Paracetamol Combination Therapy for Back Pain and Osteoarthritis: A Systematic Review and Meta-Analyses.
Journal
Drugs
ISSN: 1179-1950
Titre abrégé: Drugs
Pays: New Zealand
ID NLM: 7600076
Informations de publication
Date de publication:
28 Jun 2024
28 Jun 2024
Historique:
accepted:
06
06
2024
medline:
28
6
2024
pubmed:
28
6
2024
entrez:
27
6
2024
Statut:
aheadofprint
Résumé
Although paracetamol (acetaminophen) combined with other analgesics can reduce pain intensity in some pain conditions, its effectiveness in managing low back pain and osteoarthritis is unclear. This systematic review investigated whether paracetamol combination therapy is more effective and safer than monotherapy or placebo in low back pain and osteoarthritis. Online database searches were conducted for randomised trials that evaluated paracetamol combined with another analgesic compared to a placebo or the non-paracetamol ingredient in the combination (monotherapy) in low back pain and osteoarthritis. The primary outcome was a change in pain. Secondary outcomes were (serious) adverse events, changes in disability and quality of life. Follow-up was immediate (≤ 2 weeks), short (> 2 weeks but ≤ 3 months), intermediate (> 3 months but < 12 months) or long term (≥ 12 months). A random-effects meta-analysis was conducted. Risk of bias was assessed using the original Cochrane tool, and quality of evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Twenty-two studies were included. Pain was reduced with oral paracetamol plus a non-steroidal anti-inflammatory drug (NSAID) at immediate term in low back pain (paracetamol plus ibuprofen vs ibuprofen [mean difference (MD) - 6.2, 95% confidence interval (CI) -10.4 to -2.0, moderate evidence]) and in osteoarthritis (paracetamol plus aceclofenac vs aceclofenac [MD - 4.7, 95% CI - 8.3 to - 1.2, moderate certainty evidence] and paracetamol plus etodolac vs etodolac [MD - 15.1, 95% CI - 18.5 to - 11.8; moderate certainty evidence]). Paracetamol plus oral tramadol reduced pain compared with placebo at intermediate term for low back pain (MD - 11.7, 95% CI - 19.2 to - 4.3; very low certainty evidence) and osteoarthritis (MD - 6.8, 95% CI - 12.7 to -0.9; moderate certainty evidence). Disability scores improved in half the comparisons. Quality of life was infrequently measured. All paracetamol plus NSAID combinations did not increase the risk of adverse events compared to NSAID monotherapy. Low-to-moderate quality evidence supports the oral use of some paracetamol plus NSAID combinations for short-term pain relief with no increased risk of harm for low back pain and osteoarthritis compared to its non-paracetamol monotherapy comparator.
Sections du résumé
BACKGROUND AND OBJECTIVE
OBJECTIVE
Although paracetamol (acetaminophen) combined with other analgesics can reduce pain intensity in some pain conditions, its effectiveness in managing low back pain and osteoarthritis is unclear. This systematic review investigated whether paracetamol combination therapy is more effective and safer than monotherapy or placebo in low back pain and osteoarthritis.
METHODS
METHODS
Online database searches were conducted for randomised trials that evaluated paracetamol combined with another analgesic compared to a placebo or the non-paracetamol ingredient in the combination (monotherapy) in low back pain and osteoarthritis. The primary outcome was a change in pain. Secondary outcomes were (serious) adverse events, changes in disability and quality of life. Follow-up was immediate (≤ 2 weeks), short (> 2 weeks but ≤ 3 months), intermediate (> 3 months but < 12 months) or long term (≥ 12 months). A random-effects meta-analysis was conducted. Risk of bias was assessed using the original Cochrane tool, and quality of evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE).
RESULTS
RESULTS
Twenty-two studies were included. Pain was reduced with oral paracetamol plus a non-steroidal anti-inflammatory drug (NSAID) at immediate term in low back pain (paracetamol plus ibuprofen vs ibuprofen [mean difference (MD) - 6.2, 95% confidence interval (CI) -10.4 to -2.0, moderate evidence]) and in osteoarthritis (paracetamol plus aceclofenac vs aceclofenac [MD - 4.7, 95% CI - 8.3 to - 1.2, moderate certainty evidence] and paracetamol plus etodolac vs etodolac [MD - 15.1, 95% CI - 18.5 to - 11.8; moderate certainty evidence]). Paracetamol plus oral tramadol reduced pain compared with placebo at intermediate term for low back pain (MD - 11.7, 95% CI - 19.2 to - 4.3; very low certainty evidence) and osteoarthritis (MD - 6.8, 95% CI - 12.7 to -0.9; moderate certainty evidence). Disability scores improved in half the comparisons. Quality of life was infrequently measured. All paracetamol plus NSAID combinations did not increase the risk of adverse events compared to NSAID monotherapy.
