Drugs & Aging

, Volume 22, Issue 5, pp 419–432

Dextropropoxyphene

Safety and Efficacy in Older Patients
Review Article

Abstract

Dextropropoxyphene, alone or in combination with acetaminophen (paracetamol), is among the most frequently prescribed opioid analgesics in the elderly in the US despite the American Geriatric Society recommendation that its use should be restricted. However, this recommendation is based on expert opinion in an apparent absence of data. Accordingly, we conducted a literature search which identified nine studies that reported efficacy and safety data for dextropropoxyphene in predominantly older patients (≥55 years of age). These studies were evaluated to assess the efficacy and safety of dextropropoxyphene compared with other opioids and to evaluate whether safety and tolerability differed in older versus younger patients. The efficacy of dextropropoxyphene appeared to be similar to that of other analgesics, and its safety was comparable to that of other opioid analgesics. Although the adverse event profile suggests that elderly patients might have more frequent gastrointestinal and CNS complaints than younger patients treated with dextropropoxyphene, the frequency of reports appears similar to that of other opioids. The incidences of dizziness and somnolence were not significantly greater in older patients (1–2% and 0–21%, respectively) than in younger patients (8% and 13%, respectively). The absence of clinical studies directly addressing the safety and tolerability of dextropropoxyphene in elderly patients (>65 years of age) versus younger patients encumbers assessment of the validity of restricting its use in the elderly. Careful outcomes research is needed to assess the effectiveness and safety of dextropropoxyphene in older patients and to develop evidence-based risk/benefit prescribing criteria for use of this drug in this age group.

