Skip to main content

Advertisement

SpringerLink
Log in

Non-steroidal anti-inflammatory drug use in chronic pain conditions with special emphasis on the elderly and patients with relevant comorbidities: management and mitigation of risks and adverse effects

  • Review Article
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently used drugs, and this widespread use is complicated by safety issues.

Method

A Literature review was conducted.

Results

NSAIDs are a leading cause of drug-related morbidity, especially in the elderly and patients with comorbidities. Most adverse effects are related to generalized inhibition of the major targets of NSAIDs: cyclooxygenases I and II. These enzymes are not only involved in pain and inflammation pathogenesis but are also required in the gastrointestinal (GI) tract for mucosal protection and gut motility, and in the kidneys for functional integrity. Thus, the mechanisms of NSAID toxicity are well understood, but the consequences are largely uncontrolled in clinical practice. GI ulcers, including bleeding ulcers, may occur in several percent of all chronic unprotected, high-dose NSAID users. Renal side effects may precipitate renal failure, resulting in acute dialysis and chronic retention. This includes sodium retention, resulting in arterial hypertension, heart failure, and atherosclerotic events. Cardiovascular risk may be tripled by chronic high-dose NSAID use in long-term clinical trials though “real-life studies” indicate lower risk ratios. Off-target side effects include allergic reactions, drug-induced liver injury, and central nervous system effects.

Conclusions

Management of pain and inflammation must consider those risks and find alternative drugs or approaches to limit the negative impact of NSAIDs on mortality and morbidity. Alternative drugs, low-dose/short-term use, but especially non-pharmacologic approaches, such as physiotherapy, exercise, neurophysiologic measures, and local therapies, need to be further utilized. The appalling equation “less pain–more deaths/morbidity” ultimately necessitates treatment optimization in the individual patient.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

Pivotal references on major controlled clinical trials, systematic reviews, or relevant meta-analyses are marked by an asterisk.

  1. Racine M, Dion D, Dupuis G, Guerriere DN, Zagorski B, Choinière M et al (2014) The Canadian STOP-PAIN project: the burden of chronic pain—does sex really matter? Clin J Pain 30:443–452

    PubMed  Google Scholar 

  2. Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M et al (2013) Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380:2163–2196

    Article  Google Scholar 

  3. Hochberg MC, Altman RD, April KT, Benkhalti M, Guyatt G, McGowan J et al (2012) American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res 64:465–474

    Article  CAS  Google Scholar 

  4. National Institute for Health and Clinical Excellence. Osteoarthritis: national clinical guideline for care and management in adults CG59. 2008. www.nice.org.uk/nicemedia/pdf/CG059FullGuideline.pdf. Accessed 27 Feb. 2014

  5. Zhang W, Nuki G, Moskowitz RW, Abramson S, Altman RD, Arden NK et al (2010) OARSI recommendations for the management of hip and knee osteoarthritis: part III: changes in evidence following systematic cumulative update of research published through January 2009. Osteoarthr Cartil 18:476–499

    Article  CAS  PubMed  Google Scholar 

  6. IMS Institute for Healthcare Informatics (2011) The use of medicines in the United States: review of 2010. http://www.imshealth.com/imshealth/Global/Content/IMS%20Institute/Documents/IHII_UseOfMed_report%20.pdf. Accessed 27 Feb 2014

  7. Zhou Y, Boudreau DM, Freedman AN (2014) Trends in the use of aspirin and non-steroidal anti-inflammatory drugs in the general US population. Pharmacoepidemiol Drug Saf 23:43–50

    Article  CAS  PubMed  Google Scholar 

  8. Schneider S, Schmitt G, Mau H, Schmitt H, Sabo D, Richter W (2005) Prevalence and correlates of osteoarthritis in Germany. Representative data from the First National Health Survey. Orthopade 34:782–790, Article in German

    Article  CAS  PubMed  Google Scholar 

  9. Consumer Reports, Best Buy Drugs (2013) http://www.consumerreports.org/health/resources/pdf/Best-Drugs-for-Less-magazine.pdf. Accessed 27 Feb 2014

  10. Brattwall M, Turan I, Jakobsson J (2010) Musculoskeletal pain: prescription of NSAID and weak opioid by primary health care physicians in Sweden 2004–2008—a retrospective patient record review. J Pain Res 3:131–135

    PubMed Central  PubMed  Google Scholar 

  11. Conaghan PG (2012) A turbulent decade for NSAIDs: update on current concepts of classification, epidemiology, comparative efficacy, and toxicity. Rheumatol Int 32:1491–1502

