ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Ibuprofen: Drug information

Ibuprofen: Drug information
(For additional information see "Ibuprofen: Patient drug information" and see "Ibuprofen: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Serious cardiovascular thrombotic events (excluding NeoProfen):

Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction, and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use.

Ibuprofen is contraindicated in the setting of coronary artery bypass graft (CABG) surgery.

Serious gastrointestinal bleeding, ulcerations, and perforation (excluding NeoProfen):

NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events.

Brand Names: US
  • Addaprin [OTC] [DSC];
  • Advil Junior Strength [OTC];
  • Advil Liqui-Gels minis [OTC];
  • Advil Migraine [OTC];
  • Advil [OTC];
  • Caldolor;
  • Childrens Advil [OTC];
  • Childrens Ibuprofen [OTC];
  • Childrens Motrin [OTC];
  • Dyspel [OTC] [DSC];
  • Genpril [OTC] [DSC];
  • GoodSense Ibuprofen Childrens [OTC];
  • GoodSense Ibuprofen [OTC];
  • IBU;
  • IBU 600-EZS [DSC];
  • IBU-200 [OTC];
  • Ibupak;
  • Ibuprofen Childrens [OTC];
  • Ibuprofen Comfort Pac [DSC];
  • Infants Advil [OTC];
  • KS Ibuprofen [OTC] [DSC];
  • Motrin Childrens [OTC];
  • Motrin IB [OTC];
  • Motrin Infants Drops [OTC];
  • NeoProfen;
  • Provil [OTC]
Brand Names: Canada
  • APO-Ibuprofen;
  • Caldolor;
  • PMS-Ibuprofen [DSC];
  • TEVA-Profen
Pharmacologic Category
  • Analgesic, Nonopioid;
  • Nonsteroidal Anti-inflammatory Drug (NSAID), Oral;
  • Nonsteroidal Anti-inflammatory Drug (NSAID), Parenteral
Dosing: Adult

Note: Safety: Use the lowest effective dose for the shortest duration of time. Avoid or use with caution in patients at risk for or with existing cardiovascular disease, GI disease, kidney impairment, chronic liver disease, or a bleeding diathesis due to greater risk for adverse events. Consider administering in combination with a proton pump inhibitor in patients at risk for GI bleeding (eg, taking dual antiplatelet therapy or an anticoagulant, ≥60 years of age, high doses) (Ref).

Anti-inflammatory

Anti-inflammatory (eg, for arthritis associated with rheumatic disease):

Oral: 400 to 800 mg every 6 to 8 hours; maximum dose: 3.2 g/day. Some experts generally recommend a maximum dose of 2.4 g/day for chronic use, except during a disease flare when up to 3.2 g/day may be considered for several weeks until flare resolves (Ref).

Dysmenorrhea

Dysmenorrhea:

Oral: Initial: 400 mg every 4 hours as needed or 600 to 800 mg every 6 to 8 hours as needed; maximum dose: 3.2 g/day. Begin at menses onset or 1 to 2 days prior to onset of menses for severe symptoms; usual duration: 1 to 5 days (Ref).

Fever

Fever (alternative agent):

IV, Oral: 200 to 400 mg every 4 to 6 hours as needed; if fever persists, may titrate up to 600 to 800 mg every 6 hours as needed; maximum dose: 3.2 g/day (Ref).

OTC labeling (patient-guided therapy): Oral: 200 mg every 4 to 6 hours as needed; if no relief, may increase to 400 mg every 4 to 6 hours as needed; maximum dose: 1.2 g/day. Use for >3 days is not recommended unless directed by health care provider.

Gout, treatment

Gout, treatment (acute flares) (off-label use):

Note: Some experts reserve use for patients who are not candidates for intra-articular glucocorticoids or when intra-articular glucocorticoid administration is not feasible (Ref).

Oral: Initial: 800 mg every 8 hours within 24 to 48 hours of flare onset; reduce dose as symptoms improve; discontinue 2 to 3 days after resolution of clinical signs; usual duration: 5 to 7 days (Ref).

Migraine, acute treatment

Migraine, acute treatment:

Note: Limit use to ≤14 days per month to avoid medication-overuse headache (Ref). For use as monotherapy in mild to moderate attacks not associated with vomiting or severe nausea; may be used in combination with triptans for severe migraine (Ref). Administration early in the course of a migraine attack, at the first sign of pain, may improve response to treatment (Ref).

Oral: 400 to 600 mg once (Ref).

OTC labeling (patient-guided therapy): Oral: 400 mg at onset of symptoms.

Pain

Pain (monotherapy or as an adjunctive agent):

IV, Oral: 200 to 400 mg every 4 to 6 hours as needed or 600 to 800 mg every 6 to 8 hours as needed; maximum dose: 3.2 g/day (Ref). For postoperative pain, doses may be scheduled initially (Ref). Some experts suggest a usual maximum of 2.4 g/day for chronic use due to increased adverse effects with higher doses (Ref).

OTC labeling (patient-guided therapy): Oral: 200 mg every 4 to 6 hours as needed; if no relief, may increase to 400 mg every 4 to 6 hours as needed; maximum dose: 1.2 g/day. Use for >10 days is not recommended unless directed by health care provider.

Pericarditis, acute or recurrent

Pericarditis, acute or recurrent (off-label use):

Note: In patients with an indication for aspirin (eg, coronary artery disease), aspirin is generally preferred over other nonsteroidal anti-inflammatory drugs (NSAIDs). Non-aspirin NSAIDs should be avoided in patients with pericarditis secondary to acute myocardial infarction given lack of benefit and potential harm (Ref).

Oral: Initial: 600 to 800 mg every 8 hours or 600 mg every 6 hours until resolution of symptoms for at least 24 hours and normalization of inflammatory biomarkers (eg, C-reactive protein) if monitored; initial therapy typically lasts for ≥1 to 2 weeks. Gradually taper over several weeks by decreasing each dose by 200 to 400 mg every 1 to 2 weeks; during taper, ensure patient remains asymptomatic and inflammatory biomarkers remain normal (if monitored). Use in combination with colchicine. In patients at risk of NSAID-related GI toxicity, prophylaxis (generally with a proton pump inhibitor) is recommended (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

IV, Oral:

Altered kidney function:

CrCl ≥60 mL/minute: No dosage adjustment necessary (Ref).

CrCl >30 to <60 mL/minute: No dosage adjustment necessary (Ref). Use of analgesics other than nonsteroidal anti-inflammatory drugs may be preferred. If necessary, use the lowest effective dose for the shortest duration possible; avoid in patients at high risk for acute kidney injury (ie, volume depleted, hypotensive, elderly, or taking concurrent nephrotoxic medications) (Ref).

CrCl ≤ 30 mL/minute: Avoid use due to increased risk of acute kidney injury (Ref).

Hemodialysis, intermittent (thrice weekly): Not significantly dialyzable (Ref): No dosage adjustment necessary. Avoid use in patients with residual kidney function (Ref).

Peritoneal dialysis: No dosage adjustment necessary. Avoid use in patients with residual kidney function (Ref).

CRRT: Avoid use (Ref).

PIRRT (eg, sustained, low-efficiency diafiltration): Avoid use (Ref).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling; use with caution to avoid adverse effects and discontinue if hepatic function worsens (Ref).

Dosing: Pediatric

(For additional information see "Ibuprofen: Pediatric drug information")

Note: To reduce the risk of adverse cardiovascular and GI effects, use the lowest effective dose for the shortest period of time to achieve treatment goals. Oral liquid products are available in 2 concentrations (concentrated infant drops: 50 mg/1.25 mL [40 mg/mL] and suspension: 100 mg/5 mL [20 mg/mL]); precautions should be taken to verify and avoid confusion between the different concentrations; dose should be clearly presented as "mg".

Analgesic

Analgesic:

IV: Ibuprofen injection (Caldolor): Note: Patients should be well hydrated prior to administration.

Infants ≥6 months and Children <12 years: IV: 10 mg/kg/dose (maximum dose: 400 mg/dose) every 4 to 6 hours as needed; maximum daily dose: 40 mg/kg/day or 2,400 mg/day, whichever is less.

Children ≥12 years and Adolescents ≤17 years: IV: 400 mg every 4 to 6 hours as needed; maximum daily dose: 2,400 mg/day.

Adolescents ≥18 years: IV: 400 to 800 mg every 6 hours as needed; maximum daily dose: 3,200 mg/day.

Oral:

Weight-directed dosing: Infants, Children, and Adolescents: Limited data available in infants <6 months: Oral: 4 to 10 mg/kg/dose every 6 to 8 hours; maximum dose: 400 mg/dose; maximum daily dose: 40 mg/kg/day or 3,200 mg/day, whichever is less (Ref).

Fixed dosing:

Infants ≥6 months and Children ≤11 years: Oral: See table based upon manufacturer's labeling; use of weight to select dose is preferred; if weight is not available, then use age; doses may be repeated every 6 to 8 hours; maximum: 4 doses/day; treatment of sore throat for >2 days or use in infants and children <3 years of age with sore throat is not recommended, unless directed by health care provider.

Ibuprofen Dosing

Weight (preferred)a

Age

Dosage

(mg)

kg

lbs

5.4 to 8.1

12 to 17

6 to 11 months

50

8.2 to 10.8

18 to 23

12 to 23 months

75 to 80

10.9 to 16.3

24 to 35

2 to 3 years

100

16.4 to 21.7

36 to 47

4 to 5 years

150

21.8 to 27.2

48 to 59

6 to 8 years

200

27.3 to 32.6

60 to 71

9 to 10 years

200 to 250

32.7 to 43.2

72 to 95

11 years

300

a Manufacturer's recommendations are based on weight in pounds (OTC labeling); weight in kg listed here is derived from pounds and rounded; kg weight listed also is adjusted to allow for continuous weight ranges in kg.

Children ≥12 years and Adolescents: Oral: 200 to 400 mg every 4 to 6 hours as needed; maximum daily dose: 3,200 mg/day (Ref); treatment of pain for >10 days is not recommended, unless directed by health care provider.

Antipyretic

Antipyretic:

IV: Ibuprofen injection (Caldolor): Note: Patients should be well hydrated prior to administration.

Infants ≥6 months and Children <12 years: IV: 10 mg/kg/dose (maximum dose: 400 mg/dose) every 4 to 6 hours as needed; maximum daily dose: 40 mg/kg/day or 2,400 mg/day, whichever is less.

Children ≥12 years and Adolescents ≤17 years: IV: 400 mg every 4 to 6 hours as needed; maximum daily dose: 2,400 mg/day.

Adolescents ≥18 years: IV: Initial dose: 400 mg once, followed by 400 mg every 4 to 6 hours or 100 to 200 mg every 4 hours as needed; maximum daily dose: 3,200 mg/day.

Oral:

Weight-directed dosing: Infants ≥3 months weighing ≥5 kg, Children, and Adolescents: Limited data available in infants <6 months: Oral: 5 to 10 mg/kg/dose every 6 to 8 hours; maximum dose: 400 mg/dose; maximum daily dose: 40 mg/kg/day or 2,400 mg/day, whichever is less (Ref).

Fixed dosing: Note: Treatment for >3 days is not recommended unless directed by health care provider.

Infants ≥6 months and Children ≤11 years: Oral: See table based upon manufacturer's labeling; use of weight to select dose is preferred; if weight is not available, then use age; doses may be repeated every 6 to 8 hours; maximum: 4 doses/day.

Ibuprofen Dosing

Weight (preferred)a

Age

Dosage

(mg)

kg

lbs

5.4 to 8.1

12 to 17

6 to 11 months

50

8.2 to 10.8

18 to 23

12 to 23 months

75 to 80

10.9 to 16.3

24 to 35

2 to 3 years

100

16.4 to 21.7

36 to 47

4 to 5 years

150

21.8 to 27.2

48 to 59

6 to 8 years

200

27.3 to 32.6

60 to 71

9 to 10 years

200 to 250

32.7 to 43.2

72 to 95

11 years

300

a Manufacturer's recommendations are based on weight in pounds (OTC labeling); weight in kg listed here is derived from pounds and rounded; kg weight listed also is adjusted to allow for continuous weight ranges in kg.

Children ≥12 years and Adolescents: Oral: 200 mg every 4 to 6 hours as needed; if fever does not respond may increase to 400 mg; maximum daily dose: 2,400 mg/day (Ref).

Cystic fibrosis, mild disease

Cystic fibrosis, mild disease (to slow lung disease progression): Limited data available: Children and Adolescents 6 to 17 years with FEV1 >60% predicted (Ref): Oral: Initial: 20 to 30 mg/kg/dose twice daily; titrate to achieve peak plasma concentrations of 50 to 100 mcg/mL; should not eat or take pancreatic enzymes for 2 hours after the ibuprofen dose. Dosing based on a study of 41 patients (ages: 5 to 39 years); mean required dose: ~25 mg/kg/dose twice daily; reported range: 16.2 to 31.6 mg/kg/dose every 12 hours required to achieve target concentration; results showed that chronic ibuprofen use (over 4 years) slowed the rate of decline in FEV1; patients 5 to 13 years of age with mild lung disease were observed to have greatest benefit (Ref). A follow up observational study (n=1,365; ages: 6 to 17 years) under noncontrolled conditions (real world) showed significant improvement in the rate of decline of lung disease progression with chronic ibuprofen therapy (Ref). Note: Timing of blood sampling postdose is based on dosage form: Oral suspension: Obtain blood samples at 30, 45, and 60 minutes postdose; tablets: Obtain blood samples at 1, 2, and 3 hours postdose (Ref).

Juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA): Children and Adolescents: Oral: Usual range: 30 to 40 mg/kg/day in 3 to 4 divided doses; start at lower end of dosing range and titrate; patients with more severe disease may require up to 50 mg/kg/day; maximum dose: 800 mg/dose; maximum daily dose: 2,400 mg/day (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

Infants, Children, and Adolescents: Oral, IV (Caldolor): There are no dosage adjustments provided in the manufacturer's labeling; avoid use in advanced disease.

KDIGO guidelines provide the following recommendations for NSAIDs (Ref):

eGFR 30 to <60 mL/minute/1.73 m2: Avoid use in patients with intercurrent disease that increases risk of acute kidney injury.

eGFR <30 mL/minute/1.73 m2: Avoid use.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling; use caution and discontinue if hepatic function worsens.

