Skip to main content

Combunox Side Effects

Generic name: ibuprofen / oxycodone

Medically reviewed by Last updated on Sep 10, 2022.

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

  • Feeling faint, dizzy, or lightheaded
  • feeling of warmth or heat
  • flushing or redness of the skin, especially on the face and neck
  • headache
  • sweating


  • Abdominal or stomach pain
  • blurred vision
  • changes in skin color
  • chest pain
  • confusion
  • convulsions
  • decrease in frequency of urination
  • decreased urine
  • difficulty in passing urine (dribbling)
  • difficulty with breathing
  • dizziness
  • dizziness, faintness, or lightheadedness when getting up from a lying position
  • dry mouth
  • excessive muscle tone
  • fainting
  • fast, pounding, or irregular heartbeat or pulse
  • increased need to urinate
  • increased thirst
  • loss of appetite
  • mood changes
  • muscle pain or cramps
  • muscle stiffness
  • muscle tension or tightness
  • nausea or vomiting
  • numbness or tingling in the hands, feet, or lips
  • pain, tenderness, or swelling of the foot or leg
  • painful urination
  • pale skin
  • passing urine more often
  • severe constipation
  • severe vomiting
  • troubled breathing with exertion
  • unusual bleeding or bruising
  • unusual tiredness or weakness

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

Symptoms of overdose

  • Change in consciousness
  • chest pain or discomfort
  • cold and clammy skin
  • constricted pupils
  • continuing ringing or buzzing or other unexplained noise in the ears
  • decreased awareness or responsiveness
  • difficult or troubled breathing
  • difficulty with sleeping
  • disorientation
  • drowsiness to profound coma
  • fainting
  • hearing loss
  • irregular, fast or slow, or shallow breathing
  • lethargy
  • loss of bladder control
  • loss of consciousness
  • muscle spasm or jerking of all extremities
  • pale or blue lips, fingernails, or skin
  • seeing, hearing, or feeling things that are not there
  • severe sleepiness
  • skeletal muscle flaccidity
  • sleepiness or unusual drowsiness
  • sudden fainting
  • sudden loss of consciousness

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

  • Acid or sour stomach
  • belching
  • bloated or full feeling
  • diarrhea
  • difficulty having a bowel movement (stool)
  • excess air or gas in the stomach or intestines
  • fever
  • heartburn
  • indigestion
  • lack or loss of strength
  • passing gas
  • stomach discomfort, upset, or pain


  • Back pain
  • body aches or pain
  • bruising, large, flat, blue or purplish patches in the skin
  • changes in vision
  • chills
  • congestion
  • cough or hoarseness
  • delusions
  • dementia
  • difficult urination
  • difficulty with moving
  • dryness or soreness of the throat
  • enlarged abdomen or stomach
  • false or unusual sense of well-being
  • fear
  • hoarseness
  • impaired vision
  • increase in body movements
  • lower back or side pain
  • nervousness
  • pain, swelling, or redness in the joints
  • rash
  • runny nose
  • swelling
  • taste perversion
  • tender, swollen glands in the neck
  • trouble with sleeping
  • trouble with swallowing
  • voice changes

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 2 (1971): 440-6

3. Clements D, Williams GT, Rhodes J "Colitis associated with ibuprofen." Br Med J 301 (1990): 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 42 (1992): 685-8

5. "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn (2002):

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

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

8. Wolfe TR "Ibuprofen overdose." Am J Emerg Med 13 (1995): 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 30 (1995): 289-99

10. Ribeiro A, Wolfsen HC, Wolfe JT, Loeb DS "Colonic strictures induced by nonsteroidal anti-inflammatory drugs." South Med J 91 (1998): 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 30 (2003): 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 9 (1982): 647-8

14. Agnholt J, Andreasen F "The effect of ibuprofen therapy on water and electrolyte balance." Acta Med Scand 212 (1982): 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 107 (1987): 628-35

16. Johnson AG, Nguyen TV, Day RO "Do nonsteroidal anti-inflammatory drugs affect blood pressure? A meta-analysis." Ann Intern Med 121 (1994): 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 272 (1994): 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 51 (1996): 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 158 (1998): 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 16 (2003): 135-9

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

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

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

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

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

26. Jensen S, Glud TK, Bacher T, Ersgaard H "Ibuprofen-induced meningitis in a male with systemic lupus erythematosus." Acta Med Scand 221 (1987): 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 31 (1988): 813-5

28. Gilbert GJ, Eichenbaum HW "Ibuprofen-induced meningitis in an elderly patient with systemic lupus erythematosus." South Med J 82 (1989): 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 17 (1990): 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 52 (1992): 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 10 (1991): 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 14 (1992): 479-84

33. Glare PA, Walsh TD "Dose-ranging study of oxycodone for chronic pain in advanced cancer." J Clin Oncol 11 (1993): 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 54 (1993): 546-55

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

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

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

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

39. "Product Information. OxyContin (oxycodone)." Purdue Frederick Company (2001):

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

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

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

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

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

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

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

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

48. Rault RM "Case report: hyponatremia associated with nonsteroidal antiinflammatory drugs." Am J Med Sci 305 (1993): 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 16 (1987): 375-6

50. Lindblad R, Rodjer S "A case of severe pancytopenia caused by ibuprofen." J Intern Med 229 (1991): 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 40 (1992): 176-82

52. Longenecker GL, Swift IA, Bowen RJ, et al. "Kinetics of ibuprofen effect on platelet and endothelial prostanoid release." Clin Pharmacol Ther 37 (1985): 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 146 (1992): 626-32

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

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

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

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

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

59. Fitt A, Dayan M, Gillie RF "Vortex keratopathy associated with ibuprofen therapy." Eye 10 (1996): 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.