Skip to main content

Combunox Side Effects

Generic name: ibuprofen / oxycodone

Medically reviewed by Last updated on Apr 9, 2023.

Note: This document contains side effect information about ibuprofen / oxycodone. Some dosage forms listed on this page may not apply to the brand name Combunox.

Applies to ibuprofen / oxycodone: oral tablet.


Oral route (Tablet)

Oxycodone hydrochloride/ibuprofen has the potential for addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk before prescribing, and monitor for development of these behaviors or conditions. Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely, especially upon initiation or following a dose increase. Accidental ingestion of oxycodone hydrochloride/ibuprofen, especially in children, can result in fatal overdose of oxycodone hydrochloride and ibuprofen. Prolonged use of oxycodone hydrochloride/ibuprofen during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. Concomitant use of cytochrome P450 3A4 inhibitors or discontinuation of concomitantly used cytochrome P450 3A4 inducers may affect the plasma levels of oxycodone and lead to increased adverse reactions and fatal respiratory depression. Monitor patients carefully when oxycodone hydrochloride/ibuprofen and cytochrome P450 3A4 inhibitors and inducers are concurrently used. Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for patients with inadequate alternative treatment options. Limit dosages and durations to the minimum required and follow patients for signs and symptoms of respiratory depression and sedation. NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may be increased in patients with cardiovascular disease or risk factors for cardiovascular disease. Oxycodone hydrochloride/ibuprofen is contraindicated for use in the setting of coronary artery bypass graft (CABG) surgery. NSAIDs can also increase the risk of serious gastrointestinal (GI) adverse events (eg, bleeding, ulceration, and perforation of the stomach or intestines) especially in the elderly and patients with a prior history of ulcer disease and/or GI bleeding, which can be fatal.

Serious side effects of Combunox

Along with its needed effects, ibuprofen / oxycodone may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking ibuprofen / oxycodone:

Less common


Get emergency help immediately if any of the following symptoms of overdose occur while taking ibuprofen / oxycodone:

Symptoms of overdose

Other side effects of Combunox

Some side effects of ibuprofen / oxycodone may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common


For Healthcare Professionals

Applies to ibuprofen / oxycodone: oral tablet.


The most commonly reported adverse events have included nausea, vomiting, flatulence, somnolence, and dizziness.[Ref]


Abdominal pain, enlarged abdomen, dry mouth, dyspepsia, eructation, and ileus, have been reported in less than 1% of patients.[Ref]

Common (1% to 10%): Nausea, vomiting, flatulence, constipation, diarrhea, dyspepsia

Frequency not reported: Abdominal pain, enlarged abdomen, dry mouth, eructation, ileus

Postmarketing reports:[Ref]


Hypotension, syncope, tachycardia, edema, and chest pain have been reported in less than 1% of patients.[Ref]

Common (1% to 10%): Vasodilation, thrombophlebitis

Frequency not reported: Hypotension, syncope, tachycardia, vasodilation, edema, chest pain[Ref]

Nervous system

Very common (10% or more): Dizziness (19.2%), somnolence (17.4%), headache (10.2%)

Common (1% to 10%): Hyperkinesia, hypertonia

Frequency not reported: Taste perversion

Postmarketing reports: Serotonin syndrome[Ref]


Frequency not reported: Respiratory depression[Ref]


Common (1% to 10%): Sweat, rash[Ref]


Frequency not reported: Hypokalemia[Ref]


Postmarketing reports: Anaphylaxis[Ref]


Common (1% to 10%): Ecchymosis

Frequency not reported: Anemia[Ref]


Frequency not reported: Insomnia, euphoria, nervousness, abnormal thinking, anxiety[Ref]

Insomnia, euphoria, nervousness, abnormal thinking, and anxiety have been reported in less than 1% of patients.[Ref]


Postmarketing reports: Adrenal insufficiency, androgen deficiency

Adrenal insufficiency and androgen deficiency have been reported with opioid use, most often with chronic use.


Frequency not reported: Arthritis, back pain[Ref]


Frequency not reported: Urinary frequency[Ref]


Common (1% to 10%): Fever, asthenia

Frequency not reported: Chills[Ref]


Frequency not reported: Amblyopia[Ref]


1. Product Information. Ibuprofen-Oxycodone Hydrochloride (ibuprofen-oxycodone). Actavis U.S. (Alpharma USPD). 2017.

2. Davies EF, Avery GS. Ibuprofen: a review of its pharmacological properties and therapeutic efficacy in rheumatic disorders. Drugs. 1971;2:440-6.

3. Clements D, Williams GT, Rhodes J. Colitis associated with ibuprofen. Br Med J. 1990;301:987.

4. Bergmann JF, Chassany O, Geneve J, et al. Endoscopic evaluation of the effect of ketoprofen, ibuprofen and aspirin on the gastroduodenal mucosa. Eur J Clin Pharmacol. 1992;42:685-8.