Dosing: Older Adult

Refer to adult dosing. Use with caution; consider reduced initial dosage.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Oral:

Advil: 200 mg

Advil Liqui-Gels minis: 200 mg

Advil Migraine: 200 mg

GoodSense Ibuprofen: 200 mg [gluten free; contains fd&c blue #1 (brilliant blue)]

KS Ibuprofen: 200 mg [DSC] [contains fd&c blue #2 (indigo carmine,indigotine)]

Motrin IB: 200 mg

Generic: 200 mg

Kit, Combination:

Ibuprofen Comfort Pac: 800 mg [DSC] [contains methylparaben, trolamine (triethanolamine)]

Kit, Oral:

IBU 600-EZS: 600 mg [DSC] [contains sodium benzoate]

Ibupak: 600 mg [contains sodium benzoate]

Solution, Intravenous [preservative free]:

Caldolor: 800 mg/200 mL (200 mL); 800 mg/8 mL (8 mL)

Solution, Intravenous, as lysine [preservative free]:

NeoProfen: 10 mg/mL (2 mL)

Generic: 10 mg/mL (2 mL)

Suspension, Oral:

Childrens Advil: 100 mg/5 mL (120 mL) [fruit flavor]

Childrens Advil: 100 mg/5 mL (120 mL) [contains edetate (edta) disodium, fd&c red #40 (allura red ac dye), polysorbate 80, propylene glycol, sodium benzoate]

Childrens Advil: 100 mg/5 mL (120 mL) [alcohol free; grape flavor]

Childrens Advil: 100 mg/5 mL (120 mL) [alcohol free; contains edetate (edta) disodium, fd&c blue #1 (brilliant blue), fd&c red #40 (allura red ac dye), polysorbate 80, propylene glycol, sodium benzoate; grape flavor]

Childrens Advil: 100 mg/5 mL (120 mL [DSC]) [alcohol free; contains fd&c blue #1 (brilliant blue), propylene glycol, sodium benzoate; blue raspberry flavor]

Childrens Advil: 100 mg/5 mL (30 mL, 120 mL) [alcohol free, dye free; contains edetate (edta) disodium, polysorbate 80, propylene glycol, sodium benzoate; white grape flavor]

Childrens Advil: 100 mg/5 mL (120 mL) [alcohol free, dye free, sugar free; contains edetate (edta) disodium, polysorbate 80, propylene glycol, sodium benzoate; berry flavor]

Childrens Ibuprofen: 100 mg/5 mL (5 mL) [contains fd&c red #40 (allura red ac dye), polysorbate 80, quinoline yellow (d&c yellow #10), sodium benzoate]

Childrens Ibuprofen: 100 mg/5 mL (5 mL) [alcohol free, dye free; contains corn starch, polysorbate 80, sodium benzoate; berry flavor]

Childrens Motrin: 100 mg/5 mL (120 mL) [alcohol free; contains fd&c blue #1 (brill blue) aluminum lake, fd&c red #40 (allura red ac dye), polysorbate 80, sodium benzoate]

Childrens Motrin: 100 mg/5 mL (30 mL, 120 mL) [alcohol free; contains fd&c red #40 (allura red ac dye), polysorbate 80, quinoline yellow (d&c yellow #10), sodium benzoate; berry flavor]

Childrens Motrin: 100 mg/5 mL (120 mL) [alcohol free; contains fd&c red #40 (allura red ac dye), polysorbate 80, sodium benzoate]

Childrens Motrin: 100 mg/5 mL (120 mL, 240 mL) [alcohol free, dye free; contains polysorbate 80, sodium benzoate; berry flavor]

GoodSense Ibuprofen Childrens: 100 mg/5 mL (120 mL) [alcohol free, dye free, gluten free; contains polysorbate 80, sodium benzoate, sorbitol; berry flavor]

GoodSense Ibuprofen Childrens: 100 mg/5 mL (240 mL) [alcohol free, gluten free; contains fd&c red #40 (allura red ac dye), polysorbate 80, sodium benzoate; bubble-gum flavor]

Ibuprofen Childrens: 100 mg/5 mL (118 mL, 237 mL) [contains fd&c blue #1 (brilliant blue), polysorbate 80, propylene glycol, sodium benzoate]

Ibuprofen Childrens: 100 mg/5 mL (118 mL, 237 mL) [contains fd&c red #40 (allura red ac dye), polysorbate 80, propylene glycol, sodium benzoate]

Ibuprofen Childrens: 100 mg/5 mL (5 mL, 10 mL) [alcohol free; contains corn starch, fd&c blue #1 (brilliant blue), fd&c red #40 (allura red ac dye), polysorbate 80, sodium benzoate; grape flavor]

Ibuprofen Childrens: 100 mg/5 mL (118 mL [DSC]) [alcohol free; contains corn starch, fd&c red #40 (allura red ac dye), polysorbate 80, quinoline yellow (d&c yellow #10), sodium benzoate; berry flavor]

Ibuprofen Childrens: 100 mg/5 mL (118 mL) [alcohol free; contains corn starch, fd&c red #40 (allura red ac dye), polysorbate 80, sodium benzoate; bubble-gum flavor]

Ibuprofen Childrens: 100 mg/5 mL (118 mL, 237 mL) [alcohol free; contains fd&c red #40 (allura red ac dye), polysorbate 80, propylene glycol, quinoline yellow (d&c yellow #10), sodium benzoate; berry flavor]

Ibuprofen Childrens: 100 mg/5 mL (120 mL) [alcohol free; contains fd&c red #40 (allura red ac dye), polysorbate 80, propylene glycol, quinoline yellow (d&c yellow #10), sodium benzoate, starch; berry flavor]

Ibuprofen Childrens: 100 mg/5 mL (120 mL, 240 mL) [alcohol free; contains fd&c red #40 (allura red ac dye), polysorbate 80, quinoline yellow (d&c yellow #10), sodium benzoate]

Ibuprofen Childrens: 100 mg/5 mL (120 mL [DSC], 240 mL) [alcohol free; contains fd&c red #40 (allura red ac dye), polysorbate 80, quinoline yellow (d&c yellow #10), sodium benzoate; berry flavor]

Ibuprofen Childrens: 100 mg/5 mL (118 mL [DSC]) [alcohol free, dye free; contains corn starch, polysorbate 80, sodium benzoate; berry flavor]

Ibuprofen Childrens: 100 mg/5 mL (5 mL) [alcohol free, dye free, gluten free; contains fd&c red #40 (allura red ac dye), propylene glycol, quinoline yellow (d&c yellow #10), sodium benzoate]

Ibuprofen Childrens: 100 mg/5 mL (118 mL, 237 mL) [dye free; contains polysorbate 80, propylene glycol, sodium benzoate; berry flavor]

Infants Advil: 50 mg/1.25 mL (30 mL) [alcohol free, dye free; contains edetate (edta) disodium, polysorbate 80, propylene glycol, sodium benzoate]

Infants Advil: 50 mg/1.25 mL (15 mL) [alcohol free, dye free; contains edetate (edta) disodium, polysorbate 80, propylene glycol, sodium benzoate; white grape flavor]

Motrin Infants Drops: 50 mg/1.25 mL (15 mL) [alcohol free; contains fd&c red #40 (allura red ac dye), polysorbate 80, sodium benzoate, sorbitol]

Motrin Infants Drops: 50 mg/1.25 mL (15 mL) [alcohol free; contains fd&c red #40 (allura red ac dye), polysorbate 80, sodium benzoate, sorbitol; berry flavor]

Motrin Infants Drops: 50 mg/1.25 mL (30 mL) [alcohol free, dye free; contains polysorbate 80, sodium benzoate, sorbitol]

Generic: 100 mg/5 mL (5 mL, 118 mL, 120 mL, 473 mL)

Tablet, Oral:

Addaprin: 200 mg [DSC]

Addaprin: 200 mg [DSC] [contains corn starch]

Advil: 200 mg

Advil: 200 mg [contains methylparaben, propylparaben, sodium benzoate]

Advil Junior Strength: 100 mg

Dyspel: 200 mg [DSC]

Genpril: 200 mg [DSC]

GoodSense Ibuprofen: 200 mg [gluten free; contains corn starch, fd&c red #40(allura red ac)aluminum lake, fd&c yellow #6(sunset yellow)alumin lake]

IBU: 400 mg, 600 mg, 800 mg

IBU-200: 200 mg [dye free; contains corn starch]

Motrin IB: 200 mg [contains corn starch, fd&c red #40(allura red ac)aluminum lake, fd&c yellow #6(sunset yellow)alumin lake]

Provil: 200 mg

Generic: 200 mg, 400 mg, 600 mg, 800 mg

Tablet Chewable, Oral:

Advil Junior Strength: 100 mg [scored; contains aspartame, fd&c blue #2(indig carmine)aluminum lake; grape flavor]

Motrin Childrens: 100 mg [contains aspartame, fd&c blue #1 (brill blue) aluminum lake, soybean oil]

Motrin Childrens: 100 mg [dye free; contains aspartame, soybean oil]

Generic Equivalent Available: US

May be product dependent

Dosage Forms Considerations

EnovaRX-Ibuprofen cream is compounded from a kit. Refer to manufacturer’s labeling for compounding instructions.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Caldolor: 100 mg/mL (4 mL, 8 mL)

Tablet, Oral:

Generic: 600 mg

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/UCM387559.pdf, must be dispensed with this medication.

Administration: Adult

Oral: Administer with food or milk.

IV: Caldolor: For IV administration only; infuse over at least 30 minutes (adults).

Administration: Pediatric

Oral: Administer with food or milk to decrease GI upset.

Oral suspension: Shake suspension well before use. Administer with an accurate measuring device (calibrated oral syringe or measuring cup); do not use a household teaspoon or tablespoon to measure dose (overdosage may occur).

IV:

Ibuprofen injection (Caldolor): For IV administration only; in pediatric patients, doses are infused over ≥10 minutes; in adults, doses are infused over ≥30 minutes.

Ibuprofen lysine injection (NeoProfen): For IV administration only; administration via umbilical arterial line has not been evaluated. Infuse over 15 minutes through IV port closest to insertion site. Avoid extravasation. Do not administer simultaneously via same line with TPN. If needed, interrupt TPN for 15 minutes prior to and after ibuprofen administration, keeping line open with dextrose or saline.

Use: Labeled Indications

Oral: Management of inflammatory diseases and rheumatoid disorders, mild to moderate pain, fever, dysmenorrhea, and osteoarthritis

Ibuprofen injection (Caldolor): Management of mild to moderate pain and management of moderate to severe pain as an adjunct to opioid analgesics in adults and children 6 months and older; reduction of fever in adults and children 6 months and older.

Ibuprofen lysine injection (NeoProfen): Patent ductus arteriosus: To close a clinically significant patent ductus arteriosus in premature infants weighing between 500 and 1,500 g who are no more than 32 weeks of gestational age when usual medical management (eg, diuretics, fluid restriction, respiratory support) is ineffective.

OTC labeling: Reduction of fever; management of pain due to headache, acute migraine, sore throat, arthritis, or physical or athletic overexertion (eg, sprains/strains), menstrual pain, dental pain, minor muscle/bone/joint pain, backache, and pain due to the common cold and flu.

Use: Off-Label: Adult

Gout, treatment (acute flares); Pericarditis, acute or recurrent

Medication Safety Issues
Sound-alike/look-alike issues:

Haltran may be confused with Halfprin

Motrin may be confused with Neurontin

Older Adult: High-Risk Medication:

Beers Criteria: Ibuprofen is identified in the Beers Criteria as a potentially inappropriate medication to be avoided for chronic use in patients 65 years and older (unless alternative agents ineffective and patient can receive concomitant gastroprotective agent) due to increased risk of GI bleeding and peptic ulcer disease in older adults in high risk category (eg, older than 75 years of age or receiving concomitant oral/parenteral corticosteroids, anticoagulants, or antiplatelet agents) (Beers Criteria [AGS 2019]).

Administration issues:

Injectable formulations: Both ibuprofen and ibuprofen lysine are available for parenteral use. Ibuprofen lysine is only indicated for closure of a clinically-significant patent ductus arteriosus.

Adverse Reactions (Significant): Considerations
Cardiovascular effects

Use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk of serious adverse cardiovascular (CV) events, including acute myocardial infarction (MI), cerebrovascular accident, and CV death. New-onset hypertension or exacerbation of hypertension may occur with NSAID use which may also contribute to an increased risk of CV events (Ref). New-onset or exacerbation of heart failure may also occur with cyclooxygenase (COX) NSAIDs (ie, coxibs) and nonselective NSAIDs, including ibuprofen, resulting in an increased risk of hospitalizations for heart failure and death in patients with heart failure (Ref).

Data collected by the Coxib and traditional NSAID Trialists’ (CNT) Collaborative have shown that high-dose ibuprofen (2,400 mg daily) and diclofenac are associated with a similar CV risk as compared to coxibs and that naproxen may have the most favorable CV risk profile among NSAIDs analyzed (Ref); however, data from the PRECISION trial showed no difference with regards to risk between naproxen, ibuprofen, or celecoxib after a treatment duration of therapy of ~3 years (Ref). The FDA states that there are insufficient data to determine if risk of MI or stroke is definitely higher or lower for any particular NSAID as compared to another (Ref).

Mechanism: Dose- and time-related; inhibition of COX-2 by NSAIDs results in a reduction in the production of prostaglandin I2 (prostacyclin) in the vascular endothelium (Ref); animal studies have shown that reduced prostacyclin activity may result in a predisposition to vascular injury (Ref). In addition, prostaglandins inhibit sodium resorption in the thick ascending loop of Henle and collecting tubule; therefore, a reduction in prostaglandin synthesis by NSAIDs may cause sodium and fluid retention and result in hypertension and decreased efficacy of diuretics (Ref).

Onset: Varied; increased risk may be apparent within the first weeks following initiation of treatment (Ref); longer duration of therapy may further increase risk (Ref).

Risk factors:

• ≥65 years of age

• Higher doses (especially with regards to CV thrombotic risk (Ref))

• Longer duration of use and frequent use (eg, ≥22 days per month (Ref)

• Preexisting cardiovascular disease (CVD) or presence of risk factors for CVD, including use following coronary artery bypass graft surgery (Ref)

- Note: Relative risk appears to be similar in those with and without known CVD or risk factors for CVD; however, absolute incidence of serious CV thrombotic events appears to be higher in patients with known CVD or risk factors for CVD due to an increased baseline risk (Ref)

Gastrointestinal events

Use of nonsteroidal anti-inflammatory drugs (NSAIDs), especially nonselective NSAIDs, such as ibuprofen, is associated with an increased risk of serious GI adverse events, including gastrointestinal inflammation, gastrointestinal hemorrhage, gastrointestinal ulcer, and gastrointestinal perforation; severity may range from asymptomatic to fatal (Ref).

Mechanism: Dose- and time-related; inhibition of cyclooxygenase (COX)-1 by NSAIDs results in a reduction in the production of mucosal-protective prostaglandin E2 (Ref).

Onset: Varied; GI events can occur at any time during use and without warning symptoms. A longer duration of use (eg, ≥7 days (Ref)) is associated with a greater risk.

Risk factors:

• ≥65 years of age (Ref)

• Longer duration of use (eg, ≥7 days (Ref))

• Higher doses (Ref)

• Prior history of peptic ulcer disease and/or GI bleeding (Ref)

• Concomitant use of agents known to increase the risk of GI bleeding (eg, aspirin (Ref), anticoagulants, corticosteroids (Ref), selective serotonin reuptake inhibitors (Ref))

• Comorbid Helicobacter pylori infection (Ref)

• Advanced liver disease/cirrhosis

• Coagulopathy

• Smoking

• Consumption of alcohol

• People with poor general health status

• Small intestine damage: Small intestine bacterial overgrowth (SIBO), including SIBO induced by proton pump inhibitor therapy, may be associated with an increased risk of small intestine damage (Ref)

Hematologic effects

Use of nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen, is associated with prolonged bleeding time and an increased risk for hemorrhage (Ref).

In addition, drug-induced hemolytic anemia may occur (Ref). Rarely, NSAID use has been associated with potentially severe blood dyscrasias (eg, agranulocytosis, aplastic anemia, neutropenia, thrombocytopenia) (Ref).

Mechanism:

Prolonged bleeding time: Inhibition of cyclooxygenase (COX)-1 by nonselective NSAIDs causes a decrease in the production of prostaglandins, prostacyclins, and thromboxanes, including thromboxane A2 (TxA2) (Ref). As a result, patients may exhibit a decrease in platelet adhesion and aggregation and subsequent prolonged bleeding time (Ref).

Blood dyscrasias: Not clearly established; anemia may be due to occult or gross blood loss, fluid retention, or an incompletely described effect on erythropoiesis.

Onset:

Prolonged bleeding time: Rapid; suppression of platelet COX-1 activity occurs within hours of administration (Ref). In patients receiving antithrombotic therapy after myocardial infarction, the use of NSAIDs has been associated with an increased risk of bleeding and excess thrombotic events, even after short-term treatment (eg, <3 days) (Ref).

Risk factors:

• Bleeding events:

- Preexisting coagulation disorders

- Concomitant use of agents known to increase the risk of bleeding (eg, anticoagulants (Ref), antithrombotics (Ref), antiplatelet agents [eg, aspirin], selective serotonin reuptake inhibitors (Ref), or serotonin norepinephrine reuptake inhibitors)

- Use during and immediately following surgical procedures (Ref)

Hepatic effects

Use of nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen, may result in mild transaminase elevations, especially with higher doses (ie, ibuprofen 2,400 to 3,200 mg/day) (Ref); rarely, serious liver injury may also occur (Ref). Idiopathic liver injuries with a mixed or cholestatic pattern have been reported; these reactions may occur following severe hypersensitivity reactions (eg, toxic epidermal necrosis, Stevens-Johnson syndrome) and are characterized by immune-mediated symptoms (eg, fever rash, eosinophilia, lymphadenopathy) (Ref). Severe liver injury requiring liver transplantation has also been reported (Ref). Most cases of liver injury are likely reversible following discontinuation; full recovery may take several months (Ref). However, chronic vanishing bile duct syndrome with chronic liver failure has been described following cholestatic liver injury (Ref).

Mechanism: Not clearly established; may be a result of a toxic metabolite or an immune-mediated reaction (Ref).

Onset: Varied; liver injury that appears to be immune-mediated usually occur within a few days to 3 weeks after treatment initiation (Ref).

Risk factors:

• Prior NSAID-related liver injury (Ref)

- Note: Cross-reactivity may occur among propionic acid derivatives (eg, ibuprofen, naproxen, ketoprofen) (Ref)

Hypersensitivity reactions (immediate and delayed)

Hypersensitivity reactions (immediate and delayed) involving the skin (eg, angioedema, urticaria), airways (eg, dyspnea, rhinorrhea), and/or other organs have been reported (Ref). Clinical phenotypes of nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity reactions include NSAID-exacerbated respiratory disease (NERD), NSAID-induced urticaria/angioedema (NIUA), NSAID-exacerbated cutaneous disease (NECD), and single NSAID-induced urticaria/angioedema or anaphylaxis (Ref). Delayed hypersensitivity reactions, including acute generalized exanthematous pustulosis (AGEP), drug rash with eosinophilia and systemic symptoms (DRESS), and Stevens-Johnson syndrome (SJS) have also been associated with ibuprofen (Ref).

