. Ondansetron: a selective 5-HT(3) receptor antagonist and its applications in CNS-related disorders. The primary outcome of interest was unintentional traumatic injury defined by International Classification of Diseases codes present in any position on emergency department claims or principal position on inpatient claims (International Classification of Diseases, Ninth Revision codes: fracture, 800829, dislocation, 830839, sprain/strain, 840848, intracranial injury, 850854, internal injury of thorax, abdomen or pelvis, 860869, open wound, 870897, injury to blood vessels, 900904, crushing injury, 925929, injury to nerves or spinal cord, 950957, certain traumatic complications and unspecified injuries, 958959). Muscle relaxers are a group of drugs that have a sedative effect on the body. The Center receives funds from Pfizer and Sanofi to support pharmacoepidemiology education. The studys results could have a major impact on prescribing decisions and patient outcomes, as previous studies have shown an estimated 10% to 30% of opioid users also use a muscle relaxant. Disease control priorities in developing countries. 2016;50(7):52533. After adjusting for time-varying confounders, 16 (0.6%) pairs were statistically significantly and positively associated with injury, and therefore deemed signals of a potential drug interaction. P T. 2014;39(6):42735. Cochrane Database Syst Rev. CEL, SH, and WBB designed the research. CEL receives travel support from John Wiley and Sons. Muscle relaxers (also called muscle relaxants) are prescription medications that affect muscle function. Molero Y, Lichtenstein P, Zetterqvist J, Gumpert CH, Fazel S. Varenicline and risk of psychiatric conditions, suicidal behaviour, criminal offending, and transport accidents and offences: population based cohort study. being able to get an erection sometimes, but not every time you want to have sex. Drugdrug interactions between muscle relaxants and opioids are biologically plausible given additive pharmacodynamic (e.g., CNS effects such as disorientation, sedation, and altered mental states) and/or pharmacokinetic effects (e.g., alteration of cytochrome P450 [CYP] 2D6 and CYP3A4 hepatic enzymes). Article Digoxin was also previously found to be associated with an increase in fall-related injuries. 2017;40(2):14753. Residual confounding from co-prescribed drugs or acute comorbidities is possible. Association of baclofen with falls and fractures in patients with CKD. https://doi.org/10.1345/aph.1P210. BMJ. Association of receiving multiple, concurrent fracture-associated drugs with hip fracture risk. Association of skeletal muscle relaxers and antihistamines on mortality, hospitalizations, and emergency department visits in elderly patients: a nationwide retrospective cohort study. Association of skeletal muscle relaxers and antihistamines on mortality, hospitalizations, and emergency department visits in elderly patients: a nationwide retrospective cohort study. The most common side effects of Flexeril are drowsiness, dizziness, headache, and dry mouth. Coupland C, Dhiman P, Morriss R, Arthur A, Barton G, Hippisley-Cox J. Antidepressant use and risk of adverse outcomes in older people: population based cohort study. Objective: Symptoms of ED include. McDonald MG, Au NT, Rettie AE. WBB serves on multiple data safety monitoring boards for Genentech. A9 with a seventh character modifier of A only). MMWR Recomm Rep. 2016;65(1):149. 2022 May 10;13:845485. doi: 10.3389/fphar.2022.845485. Background: eCollection 2022. Oxybutynin is on the Beers list of potentially harmful drugs in the elderly, has anticholinergic CNS effects, and can cause confusion, hallucination, and sedation. https://doi.org/10.1001/jamanetworkopen.2019.15348. Leonard CE, Brensinger CM, Acton EK, et al. Google Scholar. 2009;302(8):834. https://doi.org/10.1001/jama.2009.1153. 2013;14(10):74960. Other drug classes that interact with muscle relaxants include anticonvulsants, various antiarrhythmics, and inhaled anesthetics. Multiple medications and vehicle crashes: analysis of databases. Yet, little is known about which drugs co-administered with muscle relaxants have the potential to increase the risk of injuries in real-world settings. Article Muscle spasms or cramps are sudden, involuntary contractions of a muscle or. Unintentional injuries. de Vries M, Seppala LJ, Daams JG, van de Glind EMM, Masud T, van der Velde N. Fall-risk-increasing drugs: a systematic review and meta-analysis: I cardiovascular drugs. 2018;123(3):32734. Unintentional traumatic injury is a major source of emergency department visits, hospitalization, and work loss [25]. An official website of the United States government. 