CONCLUSIONS
CONCLUSIONS
Low-to-moderate quality evidence supports the oral use of some paracetamol plus NSAID combinations for short-term pain relief with no increased risk of harm for low back pain and osteoarthritis compared to its non-paracetamol monotherapy comparator.
Identifiants
pubmed: 38937394
doi: 10.1007/s40265-024-02065-w
pii: 10.1007/s40265-024-02065-w
doi:
Types de publication
Journal Article
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. Crown.
Références
GBD 2017 Disease and Injury Incidence and Prevalence Collaborators, James SL, Abate D, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392(10159):1789–858.
Ferreira ML, de Luca K, Haile LM, et al. Global, regional, and national burden of low back pain, 1990–2020, its attributable risk factors, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021. Lancet Rheumatol. 2023;5(6):e316–29.
Qaseem A, McLean RM, O’Gurek D, Batur P, Lin K, Kansagara DL, et al. Nonpharmacologic and pharmacologic management of acute pain from non-low back, musculoskeletal injuries in adults: a clinical guideline from the American College of Physicians and American Academy of Family Physicians. Ann Intern Med. 2020;173(9):739–48.
pubmed: 32805126
Abdel Shaheed C, Ferreira G, Dmitritchenko A, McLachlan AJ, Day RO, Saragiotto B, et al. The efficacy and safety of paracetamol for pain relief: an overview of systematic reviews. Med J Aust. 2021;214(7):324–31.
pubmed: 33786837
Leopoldino AO, Machado GC, Ferreira PH, et al. Paracetamol versus placebo for knee and hip osteoarthritis. Cochrane Database Syst Rev. 2019;2(2):CD013273.
pubmed: 30801133
Williams CM, Maher CG, Latimer J, et al. Efficacy of paracetamol for acute low-back pain: a double-blind, randomised controlled trial. Lancet. 2014;384(9954):1586–96.
pubmed: 25064594
Australian Commission on Safety and Quality in Health Care (ACSQHC). Low back pain clinical care standard. 2022. https://www.safetyandquality.gov.au/standards/clinical-care-standards/low-back-pain-clinical-care-standard/implementation-resources . Accessed 19 Jun 2024.
National Institute for Health and Care Excellence (NICE). Low back pain and sciatica in over 16s: assessment and management [NG59]. 2020. https://www.nice.org.uk/guidance/ng59 . Accessed 19 Jun 2024.
National Institute for Health and Care Excellence (NICE). Osteoarthritis in over 16s: diagnosis and management [NG226]. 2022. https://www.nice.org.uk/guidance/ng226 . Accessed 19 Jun 2024.
Bannuru RR, Osani MC, Vaysbrot EE, et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthr Cartil. 2019;27(11):1578–89.
Elshaug AG, Rosenthal MB, Lavis JN, et al. Levers for addressing medical underuse and overuse: achieving high-value health care. Lancet. 2017;390(10090):191–202.
pubmed: 28077228
Daniels SE, Goulder MA, Aspley S, Reader S. A randomised, five-parallel-group, placebo-controlled trial comparing the efficacy and tolerability of analgesic combinations including a novel single-tablet combination of ibuprofen/paracetamol for postoperative dental pain. Pain. 2011;152(3):632–42.
pubmed: 21257263
Mehlisch DR, Aspley S, Daniels SE, Southerden KA, Christensen KS. A single-tablet fixed-dose combination of racemic ibuprofen/paracetamol in the management of moderate to severe postoperative dental pain in adult and adolescent patients: a multicenter, two-stage, randomized, double-blind, parallel-group, placebo-controlled, factorial study. Clin Ther. 2010;32(6):1033–49.
pubmed: 20637958
Derry CJ, Derry S, Moore RA. Single dose oral ibuprofen plus paracetamol (acetaminophen) for acute postoperative pain. Cochrane Database Syst Rev. 2013;2013(6):CD010210.
pubmed: 23794268
pmcid: 6485825
Thybo KH, Hägi-Pedersen D, Dahl JB, et al. Effect of combination of paracetamol (acetaminophen) and ibuprofen vs either alone on patient-controlled morphine consumption in the first 24 hours after total hip arthroplasty: the PANSAID randomized clinical trial. JAMA. 2019;321(6):562–71.