5. Product Information. Motrin (ibuprofen). Pharmacia and Upjohn. 2002;PROD.

6. Singh G, Ramey DR, Morfeld D, Fries JF. Comparative toxicity of non-steroidal anti-inflammatory agents. Pharmacol Ther. 1994;62:175-91.

7. Kwo PY, Tremaine WJ. Nonsteroidal anti-inflammatory drug-induced enteropathy: case discussion and review of the literature. Mayo Clin Proc. 1995;70:55-61.

8. Wolfe TR. Ibuprofen overdose. Am J Emerg Med. 1995;13:375.

9. Somasundaram S, Hayllar H, Rafi S, Wrigglesworth JM, Macpherson AJS, Bjarnason I. The biochemical basis of non-steroidal anti-inflammatory drug-induced damage to the gastrointestinal tract: a review and a hypothesis. Scand J Gastroenterol. 1995;30:289-99.

10. Ribeiro A, Wolfsen HC, Wolfe JT, Loeb DS. Colonic strictures induced by nonsteroidal anti-inflammatory drugs. South Med J. 1998;91:568-72.

11. Fries JF, Bruce B. Rates of Serious Gastrointestinal Events from Low Dose Use of Acetylsalicylic Acid, Acetaminophen, and Ibuprofen in Patients with Osteoarthritis and Rheumatoid Arthritis. J Rheumatol. 2003;30:2226-2233.

12. Product Information. Combunox (ibuprofen-oxycodone). Forest Pharmaceuticals. 2004.

13. Seibold JR, Kim HC. Acral vasospasm complicating therapy with ibuprofen and tolmetin. J Rheumatol. 1982;9:647-8.

14. Agnholt J, Andreasen F. The effect of ibuprofen therapy on water and electrolyte balance. Acta Med Scand. 1982;212:65-9.

15. Radack KL, Deck CC, Bloomfield SS. Ibuprofen interferes with the efficacy of antihypertensive drugs: a randomized, double-blind, placebo-controlled trial of ibuprofen compared with acetaminophen. Ann Intern Med. 1987;107:628-35.

16. Johnson AG, Nguyen TV, Day RO. Do nonsteroidal anti-inflammatory drugs affect blood pressure? A meta-analysis. Ann Intern Med. 1994;121:289-300.

17. Gurwitz JH, Avron J, Bohn RL, Glynn RJ, Monane M, Mogun H. Initiation of antihypertensive treatment during nonsteroidal anti-inflammatory drug therapy. JAMA. 1994;272:781-6.

18. Gurwitz JH, Everitt DE, Monane M, et al. The impact of ibuprofen on the efficacy of antihypertensive treatment with hydrochlorothiazide in elderly persons. J Gerontol A Biol Sci Med Sci. 1996;51:m74-9.

19. Heerdink ER, Leufkens HG, Herings RM, Ottervanger JP, Stricker BH, Bakker A. NSAIDs associated with increased risk of congestive heart failure in elderly patients taking diuretics. Arch Intern Med. 1998;158:1108-12.

20. Palmer R, Weiss R, Zusman RM, Haig A, Flavin S, MacDonald B. Effects of nabumetone, celecoxib, and ibuprofen on blood pressure control in hypertensive patients on angiotensin converting enzyme inhibitors. Am J Hypertens. 2003;16:135-9.

21. Giansiracusa DF, Blumberg S, Kantrowitz FG. Aseptic meningitis associated with ibuprofen. Arch Intern Med. 1980;140:1553.

22. Peck MG, Joyner PU. Ibuprofen-associated aseptic meningitis. Clin Pharm. 1982;1:561-5.

23. Quinn JP, Weinstein RA, Caplan LR. Eosinophilic meningitis and ibuprofen therapy. Neurology. 1984;34:108-9.

24. Lawson JM, Grady MJ. Ibuprofen-induced aseptic meningitis in a previously healthy patient. West J Med. 1985;143:386-7.

25. Bouland DL, Specht NL, Hegstad DR. Ibuprofen and aseptic meningitis. Ann Intern Med. 1986;104:731.

26. Jensen S, Glud TK, Bacher T, Ersgaard H. Ibuprofen-induced meningitis in a male with systemic lupus erythematosus. Acta Med Scand. 1987;221:509-11.

27. Durback MA, Freeman J, Schumacher HR Jr. Recurrent ibuprofen-induced aseptic meningitis: third episode after only 200 mg of generic ibuprofen. Arthritis Rheum. 1988;31:813-5.

28. Gilbert GJ, Eichenbaum HW. Ibuprofen-induced meningitis in an elderly patient with systemic lupus erythematosus. South Med J. 1989;82:514-5.

29. Agus B, Nelson J, Kramer N, et al. Acute central nervous system symptoms caused by ibuprofen in connective tissue disease. J Rheumatol. 1990;17:1094-6.

30. Leow KP, Smith MT, Williams B, Cramond T. Single-dose and steady-state pharmacokinetics and pharmacodynamics of oxycodone in patients with cancer. Clin Pharmacol Ther. 1992;52:487-95.

