Diphenhydramine / ibuprofen Side Effects
For the Consumer
Applies to diphenhydramine / ibuprofen: capsules, tablets
All medicines can cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:
Seek medical attention right away if any of these SEVERE side effects occur while taking diphenhydramine / ibuprofen:
Constipation; diarrhea; dizziness; drowsiness; dry mouth, throat, and nose; excitability; gas; headache; heartburn; nausea; stomach pain or upset; thickening of mucus in nose or throat.
Severe allergic reactions (rash; hives; itching; trouble breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); bloody or black, tarry stools; change in the amount of urine produced; chest pain; confusion; dark urine; depression; fainting; fast or irregular heartbeat; fever, chills, or persistent sore throat; hallucinations; mental or mood changes; numbness of an arm or leg; one-sided weakness; red, swollen, blistered, or peeling skin; ringing in the ears; seizures; severe headache or dizziness; severe or persistent stomach pain or nausea; severe vomiting; shortness of breath; stiff neck; sudden or unexplained weight gain; swelling of hands, legs, or feet; tremor; unusual bruising or bleeding; unusual joint or muscle pain; unusual tiredness or weakness; vision or speech changes; vomit that looks like coffee grounds; wheezing; yellowing of the skin or eyes.
For Healthcare Professionals
Applies to diphenhydramine / ibuprofen: oral capsule, oral tablet
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. Toxic encephalopathy has been reported in a child with chicken pox treated generously with topical diphenhydramine. 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]
Nervous system side effects of diphenhydramine have frequently included depression with drowsiness and sedation in nearly all patients treated. Motor skills may be impaired. Dystonic reactions have been reported after single doses of diphenhydramine.
Nervous system side effects of ibuprofen have rarely incuded headache, drowsiness, and dizziness. Aseptic meningitis, paresthesias, and pseudotumor cerebri have rarely been associated with the use of ibuprofen. Other nervous system side effects of ibuprofen have included tinnitus (1% to 3%) and vertigo.[Ref]
A rare case of painful, persistent peripheral cyanosis and swelling of the fingers and toes which progressed to desquamation and digital pitting infarctions has been associated with ibuprofen.[Ref]
Cardiovascular side effects of diphenhydramine have included hypotension, tachycardia, and palpitations.
Cardiovascular side effects of ibuprofen include peripheral edema (1% to 3%) and elevated blood pressure (less than 1%). These problems may be important in some patients with preexisting hypertension or congestive heart failure.[Ref]
Gastrointestinal side effects of diphenhydramine have been usually mild and included nausea and dry mouth.
Gastrointestinal side effects of ibuprofen have included dyspepsia, nausea, diarrhea, abdominal pain, and 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]
Genitourinary side effects of diphenhydramine have included urinary retention and dysuria as a result of the anticholinergic effects of diphenhydramine.[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]
Hematologic side effects of diphenhydramine have rarely included hemolytic anemia, thrombocytopenia, and agranulocytosis.
Hematologic side effects of ibuprofen have included platelet dysfunction, neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia, thrombocytopenia, eosinophilia, and decreases in hemoglobin and hematocrit.[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.[Ref]
Hypersensitivity side effects of diphenhydramine have included rash, pruritus, and eczema. Photosensitivity reactions have also been reported.
Hypersensitivity side effects of ibuprofen have included erythematous or urticarial rashes, pruritus, angioedema, bronchospasm, and anaphylactoid reactions. 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]
Ocular side effects of diphenhydramine have included blurred vision, diplopia, and dry eyes due to anticholinergic effects.
Ocular side effects of ibuprofen have included blurred vision (less than 1%), scotomata, and diplopia.[Ref]
Dermatologic side effects of ibuprofen have included maculopapular rash, pruritus, vesiculobullous eruptions, erythema multiforme, Stevens-Johnson syndrome, alopecia, toxic epidermal necrolysis, and photosensitivity reactions.[Ref]
Hepatic side effects of ibuprofen have included elevations in liver function tests in up to 15% of patients. Jaundice and hepatitis have rarely been reported.[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]
Metabolic side effects of ibuprofen have included hyponatremia and the Syndrome of Inappropriate Antidiuretic Hormone (SIADH), gynecomastia, hypoglycemia, and metabolic acidosis.[Ref]
Renal side effects of ibuprofen have included new or worsened renal insufficiency. Patients at higher risk of developing renal insufficiency during therapy include the elderly, patients with preexisting renal insufficiency, and any patients with a history of heart failure or renal artery stenosis. Rarer renal side effects associated with the use of ibuprofen include the nephrotic syndrome with and without renal failure and 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]
Respiratory side effects of ibuprofen have included 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]
1. Tejera CA, Saravay SM, Goldman E, Gluck L "Diphenhydramine-induced delirium in elderly hospitalized patients with mild dementia." Psychosomatics 35 (1994): 399-402
2. Tullio CJ "Ibuprofen-induced visual disturbance." Am J Hosp Pharm 38 (1981): 1362
3. Sexton JD, Pronchik DJ "Diphenhydramine induced psychosis with therapeutic doses." Am J Emerg Med 15 (1997): 548-9
4. Halbrecht I, Komlos L, Shabtay F, Solomon M, Book JA "Triploidy 69, XXX in a stillborn girl." Clin Genet 4 (1973): 210-2
5. Roila F, Donati D, Basurto C, Del Favero A "Diphenhydramine and acute dystonia ." Ann Intern Med 111 (1989): 92-3
6. Carruthers SG, Shoeman DW, Hignite CE, Azarnoff DL "Correlation between plasma diphenhydramine level and sedative and antihistamine effects." Clin Pharmacol Ther 23 (1978): 375-82
7. "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn, Kalamazoo, MI.
