Skip to main content

Ibuprofen PM Side Effects

Generic name: diphenhydramine / ibuprofen

Medically reviewed by Last updated on Jan 31, 2024.

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

Applies to diphenhydramine / ibuprofen: oral tablet.

Serious side effects of Ibuprofen PM

Along with its needed effects, diphenhydramine/ibuprofen 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 diphenhydramine / ibuprofen:

Incidence not known

For Healthcare Professionals

Applies to diphenhydramine / ibuprofen: oral capsule, oral tablet.


The more commonly reported adverse effects include drowsiness and dyspepsia.[Ref]



Frequency not reported: Hypotension, tachycardia, palpitations


Common (1% to 10%): Peripheral edema

Uncommon (Less than 1%): Elevated blood pressure[Ref]

Nervous system

The CNS depressant effect of diphenhydramine parallels its plasma concentrations. The plasma concentration threshold for sedation is 30 to 42 ng/mL, and to cause mental impairment is 58 to 74 ng/mL. Dystonic reactions have been accompanied by dizziness, mental confusion, rigidity, lip and tongue protrusion, trismus, torticollis, and swallowing difficulties and generally resolve spontaneously. Delirium has been reported in elderly patients with mild dementia following a small oral dose of diphenhydramine.

The incidence of aseptic meningitis associated with ibuprofen is higher in patients with systemic lupus erythematosus and other connective tissue disease, although it has been reported in patients without such underlying disease states.[Ref]


Very common (Greater than 10%): Drowsiness, sedation

Frequency not reported: Impaired motor skills, dystonic reactions, delirium


Rare (less than 0.1%): Aseptic meningitis, paresthesias, and pseudotumor cerebri

Frequency not reported: Headache, drowsiness, dizziness[Ref]



Frequency not reported: Nausea, dry mouth


Frequency not reported: Dyspepsia, nausea, diarrhea, abdominal pain, flatulence[Ref]

More serious gastrointestinal effects of ibuprofen are uncommon but include occult blood loss, ulcer, gastrointestinal hemorrhage with or without perforation, and pancreatitis. In addition, a case of ibuprofen-associated colitis has been reported.

The incidence of gastrointestinal blood loss with ibuprofen is dose-related, occurring in up to 17% of patients receiving 1,600 mg per day and in 23% of patients receiving 2,400 mg per day.

Patients with a history of serious gastrointestinal events or alcohol abuse are at increased risk for severe gastrointestinal side effect. Ibuprofen should be used with caution in these patients.[Ref]



Frequency not reported: New or worsened renal insufficiency, nephrotic syndrome with and without renal failure, acute renal failure due to tubulointerstitial nephritis, papillary necrosis, and acute tubular necrosis[Ref]

Ibuprofen may impair the ability of the kidney to cope with low renal blood flow states due to inhibition of prostaglandin-dependent afferent arteriolar vasodilation. Renal function may be further compromised in patients with heart failure, hypovolemia, cirrhosis, nephrotic syndrome, or hypoalbuminemia. Additional risk factors for ibuprofen-induced renal insufficiency are advanced age and concomitant use of diuretics.

A case-controlled study suggested that patients who consumed 5000 or more pills containing NSAIDs during their lifetime may be at increased risk of end-stage renal disease.[Ref]


Most commonly, hypersensitivity to diphenhydramine has manifested itself in patients receiving systemic drug after being sensitized to it by topical application. Sensitization with systemic administration has also been reported.

Patients who are at higher risk of hypersensitivity reactions to ibuprofen include those with the syndrome of asthma, nasal polyps, and angioedema and/or bronchospastic reactivity to aspirin. Rare cases of systemic reactions, including interstitial nephritis and diffuse pulmonary infiltrates, have also been reported.[Ref]


Frequency not reported: Rash, pruritus, eczema, photosensitivity reactions


Frequency not reported: Erythematous or urticarial rashes, pruritus, angioedema, bronchospasm, anaphylactoid reactions[Ref]



Frequency not reported: Urinary retention, dysuria[Ref]



Frequency not reported: Hemolytic anemia, thrombocytopenia, agranulocytosis


Frequency not reported: Platelet dysfunction, neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia, thrombocytopenia, eosinophilia, decreases in hemoglobin and hematocrit[Ref]

Reductions in serum hemoglobin concentrations are uncommon and are usually associated with occult gastrointestinal blood loss. Rare cases of ibuprofen-associated hemolytic anemia, autoimmune thrombocytopenia, and leukopenia have been reported.[Ref]



Frequency not reported: Blurred vision, diplopia, dry eyes


Rare (less than 1%): Blurred vision

Frequency not reported: Scotomata, diplopia[Ref]



Frequency not reported: Maculopapular rash, pruritus, vesiculobullous eruptions, erythema multiforme, Stevens-Johnson syndrome, alopecia, toxic epidermal necrolysis, photosensitivity reactions[Ref]



