Oxycodone/acetaminophen at low dosage: An alternative pain treatment for patients with rheumatoid arthritis


  • William Raffaeli, MD
  • Claudia Pari, MD
  • Angelo Corvetta, MD
  • Donatella Sarti, PhD
  • Valentina Di Sabatino, MD
  • Giovanni Biasi, MD
  • Maurizio Galeazzi, MD




opioids, pain control, rheumatoid arthritis, association oxicodone/acetaminophen


Objectives: To assess efficacy and safety of the association oxycodone/acetaminophen (oxycodone/ acetaminophen) for pain treatment and disability improvement in patients with rheumatoid arthritis (RA).
Methods: Patients with RA (n = 29), suffering from moderate to severe pain for more than 3 months, were included in the study, except those under RA therapy with biological drugs. The treatment started with oxycodone/acetaminophen at the dosage of 5 mg/325 mg, and then the dosage was titrated until the attainment of good pain relief. Antiemetic and laxative therapy was used for the prophylaxis of known opioid-related adverse events.
Results: Patients continued their RA therapy without changing the dosages, reported reduced pain intensity and disease activity, and improvement of disability. Forty-two percent of patients had a good clinical response to oxycodone/acetaminophen treatment, according to European League against Rheumatism (EULAR) assessment criteria, and 50 percent of patients reached the American College of Rheumatology 20 percent improvement criteria (ACR20). At the end of the study, the mean (±SD) daily effective oxycodone/acetaminophen dose was 13.8 (±6.8) mg/720.4 (±291.0) mg. No serious adverse event was observed. Nausea, vomiting, and stipsis of mild-moderate intensity were the most common adverse events.
Conclusion: Oxycodone/acetaminophen at low dosages for the treatment of chronic pain in RA patients can be a good alternative to non-steroidal anti-inflammatory drugs (NSAIDs), allowing the reduction of their consumption, while keeping RA therapy stable.

Author Biographies

William Raffaeli, MD

Pain Therapy and Palliative Care Unit, “Infermi” Hospital, Rimini, Italy.

Claudia Pari, MD

Internal Medicine and Rheumathology Unit, “Infermi” Hospital, Rimini, Italy.

Angelo Corvetta, MD

Internal Medicine and Rheumathology Unit, “Infermi” Hospital, Rimini, Italy.

Donatella Sarti, PhD

Pain Therapy and Palliative Care Unit, “Infermi” Hospital, Rimini, Italy.

Valentina Di Sabatino, MD

Rheumathology Unit, “Santa Maria alle Scotte” University Hospital, Siena, Italy.

Giovanni Biasi, MD

Rheumathology Unit, “Santa Maria alle Scotte” University Hospital, Siena, Italy.

Maurizio Galeazzi, MD

Rheumathology Unit, “Santa Maria alle Scotte” University Hospital, Siena, Italy.


Rindfleisch JA, Muller D: Diagnosis and management of rheumatoid arthritis. Am Fam Physician. 2005; 72(6): 1037-1047.

Brent LH: Inflammatory arthritis: An overview for primary care physicians. Postgrad Med. 2009; 121(2): 148-162.

Alamanos Y, Drosos AA: Epidemiology of adult rheumatoid arthritis. Autoimmun Rev. 2005; 4(3): 130-136.

Leeb BF, Haindl PM, Maktari A, et al.: Disease activity score—28 values differ considerably depending on patient’s pain perception and sex. J Rheumatol. 2007; 34(12): 2382-2387.

Odegård S, Finset A, Mowinckel P, et al.: Pain and psychological health status over a 10-year period in patients with recent onset rheumatoid arthritis. Ann Rheum Dis. 2007; 66(9): 1195-1201.

Deyo RA: Drug therapy for back pain: Which drugs help which patients? Spine. 1996; 21: 2840-50.

Mukherjee D, Nissen SE, Topol EJ: Risk of cardio-vascular events associated with selective COX-2 inhibitors. JAMA. 2001; 286: 954-959.

Dequeker J: NSAIDs/corticosteroids—Primum non nocere. Adv Exp Med Biol. 1999; 455: 319-325.

Kirwan JR; Arthritis and Rheumatism Council Low-Dose Glucocorticoid Study Group: The effect of glucocorticoids on joint destruction in rheumatoid arthritis. N Engl J Med. 1995; 333: 142-146.

Chou R, Qaseem A, Snow V, et al.: Diagnosis and treatment of low back pain: A joint clinical practice guideline from the American College of Physicians and the American Pain Society. Ann Intern Med. 2007; 147: 478-491.