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Chan FK, Abraham NS, Scheiman JM, Laine L (2008) Management of patients on nonsteroidal anti-inflammatory drugs: a clinical practice recommendation from the First International Working Party on Gastrointestinal and Cardiovascular Effects of Nonsteroidal Anti-inflammatory Drugs and Anti-platelet Agents. Am J Gastroenterol 103:2908–2918

    Article  CAS  PubMed  Google Scholar 

  13. Lanza FL, Chan FK, Quigley EM (2009) Guidelines for prevention of NSAID-related ulcer complications. Am J Gastroenterol 104:728–738

    Article  PubMed  Google Scholar 

  14. Adams RJ, Appleton SL, Gill TK, Taylor AW, Wilson DH, Hill CL (2011) Cause for concern in the use of non-steroidal anti-inflammatory medications in the community—a population-based study. BMC Fam Pract 12:70

    Article  PubMed Central  PubMed  Google Scholar 

  15. Rahme E, Roussy JP, Lafrance JP, Nedjar H, Morin S (2012) Concordance with guideline recommendations: previous and more recent nonsteroidal anti-inflammatory drug prescriptions in Quebec, Canada. Pharmacoepidemiol Drug Saf 21:420–427

    Article  PubMed  Google Scholar 

  16. Stagnitti MN (2009) Trends in outpatient prescription analgesics utilization and expenditures for the U.S. civilian noninstitutionalized population, 1996 and 2006. http://www.meps.ahrq.gov/mepsweb/data_files/publications/st235/stat235.pdf. Accessed 27 Feb 2014

  17. Seager JM, Hawkey CJ (2001) ABC of the upper gastrointestinal tract: indigestion and non-steroidal anti-inflammatory drugs. BMJ 323:1236–1239

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Lapane KL, Spooner JJ, Mucha L, Straus WL (2001) Effect of nonsteroidal anti-inflammatory drug use on the rate of gastrointestinal hospitalizations among people living in long-term care. J Am Geriatr Soc 49:577–584

    Article  CAS  PubMed  Google Scholar 

  19. Ljung R, Lu Y, Lagergren J (2011) High concomitant use of interacting drugs and low use of gastroprotective drugs among NSAID users in an unselected elderly population: a nationwide register-based study. Drugs Aging 28:469–476

    Article  PubMed  Google Scholar 

  20. Van den Akker M, Buntinx F, Metsemakers JF, Roos S, Knottnerus JA (1998) Multimorbidity in general practice: prevalence, incidence, and determinants of co-occurring chronic and recurrent diseases. J Clin Epidemiol 5:367–375

    Article  Google Scholar 

  21. Kaufman DW, Kelly JP, Rosenberg L, Anderson TE, Mitchell AA (2002) Recent patterns of medication use in the ambulatory adult population of the United States: the Slone survey. JAMA 287:337–344

    Article  PubMed  Google Scholar 

  22. Luutonen S, Antila K, Erkko M, Raiha I, Rajala T, Sourander L (1995) Haemodynamic response to head-up tilt in elderly hypertensives and diabetics. Age Ageing 24:315–320

    Article  CAS  PubMed  Google Scholar 

  23. Begaud B, Martin K, Fourrier A, Haramburu F (2002) Does age increase the risk of adverse drug reactions? Br J Clin Pharmacol 54:550–552

    Article  PubMed Central  PubMed  Google Scholar 

  24. Franceschi M, Scarcelli C, Niro V, Seripa D, Pazienza AM, Pepe G et al (2008) Prevalence, clinical features and avoidability of adverse drug reactions as cause of admission to a geriatric unit: a prospective study of 1756 patients. Drug Saf 31:545–56*

  25. Koffeman A, ‘t Jong G, Valkhoff V, Warle-van Herwaarden M, Luijsterburg P, Sturkenboom M et al (2012) Potentially harmful prescription of NSAIDs in a primary care population with musculoskeletal complaints. Ann Rheum Dis 71(Suppl 3):118

    Article  Google Scholar 

  26. Koffeman A, Valkhoff V, Celik S, ‘t Jong G, Sturkenboom M, Bindels P et al (2013) Use of over-the-counter non-steroidal anti-inflammatory drugs in the general population and in patients with a high risk of adverse drug events. Ann Rheum Dis 72(Suppl 3):120–121