Mechanism:

Immediate reactions: Non–dose-related; most reactions (ie, NERD, NECD, NIUA) are non-immunologic related to inhibition of cyclooxygenase-1 (COX-1) with subsequent activation of mast cells and eosinophils causing release of inflammatory mediators including cysteinyl-leukotrienes (cysLTs) (Ref). Some immediate reactions are IgE-mediated (Ref).

Delayed reactions: Delayed hypersensitivity reactions are T-cell–mediated (Ref).

Onset:

Immediate reactions: Rapid; occur within 1 hour of administration but may occur several hours after exposure (Ref).

Delayed reactions (including DRESS, AGEP, and SJS): Varied, generally occurs after 1 to 8 weeks after initiation (Ref), although some patients may develop symptoms within 24 hours (Ref).

Risk factors:

• Presence of chronic rhinosinusitis with nasal polyps, family history of NERD, and/or severe asthma may increase the risk of NERD (Ref). The prevalence of NERD in adult patients with asthma is ~10% to 20% (Ref).

• Chronic urticaria increases the risk of NECD (Ref). NSAID-induced reactions are less frequent and less intense when chronic urticaria is in remission or under control (Ref). Approximately 12% to 30% of patients with chronic idiopathic urticaria develop exacerbations of their disease with use of ibuprofen and other COX-1 inhibitors (Ref).

• Cross-reactivity between aspirin and NSAIDs, including ibuprofen (with predominant COX-1 inhibition) have been described in patients with a history of NERD, NECD, and NIUA (Ref). Cross-reactivity between aspirin/NSAID and acetaminophen, a weak COX inhibitor, and between aspirin/NSAID and nonselective COX-2 inhibitors (eg, meloxicam, nimesulide) may occur (Ref). Although selective COX-2 inhibitors (eg, celecoxib, etoricoxib) are generally tolerated in patients with NERD (Ref), cross-reactions may occur, especially in patients with histories of urticaria/angioedema (Ref).

• Cross-reactivity may occur among propionic acid derivatives (eg, ibuprofen, naproxen, ketoprofen) in patients with histories of immediate hypersensitivity reactions to ibuprofen but tolerance to aspirin (Ref)

Kidney effects

Use of nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen, is associated with an increased risk of several kidney-specific effects: Hemodynamically-mediated acute kidney injury, interstitial nephritis (with or without nephrotic syndrome), and renal papillary necrosis in all ages.

Hemodynamically-mediated acute kidney injury (AKI): Hemodynamically-mediated AKI may occur following use of either cyclooxygenase (COX)-2 selective NSAIDs (ie, coxibs) or nonselective NSAIDs, including ibuprofen (Ref); the risk may be greater with nonselective NSAIDs, especially indomethacin (Ref). The risk of developing AKI is decreased upon discontinuation (Ref). In patients who develop AKI, kidney function is likely to return to baseline following prompt discontinuation of the offending NSAID and supportive care (Ref); however, the mechanism of the damage and other concurrent factors can contribute to irreversibility.

Acute interstitial nephritis (AIN) with or without nephrotic syndrome: Patients may develop NSAID-associated proteinuria combined with interstitial nephritis and varying degrees of kidney impairment; the “classic triad” of fever, rash, and eosinophilia is less commonly observed in NSAID-associated AIN than with antibiotic-induced AIN (Ref). Kidney histology may reveal minimal change glomerulonephritis or membranous nephropathy (Ref). While use of ibuprofen has been associated with this clinical picture, the risk may be greatest with fenoprofen as compared to other NSAIDS (Ref). Proteinuria generally improves within weeks following discontinuation; full recovery may require treatment and take up to a year (Ref).

Papillary necrosis: Chronic use of NSAIDs, including ibuprofen, has resulted in the development of papillary necrosis, which may occur in conjunction with chronic interstitial nephritis and progressive decline in glomerular filtration rate as a clinical syndrome known as analgesic nephropathy (Ref). However, controversy exists on the degree to which NSAID use increases the risk for chronic kidney disease and analgesic nephropathy (Ref). Acute papillary necrosis may occur following NSAID overdose, especially in a setting of severe dehydration or intravascular volume depletion (Ref).

Mechanism:

Hemodynamically-mediated AKI: Dose- and time-related; inhibition of cyclooxygenase (COX)-1 and COX-2 by NSAIDs results in a reduced production of nephroprotective prostaglandins and subsequent attenuation of renal vasodilation (Ref). In addition, an increase in vasoconstriction of the afferent arteriole and impaired renal blood flow causes a reduction in the glomerular capillary pressure and filtration (Ref).

AIN with or without nephrotic syndrome: Not clearly established. Following inhibition of COX-1 and COX-2 by NSAIDs, arachidonic acid is formed which may be further metabolized to leukotrienes via the lipoxygenase pathway; leukotrienes may increase vascular permeability within glomerular capillaries and peritubular capillaries and increase lymphocyte recruitment and activation (Ref).

Papillary necrosis: Time-related; exact mechanism is not clearly established; may be due to direct toxicity and/or inhibition of prostaglandin-mediated vasodilation resulting in ischemic necrosis (Ref).

Onset:

AKI: Rapid; may occur within days of treatment initiation (Ref).

AIN with or without nephrotic syndrome: Varied; mean time of onset of ~5 months (range: 2 weeks to 18 months) has been described (Ref).

Risk factors:

• AKI:

- Preexisting kidney impairment

- Chronic kidney disease

Note: High cumulative doses (eg, ibuprofen >700 mg/day) may increase the risk for progression of chronic kidney disease (Ref)

- ≥65 years of age (Nash 2019)

Note: NSAID-associated AKI may also occur in pediatric patients, even at therapeutic doses (Brophy 2013, Misurac 2013)

• Hemodynamically-mediated AKI:

- Preexisting conditions which result in decreased effective arterial circulation (ie, conditions where renal blood flow/renal perfusion may be dependent on prostaglandin-mediated vasodilation) (Baker 2020):

Volume depletion (eg, due to concomitant diuretic use, nausea, vomiting)

Heart failure (Ref)

Cirrhosis and ascites (Ref)

Nephrotic syndrome

- Concomitant use of diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or calcineurin inhibitors (Ref)

• AIN with or without nephrotic syndrome: Prior history of NSAID-induced nephrotic syndrome; recurrence has been described (Ref)

• Papillary necrosis (acute):

- Massive NSAID ingestion (Ref)

- Dehydration (Ref)

- Intravascular volume depletion (Ref)

• Papillary necrosis (chronic)/analgesic nephropathy: Chronic concomitant use of other analgesics (eg, aspirin, acetaminophen) (Ref)

Pulmonary hypertension

Pulmonary hypertension has occurred following early (prophylactic) administration and treatment of patent ductus arteriosus (PDA) in preterm or low birth weight neonates; cases have been reported with both tromethamine ibuprofen (not available in the United States) and L-lysine ibuprofen therapy (Ref).

Mechanism: Unknown; several hypotheses have been proposed. The first relates to timing of treatment in which the administration of drug and PDA closure occurs before the normal decrease in pulmonary vascular resistance has occurred (Ref). Another hypothesis involves the effects of the acidic pH of the ibuprofen solution, namely tromethamine buffered solutions, which may lead to precipitation and microembolism of the lung (Ref).

Onset: Variable; has occurred within the first hour following the administration of the first or second dose of treatment (Ref).

Risk factors:

• Lower gestational age (Ref)

• Lower birthweight (less than third percentile for age) (Ref)

• Preexisting pulmonary hypertension (Ref)

• Early administration of treatment (<6 hours postnatal age in premature neonates) (Ref)

• Maternal hypertension of pregnancy (Ref)

• Maternal oligohydramnios (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Oral:

>10%: Hematologic & oncologic: Decreased hemoglobin (17% to 23%)

1% to 10%:

Cardiovascular: Edema (1% to 3%)

Dermatologic: Maculopapular rash, pruritus (1% to 3%), skin rash (3% to 9%)

Endocrine & metabolic: Fluid retention (1% to 3%)

Gastrointestinal: Abdominal cramps (1% to 3%), abdominal distress (1% to 3%), abdominal pain (1% to 3%), bloating (1% to 3%), constipation (1% to 3%), decreased appetite (1% to 3%), diarrhea (1% to 3%), dyspepsia (1% to 3%), epigastric pain (3% to 9%), flatulence (1% to 3%), heartburn (3% to 9%), nausea (3% to 9%), nausea and vomiting (1% to 3%)

Nervous system: Dizziness (3% to 9%), headache (1% to 3%), nervousness (1% to 3%)

Otic: Tinnitus (1% to 3%)

<1%:

Cardiovascular: Cardiac arrhythmia, increased blood pressure, palpitations, sinus bradycardia, sinus tachycardia

Dermatologic: Alopecia, erythema multiforme, skin photosensitivity, urticaria, vesiculobullous dermatitis

Endocrine & metabolic: Acidosis, gynecomastia, heavy menstrual bleeding, hypoglycemia

Gastrointestinal: Duodenal ulcer, gastric ulcer, gastritis, gingival ulceration, melena, pancreatitis, xerostomia

Genitourinary: Azotemia, cystitis, hematuria

Hematologic & oncologic: Agranulocytosis, aplastic anemia, decreased hematocrit, eosinophilia, hemolytic anemia, hemorrhage, Henoch-Schonlein purpura, neutropenia, thrombocytopenia, ulcer with hemorrhage

Hepatic: Abnormal hepatic function tests, hepatitis, jaundice

Hypersensitivity: Angioedema, serum sickness

Nervous system: Abnormal dreams, chills, confusion, depression, drowsiness, emotional lability, hallucination, idiopathic intracranial hypertension, insomnia, paresthesia

Neuromuscular & skeletal: Systemic lupus erythematosus

Ophthalmic: Amblyopia, cataract, conjunctivitis, diplopia, optic neuritis, xerophthalmia

Otic: Hearing loss

Renal: Decreased creatinine clearance, polyuria, renal papillary necrosis

Respiratory: Bronchospasm, epistaxis, rhinitis

Miscellaneous: Fever

Injection: Ibuprofen (Caldolor):

>10%:

Endocrine & metabolic: Hypokalemia (4% to 19%)

Gastrointestinal: Flatulence (16%), vomiting (22%; children: ≥2%)

Hematologic & oncologic: Anemia (4% to 36%; children: ≥2%), eosinophilia (26%), hypoproteinemia (10% to 13%), neutropenia (7% to 13%) (table 1)

Ibuprofen: Adverse Reaction: Neutropenia

Drug (Ibuprofen)

Placebo

Population

Dose

Dosage Form

Indication

Number of Patients (Ibuprofen)

Number of Patients (Placebo)

13%

7%

Adults

400 mg every 4 hours for 24 hours

IV

Fever

31

28

7%

7%

Adults

200 mg every 4 hours for 24 hours

IV

Fever

30

28

7%

7%

Adults

100 mg every 4 hours for 24 hours

IV

Fever

30

28

Infection: Bacteremia (13%)

Nervous system: Headache (12%; children: ≥2%)

1% to 10%:

Cardiovascular: Hypertension (≤10%) (table 2), hypotension (7% to 10%), peripheral edema (3%)

Ibuprofen: Adverse Reaction: Hypertension

Drug (Ibuprofen)

Placebo

Population

Dose

Dosage Form

Indication

Number of Patients (Ibuprofen)

Number of Patients (Placebo)

10%

0%

Adults

400 mg every 4 hours for 24 hours

IV

Fever

31

28

0%

0%

Adults

200 mg every 4 hours for 24 hours

IV

Fever

30

28

0%

0%

Adults

100 mg every 4 hours for 24 hours

IV

Fever

30

28

Endocrine & metabolic: Hypernatremia (7% to 10%), hypoalbuminemia (10%), increased lactate dehydrogenase (7% to 10%)

Gastrointestinal: Abdominal distress (≤3%), diarrhea (10%), dyspepsia (1% to 4%), nausea (children: ≥2%)

Genitourinary: Urinary retention (5%)

Hematologic & oncologic: Hemorrhage (10%), thrombocythemia (3% to 10%), wound hemorrhage (3%)

Local: Infusion-site pain (children: ≥2%)

Nervous system: Dizziness (4% to 6%)

Renal: Increased blood urea nitrogen (10%)

Respiratory: Bacterial pneumonia (3% to 10%), cough (3%)

Injection: Ibuprofen lysine (NeoProfen) (as reported in premature infants):

>10%:

Dermatologic: Skin irritation (≤16%), skin lesion (≤16%)

Endocrine & metabolic: Hypocalcemia (12%), hypoglycemia (12%)

Gastrointestinal: Enterocolitis (22%)

Hematologic & oncologic: Anemia (32%), hemorrhage (32%; primarily intraventricular)

Infection: Sepsis (43%)

Nervous system: Intraventricular hemorrhage (29%)

Respiratory: Apnea (28%), respiratory tract infection (19%)

1% to 10%:

Cardiovascular: Edema (4%)

Endocrine & metabolic: Adrenocortical insufficiency (7%), hypernatremia (7%)

Genitourinary: Decreased urine output (3%), urinary tract infection (9%)

Renal: Increased blood urea nitrogen (7%), increased serum creatinine (3%), renal insufficiency (6%)

Respiratory: Atelectasis (4%), respiratory failure (10%)

Frequency not defined (any formulation):

Cardiovascular: Hypotension, tachycardia

Endocrine & metabolic: Hyperglycemia

Gastrointestinal: Abdominal distention, cholestasis, gastritis, gastroesophageal reflux disease, intestinal obstruction

Hematologic & oncologic: Neutropenia, prolonged bleeding time

Hepatic: Jaundice

Infection: Infection

Local: Injection site reaction

Nervous system: Seizure

Miscellaneous: Reduced intake of food/fluids

Postmarketing (any formulation):

Cardiovascular: Acute myocardial infarction (FDA 2015), cerebrovascular accident (FDA 2015), exacerbation of hypertension (Ruschitzkha 2017), heart failure (FDA 2015), thrombosis

Dermatologic: Exfoliative dermatitis, skin rash, Stevens-Johnson syndrome (Sternlieb 1978), toxic epidermal necrolysis (Balint 2014; Barry 2018)

Gastrointestinal: Gastrointestinal hemorrhage (Yeomans 2018), gastrointestinal inflammation, gastrointestinal perforation (including esophageal perforation, intestinal, stomach) (Yeomans 2018), gastrointestinal ulcer (Yeomans 2018), necrotizing enterocolitis

Genitourinary: Oliguria (Brandstetter 1978)

Hematologic & oncologic: Thrombocytopenia (Jain 1994)

Hepatic: Hepatotoxicity (idiosyncratic) (Chalasani 2021), increased serum alanine aminotransferase, increased serum aspartate aminotransferase

Hypersensitivity: Anaphylaxis (Kay 2013), hypersensitivity reaction

Immunologic: Drug reaction with eosinophilia and systemic symptoms syndrome (Koca 2016; Roales-Gómez 2014)

Nervous system: Aseptic meningitis (Pires 2019)

Ophthalmic: Blurred vision, scotoma, vision color changes, visual disturbance

Renal: Acute kidney injury (Rahman 2014; Misurac 2013), interstitial nephritis (Rahman 2014), renal failure syndrome (Marasco 1987; Poirier 1984)

Respiratory: Pulmonary hypertension (Bellini 2006; Gournay 2002; Ohlsson 2013)

Contraindications

Hypersensitivity to ibuprofen (eg, anaphylactic reactions, serious skin reactions) or any component of the formulation; history of asthma, urticaria, or allergic-type reaction to aspirin or other NSAIDs; aspirin triad (eg, bronchial asthma, aspirin intolerance, rhinitis); use in the setting of coronary artery bypass graft (CABG) surgery

Ibuprofen lysine (NeoProfen): Proven or suspected infection that is untreated; congenital heart disease in whom patency of the PDA is necessary for satisfactory pulmonary or systemic blood flow (eg, pulmonary atresia, severe coarctation of the aorta, severe tetralogy of Fallot); bleeding (especially those with active intracranial hemorrhage or GI bleeding); thrombocytopenia; coagulation defects; proven or suspected necrotizing enterocolitis; or significant renal function impairment.