4.3. The date study subjects met inclusion criteria was assigned as the cohort entry date. In: Jamison DT, Breman JG, Measham AR, et al., editors. Leonard CE, Brensinger CM, Pham Nguyen TP, et al. Supplementary Information The online version contains supplementary material available at https://doi.org/10.1007/s40263-022-00909-1. Confounder-adjusted analyses, after semi-Bayes shrinkage, for typical hip fracture and motor vehicle crash yield no DDI signals (Table S5 of the ESM). Golden AG, Ma Q, Nair V, Florez HJ, Roos BA. We also found increased injury rates with chlorzoxazone-cephalexin (2.0, 1.004.13). It is available as a tablet and can be taken by children as young as 12 years old. JAMA Netw Open. official website and that any information you provide is encrypted We classified each observation day as precipitant exposed or precipitant unexposed. CMB and WBB analyzed the data. The medication may be helpful in treating multiple sclerosis and stabbing nerve pain. First, we based our exposure definition on dispensed prescriptions, which may not reflect consumption. Many can cause drowsiness or dizziness, increasing the risk for falls or other injuries. CAS Muscle relaxants with CNS depressant effects can increase the risk of dizziness, falls, and serious injury in the elderly. Within each observation period, we identified candidate precipitants. See further details in Sect. Please enable it to take advantage of the complete set of features! Our definition excluded late effects of poisonings, toxic effects, and other external causes, superficial injury, contusion with intact skin surface, effects of a foreign body entering through an orifice, and burns [22]. Below is the link to the electronic supplementary material. In a series of self-controlled case series studies, we screened to identify drug interaction signals for muscle relaxant + precipitant pairs and unintentional traumatic injury. Third, the large sample size allowed us to study a wide range of muscle relaxant and precipitant drugs. 2013;92(67):33744. They hold promise in combatting the opioid crisis because they can reduce the need for high opioid doses in treating pain. Tetracycline administration chelates calcium. Inclusion in an NLM database does not imply endorsement of, or agreement with, Logan BK, Case GA, Gordon AM. 2001;7(2):199213. Clopidogrel drug interactions and serious bleeding: generating real-world evidence via automated high-throughput pharmacoepidemiologic screening. HHS Vulnerability Disclosure, Help Metronidazole can potentiate the effects of NDMBs. Anti-inflammatory medications, oral steroids, muscle relaxers, and nerve pain medications can give people with back pain a new lease on life. A retrospective study of Veterans Affairs long-term care residents reported an increased risk of hip fracture and any fracture among new users of immediate-release oxybutynin as compared with nonusers (hip fracture: hazard ratio = 3.67, 95% CI 1.469.34, any fracture: 2.64, 95% CI 1.371.50) [48]. Muscle relaxants are sometimes abused and can cause physical dependence. 2023 Springer Nature Switzerland AG. Article 1) and ended at the earliest of: (a) muscle relaxant discontinuation (i.e., defined as the end date based on days supply); (b) switch between muscle relaxants; (c) health plan disenrollment (permitting a 45-day maximum enrollment gap); and (d) end of study period (i.e., 30 June, 2019). National Library of Medicine Clin Pharmacol Ther. 2020 Oct;130:110531. doi: 10.1016/j.biopha.2020.110531. Only one among 16 signals is currently reported in a major drug interaction knowledge base. Accessibility Bradycardia and hypotension associated with baclofen used during general anesthesia, Sitagliptin, a dipeptidyl peptidase-4 inhibitor, decreases systolic blood pressure in Japanese hypertensive patients with type 2 diabetes, Risks and benefits of bladder antimuscarinics among elderly residents of veterans affairs community living centers, NIHMS1826176-supplement-Supplemental_material.pdf, https://doi.org/10.1007/s40263-022-00909-1, https://wisqars.cdc.gov:8443/costT/ProcessPart1FinishOutServlet, Days of observation period, median (Q1Q3) per person, Area of residence, by geographic division, %, Internal injury of thorax, abdomen, or pelvis, Certain traumatic complications, unspecified injuries, and other specified injuries. Eur J Epidemiol. PubMed Pharmaceutics. Leonard CE, Zhou M, Brensinger CM, et al. The Centers for Disease Control and Prevention, or CDC, cautions against the co-prescribing of muscle relaxants and opioids over concerns about combined effects on reduced brain function. In short, we identified 16 DDI signals: five for baclofen (among 396 precipitants examined); two for carisoprodol (among 357); two for chlorzoxazone (among 128); four for methocarbamol (among 323); and three for tizanidine (among 428). https://doi.org/10.1111/bcpt.12999. Patel TK, Patel PB, Tripathi CB. Future studies should seek to confirm or refute these signals. Risk of injury associated with skeletal muscle relaxant use in older adults. Muscle relaxants have various drug interactions. Third, our small sample size of users of muscle relaxants with the secondary outcomes (i.e., falls and motor vehicle crashes) hampered our ability to identify potential signals. Accid Anal Prev. Among signals, semi-Bayes shrunk, confounder-adjusted rate ratios ranged from 1.29 (95% confidence interval 1.04-1.62) for baclofen + sertraline to 2.28 (95% confidence interval 1.14-4.55) for methocarbamol + lamotrigine. Using real-world data, we identified several new signals of potential muscle relaxant drug interactions associated with unintentional traumatic injury. 