    Article  Google Scholar 

  27. Tielemans MM, van Rossum LG, Eikendal T, Focks JJ, Laheij RJ, Jansen JB, van Oijen MG (2014) Gastrointestinal symptoms in NSAID users in an ‘average risk population’: results of a large population-based study in randomly selected Dutch inhabitants. Int J Clin Pract 68:512-9*

  28. Koffeman AR, Valkhoff VE, Celik S, Jong GW, Sturkenboom MC, Bindels PJ et al (2014) High-risk use of over-the-counter non-steroidal anti-inflammatory drugs: a population-based cross-sectional study. Br J Gen Pract 64:e191–e198

    Article  PubMed  Google Scholar 

  29. Moore N, Van Ganse E, Le Parc J, Wall R, Schneid H, Farhan M et al (1999) The PAIN study: Paracetamol, Aspirin and Ibuprofen New tolerability study. A large scale, randomized clinical trial comparing the tolerability of aspirin, ibuprofen and paracetamol for short-term analgesia. Clin Drug Invest 18:89-98*

  30. Duong M, Salvo F, Pariente A, Abouelfath A, Lassalle R, Droz C et al (2014) Usage patterns of ‘over the counter’ vs. prescription-strength nonsteroidal anti-inflammatory drugs in France. Br J Clin Pharmacol 77:887–895

    Article  PubMed  Google Scholar 

  31. Depont F, Fourrier A, Merliere Y, Droz C, Amouretti M, Begaud B et al (2007) Channelling of COX-2 inhibitors to patients at higher gastrointestinal risk but not at lower cardiovascular risk: the Cox2 inhibitors and tNSAIDs description of users (CADEUS) study. Pharmacoepidemiol Drug Saf 16:891–900

    Article  CAS  PubMed  Google Scholar 

  32. Moore N (2003) Place of OTC analgesics and NSAIDs in osteoarthritis. Inflammopharmacology 11:355–362

    Article  CAS  PubMed  Google Scholar 

  33. Moore N, Diris H, Martin K, Viale R, Fourrier A, Moride Y et al (2004) NSAID use profiles derived from reimbursement data in France. Therapie 59:541–546

    Article  PubMed  Google Scholar 

  34. Henry D, Lim LL, Garcia Rodriguez LA, Perez Gutthann S, Carson JL, Griffin M et al (1996) Variability in risk of gastrointestinal complications with individual non-steroidal anti-inflammatory drugs: results of a collaborative meta-analysis. BMJ 312:1563-6*

  35. Henry D, McGettigan P (2003) Epidemiology overview of gastrointestinal and renal toxicity of NSAIDs. Int J Clin Pract Suppl 135:43–49

    PubMed  Google Scholar 

  36. Griffin MR, Yared A, Ray WA (2000) Nonsteroidal antiinflammatory drugs and acute renal failure in elderly persons. Am J Epidemiol 151:488–496

    Article  CAS  PubMed  Google Scholar 

  37. Moore N (2001) Comment on ‘Quantitative estimation of rare adverse events which follow a biological progression: a new model applied to chronic NSAID use’ Tramer et al., Pain 2000;85:169–182. Pain 91:401–2

  38. Tramer MR, Moore RA, Reynolds DJ, McQuay HJ (2000) Quantitative estimation of rare adverse events which follow a biological progression: a new model applied to chronic NSAID use. Pain 85:169–182

    Article  CAS  PubMed  Google Scholar 

  39. Dannhardt G, Kiefer W (2001) Cyclooxygenase inhibitors—current status and future prospects. Eur J Med Chem 36:109–126

    Article  CAS  PubMed  Google Scholar 

  40. Therland KL, Stubbe J, Thiesson HC, Ottosen PD, Walter S, Sørensen GL et al (2004) Cycloxygenase-2 is expressed in vasculature of normal and ischemic adult human kidney and is colocalized with vascular prostaglandin E2 EP4 receptors. J Am Soc Nephrol 15:1189–1198

    Article  CAS  PubMed  Google Scholar 

  41. Goldkind L, Laine L (2006) A systematic review of NSAIDs withdrawn from the market due to hepatotoxicity: lessons learned from the bromfenac experience. Pharmacoepidemiol Drug Saf 15:213–20*

  42. Paulus H (1985) FDA Arthritis Advisory Committee meeting: postmarketing surveillance of nonsteroidal anti-inflammatory drugs. Arthritis Rheum 28:1168–1169