Canadian labeling: Additional contraindications (not in US labeling): Cerebrovascular bleeding or other bleeding disorders; active gastric/duodenal/peptic ulcer, active GI bleeding; inflammatory bowel disease; uncontrolled heart failure; moderate [IV formulation only] to severe renal impairment (creatinine clearance [CrCl] <30 mL/minute); deteriorating renal disease; moderate [IV formulation only] to severe hepatic impairment; active hepatic disease; hyperkalemia; third trimester of pregnancy; breast-feeding; patients <18 years of age [IV formulation only]; patients <12 years of age [oral formulation only]; systemic lupus erythematosus [oral formulation only]; children suffering from dehydration as a result of acute diarrhea, vomiting, or lack of fluid intake

OTC labeling: When used for self-medication, do not use if previous allergic reaction to any other pain reliever/fever reducer; prior to or following cardiac surgery.

Warnings/Precautions

Concerns related to adverse effects:

• CNS effects: May cause drowsiness, dizziness, blurred vision, and other neurologic effects which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

• Hyperkalemia: Nonsteroidal anti-inflammatory drug (NSAID) use may increase the risk of hyperkalemia, particularly in patients ≥65 years of age, in patients with diabetes or renal disease, and with concomitant use of other agents capable of inducing hyperkalemia (eg, ACE inhibitors). Monitor potassium closely.

• Ophthalmic events: Blurred/diminished vision, scotomata, and changes in color vision have been reported. Discontinue therapy and refer for ophthalmologic evaluation if symptoms occur. Periodically evaluate vision in all patients receiving long-term therapy.

Disease-related concerns:

• Aseptic meningitis: May increase the risk of aseptic meningitis, especially in patients with systemic lupus erythematosus and mixed connective tissue disorders.

• Asthma: Contraindicated in patients with aspirin-sensitive asthma; severe and potentially fatal bronchospasm may occur. Use caution in patients with other forms of asthma.

• Bariatric surgery: Gastric ulceration: Avoid chronic use of oral nonselective NSAIDs after bariatric surgery; development of anastomotic ulcerations/perforations may occur (Bhangu 2014; Mechanick 2020). Short-term use of celecoxib or IV ketorolac is recommended as part of a multimodal pain management strategy for postoperative pain (Chou 2016b; Horsley 2019; Thorell 2016).

• Hepatic impairment: Use with caution in patients with hepatic impairment.

• Renal impairment: Use with caution in patients with renal impairment. Use of ibuprofen lysine (NeoProfen) is contraindicated in preterm infants with significant renal impairment.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.

• Ibuprofen injection (Caldolor): Must be diluted prior to administration; hemolysis can occur if not diluted.

• Ibuprofen lysine injection (NeoProfen): Hold second or third doses if urinary output is <0.6 mL/kg/hour. May alter signs of infection. May inhibit platelet aggregation; monitor for signs of bleeding. May displace bilirubin; use caution when total bilirubin is elevated. Long-term evaluations of neurodevelopment, growth, or diseases associated with prematurity following treatment have not been conducted. Avoid extravasation.

• Phenylalanine: Some products may contain phenylalanine.

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures and respiratory depression; use caution (AAP ["Inactive" 1997]; Zar 2007).

Other warnings/precautions:

• Self-medication (OTC use): Prior to self-medication, patients should contact health care provider if they have had recurring stomach pain or upset, ulcers, bleeding problems, high blood pressure, heart or kidney disease, other serious medical problems, are currently taking a diuretic, aspirin, anticoagulant, or are ≥60 years of age. If patients are using for migraines, they should also contact health care provider if they have not had a migraine diagnosis by health care provider, a headache that is different from usual migraine, worst headache of life, fever and neck stiffness, headache from head injury or coughing, first headache at ≥50 years of age, daily headache, or migraine requiring bed rest. Recommended dosages should not be exceeded, due to an increased risk of GI bleeding. Stop use and consult a health care provider if symptoms do not improve within first 24 hours of use (children) get worse, or newly appear, fever lasts for >3 days or pain lasts >3 days (children) and >10 days (adults). Do not give for >10 days unless instructed by healthcare provider. Consuming ≥3 alcoholic beverages/day or taking longer than recommended may increase the risk of GI bleeding.

• Surgical/dental procedures: Withhold for at least 4 to 6 half-lives prior to surgical or dental procedures.

Warnings: Additional Pediatric Considerations

Oral liquid products are available in 2 concentrations (concentrated infant drops: 50 mg/1.25 mL [40 mg/mL] and suspension: 100 mg/5 mL [20 mg/mL]); precautions should be taken to verify and avoid confusion between the different concentrations; dose should be clearly presented as "mg".

IV ibuprofen is as effective as IV indomethacin for the treatment of patent ductus arteriosus (PDA) in preterm neonates, but is less likely to cause adverse effects on renal function (eg, oliguria, increased serum creatinine) (Aranda 2006; Lago 2002; Ohlsson 2013; Van Overmeire 2000). Ibuprofen (compared to indomethacin) also has been shown to decrease the risk of developing NEC (Ohlsson 2013).

Use with caution in neonates with controlled infection or those at risk for infection; ibuprofen may alter the usual signs of infection. Use with caution in neonates when total bilirubin is elevated; ibuprofen may displace bilirubin from albumin-binding sites.

Avoid extravasation of ibuprofen lysine injection (NeoProfen); IV solution may be irritating to tissues.

Some dosage forms may contain propylene glycol; in neonates, large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).

Metabolism/Transport Effects

Substrate of CYP2C19 (minor), CYP2C9 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits OAT1/3

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of 5-Aminosalicylic Acid Derivatives. Risk C: Monitor therapy

Abrocitinib: Agents with Antiplatelet Properties may enhance the antiplatelet effect of Abrocitinib. Management: Do not use antiplatelet drugs with abrocitinib during the first 3 months of abrocitinib therapy. The abrocitinib prescribing information lists this combination as contraindicated. This does not apply to low dose aspirin (81 mg/day or less). Risk X: Avoid combination

Acalabrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Acemetacin: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Risk C: Monitor therapy

Alcohol (Ethyl): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of GI bleeding may be increased with this combination. Risk C: Monitor therapy

Aliskiren: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Aliskiren. Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Aliskiren. Risk C: Monitor therapy

Aminoglycosides: Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants. Risk C: Monitor therapy

Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Risk X: Avoid combination

Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Risk C: Monitor therapy

Angiotensin II Receptor Blockers: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Angiotensin II Receptor Blockers. The combination of these two agents may also significantly decrease glomerular filtration and renal function. Risk C: Monitor therapy

Angiotensin-Converting Enzyme Inhibitors: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Apixaban: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Apixaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of apixaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Bemiparin: Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin and nonsteroidal anti-inflammatory agents (NSAIDs) due to the increased risk of bleeding. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Bemiparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin with antiplatelet agents. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Beta-Blockers: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Beta-Blockers. Risk C: Monitor therapy

Bile Acid Sequestrants: May decrease the absorption of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy

Bisphosphonate Derivatives: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Bisphosphonate Derivatives. Both an increased risk of gastrointestinal ulceration and an increased risk of nephrotoxicity are of concern. Risk C: Monitor therapy

Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. Risk C: Monitor therapy

Clofarabine: OAT1/3 Inhibitors may increase the serum concentration of Clofarabine. Risk C: Monitor therapy

Collagenase (Systemic): Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and or bleeding may be increased. Risk C: Monitor therapy

Corticosteroids (Systemic): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Risk C: Monitor therapy

CycloSPORINE (Systemic): Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of CycloSPORINE (Systemic). Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase the serum concentration of Nonsteroidal Anti-Inflammatory Agents. Management: Consider alternatives to nonsteroidal anti-inflammatory agents (NSAIDs). Monitor for evidence of nephrotoxicity, as well as increased serum cyclosporine concentrations and systemic effects (eg, hypertension) during concomitant therapy with NSAIDs. Risk D: Consider therapy modification

Dabigatran Etexilate: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Dabigatran Etexilate. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of dabigatran and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Deferasirox: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Risk C: Monitor therapy

Deoxycholic Acid: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Risk C: Monitor therapy

Desmopressin: Nonsteroidal Anti-Inflammatory Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy

Dichlorphenamide: OAT1/3 Inhibitors may increase the serum concentration of Dichlorphenamide. Risk C: Monitor therapy

Digoxin: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Digoxin. Risk C: Monitor therapy

Drospirenone-Containing Products: May enhance the hyperkalemic effect of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy

Edoxaban: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of edoxaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Enoxaparin: Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue nonsteroidal anti-inflammatory agents (NSAIDs) prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Enoxaparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue antiplatelet agents prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Eplerenone: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Eplerenone. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Eplerenone. Risk C: Monitor therapy

Fluconazole: May increase the serum concentration of Ibuprofen. Risk C: Monitor therapy

Heparin: Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or nonsteroidal anti-inflammatory agents (NSAIDs) if coadministration is required. Risk D: Consider therapy modification

Heparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or agents with antiplatelet properties if coadministration is required. Risk D: Consider therapy modification

Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Risk C: Monitor therapy

Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Bleeding may occur. Risk C: Monitor therapy

HydrALAZINE: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of HydrALAZINE. Risk C: Monitor therapy

Ibritumomab Tiuxetan: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Risk C: Monitor therapy

Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Icosapent Ethyl: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Imatinib: Ibuprofen may decrease the serum concentration of Imatinib. Specifically, ibuprofen may decrease intracellular concentrations of imatinib, leading to decreased clinical response. Management: Consider using an alternative to ibuprofen in patients who are being treated with imatinib. Available evidence suggests other NSAIDs do not interact in a similar manner. Risk D: Consider therapy modification

Inotersen: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Ketorolac (Nasal): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination

Ketorolac (Systemic): Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Ketorolac (Systemic). Risk X: Avoid combination

Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Lipid Emulsion (Fish Oil Based): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Lithium: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Lithium. Management: Consider reducing the lithium dose when initiating a NSAID. Monitor for increased lithium therapeutic/toxic effects if a NSAID is initiated/dose increased, or decreased effects if a NSAID is discontinued/dose decreased. Risk D: Consider therapy modification

Loop Diuretics: Nonsteroidal Anti-Inflammatory Agents may diminish the diuretic effect of Loop Diuretics. Loop Diuretics may enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Management: Monitor for evidence of kidney injury or decreased therapeutic effects of loop diuretics with concurrent use of an NSAID. Consider avoiding concurrent use in CHF or cirrhosis. Concomitant use of bumetanide with indomethacin is not recommended. Risk D: Consider therapy modification

Lumacaftor and Ivacaftor: May decrease the serum concentration of Ibuprofen. Risk C: Monitor therapy

Macimorelin: Nonsteroidal Anti-Inflammatory Agents may diminish the diagnostic effect of Macimorelin. Risk X: Avoid combination

MetFORMIN: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of MetFORMIN. Risk C: Monitor therapy

Methotrexate: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Methotrexate. Management: Avoid coadministration of higher dose methotrexate (such as that used for the treatment of oncologic conditions) and NSAIDs. Use caution if coadministering lower dose methotrexate and NSAIDs. Risk D: Consider therapy modification

Methoxsalen (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Methoxsalen (Systemic). Risk C: Monitor therapy

Mifamurtide: Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Mifamurtide. Risk X: Avoid combination

Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Naftazone: May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of other Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk for gastrointestinal toxicity is increased. Risk X: Avoid combination

Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of gastrointestinal (GI) toxicity is increased. Management: Coadministration of systemic nonsteroidal anti-inflammatory drugs (NSAIDs) and topical NSAIDs is not recommended. If systemic NSAIDs and topical NSAIDs, ensure the benefits outweigh the risks and monitor for increased NSAID toxicities. Risk D: Consider therapy modification

Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Risk C: Monitor therapy

Omacetaxine: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Risk C: Monitor therapy

Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

PEMEtrexed: Ibuprofen may increase the serum concentration of PEMEtrexed. Management: In patients with an estimated creatinine clearance of 45 to 79 mL/min, avoid ibuprofen for 2 days before, the day of, and 2 days following the administration of pemetrexed. Monitor for increased pemetrexed toxicities if combined. Risk D: Consider therapy modification

Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Risk C: Monitor therapy

Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Phenylbutazone: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination

Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy

Potassium Salts: Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium Salts. Risk C: Monitor therapy

Potassium-Sparing Diuretics: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy

PRALAtrexate: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of PRALAtrexate. More specifically, NSAIDS may decrease the renal excretion of pralatrexate. Management: Avoid coadministration of pralatrexate with nonsteroidal anti-inflammatory drugs (NSAIDs). If coadministration cannot be avoided, closely monitor for increased pralatrexate serum levels or toxicity. Risk D: Consider therapy modification

Probenecid: May increase the serum concentration of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Prostaglandins (Ophthalmic): Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Prostaglandins (Ophthalmic). Nonsteroidal Anti-Inflammatory Agents may also enhance the therapeutic effects of Prostaglandins (Ophthalmic). Risk C: Monitor therapy

Quinolones: Nonsteroidal Anti-Inflammatory Agents may enhance the neuroexcitatory and/or seizure-potentiating effect of Quinolones. Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Quinolones. Risk C: Monitor therapy

Rivaroxaban: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Rivaroxaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of rivaroxaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Salicylates: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Salicylates. An increased risk of bleeding may be associated with use of this combination. Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the cardioprotective effect of Salicylates. Salicylates may decrease the serum concentration of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Management: Nonselective NSAIDs may reduce aspirin's cardioprotective effects. Administer ibuprofen 30-120 minutes after immediate-release aspirin, 2 to 4 hours after extended-release aspirin, or 8 hours before aspirin. Risk D: Consider therapy modification

Selective Serotonin Reuptake Inhibitors: May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Consider alternatives to NSAIDs. Monitor for evidence of bleeding and diminished antidepressant effects. It is unclear whether COX-2-selective NSAIDs reduce risk. Risk D: Consider therapy modification

Selumetinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Risk C: Monitor therapy

Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider therapy modification

Sodium Phosphates: May enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with NSAIDs, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, maintain adequate hydration and monitor renal function closely. Risk D: Consider therapy modification

Tacrolimus (Systemic): Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Tacrolimus (Systemic). Risk C: Monitor therapy

Tenofovir Products: Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Tenofovir Products. Management: Seek alternatives to these combinations whenever possible. Avoid use of tenofovir with multiple NSAIDs or any NSAID given at a high dose due to a potential risk of acute renal failure. Diclofenac appears to confer the most risk. Risk D: Consider therapy modification

Tenoxicam: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination

Thiazide and Thiazide-Like Diuretics: May enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy

Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Tolperisone: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Tolperisone. Specifically, the risk of hypersensitivity reactions may be increased. Tolperisone may enhance the therapeutic effect of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy

Tricyclic Antidepressants: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of major adverse cardiac events (MACE), hemorrhagic stroke, ischemic stroke, and heart failure may be increased. Tricyclic Antidepressants may enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy

Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Risk X: Avoid combination

Valproate Products: Ibuprofen may decrease the serum concentration of Valproate Products. Risk C: Monitor therapy

Vancomycin: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Vancomycin. Risk C: Monitor therapy

Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Risk C: Monitor therapy

Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the anticoagulant effect of Vitamin K Antagonists. Management: Consider alternatives to this combination when possible. If the combination must be used, monitor coagulation status closely and advise patients to promptly report any evidence of bleeding or bruising. Risk D: Consider therapy modification

Voriconazole: May increase the serum concentration of Ibuprofen. Specifically, concentrations of the S-(+)-ibuprofen enantiomer may be increased. Risk C: Monitor therapy

Zanubrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Reproductive Considerations

Nonsteroidal anti-inflammatory drugs (NSAIDs) may delay or prevent rupture of ovarian follicles. This may be associated with infertility that is reversible upon discontinuation of the medication. Consider discontinuing use in patients having difficulty conceiving or those undergoing investigation of fertility.

Based on available information, NSAIDs can be continued in males with rheumatic and musculoskeletal diseases who are planning to father a child (ACR [Sammaritano 2020]).

Pregnancy Considerations

The use of nonsteroidal anti-inflammatory drugs (NSAIDs) close to conception may be associated with an increased risk of miscarriage due to cyclooxygenase-2 inhibition interfering with implantation (Bermas 2014; Bloor 2013).

Birth defects have been observed following in utero NSAID exposure in some studies; however, data are conflicting (Bloor 2013). Nonteratogenic effects, including prenatal constriction of the ductus arteriosus, persistent pulmonary hypertension of the newborn, oligohydramnios, necrotizing enterocolitis, renal dysfunction or failure, and intracranial hemorrhage, have been observed in the fetus/neonate following in utero NSAID exposure (Bermas 2014; Bloor 2013). Maternal NSAID use may cause fetal renal dysfunction leading to oligohydramnios. Although rare, this may occur as early as 20 weeks' gestation and is more likely to occur with prolonged maternal use. Oligohydramnios may be reversible following discontinuation of the NSAID (Dathe 2019; FDA 2020). In addition, nonclosure of the ductus arteriosus postnatally may occur and be resistant to medical management (Bermas 2014; Bloor 2013).