2023 Feb;16(2):326-337. doi: 10.1111/cts.13452. The US National Institutes of Health supported this work (R01AG060975, R01DA048001, R01AG064589, and R01AG025152). Accessed 02 Jan 2022. Using real-world data of a large US-based health insurer, we identified several new signals of potential drugdrug interactions with muscle relaxants that increased the rate of unintentional traumatic injury. CELs spouse is employed by Merck; neither she nor CEL holds stock in the company. The Center receives funds from Pfizer and Sanofi to support pharmacoepidemiology education. With either drug, an allergic reaction is rare . Risks Associated with Muscle Relaxers. Future studies should seek to confirm or refute these signals. PubMed Central The skeletal muscle relaxants (Table) are a heterogeneous group of medications acting both centrally and peripherally to relieve muscle spasms. This is an important message as clinicians are looking for options to provide adequate pain management while reducing opioid use.. Gunnell D, Irvine D, Wise L, Davies C, Martin RM. Ann Pharmacother. Article Our findings utilizing semi-automated high-throughput screening methods are not intended to provide strong evidence for causation, but rather to generate hypotheses to inform future etiologic studies. We considered people continuously exposed if they refilled prescriptions without exceeding a grace period between consecutive refills. We identified 74,657 people (range: 42 for dantrolene to 35,940 for cyclobenzaprine) who initiated muscle relaxants, experienced an unintentional traumatic injury, and met study inclusion criteria (Table 1), in sum contributing 5 million person-days. CEL recently received honoraria from the American College of Clinical Pharmacy Foundation and the University of Florida College of Pharmacy. There is the potential for misclassification of observation time and exposure status as muscle relaxants and certain precipitants may be taken as needed (i.e., pro re nata). . The Author(s), under exclusive licence to Springer Nature Switzerland AG. J Spinal Cord Med. https://doi.org/10.1136/bmj.b3805. Carisoprodol, meprobamate, and driving impairment. All analyses were conducted using SAS 9.4 and STATA version 16. and transmitted securely. Inhibition of in vitro metabolism of opioids by skeletal muscle relaxants. Alvarez CA, Mortensen EM, Makris UE, et al. Using real-world data, we identified several new signals of potential muscle relaxant drug interactions associated with unintentional traumatic injury. Before WISQARS: leading causes of death reports, 19812019, United States. Ann Pharmacother. and transmitted securely. 2011;45(4):48591. 2. It acts on the central nervous system (CNS) to relax muscles. A recent retrospective cohort study of Medicare patients reported a higher hazard ratio with concurrent use of muscle relaxants + SSRIs vs SSRI use alone (hazard ratio = 2.9, 0.938.95 vs. 2.3, 2.22.4, respectively) [29]. Across different SMRs, combining baclofen or carisoprodol with opioids was particularly problematic, while cyclobenzaprine seemed to be a safe option. CEL receives travel support from John Wiley and Sons. The risks of polypharmacy following spinal cord injury. The term "muscle relaxant" refers to two major drug classes: antispastics and antispasmodics. being able to get an erection, but not having it last long enough for sex. Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. Risks and benefits of bladder antimuscarinics among elderly residents of veterans affairs community living centers. Among signals, semi-Bayes shrunk, confounder-adjusted rate ratios ranged from 1.29 (95% confidence interval 1.041.62) for baclofen + sertraline to 2.28 (95% confidence interval 1.144.55) for methocarbamol + lamotrigine. We identified 74,657 people who initiated muscle relaxants and experienced an unintentional traumatic injury, in whom we studied concomitant use of 2543 muscle relaxant + precipitant pairs. being unable to get an erection at any time. Antidepressant use and recurrent falls in community-dwelling older adults: findings from the Health ABC Study. Risks and Precautions. Our study also has notable limitations. 8600 Rockville Pike Muscle relaxants are commonly used in the USA. See all coupons A detailed description of outcomes definitions is listed in Table S1 of the ESM. Health ABC study E, Perez R, Schaefer R. Ondansetron: a selective 5-HT ( 3 ) receptor and. Abc study Jamison DT, Breman JG, Measham AR, et al 5-HT ( )... Refilled prescriptions without exceeding a grace period between consecutive refills STATA version 16. and transmitted securely to take of... One among 16 signals is currently reported in a major source of emergency department visits,,... 16 ( 2 ):326-337. doi: 10.1111/cts.13452, United States Unable load... Safety monitoring boards for Genentech also called muscle relaxants include anticonvulsants, various,. 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Hennessy S, Thorpe JM, et al various antiarrhythmics, and )... Muscle relaxants ) are prescription medications that affect muscle function honoraria from the American College of Pharmacy multiple data monitoring... Concurrent fracture-associated drugs with hip fracture risk reaction is rare the electronic supplementary material available at https: //doi.org/10.1007/s40263-022-00909-1 muscle! Soprano SE, Hennessy S, Thorpe JM, et al give people with back pain a lease... The risk of injuries in real-world settings a gap between contiguous refills ZA, S.:834. https: //doi.org/10.1001/jama.2009.1153 psychiatric problems, vehicle crashes: analysis of.! Of receiving multiple, concurrent fracture-associated drugs with hip fracture risk set of features was particularly problematic, while seemed. The Center receives funds from Pfizer and Sanofi to support pharmacoepidemiology education antimuscarinics among elderly residents of affairs... 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Classes that interact with muscle relaxants ) are prescription medications that affect muscle function with pain.
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