    Article  CAS  PubMed  Google Scholar 

  43. Hegeman J, van den Bemt BJ, Duysens J, van Limbeek J (2009) NSAIDs and the risk of accidental falls in the elderly: a systematic review. Drug Saf 32:489–98*

  44. Lazzaroni M, Porro GB (2009) Management of NSAID-induced gastrointestinal toxicity: focus on proton pump inhibitors. Drugs 69:51–69

    Article  CAS  PubMed  Google Scholar 

  45. Laharie D, Droz-Perroteau C, Benichou J, Amouretti M, Blin P, Begaud B et al (2010) Hospitalizations for gastrointestinal and cardiovascular events in the CADEUS cohort of traditional or coxib NSAID users. Br J Clin Pharmacol 69:295-302*

  46. Fries JF, Murtagh KN, Bennett M, Zatarain E, Lingala B, Bruce B (2004) The rise and decline of nonsteroidal antiinflammatory drug-associated gastropathy in rheumatoid arthritis. Arthritis Rheum 50:2433–2440

    Article  PubMed  Google Scholar 

  47. Bjarnason I (2013) Gastrointestinal safety of NSAIDs and over-the-counter analgesics. Int J Clin Pract Suppl 178:37–42

    Article  PubMed  Google Scholar 

  48. Dib RA, Chinzon D, Fontes LH, de Sá Teixeira AC, Navarro-Rodriguez T (2014) Ulcer and bleeding complications and their relationship with dyspeptic symptoms in NSAIDs users: a transversal multicenter study. Scand J Gastroenterol 49:785–789

    Article  CAS  PubMed  Google Scholar 

  49. Bolten WW (2001) Number needed to kill. Individual drug risk with NSAIDs. Z Rheumatol 60:288

    Article  CAS  PubMed  Google Scholar 

  50. Cryer B (2005) NSAID-associated death: the rise and fall of NSAID associated GI mortality. Am J Gastroenterol 100:1694–1695

    Article  CAS  PubMed  Google Scholar 

  51. Czernichow P, Hochain P, Nousbaum JB, Raymond JM, Rudelli A, Dupas JL et al (2000) Epidemiology and course of acute upper gastro-intestinal haemorrhage in four French geographical areas. Eur J Gastroenterol Hepatol 12:175–181

    Article  CAS  PubMed  Google Scholar 

  52. Thomsen RW, Riis A, Munk EM, Norgaard M, Christensen S, Sorensen HT (2006) 30-day mortality after peptic ulcer perforation among users of newer selective COX-2 inhibitors and traditional NSAIDs: a population-based study. Am J Gastroenterol 101:2704–2710

    Article  CAS  PubMed  Google Scholar 

  53. Wehling M, Peiter A (2003) Drug therapy of elderly patients from the viewpoint of the clinical pharmacologist. Internist (Berl) 44:1003–1009, Article in German

    Article  CAS  Google Scholar 

  54. Wolfe R (1991) The epidemiology of NSAID associated gastrointestinal disease. Eur J Rheumatol Inflamm 11:12–28

    CAS  PubMed  Google Scholar 

  55. American Geriatrics Society 2012 Beers Criteria Update Expert Panel (2012) American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc 60:616–631

    Article  Google Scholar 

  56. Wehling M (2013) Drug therapy for the elderly. Springer, Vienna

    Book  Google Scholar 

  57. Coxib and Traditional NSAID Trialists’ Collaboration 2013 (2013) Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet 382:769–79*

  58. Wang X, Tian HJ, Yang HK, Wanyan P, Peng YJ (2011) Meta-analysis: cyclooxygenase-2 inhibitors are no better than nonselective nonsteroidal anti-inflammatory drugs with proton pump inhibitors in regard to gastrointestinal adverse events in osteoarthritis and rheumatoid arthritis. Eur J Gastroenterol Hepatol 23:876–80*

  59. Pilotto A, Franceschi M, Leandro G, Paris F, Cascavilla L, Longo MG et al (2004) Proton-pump inhibitors reduce the risk of uncomplicated peptic ulcer in elderly either acute or chronic users of aspirin/non-steroidal anti-inflammatory drugs. Aliment Pharmacol Ther 20:1091–1097

    Article  CAS  PubMed  Google Scholar 

  60. No authors listed (2005) H. pylori eradication in NSAID-associated ulcers. Drug Ther Bull 43:37–40

  61. Van Weyenberg SJ, Van Turenhout ST, Jacobs MA, Bouma G, Mulder CJ (2012) Video capsule endoscopy for previous overt obscure gastrointestinal bleeding in patients using anti-thrombotic drugs. Dig Endosc 24:247–254