References

  1. 1.
    Cramer GW, Galer BS, Mendelson MA, et al. A drug use evaluation of selected opioid and nonopioid analgesics in the nursing facility setting. J Am Geriatr Soc 2000; 48: 398–404PubMedGoogle Scholar
  2. 2.
    Mott DA, Meek PD. Evaluating prescriptions for the elderly: drug/age criteria as a tool to help community pharmacists. J Am Pharm Assoc (Wash) 2000; 40: 417–24Google Scholar
  3. 3.
    Beers MH. Explicit criteria for determining potentially inappropriate medication use by the elderly: an update. Arch Intern Med 1997; 157: 1531–6PubMedCrossRefGoogle Scholar
  4. 4.
    Chernish SM, Finneran J, Gruber JCM, et al. The effectiveness of D-propoxyphene hydrochloride and codeine phosphate as determined by two methods of clinical testing for relief of chronic pain. J Pharmacol Exp Ther 1956; 118: 280–5PubMedGoogle Scholar
  5. 5.
    Gruber Jr CM, King EP, Best MM, et al. Clinical bio-assay of oral analgesic activity of propoxyphene (Lilly) acetylsalicylic acid, and codeine phosphate, and observations on placebo reactions. Arch Int Pharmacodyn Ther 1955; 104: 156–66PubMedGoogle Scholar
  6. 6.
    Beaver WT. Analgesic efficacy of dextropropoxyphene and dextropropoxyphene-containing combinations: a review. Hum Toxicol 1984; 3 Suppl.: 191S–220SPubMedCrossRefGoogle Scholar
  7. 7.
    Lopez-Munoz FJ, Salazar LA. Determination of analgesic interaction between acetaminophen and d-propoxyphene obtained by means of the surface of synergistic interaction. Methods Find Exp Clin Pharmacol 1995; 17: 311–20PubMedGoogle Scholar
  8. 8.
    Jacobson J, Bertilson SO. Analgesic efficacy of paracetamol/codeine and paracetamol/dextropropoxyphene in pain after episiotomy and ruptures in connection with childbirth. J Int Med Res 1987; 15: 89–95PubMedGoogle Scholar
  9. 9.
    Crighton IM, Hobbs GJ, Wrench IJ. Analgesia after day case laparoscopic sterilization. Anesthesia 1997; 52: 649–52CrossRefGoogle Scholar
  10. 10.
    Cooper SA, Breen JF, Giuliani RL. The relative efficacy of indoprofen compared with opioid-analgesic combinations. J Oral Surg 1981; 39: 21–5PubMedGoogle Scholar
  11. 11.
    Cooper SA. Double-blind comparison of zomepirac sodium, propoxyphene/acetaminophen, and placebo in the treatment of oral surgical pain. Cur Therapeutic Res 1980; 28: 630–8Google Scholar
  12. 12.
    Forbes JA, Foor VM, Bowser MW, et al. A 12-hour evaluation of the analgesic efficacy of diflunisal, propoxyphene, a propoxyphene-acetaminophen combination and placebo in postoperative oral surgery pain. Pharmacotherapy 1982; 2: 43–9Google Scholar
  13. 13.
    Evans PJD, McQuay HJ, Rolfe M, et al. Zomepirac, placebo, and paracetamol/dextropropoxyphene combination compared in orthopedic postoperative pain. Br J Anaesth 1982; 54: 927–33PubMedCrossRefGoogle Scholar
  14. 14.
    Winter Jr L, Caiman HI, Caruso WA, et al. A double-blind comparison of ethoheptazine citrate, propoxyphene hydrochloride, and placebo. Curr Ther Res Clin Exp 1973; 15: 383–90PubMedGoogle Scholar
  15. 15.
    Sadove MS, Schiffrin MJ, Ali SM. A controlled study of codeine, dextropropoxyphene and RO 4-11778/1. Am J Med Sci 1962; 241: 103–8CrossRefGoogle Scholar
  16. 16.
    Hopkinson JH. Ibuprofen versus propoxyphene hydrochloride and placebo in the relief of postepisiotomy pain. Curr Ther Res Clin Exp 1980; 27: 55–63Google Scholar
  17. 17.
    Berry FN, Miller JM, Levin HM, et al. Relief of severe pain with acetaminophen in a new dose formulation versus propoxyphene hydrochloride 65mg and placebo: a comparative-double blind study. Curr Ther Res Clin Exp 1975; 17: 361–8PubMedGoogle Scholar
  18. 18.
    Bloomfield SDS, Barden TP, Mitchell J. Nefopam and propoxyphene in episiotomy pain. Pharmacol Ther 1980; 27: 502–7CrossRefGoogle Scholar
  19. 19.
    Sunshine A, Slafta J, Gruber C. A comparative analgesic study of propoxyphene, fenoprofen, the combination of propoxyphene and fenoprofen, aspirin, and placebo. J Clin Pharm 1978; 18: 556–63Google Scholar
  20. 20.
    Honig S, Murray KA. Surgical pain: zomepirac sodium, propoxyphene/acetaminophen combination, and placebo. J Clin Pharmacol 1981; 21: 443–8PubMedGoogle Scholar
  21. 21.
    Sunshine A, Olson NZ, Zighelboim I, et al. Analgesic oral efficacy of tramadol hydrochloride in postoperative pain. Clin Pharmacol Ther 1992; 51: 740–6PubMedCrossRefGoogle Scholar