31. Glare P, Walsh D. Dose-ranging study of oxycodone for advanced cancer pain (meeting abstract). Proc Annu Meet Am Soc Clin Oncol. 1991;10:a1201.

32. Leow KP, Smith MT, Watt JA, Williams BE, Cramond T. Comparative oxycodone pharmacokinetics in humans after intravenous, oral, and rectal administration. Ther Drug Monit. 1992;14:479-84.

33. Glare PA, Walsh TD. Dose-ranging study of oxycodone for chronic pain in advanced cancer. J Clin Oncol. 1993;11:973-8.

34. Sunshine A, Olson NZ, Zighelboim I, Decastro A. Ketoprofen, acetaminophen plus oxycodone, and acetaminophen in the relief of postoperative pain. Clin Pharmacol Ther. 1993;54:546-55.

35. Katona BG, Wigley FM, Walters JK, Caspi M. Aseptic meningitis from over-the-counter ibuprofen. Lancet. 1988;1:59.

36. Horn AC, Jarrett SW. Ibuprofen-induced aseptic meningitis in rheumatoid arthritis. Ann Pharmacother. 1997;31:1009-11.

37. Nguyen HT, Juurlink DN. Recurrent ibuprofen-induced aseptic meningitis. Ann Pharmacother. 2004;38:408-10.

38. Chetty KG, Ramirez MM, Mahutte CK. Drug-induced pulmonary edema in a patient infected with human immunodeficiency virus. Chest. 1993;104:967-9.

39. Product Information. OxyContin (oxycodone). Purdue Frederick Company. 2001;PROD.

40. Bar-Sela S, Levo Y, Zeevi D, et al. A lupus-like syndrome due to ibuprofen hypersensitivity. J Rheumatol. 1980;7:379-80.

41. Shelley ED, Shelley WB. Ibuprofen urticaria. J Am Acad Dermatol. 1987;17:1057-8.

42. Laing VB, Sherertz EF, Flowres FP. Pemphigoid-like bullous eruption related to ibuprofen. J Am Acad Dermatol. 1988;19:91-4.

43. Bergner T, Przybilla B. Photosensitization caused by ibuprofen. J Am Acad Dermatol. 1992;26:114-6.

44. Halpern SM, Volans GN. Cutaneous toxicity of ibuprofen. Arch Dermatol. 1994;130:259-60.

45. Peters F, Maessenvisch B, Kho L. Leukocytoclastic vasculitis induced by a nonsteroidal antiinflammatory drug. J Rheumatol. 1996;23:2008-9.

46. Meggitt SJ, Farr PM. Pseudoporphyria and propionic acid non-steroidal anti-inflammatory drugs. Br J Dermatol. 1999;141:591-2.

47. Krasowska D, Schwartz RA, Lecewicz-Torun B. Generalized lichenoid drug eruption following Blaschko lines. Int J Dermatol. 2001;40:774-6.

48. Rault RM. Case report: hyponatremia associated with nonsteroidal antiinflammatory drugs. Am J Med Sci. 1993;305:318-20.

49. Hakala M, Timonen TT, Rossi O, et al. Agranulocytosis in a patient with psoriatic arthritis receiving auranofin and ibuprofen. Scand J Rheumatol. 1987;16:375-6.

50. Lindblad R, Rodjer S. A case of severe pancytopenia caused by ibuprofen. J Intern Med. 1991;229:281-3.

51. Ragni MV, Miller BJ, Whalen R, Ptachcinski R. Bleeding tendency, platelet function, and pharmacokinetics of ibuprofen and zidovudine in HIV(+) hemophilic men. Am J Hematol. 1992;40:176-82.

52. Longenecker GL, Swift IA, Bowen RJ, et al. Kinetics of ibuprofen effect on platelet and endothelial prostanoid release. Clin Pharmacol Ther. 1985;37:343-8.

53. Walson PD, Galletta G, Chomilo F, Braden NJ, Sawyer LA, Scheinbaum ML. Comparison of multidose ibuprofen and acetaminophen therapy in febrile children. Am J Dis Child. 1992;146:626-32.

54. Gardos G. Dyskinesia after discountinuation of compound analgesic containing oxycodone . Lancet. 1977;1:759-60.

55. Fishbain DA, Goldberg M, Rosomoff RS, Rosomoff H. Atypical withdrawal syndrome (organic delusional syndrome) secondary to oxycodone detoxification . J Clin Psychopharmacol. 1988;8:441-2.

56. Katz N, Zemishlany Z, Weizman A. Ibuprofen and Psychotic Exacerbation. Am J Psychiatry. 2002;159:1606-1607.

57. Tullio CJ. Ibuprofen-induced visual disturbance. Am J Hosp Pharm. 1981;38:1362.

58. Asherov J, Schoenberg A, Weinberger A. Diplopia following ibuprofen administration. JAMA. 1982;248:649.

59. Fitt A, Dayan M, Gillie RF. Vortex keratopathy associated with ibuprofen therapy. Eye. 1996;10:145-6.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.