    Article  PubMed  Google Scholar 

  62. Loo RL, Chan Q, Brown IJ, Robertson CE, Stamler J, Nicholson JK et al (2012) A comparison of self-reported analgesic use and detection of urinary ibuprofen and acetaminophen metabolites by means of metabonomics: the INTERMAP Study. Am J Epidemiol 175:348–358

    Article  PubMed Central  PubMed  Google Scholar 

  63. Swan SK, Rudy DW, Lasseter KC, Ryan CF, Buechel KL, Lambrecht LJ et al (2000) Effect of cyclooxygenase-2 inhibition on renal function in elderly persons receiving a low-salt diet. A randomized, controlled trial. Ann Intern Med 133:1–9

    Article  CAS  PubMed  Google Scholar 

  64. van der Woude FJ, Heinemann LA, Graf H, Lewis M, Moehner S, Assmann A et al (2007) Analgesics use and ESRD in younger age: a case–control study. BMC Nephrol 8:15

    Article  PubMed Central  PubMed  Google Scholar 

  65. Lindeman RD, Tobin J, Shock NW (1985) Longitudinal studies on the rate of decline in renal function with age. J Am Geriatr Soc 33:278–285

    CAS  PubMed  Google Scholar 

  66. Coresh J, Selvin E, Stevens LA, Manzi J, Kusek JW, Eggers P et al (2007) Prevalence of chronic kidney disease in the United States. JAMA 298:2038–2047

    Article  CAS  PubMed  Google Scholar 

  67. Chronopoulos A, Cruz DN, Ronco C (2010) Hospital-acquired acute kidney injury in the elderly. Nat Rev Nephrol 6:141–149

    Article  PubMed  Google Scholar 

  68. Kristensen SL, Fosbøl EL, Kamper AL, Køber L, Hommel K, Lamberts M et al (2012) Use of nonsteroidal anti-inflammatory drugs prior to chronic renal replacement therapy initiation: a nationwide study. Pharmacoepidemiol Drug Saf 21:428–434

    Article  PubMed  Google Scholar 

  69. Whelton A, Hamilton CW (1991) Nonsteroidal anti-inflammatory drugs: effects on kidney function. J Clin Pharmacol 31:588–598

    Article  CAS  PubMed  Google Scholar 

  70. Plouin PF, Rossignol P, Bobrie G (2006) Hypertension in the elderly. Bull Acad Natl Med 190:793–805

    PubMed  Google Scholar 

  71. Johnson AG (1997) NSAIDs and increased blood pressure. What is the clinical significance? Drug Saf 17:277–289

    Article  CAS  PubMed  Google Scholar 

  72. Snowden S, Nelson R (2011) The effects of nonsteroidal anti-inflammatory drugs on blood pressure in hypertensive patients. Cardiol Rev 19:184–91*

  73. Chan CC, Reid CM, Aw TJ, Liew D, Haas SJ, Krum H (2009) Do COX-2 inhibitors raise blood pressure more than nonselective NSAIDs and placebo? An updated meta-analysis. J Hypertens 27:2332–41*

  74. Grossman E, Messerli FH (2012) Drug-induced hypertension: an unappreciated cause of secondary hypertension. Am J Med 125:14–22

    Article  CAS  PubMed  Google Scholar 

  75. Lawes CM, Vander Hoorn S, Rodgers A (2008) Global burden of blood-pressure related disease, 2001. Lancet 371:1513–1518

    Article  PubMed  Google Scholar 

  76. Trelle S, Reichenbach S, Wandel S, Hildebrand P, Tschannen B, Villiger PM et al (2011) Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ 342:c7086*

  77. McGettigan P, Henry H (2013) Use of non-steroidal anti-inflammatory drugs that elevate cardiovascular risk: an examination of sales and essential medicines in low-, middle-, and high-income countries. PLoS Med 10:e1001388

    Article  PubMed Central  PubMed  Google Scholar 

  78. Garcia Rodriguez LA, Tacconelli S, Patrignani P (2008) Role of dose potency in the prediction of risk of myocardial infarction associated with nonsteroidal anti-inflammatory drugs in the general population. J Am Coll Cardiol 52:1628–1636

    Article  PubMed  Google Scholar 

  79. Schjerning Olsen AM, Fosbøl EL, Gislason GH (2014) The impact of NSAID treatment on cardiovascular risk—insight from Danish observational data. Basic Clin Pharmacol Toxicol 115:179–184