Maternal use of NSAIDs should be avoided beginning at 20 weeks' gestation. If NSAID use is necessary between 20 and 30 weeks' gestation, limit use to the lowest effective dose and shortest duration possible; consider ultrasound monitoring of amniotic fluid if treatment extends beyond 48 hours, and discontinue the NSAID if oligohydramnios is found (FDA 2020). Because NSAIDs may cause premature closure of the ductus arteriosus, prescribing information for ibuprofen specifically states use should be avoided starting at 30 weeks' gestation.

Based on available information, NSAIDs can be continued during the first 2 trimesters of pregnancy in patients with rheumatic and musculoskeletal diseases; use in the third trimester is not recommended (ACR [Sammaritano 2020]).

NSAIDs may be used as part of a multimodal approach to pain relief following cesarean delivery (ACOG 2019).

NSAIDs are not preferred for the acute management of migraine during pregnancy (Burch 2020; van Casteren 2020). However, use of ibuprofen during the second trimester may be considered when an NSAID is required (Burch 2020).

Breastfeeding Considerations

Ibuprofen is present in breast milk.

The relative infant dose (RID) of ibuprofen is 0.6% to 0.9% when calculated using the highest breast milk concentration located and compared to an infant therapeutic dose of 10 to 15 mg/kg/day.

In general, breastfeeding is considered acceptable when the RID is <10% (Anderson 2016; Ito 2000).

The RID of ibuprofen was calculated using a milk concentration of 0.59 mcg/mL, providing an estimated infant dose via breast milk of 0.089 mg/kg/day. This milk concentration was obtained following maternal administration of oral ibuprofen ≥600 mg/day to 13 women at least 1 week postpartum (Rigourd 2014).

A prospective cohort study evaluated the outcomes of breastfed infants whose mothers were taking various medications. Within the study, 21 mother-infant pairs reported ibuprofen exposure (dose, duration, relationship to breastfeeding not provided). There were no cases of diarrhea, drowsiness, or irritability in the breastfed infants (Ito 1993). Based on the available data, adverse events have not been reported in breastfeeding infants and milk production is not affected.

Ibuprofen is considered compatible with breastfeeding when used in usual recommended doses (WHO 2002). Nonopioid analgesics, including nonsteroidal anti-inflammatory drugs (NSAIDs), are preferred for breastfeeding patients who require pain control peripartum or for surgery outside of the postpartum period (ABM [Martin 2018]; ABM [Reece-Stremtan 2017]). NSAIDs are considered compatible for the treatment of rheumatic and musculoskeletal diseases in lactating patients; ibuprofen is the preferred NSAID (ACR [Sammaritano 2020]). Ibuprofen is also the preferred NSAID for the management of acute migraine in lactating patients (van Casteren 2020).

The manufacturer recommends that the decision to breastfeed during therapy consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. Maternal use of NSAIDs should be avoided if the breastfeeding infant has platelet dysfunction, thrombocytopenia, or a ductal-dependent cardiac lesion (ABM [Martin 2018]; ABM [Reece-Stremtan 2017]; Bloor 2013).

Dietary Considerations

Some products may contain phenylalanine and/or potassium.

Monitoring Parameters

CBC, chemistry profile, occult blood loss and periodic LFTs; monitor response (pain, range of motion, grip strength, mobility, ADL function), inflammation; observe for weight gain, edema; monitor renal function (urine output, serum BUN and creatinine); observe for bleeding, bruising (especially in patients with coagulation disorders or who are receiving anticoagulants); monitor for anemia with long-term therapy; evaluate GI effects (abdominal pain, bleeding, dyspepsia); mental confusion, disorientation; BP; periodic ophthalmic exams with long-term therapy; signs of infection (ibuprofen lysine); signs of immediate or delayed hypersensitivity reactions.

Reference Range

Plasma concentrations >200 mcg/mL may be associated with severe toxicity

Mechanism of Action

Reversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes, which results in decreased formation of prostaglandin precursors; has antipyretic, analgesic, and anti-inflammatory properties

Other proposed mechanisms not fully elucidated (and possibly contributing to the anti-inflammatory effect to varying degrees), include inhibiting chemotaxis, altering lymphocyte activity, inhibiting neutrophil aggregation/activation, and decreasing proinflammatory cytokine levels.

Pharmacokinetics

Onset of action: Oral: Analgesic: Within 30 to 60 minutes (Davies 1998; Mehlisch 2013); Antipyretic: Single oral dose 8 mg/kg (Kauffman 1992): Infants ≤1 year: 69 ± 22 minutes; Children ≥6 years: Single oral dose 8 mg/kg (Kauffman 1992): 109 ± 64 minutes; Adults: <1 hour (Sullivan 2011).

Maximum effect: Antipyretic: 2 to 4 hours.

Duration: Oral: Antipyretic: 6 to 8 hours (Sullivan 2011).

Absorption: Oral: Rapid (85%).

Distribution: Vd:

Oral: Febrile children <11 years: 0.2 L/kg; Adults: 0.12 L/kg.

IV: Ibuprofen (Caldolor):

Pediatric patients 6 months to <2 years: 0.31 L/kg.

Pediatric patients 2 to 16 years: 0.23 L/kg.

IV: Ibuprofen lysine: Premature neonates, GA <32 weeks: Variable results observed: 0.32 L/kg, others have reported: a central compartment Vd that decreases with increasing PNA and ductal closure (Van Overmeire 2001) and a Vd, apparent: 0.062 L/kg in 21 premature neonates (GA <32 weeks, PNA: <1 day) (Aranda 1997).

Protein binding: >99%; Premature infants: ~95% (Aranda 1997).

Bioavailability: 80%.

Metabolism: Hepatic via oxidation; Note: Ibuprofen is a racemic mixture of R and S isomers; the R isomer (thought to be inactive) is slowly and incompletely (~60%) converted to the S isomer (active) in adults; the amount of conversion in children is not known, but it is thought to be similar to adults; a study in preterm neonates estimated the conversion to be 61% after prophylactic ibuprofen use and 86% after curative treatment (Gregoire 2004).

Half-life elimination: IV:

Ibuprofen (Caldor):

Pediatric patients: 6 months to <2 years: 1.8 hours; 2 to 16 years: ~1.5 hours.

Adults: 2.22 to 2.44 hours.

Ibuprofen lysine (Neoprofen):

Premature neonates, GA <32 weeks: Reported data highly variable.

R-enantiomer: 10 hours; S-enantiomer: 25.5 hours (Gregoire 2004).

Age-based observations:

PNA <1 day: 30.5 ± 4.2 hours (Aranda 1997).

PNA 3 days: 43.1 ± 26.1 hours (Van Overmeire 2001).

PNA 5 days: 26.8 ± 23.6 hours (Van Overmeire 2001).

Half-life elimination: Oral:

Children 3 months to 10 years: Oral suspension: 1.6 ± 0.7 hours (Kauffman 1992).

Adults: ~2 hours; End-stage renal disease: Unchanged (Aronoff 2007).

Time to peak: Tablets: 1 to 2 hours; Suspension: 1 hour.

Children with cystic fibrosis (Scott 1999):

Suspension (n=22): 0.74 ± 0.43 hours (median: 30 minutes).

Chewable tablet (n=4): 1.5 ± 0.58 hours (median: 1.5 hours).

Tablet (n=12): 1.33 ± 0.95 hours (median: 1 hour).

Excretion: Urine (primarily as metabolites (45% to 80%); ~1% as unchanged drug and 14% as conjugated); some feces.

Pricing: US

Capsules (Advil Liqui-Gels minis Oral)

200 mg (per each): $0.24

Capsules (Advil Migraine Oral)

200 mg (per each): $0.17

Capsules (Advil Oral)

200 mg (per each): $0.13

Capsules (Ibuprofen Oral)

200 mg (per each): $0.07 - $0.10

Capsules (Motrin IB Oral)

200 mg (per each): $0.16

Chewable (Advil Junior Strength Oral)

100 mg (per each): $0.18

Chewable (Motrin Childrens Oral)

100 mg (per each): $0.29

Kit (Ibupak Oral)

600 mg (per each): $1,523.00

Solution (Caldolor Intravenous)

800 mg/200 mL (per mL): $0.14

800 mg/8 mL (per mL): $3.32

Solution (Ibuprofen Lysine Intravenous)

10 mg/mL (per mL): $206.25 - $273.74

Solution (NeoProfen Intravenous)

10 mg/mL (per mL): $590.15

Suspension (Childrens Advil Oral)

100 mg/5 mL (per mL): $0.04

Suspension (Childrens Motrin Oral)

100 mg/5 mL (per mL): $0.06

Suspension (Ibuprofen Oral)

100 mg/5 mL (per mL): $0.06 - $0.08

Suspension (Infants Advil Oral)

50 mg/1.25 mL (per mL): $0.27

Suspension (Motrin Infants Drops Oral)

50 mg/1.25 mL (per mL): $0.39

Tablets (Advil Junior Strength Oral)

100 mg (per each): $0.18

Tablets (Advil Oral)

200 mg (per each): $0.08

Tablets (IBU Oral)

400 mg (per each): $0.21

600 mg (per each): $0.29

800 mg (per each): $0.38

Tablets (Ibuprofen Oral)

200 mg (per each): $0.02 - $0.08

400 mg (per each): $0.03 - $0.39

600 mg (per each): $0.04 - $1.02

800 mg (per each): $0.04 - $1.18

Tablets (Motrin IB Oral)

200 mg (per each): $0.12

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Abfen (PL);
  • Actiprofen (IE);
  • Actron (AR, CR, DO, GT, HN, NI, PA, PY, SV, UY);
  • Adagin (RO);
  • Adex 200 (IL);
  • Adex Liqui-Gels (IL);
  • Advel (BD);
  • Advil (AU, BR, CO, EE, FR, HK, HU, IE, IL, LB, MX, PH, QA, RO, SA, VE, ZA);
  • Afebril (EC, PY);
  • Afleno (CR, DO, GT, HN, NI, PA, SV);
  • Aktren (AT);
  • Algofen (IT);
  • Am-Fam 400 (IN);
  • Ambafen (LB);
  • Anafen (ID);
  • Anco (DE);
  • Antarene (FR);
  • Arfen (ID, LB);
  • Argifen (ES);
  • Artril (BR);
  • Asfen-400 (ET);
  • Balkaprofen (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZM, ZW);
  • Bebyzal (KR);
  • Bestafen (MX);
  • Bifen (HK, SG);
  • Bofen (UA);
  • Brufen (AE, AT, AU, BD, BE, BH, CH, CY, CZ, DE, DK, EE, EG, ES, FI, FR, GB, GR, HK, HR, HU, ID, IE, IQ, IR, IT, JO, JP, KR, KW, LB, LK, LT, LU, LV, LY, MT, NL, NO, NZ, OM, PH, PK, PT, QA, RO, RU, SA, SE, SG, SI, SK, SY, TR, TW, VN, YE, ZA, ZW);
  • Brufen 400 (IL);
  • Brufen Forte (ID);
  • Brufen Retard (SG);
  • Brufen Syrup for Children (KR);
  • Brufort (IT);
  • Brupro (IE);
  • Bufect (ID, LK);
  • Bufect Forte (ID);
  • Buplex (IE);
  • Buprex (EC);
  • Buprophar (BE);
  • Burana (FI);
  • Butafen (ET);
  • Caldolor (AT);
  • Carol (KR);
  • Cefen (TH);
  • Cuprofen (TH);
  • Dafen-Q (KR);
  • Dalsy (ES);
  • Degiton (TW);
  • Diffutab SR 600 (KR);
  • Dolafen (PH);
  • Dolan FP (PH);
  • Dolex (ZW);
  • Dolgit (AE, CY, DE, EG, IQ, IR, JO, KW, LB, LY, OM, PL, QA, SA, SY, YE);
  • Dolocyl (CH);
  • Dolomax (PE);
  • Doloral (PE);
  • Dolormin (DE);
  • Dolprin (CR, DO, GT, HN, NI, PA, SV);
  • Druisel (AR);
  • Easofen (MT);
  • Evofen (MY);
  • Expanfen (FR);
  • Extrapan Gel (HK);
  • Farsifen Forte (ID);
  • Febratic (MX);
  • Febryn (HK);
  • Fenatic (ID);
  • Fenbid (AE, BF, BJ, CI, CN, CY, EG, ET, GB, GH, GM, GN, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZM, ZW);
  • Fenpaed (NZ);
  • Fever-Free (PH);
  • Flamex (BD);
  • Flarin (DK);
  • Focus (IT);
  • Genofen (ET);
  • Gofen (LK, PH, TZ);
  • Gyno-neuralgin (DE);
  • Ibufac (MY);
  • Ibufen (IL, KR);
  • Ibuflam (MX);
  • Ibufug (DE);
  • Ibugesic (IN, LB, LK);
  • Ibugic (BE);
  • Ibulgan (AE, BB, BF, BH, BJ, BM, BS, BZ, CI, CY, EG, ET, GH, GM, GN, GY, IL, IQ, IR, JM, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SL, SN, SR, SY, TN, TT, TZ, UG, YE, ZM, ZW);
  • Ibumed 400 (VN);
  • Ibumetin (AT, DK, FI, NL, NO, SE);
  • Ibunorm (UA);
  • Ibup (AR);
  • Ibupirac (AR, CL);
  • Ibuprofen (HK);
  • Ibusal (FI);
  • Ibuspan (ZW);
  • Ibutact (PL);
  • Ibutop (BH);
  • Imet (UA);
  • Infacalm (HK);
  • Inufen (ET);
  • Ipren (DK, RU, SE);
  • Iprox (ID);
  • Ipufen (TW);
  • Irfen (AE, CH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE);
  • Junifen (ES);
  • Liptan (AE, CY, IL, IQ, IR, JO, JP, KW, LB, LY, OM, QA, SA, SY, YE);
  • Medicol (PH);
  • Medicol Advance (PH);
  • Mensoton (DE);
  • Mepabrufen (EG);
  • Mofen (ID);
  • Moris (ID);
  • Moris Forte (ID);
  • Motrin (AE, CO, CR, CY, DO, EG, GT, HN, IQ, IR, JO, KW, LB, LY, MX, NI, OM, PA, PE, QA, SA, SV, SY, YE);
  • Mutrim (PH);
  • Neoprofen (BM);
  • Neutropain (HK);
  • Nobafon (TW);
  • Noritis (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZM, ZW);
  • Novogent (DE);
  • Nureflex (AT);
  • Nurofen (AT, AU, BE, BF, BG, BJ, CI, CY, CZ, DK, ES, ET, FR, GB, GH, GM, GN, HR, HU, IE, IS, KE, LR, LT, LU, LV, MA, ML, MR, MU, MW, MY, NE, NG, NL, NZ, SC, SD, SE, SG, SI, SK, SL, SN, TN, TR, TZ, UA, UG, VN, ZM, ZW);
  • Nurofen for Children (SG, TH);
  • Nurofen Gel (IL, NZ);
  • Nurofen Pro san sucre (FR);
  • Nuroffen (MT);
  • Optifen (CH);
  • Opturem (DE);
  • Ostarin (ID);
  • P-Fen (TH);
  • Panafen (NZ);
  • Pedea (AT, BE, BG, CH, CZ, DE, DK, EE, ES, FI, FR, GB, GR, IE, IT, KR, NL, NO, PL, PT, RU, SE, SK, TR);
  • Peflam (BD);
  • Perfen (TW);
  • Perofen (BB, BM, BS, BZ, GY, HK, JM, SG, SR, TT);
  • Profen (BD, HK);
  • Profinal (AE, BH, EG, KW, LB, QA, SA);
  • Proris (ID);
  • Prosinal (ID);
  • Provon (PE);
  • Quadrax (MX);
  • Rafen (AU);
  • Ranofen (ZA);
  • RatioDolor (AT);
  • Remofen (AE, BH, JO, QA);
  • Rhelafen (ID);
  • Rhelafen Forte (ID);
  • Rheumanox (TH);
  • Rupan (AE, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE);
  • Ruprofen (TH);
  • Sapofen (AE, BH, JO, KW, QA, SA);
  • Solibu (LB);
  • Spedifen (CN, FR, MY);
  • Speedifen (TH);
  • Spifen (FR);
  • Syntofene (FR);
  • Tabalon (CR, DO, GT, HN, NI, PA, SV);
  • Tabalon 400 (MX);
  • Tarein (TW);
  • Taskine (AE, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE);
  • Tefin (IE);
  • Tenvalin (EC);
  • Thomaprodol (AT);
  • Ufen (LK);
  • Upfen (FR);
  • Uprofen (TW);
  • Urem (DE);
  • Vantril (PY);
  • Xfen Flashtab (PH);
  • Zofen (HK, MY);
  • Zorafen (MY)