Very common (over 10%): Elevations in liver function tests (15%)

Frequency not reported: Jaundice, hepatitis[Ref]

Elevations in liver function tests three times normal values occur in less than 1% of patients treated with ibuprofen. Ibuprofen-induced hepatitis has been associated with a fatal outcome in some cases.[Ref]



Frequency not reported: Hyponatremia and the Syndrome of Inappropriate Antidiuretic Hormone (SIADH), gynecomastia, hypoglycemia, metabolic acidosis[Ref]



Frequency not reported: Noncardiogenic pulmonary edema[Ref]

Acute noncardiogenic pulmonary edema developed on two occasions in an HIV-positive patient. Infectious as well as cardiac etiologies were excluded. A close temporal relationship with the administration of ibuprofen and onset of symptoms was noted.[Ref]



Frequency not reported: Depression[Ref]



Common (1% to 10%): Tinnitus

Frequency not reported: Vertigo


1. Schuller DE, Turkewitz D (1986) "Adverse effects of antihistamines." Postgrad Med, 79, p. 75-86

2. (2002) "Product Information. Benadryl (diphenhydramine)." Parke-Davis

3. Seibold JR, Kim HC (1982) "Acral vasospasm complicating therapy with ibuprofen and tolmetin." J Rheumatol, 9, p. 647-8

4. Agnholt J, Andreasen F (1982) "The effect of ibuprofen therapy on water and electrolyte balance." Acta Med Scand, 212, p. 65-9

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

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

7. Tullio CJ (1981) "Ibuprofen-induced visual disturbance." Am J Hosp Pharm, 38, p. 1362

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

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

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

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

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

13. Jensen S, Glud TK, Bacher T, Ersgaard H (1987) "Ibuprofen-induced meningitis in a male with systemic lupus erythematosus." Acta Med Scand, 221, p. 509-11

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

15. Gilbert GJ, Eichenbaum HW (1989) "Ibuprofen-induced meningitis in an elderly patient with systemic lupus erythematosus." South Med J, 82, p. 514-5

16. Agus B, Nelson J, Kramer N, et al. (1990) "Acute central nervous system symptoms caused by ibuprofen in connective tissue disease." J Rheumatol, 17, p. 1094-6

17. Lavenstein BL, Cantor FK (1976) "Acute dystonia: an unusual reaction to diphenhydramine." JAMA, 236, p. 291

18. Carruthers SG, Shoeman DW, Hignite CE, Azarnoff DL (1978) "Correlation between plasma diphenhydramine level and sedative and antihistamine effects." Clin Pharmacol Ther, 23, p. 375-82

19. Gengo F, Gabos C, Miller JK (1989) "The pharmacodynamics of diphenhydramine-induced drowsiness and changes in mental performance." Clin Pharmacol Ther, 45, p. 15-21

20. Burns M, Moskowitz H (1980) "Effects of diphenhydramine and alcohol on skills performance." Eur J Clin Pharmacol, 17, p. 259-66

21. Roila F, Donati D, Basurto C, Del Favero A (1989) "Diphenhydramine and acute dystonia ." Ann Intern Med, 111, p. 92-3

22. Davenport PM, Wilhelm RE (1965) "An unusual vasculitis due to diphenhydramine. Cutaneous and central nervous system involvement." Arch Dermatol, 92, p. 577-80

23. Filloux F (1986) "Toxic encephalopathy caused by topically applied diphenhydramine." J Pediatr, 108, p. 1018-20

24. Brait KA, Zagerman AJ (1977) "Dyskinesias after antihistamine use ." N Engl J Med, 296, p. 111

25. Jones B, Lal S (1985) "Tardive dyskinesia uncovered after ingestion of Sominex, an over-the- counter drug." Can J Psychiatry, 30, p. 370-1

26. Halbrecht I, Komlos L, Shabtay F, Solomon M, Book JA (1973) "Triploidy 69, XXX in a stillborn girl." Clin Genet, 4, p. 210-2

27. Borbely AA, Youmbi-Balderer G (1988) "Effect of diphenhydramine on subjective sleep parameters and on motor activity during bedtime." Int J Clin Pharmacol Ther Toxicol, 26, p. 392-6

28. (2002) "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn

29. Tejera CA, Saravay SM, Goldman E, Gluck L (1994) "Diphenhydramine-induced delirium in elderly hospitalized patients with mild dementia." Psychosomatics, 35, p. 399-402

30. Etzel JV (1994) "Diphenhydramine-induced acute dystonia." Pharmacotherapy, 14, p. 492-6

31. Vuurman EFPM, Vanveggel LMA, Sanders RL, Muntjewerff ND, Ohanlon JF (1996) "Effects of semprex-d and diphenhydramine on learning in young adults with seasonal allergic rhinitis." Ann Allergy Asthma Immunol, 76, p. 247-52