  22. 22.
    Chan FK, Hung LC, Suen BY, et al. Celecoxib versus diclofenac plus omeprazole in high-risk arthritis patients: results of a randomized double-blind trial. Gastroenterology 2004; 127(4): 1038–43PubMedCrossRefGoogle Scholar
  23. 23.
    MacDonald TM, Morant SV, Goldstein JL, et al. Channelling bias and the incidence of gastrointestinal haemorrhage in users of meloxicam, coxibs, and older, non-specific non-steroidal anti-inflammatory drugs. Gut 2003; 52(9): 1265–70PubMedCrossRefGoogle Scholar
  24. 24.
    Laine L, Connors LG, Reicin A, et al. Serious lower gastrointestinal clinical events with nonselective NSAID or coxib use. Gastroenterology 2003; 124(2): 288–92PubMedCrossRefGoogle Scholar
  25. 25.
    Peura DA. Gastrointestinal safety and tolerability of nonselective nonsteroidal anti-inflammatory agents and cyclooxygenase-2-selective inhibitors. Cleve Clin J Med 2002; 69Suppl. 1: SI31–SI39.PubMedCrossRefGoogle Scholar
  26. 26.
    Saray A, Buyukkocak U, Cinel I, et al. Diclofenac and metamizol in postoperative analgesia in plastic surgery. Acta Chir Plast 2001; 43(3): 71–6PubMedGoogle Scholar
  27. 27.
    Sunshine A, Laska E, Slafta LJ, et al. A comparative analgesia study of propoxyphene hydrochloride, propoxyphene napsylate, and placebo. Toxicol Appl Pharmacol 1971; 19: 512–8PubMedCrossRefGoogle Scholar
  28. 28.
    Fick DM, Cooper JW, Wade WE, et al. Updating the Beers criteria for potentially inappropriate medication use in older adults: results of a US Consensus Panel of Experts. Arch Intern Med 2003; 163(22): 2716–24PubMedCrossRefGoogle Scholar
  29. 29.
    Melander A, Bodin NO, Danielson K, et al. Absorption and elimination of D-propoxyphene, acetyl salicylic acid, and phenazone in a combination tablet (Doleron): comparison between young and elderly subjects. Acta Med Scand 1978; 203: 121–4PubMedCrossRefGoogle Scholar
  30. 30.
    Flanagan RJ, Johnston A, White AS, et al. Pharmacokinetics of dextropropoxyphene and nordextropropoxyphene in young and elderly volunteers after single and multiple dextropropoxyphene dosage. Br J Clin Pharmacol 1989; 28: 463–9PubMedCrossRefGoogle Scholar
  31. 31.
    Crome P, Gain R, Ghurye R, et al. Pharmacokinetics of dextropropoxyphene and nordextropropoxyphene in elderly hospital patients after single and multiple doses of Distalgesic: preliminary analysis of results. Hum Toxicol 1984; 3 Suppl.: 41S–8SPubMedCrossRefGoogle Scholar
  32. 32.
    Forman WB. Opioid analgesic drugs in the elderly. Clin Geriatr Med 1996; 12: 489–500PubMedGoogle Scholar
  33. 33.
    Schnitzer TJ. Non-NSAID pharmacologic treatment options for the management of chronic pain. Am J Med 1998; 105: 45S–52SPubMedCrossRefGoogle Scholar
  34. 34.
    Rao SK, Sharma SK. The efficacy and safety of dolobid and distalgesic in post-traumatic pain and immobility. Br J Clin Pract 1982; 36: 266–69, 285PubMedGoogle Scholar
  35. 35.
    Oro L. A comparison between meptazinol and dextropropoxyphene plus paracetamol in elderly patients with musculoskeletal pains. Curr Med Res Opin 1984; 9: 240–5PubMedCrossRefGoogle Scholar
  36. 36.
    Lloyd RS, Costello F, Eves MJ, et al. The efficacy and tolerability of controlled-release dihydrocodeine tablets and combination dextropropoxyphene/paracetamol tablets in patients with severe osteoarthritis of the hips. Curr Med Res Opin 1992; 13: 37–48PubMedCrossRefGoogle Scholar
  37. 37.
    Parr G, Darekar B, Fletcher A, et al. Joint pain and quality of life: results of a randomised trial. Br J Clin Pharmacol 1989; 27: 235–42PubMedCrossRefGoogle Scholar
  38. 38.
    Boyle RW, Solomonson CE, Petersen JR. Analgesic effect of dextropropoxyphene hydrochloride in elderly patients with chronic pain syndromes. Ann Intern Med 1960; 52: 195–200PubMedGoogle Scholar
  39. 39.
    Brooks PM, Dougan MA, Mugford S, et al. Comparative effectiveness of 5 analgesics in patients with rheumatoid arthritis and osteoarthritis. J Rheumatol 1982; 9: 723–6PubMedGoogle Scholar
  40. 40.
    Salzman RT, Brobyn RD. Long-term comparison of suprofen and propoxyphene in patients with osteoarthritis. Pharmacology 1983; 27Suppl. 1: 55–64PubMedCrossRefGoogle Scholar
  41. 41.
    Boissier C, Perpoint B, Laporte-Simitsidis S, et al. Acceptability and efficacy of two associations of paracetamol with a central analgesic (dextropropoxyphene or codeine): comparison in osteoarthritis. J Clin Pharmacol 1992; 32: 990–5PubMedGoogle Scholar