    Article  CAS  PubMed  Google Scholar 

  80. Bavry AA, Khaliq A, Gong Y, Handberg EM, Cooper-Dehoff RM, Pepine CJ (2011) Harmful effects of NSAIDs among patients with hypertension and coronary artery disease. Am J Med 124:614–620

    Article  CAS  PubMed  Google Scholar 

  81. Cockburn A (2012) When half a million Americans died and nobody noticed. The Week 2012 April 27. http://www.theweek.co.uk/us/46535/when-half-million-americans-died-and-nobody-noticed. Accessed 27 Feb 2014

  82. Bresalier RS, Sandler RS, Quan H, Bolognese JA, Oxenius B, Horgan K et al (2005) Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med 352:1092–102*

  83. Andrade SE, Martinez C, Walker AM (1998) Comparative safety evaluation of non-narcotic analgesics. J Clin Epidemiol 51:1357–65*

  84. Grattagliano I, Bonfrate L, Diogo CV, Wang HH, Wang DQ, Portincasa P (2009) Biochemical mechanisms in drug-induced liver injury: certainties and doubts. World J Gastroenterol 15:4865–4876

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  85. Brunton LL, Lazo JS, Parker KL (2006) Goodman-Gilman’s the pharmacological basis of therapeutics, 11th edn. McGraw-Hill, New York

    Google Scholar 

  86. Rostom A, Goldkind L, Laine L (2005) Nonsteroidal anti-inflammatory drugs and hepatic toxicity: a systematic review of randomized controlled trials in arthritis patients. Clin Gastroenterol Hepatol 3:489–98*

  87. Bessone F (2010) Non-steroidal anti-inflammatory drugs: what is the actual risk of liver damage? World J Gastroenterol 16:5651–5661

    Article  PubMed Central  PubMed  Google Scholar 

  88. Reuben A, Koch DG, Lee WM; Acute Liver Failure Study Group (2010) Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology 52:2065–76*

  89. Temple R (2006) Hy's law: predicting serious hepatotoxicity. Pharmacoepidemiol Drug Saf 15:241–243

    Article  PubMed  Google Scholar 

  90. Kowalski ML, Makowska JS, Blanca M, Bavbek S, Bochenek G, Bousquet J et al (2011) Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs)—classification, diagnosis and management: review of the EAACI/ENDA(#) and GA2LEN/HANNA*. Allergy 66:818–829

    Article  CAS  PubMed  Google Scholar 

  91. Gomes E, Cardoso MF, Praca F, Gomes L, Marino E, Demoly P (2004) Self-reported drug allergy in a general adult Portuguese population. Clin Exp Allergy 34:1597–1601

    Article  CAS  PubMed  Google Scholar 

  92. Settipane RA, Constantine HP, Settipane GA (1980) Aspirin intolerance and recurrent urticaria in normal adults and children. Epidemiology and review. Allergy 35:149–154

    Article  CAS  PubMed  Google Scholar 

  93. Himly M, Jahn-Schmid B, Pittertschatscher K, Bohle B, Grubmayr K, Ferreira F et al (2003) IgE-mediated immediate-type hypersensitivity to the pyrazolone drug propyphenazone. J Allergy Clin Immunol 111:882–888

    Article  CAS  PubMed  Google Scholar 

  94. National Clinical Guideline Centre (2010) DELIRIUM: diagnosis, prevention and management. Clinical Guideline 103. www.nice.org.uk/nicemedia/live/13060/49908/49908.pdf Accessed 27 Feb 2014

  95. Clegg A, Young JB (2011) Which medications to avoid in people at risk of delirium: a systematic review. Age Ageing 40:23–9*

  96. Cunningham C, Skelly DT (2012) Non-steroidal anti-inflammatory drugs and cognitive function: are prostaglandins at the heart of cognitive impairment in dementia and delirium? J Neuroimmune Pharm 7:60–73

    Article  Google Scholar 

  97. Jaturapatporn D, Isaac MG, McCleery J, Tabet N (2012) Aspirin, steroidal and non-steroidal anti-inflammatory drugs for the treatment of Alzheimer’s disease. Cochrane Database Syst Rev 2:CD006378*