32. Simons FER, Fraser TG, Reggin JD, Simons KJ (1996) "Comparison of the central nervous system effects produced by six h-1-receptor antagonists." Clin Exp Allergy, 26, p. 1092-7

33. Sexton JD, Pronchik DJ (1997) "Diphenhydramine induced psychosis with therapeutic doses." Am J Emerg Med, 15, p. 548-9

34. Richardson GS, Roehrs TA, Rosenthal L, Koshorek G, Roth T (2002) "Tolerance to daytime sedative effects of h1 antihistamines." J Clin Psychopharmacol, 22, p. 511-5

35. Clements D, Williams GT, Rhodes J (1990) "Colitis associated with ibuprofen." Br Med J, 301, p. 987

36. Shah GM, Muhalwas KK, Winer RL (1981) "Renal papillary necrosis due to ibuprofen." Arthritis Rheum, 24, p. 1208-10

37. Fong HJ, Cohen AH (1982) "Ibuprofen-induced acute renal failure with acute tubular necrosis." Am J Nephrol, 2, p. 28-31

38. Blackshear JL, Davidman M, Stillman MT (1983) "Identification of risk for renal insufficiency from nonsteroidal anti-inflammatory drugs." Arch Intern Med, 143, p. 1130-4

39. Poitirt TI (1984) "Reversible renal failure associated with ibuprofen: case report and review of the literature." Drug Intell Clin Pharm, 18, p. 27-32

40. Moss AH, Riley R, Murgo A, Skaff LA (1986) "Over-the-counter ibuprofen and nephrotic syndrome." Ann Intern Med, 105, p. 303

41. Bonney SL, Northington RS, Hedrich DA, Walker BR (1986) "Renal safety of two analgesics used over the counter: ibuprofen and aspirin." Clin Pharmacol Ther, 40, p. 373-7

42. Rogers SY, Venning MC (1986) "Reversible acute renal failure precipitated by overdose of ibuprofen and salbutamol." Lancet, 1, p. 737-8

43. Marasco WA, Gikas PW, Azziz-Baumgartner R, et al. (1987) "Ibuprofen-associated renal dysfunction: pathophysiologic mechanisms of acute renal failure, hyperkalemia, tubular necrosis, and proteinuria." Arch Intern Med, 147, p. 2107-16

44. Morgenstern SJ, Bruns FJ, Fraley DS, et al. (1989) "Ibuprofen-associated lipoid nephrosis without interstitial nephritis." Am J Kidney Dis, 14, p. 50-2

45. Lee RP, King EG, Russell AS (1983) "Ibuprofen: a severe systemic reaction." Can Med Assoc J, 129, p. 854-5

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

47. Ayres JG, Fleming DM, Whittington RM (1987) "Asthma death due to ibuprofen." Lancet, 05/09/87, p. 1082

48. Horio T (1976) "Allergic and photoallergic dermatitis from diphenhydramine." Arch Dermatol, 112, p. 1124-6

49. Emmett EA (1974) "Diphenhydramine photoallergy." Arch Dermatol, 110, p. 249-52

50. Coskey RJ (1983) "Contact dermatitis caused by diphenhydramine hydrochloride." J Am Acad Dermatol, 8, p. 204-6

51. Lawrence CM, Byrne JP (1981) "Eczematous eruption from oral diphenhydramine." Contact Dermatitis, 7, p. 276-7

52. Heine A (1996) "Diphenhydramine: a forgotten allergen?" Contact Dermatitis, 35, p. 311-2

53. Yamada S, Tanaka M, Kawahara Y, Inada M, Ohata Y (1998) "Photoallergic contact dermatitis due to diphenhydramine hydrochloride." Contact Dermatitis, 38, p. 282

54. Barranco P, LopezSerrano MC, MorenoAncillo A (1998) "Anaphylactic reaction due to diphenhydramine." Allergy, 53, p. 814

55. Hakala M, Timonen TT, Rossi O, et al. (1987) "Agranulocytosis in a patient with psoriatic arthritis receiving auranofin and ibuprofen." Scand J Rheumatol, 16, p. 375-6

56. Lindblad R, Rodjer S (1991) "A case of severe pancytopenia caused by ibuprofen." J Intern Med, 229, p. 281-3

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

58. Seedor JA, Lamberts D, Bergmann RB, Perry HD (1986) "Filamentary keratitis associated with diphenhydramine hydrochloride (Benadryl)." Am J Ophthalmol, 101, p. 376-7

59. Hopfenbeck JR, Cowley DS, Radant A, Greenblatt DJ, Roybyrne PP (1995) "Effects of diphenhydramine on human eye movements." Psychopharmacology (Berl), 118, p. 280-6

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

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

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

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

64. Rault RM (1993) "Case report: hyponatremia associated with nonsteroidal antiinflammatory drugs." Am J Med Sci, 305, p. 318-20

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

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.