pubmed: 30747964
pmcid: 6439592
Diener HC, Gold M, Hagen M. Use of a fixed combination of acetylsalicylic acid, acetaminophen and caffeine compared with acetaminophen alone in episodic tension-type headache: Meta-analysis of four randomized, double-blind, placebo-controlled, crossover studies. J Headache Pain. 2014;15(1):76.
pubmed: 25406671
pmcid: 4256978
Bettiol A, Marconi E, Vannacci A, et al. Effectiveness of ibuprofen plus paracetamol combination on persistence of acute musculoskeletal disorders in primary care patients. Int J Clin Pharm. 2021;43(4):1045–54.
pubmed: 33411104
Mathieson SKR, Maher CG, Pinto RZ, McLachlan AJ, Koes BW, Lin CC. Combination drug therapy for the management of low back pain and sciatica; systematic review and meta-analysis. J Pain. 2019;20(1):1–15.
pubmed: 30585164
Abushanab D, Al-Badriyeh D. Efficacy and safety of ibuprofen plus paracetamol in a fixed-dose combination for acute postoperative pain in adults: meta-analysis and a trial sequential analysis. CNS Drugs. 2021;35(1):105–20.
pubmed: 33428176
Miroshnychenko A, Ibrahim S, Azab M, et al. Acute postoperative pain due to dental extraction in the adult population: a systematic review and network meta-analysis. J Dent Res. 2023;102(4):391–401.
pubmed: 36631957
Bailey E, Worthington HV, van Wijk A, Yates JM, Coulthard P, Afzal Z. Ibuprofen and/or paracetamol (acetaminophen) for pain relief after surgical removal of lower wisdom teeth. Cochrane Database Syst Rev. 2013;12:CD004624.
Sjoukes A, Venekamp RP, van de Pol AC, et al. Paracetamol (acetaminophen) or non-steroidal anti-inflammatory drugs, alone or combined, for pain relief in acute otitis media in children. Cochrane Database Syst Rev. 2016;12(12):CD011534.
pubmed: 27977844
Perrott DA, Piira T, Goodenough B, Champion GD. Efficacy and safety of acetaminophen vs ibuprofen for treating children’s pain or fever: a meta-analysis. Arch Pediatr Adolesc Med. 2004;158(6):521–6.
pubmed: 15184213
Scott G, Gong J, Kirkpatrick C, Jones P. Systematic review and meta-analysis of oral paracetamol versus combination oral analgesics for acute musculoskeletal injuries. Emerg Med Australas. 2021;33(1):107–13.
pubmed: 32864884
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, The PRISMA, et al. statement: an updated guideline for reporting systematic reviews. BMJ. 2020;2021(372): n71.
WHO Collaborating Centre for Drug Statistics Methodology. Guidelines for ATC classification and DDD assignment, 2023. Oslo 2022. https://www.whocc.no/atc_ddd_index_and_guidelines/guidelines/ . Accessed 19 Jun 2024.
Higgins JP, Altman DG, Gotzsche PC, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343: d5928.
pubmed: 22008217
pmcid: 3196245
Guyatt GH, Oxman AD, Akl EA, et al. GRADE Guidelines: 1. Introduction GRADE evidence profiles and summary of findings tables. J Clinl Epidemiol. 2011;64:383–94.
Bayram S, Sahin K, Anarat FB, et al. The effect of oral magnesium supplementation on acute non-specific low back pain: prospective randomized clinical trial. Am J Emerg Med. 2021;47:125–30.
pubmed: 33812327
Friedman BW, Irizarry E, Chertoff A, et al. Ibuprofen plus acetaminophen versus ibuprofen alone for acute low back pain: an emergency department-based randomized study. Acad Emerg Med. 2020;27(3):229–35.
pubmed: 31811673
Lasko B, Levitt RJ, Rainsford KD, Bouchard S, Rozova A, Robertson S. Extended-release tramadol/paracetamol in moderate-to-severe pain: a randomized, placebo-controlled study in patients with acute low back pain. Curr Med Res Opin. 2012;28(5):847–57.
pubmed: 22458917
Lee JH, Lee CS, Ultracet ER Study Group. A randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of the extended-release tramadol hydrochloride/acetaminophen fixed-dose combination tablet for the treatment of chronic low back pain. Clin Ther. 2013;35(11):1830–40.
pubmed: 24183364
NCT00315445. The safety and efficacy of the Buprenorphine Transdermal System (BTDS) in subjects with chronic back pain (BP96-0604). Last updated 2012. https://classic.clinicaltrials.gov/ct2/show/NCT00315445 . Accessed 19 Jun 2024.