  42. 42.
    Mercadante S, Salvaggio L, Dardanoni G, et al. Dextropropoxyphene versus morphine in opioid-naive cancer patients with pain. J Pain Symptom Manage 1998; 15: 76–81PubMedGoogle Scholar
  43. 43.
    Shorr RI, Griffin MR, Daugherty JR, et al. Opioid analgesics and the risk of hip fracture in the elderly: codeine and propoxyphene. J Gerontol 1992; 47: M111–5PubMedCrossRefGoogle Scholar
  44. 44.
    Ensrud KE, Blackwell TL, Mangione CM, et al. Central nervous system-active medications and risk for falls in older women. J Am Geriatr Soc 2002; 50: 1629–37PubMedCrossRefGoogle Scholar
  45. 45.
    Guo Z, Wills P, Viitanen M, et al. Cognitive impairment, drug use, and the risk of hip fracture in persons over 75 years old: a community-based prospective study. Am J Epidemiol 1998; 148: 887–92PubMedCrossRefGoogle Scholar
  46. 46.
    Collins SL, Edwards JE, Moore RA, et al. Single dose dextropropoxyphene, alone and with paracetamol (acetaminophen), for postoperative pain. Cochrane Database Syst Rev 2000; (2): CD001440Google Scholar
  47. 47.
    Sloane PD, Coeytaux RR, Rainer BS, et al. Dizziness: state of the science. Ann Intern Med 2001; 134: 823–32PubMedGoogle Scholar
  48. 48.
    Ganguli M, Reynolds CF, Gilby JE. Prevalence and persistence of sleep complaints in a rural older community sample: the MoVIES Project. J Am Geriatr Soc 1996; 44: 778–84PubMedGoogle Scholar
  49. 49.
    Bergeron L, Guy C, Beyens MN, et al. Dextropropoxyphene hepatotoxicity: four cases and literature review. Therapie 2002; 57: 464–72PubMedGoogle Scholar
  50. 50.
    AGS Panel on Persistent Pain in Older Persons. The management of persistent pain in older persons. J Am Geriatr Soc 2002; 50: S205–24CrossRefGoogle Scholar
  51. 51.
    Rawal N. Treating postoperative pain improves outcome. Minerva Anesthesiol 2001; 67: S200–5Google Scholar
  52. 52.
    McHugh G, Thomas G. Living with chronic pain: the patient’s perspective. Nurs Stand 2001; 15: 33–7Google Scholar
  53. 53.
    Beers MH, Ouslander JG, Rollingher I, et al. Explicit criteria for determining inappropriate medication use in nursing homes. Arch Intern Med 1991; 151: 1825–32PubMedCrossRefGoogle Scholar
  54. 54.
    Li Wan Po A, Zhang WY. Systematic overview of co-proxamol to assess analgesic effects of addition of dextropropoxyphene to paracetamol. BMJ 1997; 315: 1565–71PubMedCrossRefGoogle Scholar
  55. 55.
    Waife SO, Gruber CM, Rodda BE, et al. Analgesia, plasma levels, and dosage of propoxyphene. Int J Clin Pharmacol 1976; 13: 177–81Google Scholar
  56. 56.
    Young RES. A two-dose evaluation of propoxyphene napsylate and codeine in postoperative pain. Curr Ther Res Clin Exp 1978; 24: 495–502Google Scholar
  57. 57.
    Spore DL, Mor V, Larrat P, et al. Inappropriate drug prescription for elderly residents of board and care facilities. Am J Public Health 1997; 87: 404–9PubMedCrossRefGoogle Scholar
  58. 58.
    Moore RA, McQuay HJ. Single-patient data meta-analysis of 3453 postoperative patients: oral tramadol versus placebo, codeine and combination analgesics. Pain 1997; 69: 287–94PubMedCrossRefGoogle Scholar
  59. 59.
    Hawton K, Simkin S, Deeks J. Co-proxamol and suicide: a study of national mortality statistics and non-fatal self poisonings. BMJ 2003; 326: 463–9CrossRefGoogle Scholar
  60. 60.
    Sturrock RD. Distalgesic; safety and efficacy. Efficacy: UK experience. Hum Toxicol 1984; 3 Suppl.: 221S–7SPubMedCrossRefGoogle Scholar
  61. 61.
    Finkle BS. Self-poisoning with dextropropoxyphene and dextropropoxyphene compounds: the USA experience. Hum Toxicol 1984; 3: 115S–34SPubMedCrossRefGoogle Scholar
  62. 62.
    Collins SL, Edwards JE, Moore RA, et al. Single-dose dextropropoxyphene in post-operative pain: a quantitative systematic review. Eur J Clin Pharmacol 1998; S4: 107–12CrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  1. 1.Department of Pharmacology and ToxicologyIndiana University School of Medicine and PRN ConsultingIndianapolisUSA
  2. 2.Department of Anesthesiology, School of MedicineUniversity of WashingtonSeattleUSA
  3. 3.Department of Anesthesiology, School of MedicineUniversity of WashingtonIndianapolisUSA

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