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Clinical Drug Investigation

, Volume 18, Issue 2, pp 89–98 | Cite as

The PAIN Study: Paracetamol, Aspirin and Ibuprofen New Tolerability Study

A Large-Scale, Randomised Clinical Trial Comparing the Tolerability of Aspirin, Ibuprofen and Paracetamol for Short-Term Analgesia
  • Nicholas Moore
  • Eric Van Ganse
  • Jean-Marie Le Parc
  • Richard Wall
  • Hélène Schneid
  • Mahdi Farhan
  • François Verrière
  • François Pelen
Clinical Use

Abstract

Objective: This study aimed to compare directly aspirin (acetylsalicylic acid), ibuprofen and paracetamol (acetaminophen), first-line analgesics which are generally well tolerated, from a safety perspective in general practice.

Methods: This was a blinded, multicentre study in general practice of up to 7 days of aspirin, paracetamol (both up to 3g daily) or ibuprofen (up to 1.2g daily), administered for common painful conditions, using patient-generated data with physician assistance. The main outcome was the rate of significant adverse events (serious, severe or moderate events, events resulting in treatment discontinuation or a physician visit). Statistical analysis tested for equivalence between ibuprofen and paracetamol, and for difference with aspirin.

Results: 1108 general practitioners included 8677 adults (2900 aspirin, 2886 ibuprofen, 2888 paracetamol; three patients had no code label number). 8633 (99.5%) were evaluable, of whom 8233 (95%) adhered to the study protocol. The main indications were musculoskeletal or back pain (48%), sore throat, the common cold and flu (31%). Rates of significant adverse events were: aspirin 18.7%, ibuprofen 13.7%, and paracetamol 14.5%. Ibuprofen was statistically equivalent to paracetamol. Both were significantly better tolerated than aspirin (p < 0.001). Total gastrointestinal events (including dyspepsia) and abdominal pain were less frequent with ibuprofen (4 and 2.8%, respectively) than with paracetamol (5.3 and 3.9%) or aspirin (7.1 and 6.8%) [all p < 0.035]. There were six cases of non-serious gastrointestinal bleeding, four with paracetamol and two with aspirin, and one case of peptic ulcer with aspirin.

Conclusion: The overall tolerability of ibuprofen in this large-scale study was equivalent to that of paracetamol and better than that of aspirin. These findings could lead to a reassessment of the use of first-line analgesics for the short-term management of painful conditions in general practice, recommending ibuprofen first, because of the poor tolerability of aspirin and the potential risks of paracetamol overdose.