8. Davenport PM, Wilhelm RE "An unusual vasculitis due to diphenhydramine. Cutaneous and central nervous system involvement." Arch Dermatol 92 (1965): 577-80
9. Gilbert GJ, Eichenbaum HW "Ibuprofen-induced meningitis in an elderly patient with systemic lupus erythematosus." South Med J 82 (1989): 514-5
10. Gengo F, Gabos C, Miller JK "The pharmacodynamics of diphenhydramine-induced drowsiness and changes in mental performance." Clin Pharmacol Ther 45 (1989): 15-21
11. Etzel JV "Diphenhydramine-induced acute dystonia." Pharmacotherapy 14 (1994): 492-6
12. 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
13. Brait KA, Zagerman AJ "Dyskinesias after antihistamine use ." N Engl J Med 296 (1977): 111
14. Burns M, Moskowitz H "Effects of diphenhydramine and alcohol on skills performance." Eur J Clin Pharmacol 17 (1980): 259-66
15. Borbely AA, Youmbi-Balderer G "Effect of diphenhydramine on subjective sleep parameters and on motor activity during bedtime." Int J Clin Pharmacol Ther Toxicol 26 (1988): 392-6
16. Bouland DL, Specht NL, Hegstad DR "Ibuprofen and aseptic meningitis." Ann Intern Med 104 (1986): 731
17. Jones B, Lal S "Tardive dyskinesia uncovered after ingestion of Sominex, an over-the- counter drug." Can J Psychiatry 30 (1985): 370-1
18. Giansiracusa DF, Blumberg S, Kantrowitz FG "Aseptic meningitis associated with ibuprofen." Arch Intern Med 140 (1980): 1553
19. Davies EF, Avery GS "Ibuprofen: a review of its pharmacological properties and therapeutic efficacy in rheumatic disorders." Drugs 2 (1971): 440-6
20. Filloux F "Toxic encephalopathy caused by topically applied diphenhydramine." J Pediatr 108 (1986): 1018-20
21. Peck MG, Joyner PU "Ibuprofen-associated aseptic meningitis." Clin Pharm 1 (1982): 561-5
22. 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
23. Richardson GS, Roehrs TA, Rosenthal L, Koshorek G, Roth T "Tolerance to daytime sedative effects of h1 antihistamines." J Clin Psychopharmacol 22 (2002): 511-5
24. Quinn JP, Weinstein RA, Caplan LR "Eosinophilic meningitis and ibuprofen therapy." Neurology 34 (1984): 108-9
25. Vuurman EFPM, Vanveggel LMA, Sanders RL, Muntjewerff ND, Ohanlon JF "Effects of semprex-d and diphenhydramine on learning in young adults with seasonal allergic rhinitis." Ann Allergy Asthma Immunol 76 (1996): 247-52
26. Simons FER, Fraser TG, Reggin JD, Simons KJ "Comparison of the central nervous system effects produced by six h-1-receptor antagonists." Clin Exp Allergy 26 (1996): 1092-7
27. Lawson JM, Grady MJ "Ibuprofen-induced aseptic meningitis in a previously healthy patient." West J Med 143 (1985): 386-7
28. 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
29. "Product Information. Benadryl (diphenhydramine)." Parke-Davis, Morris Plains, NJ.
