Diphenhydramine / ibuprofen Side Effects
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.
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]
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