Keywords

Aspirin Adis International Limited Ibuprofen Paracetamol Significant Adverse Event 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Fry SW, Seeff LB. Hepatotoxicity of analgesics and anti-inflammatory agents. Gastroenterol Clin North Am 1995; 24(4): 875–905PubMedGoogle Scholar
  2. 2.
    Bray G. Liver failure induced by paracetamol. BMJ 1993; 306: 157–8PubMedCrossRefGoogle Scholar
  3. 3.
    Bridger S, Henderson K, Glucksman E, et al. Deaths from low dose paracetamol poisoning. BMJ 1998; 316: 1724–5PubMedCrossRefGoogle Scholar
  4. 4.
    Schiodt FV, Rochling FA, Casey DL, et al. Acetaminophen toxicity in an urban county hospital. N Engl J Med 1997; 337(16): 1112–7PubMedCrossRefGoogle Scholar
  5. 5.
    Weil J, Colin-Jones D, Langman M, et al. Prophylactic aspirin and risk of peptic ulcer bleeding. BMJ 1995; 310(6983): 827–30PubMedCrossRefGoogle Scholar
  6. 6.
    Kelly JP, Kaufman DW, Jurgelon JM, et al. Risk of aspirin-associated major upper-gastrointestinal bleeding with enteric-coated or buffered product. Lancet 1996; 348(9039): 1413–6PubMedCrossRefGoogle Scholar
  7. 7.
    Henry D, Lim LL, Garcia Rodriguez LA, et al. Variability in risk of gastrointestinal complications with individual non-steroidal anti-inflammatory drugs: results of a collaborative meta-analysis. BMJ 1996; 312(7046): 1563–6PubMedCrossRefGoogle Scholar
  8. 8.
    Haase W, Fischer M. Statistische Metaanalyse von multizentrischen klinischen Studien mit Ibuprofen in Hinblick auf die Kohortengroβe. Z Rheumatol 1991; 50Suppl 1.: 77–83PubMedGoogle Scholar
  9. 9.
    Furey SA, Waksman JA, Dash BH. Nonprescription ibuprofen: side effect profile. Pharmacotherapy 1992; 12(5): 403–7PubMedGoogle Scholar
  10. 10.
    Moore N, Vuillemin N, Abiteboul M, et al. Large-scale safety study of ketoprofen 25mg (Toprec®) in febrile and painful conditions. Pharmacoepidemiol Drug Saf 1996; 5: 292–302CrossRefGoogle Scholar
  11. 11.
    Rainsford KD, Roberts SC, Brown S. Ibuprofen and paracetamol: relative safety in non-prescription dosages. J Pharm Pharmacol 1997; 49(4): 345–76PubMedCrossRefGoogle Scholar
  12. 12.
    Dunnett C, Goldsmith C. When and how to do multiple comparisons. In: Buncher C, Tsay J, editors. Statistics in the pharmaceutical industry. New York: Dekker, 1981: 397–433Google Scholar
  13. 13.
    Lesko SM, Mitchell AA. An assessment of the safety of pediatric ibuprofen. A practitioner-based randomized clinical trial. JAMA 1995; 273(12): 929–33PubMedCrossRefGoogle Scholar
  14. 14.
    Lanza FL. Endoscopic studies of gastric and duodenal injury after the use of ibuprofen, aspirin, and other nonsteroidal anti-inflammatory agents. Am J Med 1984; 77(1A): 19–24PubMedCrossRefGoogle Scholar
  15. 15.
    Misra R, Pandey H, Chandra M, et al. Effects of commonly used NSAIDs on gastric mucosa. A clinico-endoscopic and histo- pathological study. J Assoc Physicians India 1990; 38(12): 913–5PubMedGoogle Scholar
  16. 16.
    Strom BL, Schinnar R, Bilker WB, et al. Gastrointestinal tract bleeding associated with naproxen sodium vs ibuprofen. Arch Intern Med 1997; 157(22): 2626–31PubMedCrossRefGoogle Scholar
  17. 17.
    Zhang WY, Li Wan Po A. Efficacy of minor analgesics in primary dysmenorrhoea: a systematic review. Br J Obstet Gynaecol 1998; 105(7): 780–9PubMedCrossRefGoogle Scholar
  18. 18.
    Cooper SA, Schachtel BP, Goldman E, et al. Ibuprofen and acetaminophen in the relief of acute pain: a randomized, double-blind, placebo-controlled study. J Clin Pharmacol 1989; 29(11): 1026–30PubMedGoogle Scholar
  19. 19.
    Schachtel BP, Furey SA, Thoden WR. Nonprescription ibuprofen and acetaminophen in the treatment of tension-type headache. J Clin Pharmacol 1996; 36(12): 1120–5PubMedGoogle Scholar
  20. 20.
    Cooper SA. Five studies on ibuprofen for postsurgical dental pain. Am J Med 1984; 77(1A): 70–7PubMedCrossRefGoogle Scholar
  21. 21.
    McQuay H, Moore A, Justins D. Treating acute pain in hospital. BMJ 1997; 314: 1531–5PubMedCrossRefGoogle Scholar
  22. 22.
    Collins SL, Edwards JE, Moore RA, et al. Single-dose dextropropoxyphene in postoperative pain: a quantitative systematic review. Eur J Clin Pharmacol 1998; 54(2): 107–12PubMedCrossRefGoogle Scholar
  23. 23.
    Durnas C, Cusack BJ. Salicylate intoxication in the elderly. Recognition and recommendations on how to prevent it. Drugs Aging 1992; 2(1): 20–34PubMedCrossRefGoogle Scholar
  24. 24.
    Veltri JC, Rollins DE. A comparison of the frequency and severity of poisoning cases for ingestion of acetaminophen, aspirin, and ibuprofen. Am J Emerg Med 1988; 6(2): 104–7PubMedCrossRefGoogle Scholar
  25. 25.
    Moore N, Noblet C, Breemeersch C. A review of the safety of ibuprofen at the analgesic-antipyretic dose. Therapie 1996; 51(4): 458–63PubMedGoogle Scholar
  26. 26.
    Halpern SM, Fitzpatrick R, Volans GN. Ibuprofen toxicity. A review of adverse reactions and overdose. Adverse Drug React Toxicol Rev 1993; 12(2): 107–28PubMedGoogle Scholar

Copyright information

© Adis International Limited 1999

Authors and Affiliations

  • Nicholas Moore
    • 1
  • Eric Van Ganse
    • 2
  • Jean-Marie Le Parc
    • 3
  • Richard Wall
    • 4
  • Hélène Schneid
    • 5
  • Mahdi Farhan
    • 4
  • François Verrière
    • 5
  • François Pelen
    • 5
  1. 1.Department of PharmacologyUniversité Victor Segalen, Hôpital PellegrinBordeauxFrance
  2. 2.Clinical Pharmacology DepartmentUniversity of LyonLyonFrance
  3. 3.Service de RhumatologieHôpital Ambroise ParéBoulogne-BillancourtFrance
  4. 4.Boots Healthcare InternationalNottinghamEngland
  5. 5.Boots HealthcareCourbevoieFrance

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