  98. Moore AR, O'Keeffe ST (1999) Drug-induced cognitive impairment in the elderly. Drugs Aging 15:15–28

    Article  CAS  PubMed  Google Scholar 

  99. Felson DT (1988) Epidemiology of hip and knee osteoarthritis. Epidemiol Rev 10:1–28

    CAS  PubMed  Google Scholar 

  100. Ingvarsson T, Hagglund G, Lohmander LS (1999) Prevalence of hip osteoarthritis in Iceland. Ann Rheum Dis 58:201–207

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  101. Lawrence RC, Helmick CG, Arnett FC, Deyo RA, Felson DT, Giannini EH et al (1998) Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis Rheum 41:778–799

    Article  CAS  PubMed  Google Scholar 

  102. Tepper S, Hochberg MC (1993) Factors associated with hip osteoarthritis: data from the First National Health and Nutrition Examination Survey (NHANES-I). Am J Epidemiol 137:1081–1088

    CAS  PubMed  Google Scholar 

  103. Fernandes L, Hagen KB, Bijlsma JW, Andreassen O, Christensen P, Conaghan PG et al (2013) EULAR recommendations for the non-pharmacological core management of hip and knee osteoarthritis. Ann Rheum Dis 72:1125–1135

    Article  PubMed  Google Scholar 

  104. Fransen M, McConnell S (2008) Exercise for osteoarthritis of the knee. Cochrane Database Syst Rev 4:CD004376*

  105. Bliddal H, Leeds AR, Stigsgaard L, Astrup A, Christensen R (2011) Weight loss as treatment for knee osteoarthritis symptoms in obese patients: 1-year results from a randomised controlled trial. Ann Rheum Dis 70:1798–803*

  106. Jones A, Silva PG, Silva AC, Colucci M, Tuffanin A, Jardim JR et al (2012) Impact of cane use on pain, function, general health and energy expenditure during gait in patients with knee osteoarthritis: a randomised controlled trial. Ann Rheum Dis 71:172–179

    Article  CAS  PubMed  Google Scholar 

  107. Conaghan P, Dickson JD, Bolten W, Cevc G, Rother M (2013) A multicenter, randomized, placebo- and active-controlled trial comparing the efficacy and safety of topical ketoprofen in Transfersome gel (IDEA-033) with ketoprofen-free vehicle (TDT 064) and oral celecoxib for knee pain associated with osteoarthritis. Rheumatology 52:1303–1312

    Article  CAS  PubMed  Google Scholar 

  108. Zhang W, Doherty M, Leeb BF, Alekseeva L, Arden NK, Bijlsma JW et al (2007) EULAR evidence based recommendations for the management of hand osteoarthritis: report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 66:377–388

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  109. Altman RD, Zinsenheim JR, Temple AR, Schweinle JE (2007) Three-month efficacy and safety of acetaminophen extended-release for osteoarthritis pain of the hip or knee: a randomized, double-blind, placebo-controlled study. Osteoarthr Cartil 15:454–461

    Article  CAS  PubMed  Google Scholar 

  110. Cepeda MS, Camargo F, Zea C, Valencia L (2006) Tramadol for osteoarthritis. Cochrane Database Syst Rev 3:CD005522*

  111. Tugwell PS, Wells GA, Shainhouse JZ (2004) Equivalence study of a topical diclofenac solution (Pennsaid®) compared with oral diclofenac in symptomatic treatment of osteoarthritis of the knee: a randomized controlled trial. J Rheumatol 31:2002–2012

    CAS  PubMed  Google Scholar 

  112. Simon LS, Grierson LM, Naseer Z, Bookman AA, Zev Shainhouse J (2009) Efficacy and safety of topical diclofenac containing dimethyl sulfoxide (DMSO) compared with those of topical placebo, DMSO vehicle and oral diclofenac for knee osteoarthritis. Pain 143:238–245

    Article  CAS  PubMed  Google Scholar 

  113. Deal CL, Schnitzer TJ, Lipstein E, Seibold JR, Stevens RM, Levy MD et al (1991) Treatment of arthritis with topical capsaicin: a double-blind trial. Clin Ther 13:383–395

    CAS  PubMed  Google Scholar 

  114. O'Neil CK, Hanlon JT, Marcum ZA (2012) Adverse effects of analgesics commonly used by older adults with osteoarthritis: focus on non-opioid and opioid analgesics. Am J Geriatr Pharmacother 10:331–342

    Article  PubMed Central  PubMed  Google Scholar 

  115. Anastassopoulos KP, Chow W, Tapia CI, Baik R, Moskowitz B, Kim MS (2013) Reported side effects, bother, satisfaction, and adherence in patients taking hydrocodone for non-cancer pain. J Opioid Manag 9:97–109