30. Lavenstein BL, Cantor FK "Acute dystonia: an unusual reaction to diphenhydramine." JAMA 236 (1976): 291
31. Seibold JR, Kim HC "Acral vasospasm complicating therapy with ibuprofen and tolmetin." J Rheumatol 9 (1982): 647-8
32. Schuller DE, Turkewitz D "Adverse effects of antihistamines." Postgrad Med 79 (1986): 75-86
33. 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
34. Agnholt J, Andreasen F "The effect of ibuprofen therapy on water and electrolyte balance." Acta Med Scand 212 (1982): 65-9
35. Clements D, Williams GT, Rhodes J "Colitis associated with ibuprofen." Br Med J 301 (1990): 987
36. 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
37. Lindblad R, Rodjer S "A case of severe pancytopenia caused by ibuprofen." J Intern Med 229 (1991): 281-3
38. Coskey RJ "Contact dermatitis caused by diphenhydramine hydrochloride." J Am Acad Dermatol 8 (1983): 204-6
39. Fong HJ, Cohen AH "Ibuprofen-induced acute renal failure with acute tubular necrosis." Am J Nephrol 2 (1982): 28-31
40. Horio T "Allergic and photoallergic dermatitis from diphenhydramine." Arch Dermatol 112 (1976): 1124-6
41. Emmett EA "Diphenhydramine photoallergy." Arch Dermatol 110 (1974): 249-52
42. Lee RP, King EG, Russell AS "Ibuprofen: a severe systemic reaction." Can Med Assoc J 129 (1983): 854-5
43. Barranco P, LopezSerrano MC, MorenoAncillo A "Anaphylactic reaction due to diphenhydramine." Allergy 53 (1998): 814
44. Yamada S, Tanaka M, Kawahara Y, Inada M, Ohata Y "Photoallergic contact dermatitis due to diphenhydramine hydrochloride." Contact Dermatitis 38 (1998): 282
45. Lawrence CM, Byrne JP "Eczematous eruption from oral diphenhydramine." Contact Dermatitis 7 (1981): 276-7
46. Ayres JG, Fleming DM, Whittington RM "Asthma death due to ibuprofen." Lancet 05/09/87 (1987): 1082
47. Shelley ED, Shelley WB "Ibuprofen urticaria." J Am Acad Dermatol 17 (1987): 1057-8
48. Heine A "Diphenhydramine: a forgotten allergen?" Contact Dermatitis 35 (1996): 311-2
49. Hopfenbeck JR, Cowley DS, Radant A, Greenblatt DJ, Roybyrne PP "Effects of diphenhydramine on human eye movements." Psychopharmacology (Berl) 118 (1995): 280-6
50. Asherov J, Schoenberg A, Weinberger A "Diplopia following ibuprofen administration." JAMA 248 (1982): 649
51. Seedor JA, Lamberts D, Bergmann RB, Perry HD "Filamentary keratitis associated with diphenhydramine hydrochloride (Benadryl)." Am J Ophthalmol 101 (1986): 376-7
52. Halpern SM, Volans GN "Cutaneous toxicity of ibuprofen." Arch Dermatol 130 (1994): 259-60
53. Laing VB, Sherertz EF, Flowres FP "Pemphigoid-like bullous eruption related to ibuprofen." J Am Acad Dermatol 19 (1988): 91-4
54. Bar-Sela S, Levo Y, Zeevi D, et al "A lupus-like syndrome due to ibuprofen hypersensitivity." J Rheumatol 7 (1980): 379-80
55. Bergner T, Przybilla B "Photosensitization caused by ibuprofen." J Am Acad Dermatol 26 (1992): 114-6
56. Rault RM "Case report: hyponatremia associated with nonsteroidal antiinflammatory drugs." Am J Med Sci 305 (1993): 318-20
57. Poitirt TI "Reversible renal failure associated with ibuprofen: case report and review of the literature." Drug Intell Clin Pharm 18 (1984): 27-32
58. Shah GM, Muhalwas KK, Winer RL "Renal papillary necrosis due to ibuprofen." Arthritis Rheum 24 (1981): 1208-10
59. Morgenstern SJ, Bruns FJ, Fraley DS, et al "Ibuprofen-associated lipoid nephrosis without interstitial nephritis." Am J Kidney Dis 14 (1989): 50-2
60. Moss AH, Riley R, Murgo A, Skaff LA "Over-the-counter ibuprofen and nephrotic syndrome." Ann Intern Med 105 (1986): 303
61. Blackshear JL, Davidman M, Stillman MT "Identification of risk for renal insufficiency from nonsteroidal anti-inflammatory drugs." Arch Intern Med 143 (1983): 1130-4
62. Bonney SL, Northington RS, Hedrich DA, Walker BR "Renal safety of two analgesics used over the counter: ibuprofen and aspirin." Clin Pharmacol Ther 40 (1986): 373-7
63. Rogers SY, Venning MC "Reversible acute renal failure precipitated by overdose of ibuprofen and salbutamol." Lancet 1 (1986): 737-8
64. Marasco WA, Gikas PW, Azziz-Baumgartner R, et al "Ibuprofen-associated renal dysfunction: pathophysiologic mechanisms of acute renal failure, hyperkalemia, tubular necrosis, and proteinuria." Arch Intern Med 147 (1987): 2107-16
65. Chetty KG, Ramirez MM, Mahutte CK "Drug-induced pulmonary edema in a patient infected with human immunodeficiency virus." Chest 104 (1993): 967-9
Not all side effects for diphenhydramine / ibuprofen may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.
More about diphenhydramine/ibuprofen
Related treatment guides
Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This material does not endorse drugs, diagnose patients, or recommend therapy. This information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate safety, effectiveness, or appropriateness for any given patient. Drugs.com does not assume any responsibility for any aspect of healthcare administered with the aid of materials provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the substances you are taking, check with your doctor, nurse, or pharmacist.