Warfield CA: Controlled-release morphine tablets in patients with chronic cancer pain: A narrative review of controlled clinical trials. Cancer. 1998; 82: 2299-2306.

Weinstein SM, Shi M, Buckley BJ, et al.: Multicenter, open-label, prospective evaluation of the conversion from previous opioid analgesics to extended-release hydromorphone hydrochloride administered every 24 hours to patients with persistent moderate to severe pain. Clin Ther. 2006; 28: 86-98.

Pergolizzi J, Böger RH, Budd K, et al.: Opioids and the management of chronic severe pain in the elderly: Consensus statement of an International Expert Panel with focus on the six clinically most often used World Health Organization Step III opioids (buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone). Pain Pract. 2008; 8(4): 287-313.

Solomon DH, Avorn J, Wang PS, et al.: Prescription opioid use among older adults with arthritis or low back pain. Arthritis Rheum. 2006; 55: 35-41.

Raffaeli W, Provinciali M, Di Stefano G, et al.: The immune system and analgesics. In Raj P, Erdine S, Niv D, et al. (eds.): Management of Pain. In A world Perspective. Bologna: Monduzzi Editore Press, 1995: 85-93.

Millett PJ, Gobezie R, Boykin RE: Shoulder osteoarthritis: Diagnosis and management. Am Fam Physician. 2008; 78(5): 605-611.

Barron MC, Rubin BR: Managing osteoarthritic knee pain. J Am Osteopath Assoc. 2007; 107(10 Suppl 6): ES21-ES27.

Caldwell JR, Hale ME, Boyd RE, et al.: Treatment of osteoarthritis pain with controlled release oxycodone or fixed combination oxycodone plus acetaminophen added to nonsteroidal antiinflammatory drugs: A double blind, randomized, multicenter, placebo controlled trial. J Rheumatol. 1999; 26(4): 862-869.

Lee EY, Lee EB, Park BJ, et al.: Tramadol 37.5-mg/acetaminophen 325-mg combination tablets added to regular therapy for rheumatoid arthritis pain: A 1-week, randomized, double-blind, placebo-controlled trial. Clin Ther. 2006; 28(12): 2052-2060.

Connelly M, Schanberg L: Opioid therapy for the treatment of refractory pain in children with juvenile rheumatoid arthritis. Nat Clin Pract Rheumatol. 2006; 2(12): 636-637.

Fries JF, Spitz PW, Kraines RG, et al.: Measurement of patient outcome in arthritis. Arthritis Rheum. 1980; 23: 137-145.

Sokka T, Makinen H: Improving outcomes in rheumatoid arthritis: What determines decisions to change ineffective therapy? J Rheumatol. 2006; 33: 1213-1215.

Wells G, Becker JC, Teng J, et al. Validation of the 28-joint Disease Activity Score (DAS28) and European League Against Rheumatism response criteria based on C-reactive protein against disease progression in patients with rheumatoid arthritis, and comparison with the DAS28 based on erythrocyte sedimentation rate. Ann Rheum Dis. 2009; 68(6): 954-960.

Huskisson EC: Measurement of pain. Lancet. 1974; 2: 1127-1131.

American College of Rheumatology Committee to Reevaluate Improvement Criteria: A proposed revision to the ACR20: The hybrid measure of American College of Rheumatology response. Arthritis Rheum. 2007; 57: 193-202.

Thomas J, Straus WL, Bloom BS: Over-the-counter nonsteroidal anti-inflammatory drugs and risk of gastrointestinal symptoms. Am J Gastroenterol. 2002; 97(9): 2215-2219.

Adams NJ, Plane MB, Fleming MF, et al.: Opioids and the treatment of chronic pain in a primary care sample. J Pain Symptom Manage. 2001; 22(3): 791-796.

Raffaeli W, Salmosky-Dekel BG: Biological consequences of long-term intrathecal administration of opiods. Minerva Anestesiol. 2005; 71: 475-478.

Corsinovi L, Martinelli E, Fonte G, et al.: Efficacy of oxycodone/acetaminophen and codeine/acetaminophen vs. conventional therapy in elderly women with persistent, moderate to severe osteoarthritis-related pain. Arch Gerontol Geriatr. 2009; 49(3): 378-382.



How to Cite

Raffaeli, MD, W., C. Pari, MD, A. Corvetta, MD, D. Sarti, PhD, V. Di Sabatino, MD, G. Biasi, MD, and M. Galeazzi, MD. “Oxycodone/Acetaminophen at Low Dosage: An Alternative Pain Treatment for Patients With Rheumatoid Arthritis”. Journal of Opioid Management, vol. 6, no. 1, Jan. 2018, pp. 40-46, doi:10.5055/jom.2010.0003.