For country code abbreviations (show table)
  1. 2019 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2019 Updated AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2019;67(4):674-694. doi:10.1111/jgs.15767 [PubMed 30693946]
  2. Abraham NS, Hlatky MA, Antman EM, et al; ACCF/ACG/AHA. ACCF/ACG/AHA 2010 expert consensus document on the concomitant use of proton pump inhibitors and thienopyridines: a focused update of the ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents. Circulation. 2010;122(24):2619-2633. doi:10.1161/CIR.0b013e318202f701 [PubMed 21060077]
  3. Abraham PA, Keane WF. Glomerular and interstitial disease induced by nonsteroidal anti-inflammatory drugs. Am J Nephrol. 1984;4(1):1-6. doi:10.1159/000166764 [PubMed 6731494]
  4. Adler Y, Charron P, Imazio M, et al; ESC Scientific Document Group. 2015 ESC guidelines for the diagnosis and management of pericardial diseases: the task force for the diagnosis and management of pericardial diseases of the European Society of Cardiology (ESC) endorsed by: the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2015;36(42):2921-2964. doi:10.1093/eurheartj/ehv318 [PubMed 26320112]
  5. Advil (ibuprofen) [prescribing information]. Warren, NJ: GlaxoSmithKline; received December 2021.
  6. Ahlfors CE. Benzyl alcohol, kernicterus, and unbound bilirubin. J Pediatr. 2001;139(2):317-319. [PubMed 11487763]
  7. Ailani J, Burch RC, Robbins MS; Board of Directors of the American Headache Society. The American Headache Society consensus statement: update on integrating new migraine treatments into clinical practice. Headache. 2021;61(7):1021-1039. doi:10.1111/head.14153 [PubMed 34160823]
  8. Alade SL, Brown RE, Paquet A Jr. Polysorbate 80 and E-Ferol toxicity. Pediatrics. 1986;77(4):593-597. [PubMed 3960626]
  9. Alam I, Ferrell LD, Bass NM. Vanishing bile duct syndrome temporally associated with ibuprofen use. Am J Gastroenterol. 1996;91(8):1626-1630. [PubMed 8759674]
  10. Alqahtani Z, Jamali F. Clinical outcomes of aspirin interaction with other non-steroidal anti-inflammatory drugs: a systematic review. J Pharm Pharm Sci. 2018;21(1s):29854. doi:10.18433/jpps29854 [PubMed 29891025]
  11. American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins—Obstetrics. ACOG Practice Bulletin No. 209: Obstetric analgesia and anesthesia. Obstet Gynecol. 2019;133(3):e208-e225. doi:10.1097/AOG.0000000000003132 [PubMed 30801474]
  12. American Pain Society (APS). Principles of Analgesic Use. 7th ed. American Pain Society; 2016.
  13. Amoozgar H, Ghodstehrani M, Pishva N. Oral ibuprofen and ductus arteriosus closure in full-term neonates: a prospective case-control study. Pediatr Cardiol. 2010;31(1):40-43. doi:10.1007/s00246-009-9542-y [PubMed 19841966]
  14. Anderson PO, Sauberan JB. Modeling drug passage into human milk. Clin Pharmacol Ther. 2016;100(1):42-52. [PubMed 27060684]
  15. Anglin R, Yuan Y, Moayyedi P, Tse F, Armstrong D, Leontiadis GI. Risk of upper gastrointestinal bleeding with selective serotonin reuptake inhibitors with or without concurrent nonsteroidal anti-inflammatory use: a systematic review and meta-analysis. Am J Gastroenterol. 2014 109(6):811-819. doi:10.1038/ajg.2014.82 [PubMed 24777151]
  16. Antal EJ, Wright CE 3rd, Brown BL, Albert KS, Aman LC, Levin NW. The influence of hemodialysis on the pharmacokinetics of ibuprofen and its major metabolites. J Clin Pharmacol. 1986;26(3):184-190. doi:10.1002/j.1552-4604.1986.tb02931.x [PubMed 3958223]
  17. Aranda JV, Thomas R. Systematic review: intravenous ibuprofen in preterm newborns. Semin Perinatol. 2006;30(3):114-120. [PubMed 16813969]
  18. Aranda JV, Varvarigou A, Beharry K, et al. Pharmacokinetics and protein binding of intravenous ibuprofen in the premature newborn infant. Acta Paediatr. 1997;86(3):289-293. [PubMed 9099319]
  19. Aronoff GR, Bennett WM, Berns JS, et al. Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children. 5th ed. Phil American College of Physicians; 2007:105.
  20. Bagheri MM, Niknafs P, Sabsevari F, et al. Comparison of oral acetaminophen versus ibuprofen in premature infants with patent ductus arteriosus. Iran J Pediatr. 2016;26(4):e3975. doi:10.5812/ijp.3975 [PubMed 27713809]
  21. Baker M, Perazella MA. NSAIDs in CKD: are they safe? Am J Kidney Dis. 2020;76(4):546-557. doi:10.1053/j.ajkd.2020.03.023 [PubMed 32479922]
  22. Balint B, Stepic N, Todorovic M, et al. Ibuprofen-induced extensive toxic epidermal necrolysis - a multidisciplinary therapeutic approach in a single case. Blood Transfus. 2014;12(3):438-439. doi:10.2450/2014.0065-14 [PubMed 25074525]
  23. Barr J, Fraser GL, Puntillo K, et al. Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit. Crit Care Med. 2013;41(1):263-306. [PubMed 23269131]
  24. Barry RJ, Zanetto U, Kolli S, Morjaria R. Toxic epidermal necrolysis: the red eye and red herrings in casualty. BMJ Case Rep. 2018;2018:bcr2018225861. doi:10.1136/bcr-2018-225861 [PubMed 30317199]
  25. Based on expert opinion.
  26. Battistella M, Mamdami MM, Juurlink DN, Rabeneck L, Laupacis A. Risk of upper gastrointestinal hemorrhage in warfarin users treated with nonselective NSAIDs or COX-2 inhibitors. Arch Intern Med. 2005;165(2):189-192. doi:10.1001/archinte.165.2.189 [PubMed 15668365]
  27. Bellini C, Campone F, Serra G. Pulmonary hypertension following L-lysine ibuprofen therapy in a preterm infant with patent ductus arteriosus. CMAJ. 2006; 174(13):1843-1844. [PubMed 16785458]
  28. Berde C, Ablin A, Glazer J, et al. American Academy of Pediatrics report of the subcommittee on disease-related pain in childhood cancer. Pediatrics. 1990;86(5, pt 2):818-825. [PubMed 2216644]
  29. Berde CB, Sethna NF. Analgesics for the treatment of pain in children. N Engl J Med. 2002;347(14):1094-1103. [PubMed 12362012]
  30. Bermas BL. Non-steroidal anti inflammatory drugs, glucocorticoids and disease modifying anti-rheumatic drugs for the management of rheumatoid arthritis before and during pregnancy. Curr Opin Rheumatol. 2014;26(3):334-340. doi:10.1097/BOR.0000000000000054 [PubMed 24663106]
  31. Bhala N, Emberson J, Merhi A, et al. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013;382(9894):769-779. doi:10.1016/S0140-6736(13)60900-9 [PubMed 23726390]
  32. Bhangu A, Singh P, Fitzgerald JE, Slesser A, Tekkis P. Postoperative nonsteroidal anti-inflammatory drugs and risk of anastomotic leak: meta-analysis of clinical and experimental studies. World J Surg. 2014;38(9):2247-2257. doi:10.1007/s00268-014-2531-1 [PubMed 24682313]
  33. Bhatt DL, Scheiman J, Abraham NS, et al; American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risk of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol. 2008;52(18):1502-1517. [PubMed 19017521]
  34. Bhave G, Neilson EG. Volume depletion versus dehydration: how understanding the difference can guide therapy. Am J Kidney Dis. 2011;58(2):302-309. doi:10.1053/j.ajkd.2011.02.395 [PubMed 21705120]
  35. Biggins SW, Angeli P, Garcia-Tsao G, et al. Diagnosis, evaluation, and management of ascites, spontaneous bacterial peritonitis and hepatorenal syndrome: 2021 practice guidance by the American Association for the Study of Liver Diseases. Hepatology. 2021;74(2):1014-1048. doi:10.1002/hep.31884 [PubMed 33942342]
  36. Blanca-López N, Pérez-Alzate D, Andreu I, et al. Immediate hypersensitivity reactions to ibuprofen and other arylpropionic acid derivatives. Allergy. 2016;71(7):1048-1056. doi:10.1111/all.12855 [PubMed 26841325]
  37. Blanca-López N, Soriano V, Garcia-Martin E, Canto G, Blanca M. NSAID-induced reactions: classification, prevalence, impact, and management strategies. J Asthma Allergy. 2019;12:217-233. doi:10.2147/JAA.S164806 [PubMed 31496752]
  38. Bloor M, Paech M. Nonsteroidal anti-inflammatory drugs during pregnancy and the initiation of lactation. Anesth Analg. 2013;116(5):1063-1075. doi:10.1213/ANE.0b013e31828a4b54 [PubMed 23558845]
  39. Blumenthal KG, Peter JG, Trubiano JA, Phillips EJ. Antibiotic allergy. Lancet. 2019;393(10167):183-198. doi:10.1016/S0140-6736(18)32218-9 [PubMed 30558872]
  40. Brandstetter RD, Mar DD. Reversible oliguric renal failure associated with ibuprofen treatment. Br Med J. 1978;2(6146):1194-1195. doi:10.1136/bmj.2.6146.1194-a [PubMed 719345]
  41. Brix AE. Renal papillary necrosis. Toxicol Pathol. 2002;30(6):672-674. doi:10.1080/01926230290166760 [PubMed 12512867]
  42. Brockow K, Przybilla B, Aberer W, et al. Guideline for the diagnosis of drug hypersensitivity reactions: S2K-Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) and the German Dermatological Society (DDG) in collaboration with the Association of German Allergologists (AeDA), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Contact Dermatitis Research Group (DKG), the Swiss Society for Allergy and Immunology (SGAI), the Austrian Society for Allergology and Immunology (ÖGAI), the German Academy of Allergology and Environmental Medicine (DAAU), the German Center for Documentation of Severe Skin Reactions and the German Federal Institute for Drugs and Medical Products (BfArM). Allergo J Int. 2015;24(3):94-105. doi:10.1007/s40629-015-0052-6 [PubMed 26120552]
  43. Brophy PD. Changing the paradigm in pediatric acute kidney injury. J Pediatr. 2013;162(6):1094-1096. [PubMed 23453549]
  44. Burch R. Epidemiology and treatment of menstrual migraine and migraine during pregnancy and lactation: a narrative review. Headache. 2020;60(1):200-216. doi:10.1111/head.13665 [PubMed 31579938]
  45. Caldolor (ibuprofen) [prescribing information]. Nashville, TN: Cumberland Pharmaceuticals Inc; November 2021.
  46. Caldolor (ibuprofen) [product monograph]. Toronto, Ontario, Canada: Alveda Pharmaceuticals Inc; May 2012.
  47. Capone ML, Tacconelli S, Sciulli MG, et al. Clinical pharmacology of platelet, monocyte, and vascular cyclooxygenase inhibition by naproxen and low-dose aspirin in healthy subjects. Circulation. 2004 Mar;109(12):1468-1471. doi:10.1161/01.CIR.0000124715.27937.78 [PubMed 15037526]
  48. Catella-Lawson F, Reilly MP, Kapoor SC, et al. Cyclooxygenase Inhibitors and the Antiplatelet Effects of Aspirin. N Engl J Med. 2001;345(25):1809-1817. [PubMed 11752357]
  49. Caughey GE, Cleland LG, Penglis PS, Gamble JR, James MJ. Roles of cyclooxygenase (COX)-1 and COX-2 in prostanoid production by human endothelial cells: selective up-regulation of prostacyclin synthesis by COX-2. J Immunol. 2001;167(5):2831-2838. doi:10.4049/jimmunol.167.5.2831 [PubMed 11509629]
  50. Centers for Disease Control (CDC). Neonatal deaths associated with use of benzyl alcohol—United States. MMWR Morb Mortal Wkly Rep. 1982;31(22):290-291. http://www.cdc.gov/mmwr/preview/mmwrhtml/00001109.htm [PubMed 6810084]
  51. Centers for Disease Control (CDC). Unusual syndrome with fatalities among premature infants: association with a new intravenous vitamin E product. MMWR Morb Mortal Wkly Rep. 1984;33(14):198-199. http://www.cdc.gov/mmwr/preview/mmwrhtml/00000319.htm. [PubMed 6423951]
  52. Chalasani NP, Hayashi PH, Bonkovsky HL, et al. ACG Clinical Guideline: the diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol. 2014;109(7):950-966. [PubMed 24935270]
  53. Chalasani NP, Maddur H, Russo MW, Wong RJ, Reddy KR. ACG clinical guideline: diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol. 2021;00:1-21. https://doi.org/10.14309/ajg.0000000000001259 [PubMed Chalasani.1]
  54. Chan AT, Manson JE, Albert CM, et al. Nonsteroidal antiinflammatory drugs, acetaminophen, and the risk of cardiovascular events. Circulation. 2006;113(12):1578-1587. doi:10.1161/CIRCULATIONAHA.105.595793 [PubMed 16534006]
  55. Chang RW, Tompkins DM, Cohn SM. Are NSAIDs safe? Assessing the risk-benefit Profile of nonsteroidal anti-inflammatory drug use in postoperative pain management. Am Surg. 2021;87(6):872-879. doi:10.1177/0003134820952834 [PubMed 33238721]
  56. Cheng Y, Austin SC, Rocca B, et al. Role of prostacyclin in the cardiovascular response to thromboxane A2. Science. 2002;296(5567):539-541. doi:10.1126/science.1068711 [PubMed 11964481]
  57. Children's Advil (ibuprofen) [product monograph]. Mississauga, Ontario, Canada: GlaxoSmithKline Consumer Healthcare ULC; March 2021.
  58. Children's Advil Suspension (ibuprofen) [prescribing information]. Madison, NJ: Pfizer Inc; received September 2018.
  59. Chou CI, Shih CJ, Chen YT, et al. Adverse effects of oral nonselective and cyclooxygenase-2-selective NSAIDs on hospitalization for acute kidney injury: a nested case-control cohort study. Medicine (Baltimore). 2016b;95(9):e2645. doi:10.1097/MD.0000000000002645 [PubMed 26945352]
  60. Chou R, Gordon DB, de Leon-Casasola OA, et al. Management of postoperative pain: a clinical practice guideline from the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists' Committee on Regional Anesthesia, Executive Committee, and Administrative Council [published correction appears in J Pain. 2016;17(4):508-510]. J Pain. 2016a;17(2):131-157. doi: 10.1016/j.jpain.2015.12.008. [PubMed 26827847]
  61. Clive DM, Stoff JS. Renal syndromes associated with nonsteroidal antiinflammatory drugs. N Engl J Med. 1984;310(9):563-572. doi:10.1056/NEJM198403013100905 [PubMed 6363936]
  62. Cryer B, Feldman M. Cyclooxygenase-1 and cyclooxygenase-2 selectivity of widely used nonsteroidal anti-inflammatory drugs. Am J Med. 1998;104(5):413-421. doi:10.1016/s0002-9343(98)00091-6 [PubMed 9626023]
  63. Dani C, Vangi V, Bertini G, et al. High-dose ibuprofen for patent ductus arteriosus in extremely preterm infants: a randomized controlled study. Clin Pharmacol Ther. 2012;91(4):590-596. [PubMed 22089267]
  64. Dathe K, Hultzsch S, Pritchard LW, Schaefer C. Risk estimation of fetal adverse effects after short-term second trimester exposure to non-steroidal anti-inflammatory drugs: a literature review. Eur J Clin Pharmacol. 2019;75(10):1347-1353. doi:10.1007/s00228-019-02712-2 [PubMed 31273431]
  65. Davidson BL, Verheijen S, Lensing AW, et al. Bleeding risk of patients with acute venous thromboembolism taking nonsteroidal anti-inflammatory drugs or aspirin. JAMA Intern Med. 2014;174(6):947-953. doi:10.1001/jamainternmed.2014.946 [PubMed 24733305]
  66. Davies NM. Clinical Pharmacokinetics of Ibuprofen. The First 30 Years. Clin Pharmacokinet. 1998;34(2):101-154. [PubMed 9515184]