    Article  PubMed  Google Scholar 

  116. Heyneman CA, Lawless-Liday C, Wall GC (2000) Oral versus topical NSAID’s in rheumatic diseases. Drugs 60:555–574

    Article  CAS  PubMed  Google Scholar 

  117. Roddy E, Doherty M (2006) Changing life-styles and osteoarthritis: what is the evidence? Best Pract Res Clin Rheumatol 20:81–97

    Article  PubMed  Google Scholar 

  118. Kneer W, Rother M, Mazgareanu S, Seidel E, European IDEA-033 study group (2013) A 12-week randomized study of topical therapy with three dosages of ketoprofen in Transfersome® gel (IDEA-033) compared with the ketoprofen-free vehicle (TDT 064), in patients with osteoarthritis of the knee. J Pain Res 6:743–753

    Article  PubMed Central  PubMed  Google Scholar 

  119. Rother M, Conaghan PG (2013) A randomized, double-blind, phase III trial in moderate osteoarthritis knee pain comparing topical ketoprofen gel with ketoprofen-free gel. J Rheumatol 40:1742–1748

    Article  CAS  PubMed  Google Scholar 

  120. Rother M, Vester JC, Bolten WW, Conaghan PG (2012) Meta-analysis of four 12-week phase III clinical trials investigating the effect of TDT 064, a transdermal gel, in osteoarthritis of the knee. Arthritis Rheum 64(Suppl 10):S111

    Google Scholar 

  121. Topp R, Brosky JA, Pieschel D (2013) The effect of either topical menthol or a placebo on functioning and knee pain among patients with knee OA. J Geriatr Phys Ther 36:92–99

    Article  PubMed  Google Scholar 

  122. McKay L, Gemmell H, Jacobsen B, Hayes B (2003) Effect of a topical herbal cream on the pain and stiffness of osteoarthritis: a randomized double-blind placebo-controlled clinical trial. J Clin Rheumatol 3:164–169

    Article  Google Scholar 

  123. Kraemer WJ, Ratamess NA, Maresh CM, Anderson JA, Volek JS, Tiberio DP et al (2005) A cetylated fatty acid topical cream with menthol reduces pain and improves functional performance in individuals with arthritis. J Strength Cond Res 2:475–480

    Google Scholar 

  124. Towheed TE, Maxwell L, Anastassiades TP, Shea B, Houpt J, Robinson V et al (2005) Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev 2:CD002946*

  125. Hawker GA, Mian S, Bednis K, Stanaitis I (2011) Osteoarthritis year 2010 in review: nonpharmacologic therapy. Osteoarthr Cartil 4:366–374

    Article  Google Scholar 

Download references

Acknowledgments

Editorial assistance with the preparation of the manuscript was provided by Kirsteen Munn of Bollin Strategies Ltd., UK, and was funded by Pro Bono Bio Entrepreneur Ltd., UK. The decision to submit the review for publication was made by the author. The author retained full editorial control over the content of the paper, and the views expressed in the submitted article are the author’s own. The manuscript does not contain the original publication of clinical studies or patient data.

Conflict of interest

Martin Wehling was employed by AstraZeneca R&D, Mölndal, as Director of Discovery Medicine (translational medicine) from 2004 to 2006, while on sabbatical leave from his professorship at the University of Heidelberg. After return to this position in January 2007, he received lecturing, reporting, and/or consulting fees from Sanofi-Aventis, Novartis, Takeda, Roche, Pfizer, Bristol-Myers Squibb, Daichii-Sankyo, Lilly, LEO, Shire, Novo-Nordisk, and Pro Bono Bioentrepreneur Ltd.

Author information

Authors and Affiliations

  1. Institute of Experimental and Clinical Pharmacology and Toxicology, Clinical Pharmacology Mannheim, Medical Faculty Mannheim, Ruprecht-Karls-University of Heidelberg, Maybachstrasse 14, 68169, Mannheim, Germany

    Martin Wehling

Authors
  1. Martin Wehling
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Martin Wehling.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wehling, M. Non-steroidal anti-inflammatory drug use in chronic pain conditions with special emphasis on the elderly and patients with relevant comorbidities: management and mitigation of risks and adverse effects. Eur J Clin Pharmacol 70, 1159–1172 (2014). https://doi.org/10.1007/s00228-014-1734-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00228-014-1734-6

Keywords

Search

Navigation