NCT00325949. A study of pain relief in low back pain. Last updated 2011. https://clinicaltrials.gov/study/NCT00325949?tab=history . Accessed 19 Jun 2024.
NCT00761150. Study to evaluate the safety and efficacy of ABT-712 in subjects with moderate to severe chronic low back pain (CLBP). Last updated 2014. https://clinicaltrials.gov/study/NCT00761150 . Accessed 19 Jun 2024.
NCT00763321. Study to evaluate the safety and efficacy of ABT-712 in subjects with moderate to severe chronic low back pain (CLBP). Last updated 2014. https://classic.clinicaltrials.gov/ct2/show/NCT00763321?term=NCT00763321&rank=1 . Accessed 19 Jun 2024.
NCT01364922. Phase 2 chronic low back pain study. Last updated 2014. https://clinicaltrials.gov/study/NCT01364922 . Accessed 19 Jun 2024.
Ostojic P, Radunovic G, Lazovic M, Tomanovic-Vujadinovic S. Ibuprofen plus paracetamol versus ibuprofen in acute low back pain: a randomized open label multicenter clinical study. Acta Reumatol Port. 2017;42(1):18–25.
pubmed: 27978532
Peloso PM, Fortin L, Beaulieu A, Kamin M, Rosenthal N. Analgesic efficacy and safety of tramadol/ acetaminophen combination tablets (Ultracet) in treatment of chronic low back pain: a multicenter, outpatient, randomized, double blind, placebo controlled trial. J Rheumatol. 2004;31(12):2454–63.
pubmed: 15570651
Perrot S, Krause D, Crozes P, Naïm C. Efficacy and tolerability of paracetamol/tramadol (325 mg/37.5 mg) combination treatment compared with tramadol (50 mg) monotherapy in patients with subacute low back pain: a multicenter, randomized, double-blind, parallel-group, 10-day treatment study. Clin Ther. 2006;28(10):1592–606.
pubmed: 17157115
Ruoff GE, Rosenthal N, Jordan D, Karim R, Kamin M. Tramadol/acetaminophen combination tablets for the treatment of chronic lower back pain: a multicenter, randomized, double-blind, placebo-controlled outpatient study. Clin Ther. 2003;25(4):1123–41.
pubmed: 12809961
Schiphorst Preuper HR, Geertzen JH, van Wijhe M, et al. Do analgesics improve functioning in patients with chronic low back pain? An explorative triple-blinded RCT. Eur Spine J. 2014;23(4):800–6.
pubmed: 24526247
pmcid: 3960442
Tervo T, Petaja L, Lepisto P. A controlled clinical trial of a muscle relaxant analgesic combination in the treatment of acute lumbago. Br J Clin Pract. 1976;30(3):62–4.
pubmed: 130920
Voicu VA, Mircioiu C, Plesa C, et al. Effect of a new synergistic combination of low doses of acetylsalicylic acid, caffeine, acetaminophen, and chlorpheniramine in acute low back pain. Front Pharmacol. 2019;10:607.
pubmed: 31281250
pmcid: 6595163
Emkey R, Rosenthal N, Wu SC, Jordan D, Kamin M. Efficacy and safety of tramadol/acetaminophen tablets (Ultracet) as add-on therapy for osteoarthritis pain in subjects receiving a COX-2 nonsteroidal antiinflammatory drug: a multicenter, randomized, double-blind, placebo-controlled trial. J Rheumatol. 2004;31(1):150–6.
pubmed: 14705234
Pareek A, Chandurkar N, Ambade R, Chandanwale A, Bartakke G. Efficacy and safety of etodolac-paracetamol fixed dose combination in patients with knee osteoarthritis flare-up: a randomized, double-blind comparative evaluation. Clin J Pain. 2010;26(7):561–6.
pubmed: 20639739
Pareek A, Chandurkar N, Sharma VD, Desai M, Kini S, Bartakke G. A randomized, multicentric, comparative evaluation of aceclofenac-paracetamol combination with aceclofenac alone in Indian patients with osteoarthritis flare-up. Expert Opin Pharmacother. 2009;10(5):727–35.
pubmed: 19351223
Rosenthal NR, Silverfield JC, Wu SC, Jordan D, Kamin M, Group C-S. Tramadol/acetaminophen combination tablets for the treatment of pain associated with osteoarthritis flare in an elderly patient population. J Am Geriatr Soc. 2004;52(3):374–80.
pubmed: 14962151
Silverfield JC, Kamin M, Wu SC, Rosenthal N. Tramadol/acetaminophen combination tablets for the treatment of osteoarthritis flare pain: a multicenter, outpatient, randomized, double-blind, placebo-controlled, parallel-group, add-on study. Clin Ther. 2002;24(2):282–97.
pubmed: 11911558
NCT00736853. An efficacy and safety study of acetaminophen plus tramadol hydrochloride (JNS013) in participants with chronic pain. Last updated 2013. https://clinicaltrials.gov/study/NCT00736853 . Accesesd 19 Jun 2024.