  67. Delzer LM, Golightly LK, Kiser TH, Biggins SW, Lewis VJ, Kim II. Calcineurin inhibitor and nonsteroidal anti-inflammatory drug interaction: implications of changes in renal function associated with concurrent use. J Clin Pharmacol. 2018;58(11):1443-1451. doi:10.1002/jcph.1264 [PubMed 29799625]
  68. Derry C, Derry S, Moore RA, McQuay HJ. Single dose oral ibuprofen for acute postoperative pain in adults. Cochrane Database Syst Rev. 2009;(3):CD001548. doi:10.1002/14651858.CD001548.pub2 [PubMed 19588326]
  69. Devlin JW, Skrobik Y, Gélinas C, et al. Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU. Crit Care Med. 2018;46(9):e825-e873. doi:10.1097/CCM.0000000000003299 [PubMed 30113379]
  70. Dionne RA, Berthold CW. Therapeutic Uses of Nonsteroidal Anti-inflammatory Drugs in Dentistry. Crit Rev Oral Biol Med. 2001;12(4):315-330. [PubMed 11603504]
  71. Doña I, Blanca-López N, Jagemann LR, et al. Response to a selective COX-2 inhibitor in patients with urticaria/angioedema induced by nonsteroidal anti-inflammatory drugs. Allergy. 2011;66(11):1428-1433. doi:10.1111/j.1398-9995.2011.02684.x [PubMed 21834936]
  72. Donati M, Conforti A, Lenti MC, et al. Risk of acute and serious liver injury associated to nimesulide and other NSAIDs: data from drug-induced liver injury case-control study in Italy. Br J Clin Pharmacol. 2016;82(1):238-248. doi:10.1111/bcp.12938 [PubMed 26991794]
  73. Doyle G, Jayawardena S, Ashraf E, et al. Efficacy and Tolerability of Nonprescription Ibuprofen Versus Celecoxib for Dental Pain. J Clin Pharmacol. 2002;42(8):912-919. [PubMed 12162474]
  74. Erdeve O, Yurttutan S, Altug N, et al. Oral versus intravenous ibuprofen for patent ductus arteriosus closure: a randomised controlled trial in extremely low birthweight infants. Arch Dis Child Fetal Neonatal Ed. 2012;97(4):F279-283. [PubMed 22147286]
  75. Ferraris VA, Saha SP, Oestreich JH, et al. 2012 Update to the Society of Thoracic Surgeons Guideline on Use of Antiplatelet Drugs in Patients Having Cardiac and Noncardiac Operations. Ann Thorac Surg. 2012;94(5):1761-1781. [PubMed 23098967]
  76. FitzGerald JD, Dalbeth N, Mikuls T, et al. 2020 American College of Rheumatology guideline for the management of gout. Arthritis Care Res (Hoboken). 2020;72(6):744-760. doi:10.1002/acr.24180 [PubMed 32391934]
  77. Food and Drug Administration (FDA). FDA Drug Safety Communication: FDA strengthens warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) can cause heart attacks or strokes. 2015. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-strengthens-warning-non-aspirin-nonsteroidal-anti-inflammatory [PubMed FDA.1]
  78. Frontera JA, Lewin JJ 3rd, Rabinstein AA, et al; Guideline for reversal of antithrombotics in intracranial hemorrhage: a statement for healthcare professionals from the Neurocritical Care Society and Society of Critical Care Medicine. Neurocrit Care. 2016;24(1):6-46. [PubMed 26714677]
  79. Funder JW, Carey RM, Mantero F, et al. The management of primary aldosteronism: case detection, diagnosis, and treatment: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101(5):1889-1916. doi:10.1210/jc.2015-4061 [PubMed 26934393]
  80. Gaffo AL. Treatment of gout flares. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 20, 2022.
  81. Gal P, Ransom JL, Davis SA. Possible ibuprofen-induced kernicterus in a near-term infant with moderate hyperbilirubinemia. J Pediatr Pharmacol Ther. 2006;11:245-250.
  82. Garratty G, Arndt PA. Drugs that have been shown to cause drug-induced immune hemolytic anemia or positive direct antiglobulin tests: some interesting findings since 2007. Immunohematology. 2014;30(2):66-79. [PubMed 25247621]
  83. Giannini EH, Brewer EJ, Miller ML, et al. Ibuprofen suspension in the treatment of juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group. J Pediatr. 1990;117(4):645-652. [PubMed 2213396]
  84. Gladding PA, Webster MW, Farrell HB, Zeng IS, Park R, Ruijne N. The antiplatelet effect of six non-steroidal anti-inflammatory drugs and their pharmacodynamic interaction with aspirin in healthy volunteers. Am J Cardiol. 2008;101(7):1060-1063. doi:10.1016/j.amjcard.2007.11.054 [PubMed 18359332]
  85. Goldenberg NA, Jacobson L, Manco-Johnson MJ. Brief communication: duration of platelet dysfunction after a 7-day course of Ibuprofen. Ann Intern Med. 2005;142(7):506-509. doi:10.7326/0003-4819-142-7-200504050-00009 [PubMed 15809462]
  86. Gooch K, Culleton BF, Manns BJ, et al. NSAID use and progression of chronic kidney disease. Am J Med. 2007;120(3):280.e1-7. doi:10.1016/j.amjmed.2006.02.015 [PubMed 17349452]
  87. Gournay V, Savagner C, Thiriez G, et al. Pulmonary hypertension after ibuprofen prophylaxis in very preterm infants. Lancet. 2002;359(9316):1486-1488. [PubMed 11988250]
  88. Gregoire N, Gualano V, Geneteau A, et al. Population pharmacokinetics of ibuprofen enantiomers in very premature neonates. J Clin Pharmacol. 2004;44(10):1114-1124. [PubMed 15342612]
  89. Gui MZ, Ni M, Yin XD, Zhang T, Li ZL. Ibuprofen induced Stevens-Johnson syndrome and liver injury in children: a case report. Transl Pediatr. 2021;10(6):1737-1742. doi:10.21037/tp-21-8 [PubMed 34295789]
  90. Gulmez SE, Larrey D, Pageaux GP, et al. Transplantation for acute liver failure in patients exposed to NSAIDs or paracetamol (acetaminophen): the multinational case-population SALT study. Drug Saf. 2013;36(2):135-144. doi:10.1007/s40264-012-0013-7 [PubMed 23325533]
  91. Gulmez SE, Unal US, Lassalle R, Chartier A, Grolleau A, Moore N. Risk of hospital admission for liver injury in users of NSAIDs and nonoverdose paracetamol: preliminary results from the EPIHAM study. Pharmacoepidemiol Drug Saf. 2018;27(11):1174-1181. doi:10.1002/pds.4640 [PubMed 30112779]
  92. Hamrick SEG, Sallmon H, Rose AT, et al. Patent ductus arteriosus of the preterm infant. Pediatrics. 2020;146(5):e20201209. doi:10.1542/peds.2020-1209 [PubMed 33093140]
  93. Hersh EV, Levin LM, Cooper SA, et al. Ibuprofen Liquigel for Oral Surgery Pain. Clin Ther. 2000;22(11):1306-1318. [PubMed 11117655]
  94. Hillier K, Jones K, MacInnis M, Mitra S. Comparison of standard versus high-dose ibuprofen for the treatment of hemodynamically significant patent ductus arteriosus in preterm infants. J Perinatol. 2021;41(5):1142-1148. doi:10.1038/s41372-021-01046-1 [PubMed 33795792]
  95. Hirt D, Van Overmeire B, Treluyer JM, et al. An optimized ibuprofen dosing scheme for preterm neonates with patent ductus arteriosus, based on a population pharmacokinetic and pharmacodynamic study. Br J Clin Pharmacol. 2008;65(5):629-636. [PubMed 18307541]
  96. Hong Y, Gengo FM, Rainka MM, Bates VE, Mager DE. Population pharmacodynamic modelling of aspirin- and Ibuprofen-induced inhibition of platelet aggregation in healthy subjects. Clin Pharmacokinet. 2008;47(2):129-137. doi:10.2165/00003088-200847020-00006 [PubMed 18193919]
  97. Horsley RD, Vogels ED, McField DAP, et al. Multimodal postoperative pain control is effective and reduces opioid use after laparoscopic Roux-en-Y gastric bypass. Obes Surg. 2019;29(2):394-400. doi:10.1007/s11695-018-3526-z [PubMed 30317488]
  98. Huerta C, Castellsague J, Varas-Lorenzo C, García Rodríguez LA. Nonsteroidal anti-inflammatory drugs and risk of ARF in the general population. Am J Kidney Dis. 2005;45(3):531-539. doi:10.1053/j.ajkd.2004.12.005 [PubMed 15754275]
  99. IBU 600-EZS (ibuprofen) [prescribing information]. Shreveport, LA: Dr. Reddy's Laboratories Louisiana LLC; April 2019.
  100. Ibuprofen [prescribing information]. Glasgow, KY: Amneal Pharmaceuticals; April 2014.
  101. Ibuprofen [summary of product characteristics]. Devon, UK: Accord-UK Ltd; January 2021.
  102. Ibuprofen tablet [prescribing information]. East Brunswick, NJ: Strides Pharma Inc; April 2021.
  103. Imazio M. Acute pericarditis: treatment and prognosis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 27, 2022.
  104. Imazio M, Brucato A, Cemin R, et al; CORP (COlchicine for Recurrent Pericarditis) Investigators. Colchicine for recurrent pericarditis (CORP): a randomized trial. Ann Intern Med. 2011;155(7):409-414. doi:10.7326/0003-4819-155-7-201110040-00359 [PubMed 21873705]
  105. Imazio M, Brucato A, Cemin R, et al; ICAP Investigators. A randomized trial of colchicine for acute pericarditis. N Engl J Med. 2013;369(16):1522-1528. doi:10.1056/NEJMoa1208536 [PubMed 23992557]
  106. "Inactive" ingredients in pharmaceutical products: update (subject review). American Academy of Pediatrics (AAP) Committee on Drugs. Pediatrics. 1997;99(2):268-278. [PubMed 9024461]
  107. Infants' Advil White Grape Concentrated Drops (ibuprofen) [prescribing information]. Madison, NJ: Pfizer Inc; No date.
  108. Isaksson M, Jansson L. Contact allergy to Tween 80 in an inhalation suspension. Contact Dermatitis. 2002;47(5):312-313. [PubMed 12534540]
  109. Ito S, Blajchman A, Stephenson M, Eliopoulos C, Koren G. Prospective follow-up of adverse reactions in breast-fed infants exposed to maternal medication. Am J Obstet Gynecol. 1993;168(5):1393-1399. [PubMed 8498418]
  110. Ito S. Drug therapy for breast-feeding women. N Engl J Med. 2000;343(2):118-126. [PubMed 10891521]
  111. Jain S. Ibuprofen-induced thrombocytopenia. Br J Clin Pract. 1994;48(1):51. [PubMed 8179987]
  112. Junior Strength Advil (ibuprofen) [prescribing information]. Madison, NJ: Pfizer Inc; No date.
  113. Junior Strength Advil Chewables (ibuprofen) [prescribing information]. Madison, NJ: Pfizer Inc; No date.
  114. Kauffman RE, Nelson MV. Effect of Age on Ibuprofen Pharmacokinetics and Antipyretic Response. J Pediatr. 1992;121(6):969-973. [PubMed 1447669]
  115. Kay E, Ben-Shoshan M. Anaphylaxis to ibuprofen in a 12-year-old boy. BMJ Case Rep. 2013;2013:bcr2012007873. doi:10.1136/bcr-2012-007873 [PubMed 23322307]
  116. Kean WF, Lock CJ, Rischke J, Butt R, Buchanan WW, Howard-Lock H. Effect of R and S enantiomers of naproxen on aggregation and thromboxane production in human platelets. J Pharm Sci. 1989;78(4):324-327. doi:10.1002/jps.2600780413 [PubMed 2724096]
  117. Kidney Disease: Improving Global Outcomes (KDIGO). KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. https://kdigo.org/wp-content/uploads/2017/02/KDIGO_2012_CKD_GL.pdf. Updated January 2013. Accessed May 17, 2021.
  118. Kim KN. Treatment of juvenile rheumatoid arthritis. Korean J Pediatr. 2010;53(11):936-941. doi:10.3345/kjp.2010.53.11.936 [PubMed 21218015]
  119. Kim SY, Shin SH, Kim HS, Jung YH, Kim EK, Choi JH. Pulmonary arterial hypertension after ibuprofen treatment for patent ductus arteriosus in very low birth weight infants. J Pediatr. 2016;179:49-53.e1. doi:10.1016/j.jpeds.2016.08.103 [PubMed 27692860]
  120. Kim YJ, Lim KH, Kim MY, et al. Cross-reactivity to acetaminophen and celecoxib according to the type of nonsteroidal anti-inflammatory drug hypersensitivity. Allergy Asthma Immunol Res. 2014;6(2):156-162. doi:10.4168/aair.2014.6.2.156 [PubMed 24587953]
  121. Klar H, Sotošek N, Šelb J, Košnik M. Selective hypersensitivity to a single nonsteroidal anti-inflammatory drug. Acta Dermatovenerol Alp Pannonica Adriat. 2019;28(3):97-101. [PubMed 31545385]
  122. Kliegman RM, St. Geme J, eds. Nelson Textbook of Pediatrics. 21st ed. Saunders Elsevier; 2020.
  123. Knight CL, Deyo RA, Staiger TO, Wipf J. Treatment of acute low back pain. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 16, 2020.
  124. Knowles SR, Drucker AM, Weber EA, Shear NH. Management options for patients with aspirin and nonsteroidal antiinflammatory drug sensitivity. Ann Pharmacother. 2007;41(7):1191-1200. doi:10.1345/aph.1K023 [PubMed 17609236]
  125. Koca T, Akcam M. Ibuprofen induced DRESS syndrome in a child. Indian Pediatr. 2016;53(8):745. [PubMed 27567654]
  126. Kohli P, Steg PG, Cannon CP, et al. NSAID use and association with cardiovascular outcomes in outpatients with stable atherothrombotic disease. Am J Med. 2014;127(1):53-60.e1. doi:10.1016/j.amjmed.2013.08.017 [PubMed 24280110]
  127. Konstan MW, Byard PJ, Hoppel CL, et al. Effect of high-dose ibuprofen in patients with cystic fibrosis. N Engl J Med. 1995;332(13):848-854. [PubMed 7503838]
  128. Konstan MW, Schluchter MD, Xue W, et al. Clinical use of Ibuprofen is associated with slower FEV1 decline in children with cystic fibrosis. Am J Respir Crit Care Med. 2007;176(11):1084-1089. [PubMed 17872492]
  129. Kowalski ML, Agache I, Bavbek S, et al. Diagnosis and management of NSAID-exacerbated respiratory disease (N-ERD)-a EAACI position paper. Allergy. 2019;74(1):28-39. doi:10.1111/all.13599 [PubMed 30216468]
  130. Kowalski ML, Asero R, Bavbek S, et al. Classification and practical approach to the diagnosis and management of hypersensitivity to nonsteroidal anti-inflammatory drugs. Allergy. 2013;68(10):1219-1232. doi:10.1111/all.12260 [PubMed 24117484]
  131. Kowalski ML, Makowska JS, Blanca M, et al. Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) - classification, diagnosis and management: review of the EAACI/ENDA(#) and GA2LEN/HANNA*. Allergy. 2011;66(7):818-829. doi:10.1111/j.1398-9995.2011.02557.x [PubMed 21631520]
  132. Kowalski ML, Makowska JS. Seven steps to the diagnosis of NSAIDs hypersensitivity: how to apply a new classification in real practice? Allergy Asthma Immunol Res. 2015;7(4):312-320. doi:10.4168/aair.2015.7.4.312 [PubMed 25749768]
  133. Kucharewicz I, Kemona-Chetnik I, Reduta T, Wierzbicka I, Flisiak R, Bodzenta-Lukaszyk A. Drug rash with eosinophilia and systemic symptoms after ibuprofen intake. J Investig Allergol Clin Immunol. 2007;17(5):347-348. [PubMed 17982931]
  134. Kumar A, Gosavi RS, Sundaram V, et al. Oral paracetamol vs oral ibuprofen in patent ductus arteriosus: a randomized, controlled, noninferiority trial. J Pediatr. 2020;222:79-84.e2. doi:10.1016/j.jpeds.2020.01.058 [PubMed 32336479]
  135. Lago P, Bettiol T, Salvadori S, et al. Safety and efficacy of ibuprofen versus indomethacin in preterm infants treated for patent ductus arteriosus: a randomised controlled trial. Eur J Pediatr. 2002;161(4):202-207. [PubMed 12014386]
  136. Laidlaw TM, Cahill KN. Current knowledge and management of hypersensitivity to aspirin and NSAIDs. J Allergy Clin Immunol Pract. 2017;5(3):537-545. doi:10.1016/j.jaip.2016.10.021 [PubMed 28483309]