Pickering G, Mezouar L, Kechemir H, Ebel-Bitoun C. Paracetamol use in patients with osteoarthritis and lower back pain: infodemiology study and observational analysis of electronic medical record data. JMIR Public Health Surveill. 2022;8(10): e37790.
pubmed: 36301591
pmcid: 9650576
Yang Z, Mathieson S, Kobayashi S, et al. Prevalence of non-steroidal anti-inflammatory drugs prescribed osteoarthritis: systematic review and meta-analysis of observational studies. Arthritis Care Res (Hoboken). 2023;75(11):2345–58.
pubmed: 37221152
Wertheimer G, Mathieson S, Maher CG, et al. The prevalence of opioid analgesic use in people with chronic noncancer pain: systematic review and meta-analysis of observational studies. Pain Med. 2021;22(2):506–17.
pubmed: 33164087
Machado GC, Maher CG, Ferreira PH, et al. Efficacy and safety of paracetamol for spinal pain and osteoarthritis: systematic review and meta-analysis of randomised placebo-controlled trials. BMJ. 2015;350: h1225.
pubmed: 25828856
pmcid: 4381278
Alexander L, Hall E, Eriksson L, Rohlin M. The combination of non-selective NSAID 400 mg and paracetamol 1000 mg is more effective than each drug alone for treatment of acute pain: a systematic review. Swed Dent J. 2014;38(1):1–14.
pubmed: 26995806
Diener HC, Gaul C, Lehmacher W, Weiser T. Aspirin, paracetamol (acetaminophen) and caffeine for the treatment of acute migraine attacks: a systemic review and meta-analysis of randomized placebo-controlled trials. Eur J Neurol. 2022;29(1):350–7.
pubmed: 34519136
Ridderikhof ML, Saanen J, Goddijn H, et al. Paracetamol versus other analgesia in adult patients with minor musculoskeletal injuries: a systematic review. Emerg Med J. 2019;36(8):493–500.
pubmed: 31230039
de Sevaux JLH, Damoiseaux RA, van de Pol AC, et al. Paracetamol (acetaminophen) or non-steroidal anti-inflammatory drugs, alone or combined, for pain relief in acute otitis media in children. Cochrane Database Syst Rev. 2023;8(8):CD011534.
pubmed: 37594020
Straube C, Derry S, Jackson KC, et al. Codeine, alone and with paracetamol (acetaminophen), for cancer pain. Cochrane Database Syst Rev. 2014;2014(9):CD006601.
Australian medicines handbook online. Adelaide (SA): Australian Medicines Handbook Pty Ltd; March 2024. https://www.amhonlineamh.net.au/ . Accessed 19 Jun 2024.
Geczy QE, Thirumaran AJ, Carroll PR, McLachlan AJ, Hunter DJ. What is the most effective and safest non-steroidal anti-inflammatory drug for treating osteoarthritis in patients with comorbidities? Expert Opin Drug Metab Toxicol. 2023;19(10):681–95.
pubmed: 37817419
Therapeutic Goods Administration (TGA). Australian Product Information: Nuromol dual action pain relief (ibuprofen 200mg and paracetamol 500mg) liquid capsule. TGA. 2020. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent=&id=CP-2022-PI-01899-1&d=20240322172310101 . Accessed 19 Jun 2024.
Medsafe. Mersynofen
Doherty M, Hawkey C, Goulder M, et al. A randomised controlled trial of ibuprofen, paracetamol or a combination tablet of ibuprofen/paracetamol in community-derived people with knee pain. Ann Rheum Dis. 2011;70(9):1534–41.
pubmed: 21804100
Murnion B. Combination analgesics in adults. Aust Prescr. 2010;33(4):113–5.
Farinelli L, Riccio M, Gigante A, De Francesco F. Pain management strategies in osteoarthritis. Biomedicines. 2024;12(4):805.
pubmed: 38672160
pmcid: 11048725