  137. Laine L, Curtis SP, Cryer B, Kaur A, Cannon CP. Risk factors for NSAID-associated upper GI clinical events in a long-term prospective study of 34 701 arthritis patients. Aliment Pharmacol Ther. 2010;32(10):1240-1248. doi:10.1111/j.1365-2036.2010.04465.x [PubMed 20955443]
  138. Lamberts M, Lip GY, Hansen ML, et al. Relation of nonsteroidal anti-inflammatory drugs to serious bleeding and thromboembolism risk in patients with atrial fibrillation receiving antithrombotic therapy: a nationwide cohort study. Ann Intern Med. 2014;161(10):690-698. doi:10.7326/M13-1581 [PubMed 25402512]
  139. Langman MJ, Weil J, Wainwright P, et al. Risks of bleeding peptic ulcer associated with individual non-steroidal anti-inflammatory drugs. Lancet. 1994;343(8905):1075-1078. doi:10.1016/s0140-6736(94)90185-6 [PubMed 7909103]
  140. Lapi F, Azoulay L, Yin H, Nessim SJ, Suissa S. Concurrent use of diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with non-steroidal anti-inflammatory drugs and risk of acute kidney injury: nested case-control study. BMJ. 2013;346:e8525. doi:10.1136/bmj.e8525 [PubMed 23299844]
  141. Lee CH, Chen HN, Tsao LY, et al. Oral ibuprofen versus intravenous indomethacin for closure of patent ductus arteriosus in very low birth weight infants. Pediatr Neonatol. 2012;53(6):346-353. [PubMed 23276438]
  142. Lee EY, Teitelbaum D, Chiam M, Vadas P. Characterization of patients with ibuprofen hypersensitivity. Int Arch Allergy Immunol. 2019;178(2):177-181. doi:10.1159/000494388 [PubMed 30544107]
  143. Lesko SM, Mitchell AA. An assessment of the safety of pediatric ibuprofen. A practitioner-based randomized clinical trial. JAMA. 1995;273(12):929-933. [PubMed 7884951]
  144. Lesko SM, Mitchell A. The safety of acetaminophen and ibuprofen among children younger than two years old. Pediatrics. 1999;104(4). Available at: http://www.fda.gov/cder/drug/advisory/codeine.htm [PubMed 10506264]
  145. LeWinter MM. Pericardial complications of myocardial infarction. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed August 2, 2022.
  146. Litalien C, Jacqz-Aigrain E. Risks and benefits of nonsteroidal anti-inflammatory drugs in children: a comparison with paracetamol. Paediatr Drugs. 2001;3(11):817-858. [PubMed 11735667]
  147. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012. Ibuprofen. https://www.ncbi.nlm.nih.gov/books/NBK547845/?report=classic. Updated April 16, 2018. [PubMed LiverTox.1]
  148. Lucente P, Iorizzo M, Pazzaglia M. Contact sensitivity to Tween 80 in a child. Contact Dermatitis. 2000;43(3):172. [PubMed 10985636]
  149. Maisch B, Seferović PM, Ristić AD, et al. Guidelines on the Diagnosis and Management of Pericardial Diseases Executive Summary; The Task Force on the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology. Eur Heart J. 2004;25(7):587-610. [PubMed 15120056]
  150. Marasco WA, Gikas PW, Azziz-Baumgartner R, Hyzy R, Eldredge CJ, Stross J. Ibuprofen-associated renal dysfunction. Pathophysiologic mechanisms of acute renal failure, hyperkalemia, tubular necrosis, and proteinuria. Arch Intern Med. 1987;147(12):2107-2116. doi:10.1001/archinte.147.12.2107 [PubMed 3689062]
  151. Marchei E, Pellegrini M, Pichini S, et al. Are False-Positive Phencyclidine Immunoassay Instant-View Multi-Test Results Caused by Overdose Concentrations of Ibuprofen, Metamizol, and Dextromethorphan? Ther Drug Monit. 2007;29(5):671-673. [PubMed 17898664]
  152. Marjoribanks J, Ayeleke RO, Farquhar C, Proctor M. Nonsteroidal anti-inflammatory drugs for dysmenorrhoea. Cochrane Database Syst Rev. 2015;2015(7):CD001751. doi:10.1002/14651858.CD001751.pub3 [PubMed 26224322]
  153. Martin E, Vickers B, Landau R, Reece-Stremtan S. ABM clinical protocol #28, peripartum analgesia and anesthesia for the breastfeeding mother. Breastfeed Med. 2018;13(3):164-171. doi:10.1089/bfm.2018.29087.ejm [PubMed 29595994]
  154. Mechanick JI, Apovian C, Brethauer S, et al. Clinical practice guidelines for the perioperative nutrition, metabolic, and nonsurgical support of patients undergoing bariatric procedures - 2019 update: cosponsored by American Association of Clinical Endocrinologists/American College of Endocrinology, The Obesity Society, American Society for Metabolic and Bariatric Surgery, Obesity Medicine Association, and American Society of Anesthesiologists. Surg Obes Relat Dis. 2020;16(2):175-247. doi:10.1016/j.soard.2019.10.025 [PubMed 31917200]
  155. Mehlisch DR, Sykes J. Ibuprofen blood plasma levels and onset of analgesia. Int J Clin Pract Suppl. 2013;(178):3-8. doi:10.1111/ijcp.12053 [PubMed 23163542]
  156. Meißner U, Chakrabarty R, Topf HG, et al. Improved closure of patent ductus arteriosus with high doses of ibuprofen. Pediatr Cardiol. 2012;33(4):586-590. [PubMed 22307401]
  157. Mérida E, Praga M. NSAIDs and nephrotic syndrome. Clin J Am Soc Nephrol. 2019;14(9):1280-1282. doi:10.2215/CJN.08090719 [PubMed 31416889]
  158. Midol liquid gels (ibuprofen) [prescribing information]. Morristown, NJ: Bayer HealthCare LLC; received May 2017.
  159. Misurac JM, Knoderer CA, Leiser JD, et al. Nonsteroidal anti-inflammatory drugs are an important cause of acute kidney injury in children. J Pediatr. 2013;162(6):1153-1159. [PubMed 23360563]
  160. Mitra S, Florez ID, Tamayo ME, et al. Association of placebo, indomethacin, ibuprofen, and acetaminophen with closure of hemodynamically significant patent ductus arteriosus in preterm infants: a systematic review and meta-analysis. JAMA. 2018;319(12):1221-1238. doi:10.1001/jama.2018.1896 [PubMed 29584842]
  161. Mogayzel PJ Jr, Naureckas ET, Robinson KA, et al. Cystic fibrosis pulmonary guidelines. Chronic medications for maintenance of lung health. Am J Respir Crit Care Med. 2013;187(7):680-689. [PubMed 23540878]
  162. Mohammed EP, Stevens JM. Recurrence of Arthrotec-associated nephrotic syndrome with re-challenge. Clin Nephrol. 2000;53(6):483-485 [PubMed 10879670]
  163. Motrin IB (ibuprofen) [prescribing information]. Fort Washington, PA: Johnson & Johnson Consumer Inc; received March 2017.
  164. Motrin IB (ibuprofen) [prescribing information]. Fort Washington, PA: Johnson & Johnson Consumer Inc; received November 2021.
  165. Motrin (ibuprofen) [prescribing information]. Fort Washington, PA: Johnson & Johnson Consumer Inc; August 2016.
  166. Murray KL, Wright D, Laxton B, Miller KM, Meyers J, Englebright J. Implementation of standardized pediatric i.v. medication concentrations. Am J Health Syst Pharm. 2014;71(17):1500-1508. doi:10.2146/ajhp140024 [PubMed 25147175]
  167. Nash DM, Markle-Reid M, Brimble KS, et al. Nonsteroidal anti-inflammatory drug use and risk of acute kidney injury and hyperkalemia in older adults: a population-based study. Nephrol Dial Transplant. 2019;34(7):1145-1154. doi:10.1093/ndt/gfz062 [PubMed 31264694]
  168. National Institute for Health and Care Excellence (NICE). Drug allergy: diagnosis and management. Clinical guideline 183. 2014. [PubMed NICE.1]
  169. Neoprofen (ibuprofen) [prescribing information]. Lebanon, NJ: Recordati Rare Diseases; December 2018.
  170. Nguyen AM, Graham DY, Gage T, et al. Nonsteroidal Anti-inflammatory Drug Use in Dentistry: Gastrointestinal Implications. Gen Dent. 1999;47(6):590-596. [PubMed 10687453]
  171. Nissen SE, Yeomans ND, Solomon DH, et al. Cardiovascular safety of celecoxib, naproxen, or ibuprofen for arthritis. N Engl J Med. 2016;375(26):2519-2529. doi:10.1056/NEJMoa1611593 [PubMed 27959716]
  172. Oates JA, FitzGerald GA, Branch RA, Jackson EK, Knapp HR, Roberts LJ 2nd. Clinical implications of prostaglandin and thromboxane A2 formation (2). N Engl J Med. 1988;319(12):761-767. doi:10.1056/NEJM198809223191206 [PubMed 3045551]
  173. O'Donnell FT, Rosen KR. Pediatric pain management: a review. Mo Med. 2014;111(3):231-237. [PubMed 25011346]
  174. O'Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127(4):e362-e425. [PubMed 23247304]
  175. Ohlsson A, Walia R, Shah S. Ibuprofen for the treatment of patent ductus arteriosus in preterm and/or low birth weight infants. Cochrane Database Syst Rev. 2013;(4):CD003481. [PubMed 23633310]
  176. Ohlsson A, Walia R, Shah SS. Ibuprofen for the treatment of patent ductus arteriosus in preterm or low birth weight (or both) infants. Cochrane Database Syst Rev. 2020;2(2):CD003481. doi:10.1002/14651858.CD003481.pub8 [PubMed 32045960]
  177. Ohlsson A, Walia R, Shah SS. Ibuprofen for the treatment of patent ductus arteriosus in preterm or low birth weight (or both) infants. Cochrane Database Syst Rev. 2018;9(9):CD003481. doi:10.1002/14651858.CD003481.pub7 [PubMed 30264852]
  178. Olson NZ, Otero AM, Marrero I, et al. Onset of Analgesia for Liquigel Ibuprofen 400 mg, Acetaminophen 1000 mg, Ketoprofen 25 mg, and Placebo in the Treatment of Postoperative Dental Pain. J Clin Pharmacol. 2001;41(11):1238-1247. [PubMed 11697757]
  179. Otani K, Tanigawa T, Watanabe T, et al. Microbiota plays a key role in non-steroidal anti-inflammatory drug-induced small intestinal damage. Digestion. 2017;95(1):22-28. doi:10.1159/000452356 [PubMed 28052268]
  180. Pai VB, Sakadjian A, Puthoff TD. Ibuprofen lysine for the prevention and treatment of patent ductus arteriosus. Pharmacotherapy. 2008;28(9):1162-1182. [PubMed 18752387]
  181. Pandharipande P, McGrane S. Pain control in the critically ill adult patient. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 16, 2020.
  182. Papatheodoridis GV, Sougioultzis S, Archimandritis AJ. Effects of Helicobacter pylori and nonsteroidal anti-inflammatory drugs on peptic ulcer disease: a systematic review. Clin Gastroenterol Hepatol. 2006;4(2):130-142. doi:10.1016/j.cgh.2005.10.006 [PubMed 16469671]
  183. Pearlman B, Boyatzis S, Daly C, et al. The Analgesic Efficacy of Ibuprofen in Periodontal Surgery: A Multicentre Study. Aust Dent J. 1997;42(5):328-334. [PubMed 9409050]
  184. Petty RE, Laxer RM, Lindsley CB, Wedderburn LR. Textbook of Pediatric Rheumatology. 7th ed. Elsevier; 2016.
  185. Piper JM, Ray WA, Daugherty JR, Griffin MR. Corticosteroid use and peptic ulcer disease: role of nonsteroidal anti-inflammatory drugs. Ann Intern Med. 1991;114(9):735-740. doi:10.7326/0003-4819-114-9-735 [PubMed 2012355]
  186. Pires SAP, Lemos AP, Pereira EPMN, Maia PADSV, Agro JPSEABD. Ibuprofen-induced aseptic meniingitis: a case report. Rev Paul Pediatr. 2019;37(3):382-385. doi:10.1590/1984-0462/;2019;37;3;00016 [PubMed 31166468]
  187. Poirier TI. Reversible renal failure associated with ibuprofen: case report and review of the literature. Drug Intell Clin Pharm. 1984;18(1):27-32. doi:10.1177/106002808401800103 [PubMed 6420135]
  188. Pourarian S, Takmil F, Cheriki S, Amoozgar H. The effect of oral high-dose ibuprofen on patent ductus arteriosus closure in preterm infants. Am J Perinatol. 2015;32(12):1158-1163. doi:10.1055/s-0035-1551671 [PubMed 26007314]
  189. Pringsheim T, Davenport WJ, Marmura MJ, Schwedt TJ, Silberstein S. How to apply the AHS evidence assessment of the acute treatment of migraine in adults to your patient with migraine. Headache. 2016;56(7):1194-1200. doi:10.1111/head.12870 [PubMed 27322907]
  190. Promes JT, Safcsak K, Pavliv L, Voss B, Rock A. A prospective, multicenter, randomized, double-blind trial of IV ibuprofen for treatment of fever and pain in burn patients. J Burn Care Res. 2011;32(1):79-90. doi:10.1097/BCR.0b013e3182037300 [PubMed 21127424]
  191. Rabbie R, Derry S, Moore RA. Ibuprofen with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev. 2013;2013(4):CD008039. doi:10.1002/14651858.CD008039.pub3 [PubMed 23633348]
  192. Rahman S, Malcoun A. Nonsteroidal antiinflammatory drugs, cyclooxygenase-2, and the kidneys. Prim Care. 2014;41(4):803-821. doi:10.1016/j.pop.2014.09.001 [PubMed 25439535]
  193. Rainsford KD. Ibuprofen: pharmacology, efficacy and safety. Inflammopharmacology. 2009;17(6):275-342. doi:10.1007/s10787-009-0016-x [PubMed 19949916]
  194. Ray WA, Varas-Lorenzo C, Chung CP, et al. Cardiovascular risks of nonsteroidal antiinflammatory drugs in patients after hospitalization for serious coronary heart disease. Circ Cardiovasc Qual Outcomes. 2009;2(3):155-163. doi:10.1161/CIRCOUTCOMES.108.805689 [PubMed 20031832]
  195. Reece-Stremtan S, Campos M, Kokajko L; Academy of Breastfeeding Medicine. ABM clinical protocol #15: analgesia and anesthesia for the breastfeeding mother, revised 2017. Breastfeed Med. 2017;12(9):500-506. doi:10.1089/bfm.2017.29054.srt [PubMed 29624435]
  196. Refer to manufacturer's labeling.
  197. Richette P, Doherty M, Pascual E, et al. 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis. 2017;76(1):29-42. doi:10.1136/annrheumdis-2016-209707 [PubMed 27457514]
  198. Rigourd V, de Villepin B, Amirouche A, et al. Ibuprofen concentrations in human mature milk--first data about pharmacokinetics study in breast milk with AOR-10127 "Antalait" study. Ther Drug Monit. 2014;36(5):590-596. [PubMed 24695355]
  199. Roales-Gómez V, Molero AI, Pérez-Amarilla I, et al. DRESS syndrome secondary to ibuprofen as a cause of hyperacute liver failure. Rev Esp Enferm Dig. 2014;106(7):482-486. [PubMed 25490169]
  200. Rodríguez-González F, Montero JL, Puente J, et al. Orthotopic liver transplantation after subacute liver failure induced by therapeutic doses of ibuprofen. Am J Gastroenterol. 2002;97(9):2476-2477. doi:10.1111/j.1572-0241.2002.06015.x [PubMed 12358284]
  201. Roelofs PD, Deyo RA, Koes BW, Scholten RJ, van Tulder MW. Non-steroidal anti-inflammatory drugs for low back pain. Cochrane Database Syst Rev. 2008;(1):CD000396. [PubMed 18253976]
  202. Runyon BA; AASLD. Introduction to the revised American Association for the Study of Liver Diseases Practice Guideline management of adult patients with ascites due to cirrhosis 2012. Hepatology. 2013;57(4):1651-1653. doi:10.1002/hep.26359 [PubMed 23463403]
  203. Ruschitzka F, Borer JS, Krum H, et al. Differential blood pressure effects of ibuprofen, naproxen, and celecoxib in patients with arthritis: the PRECISION-ABPM (Prospective Randomized Evaluation of Celecoxib Integrated Safety Versus Ibuprofen or Naproxen Ambulatory Blood Pressure Measurement) Trial. Eur Heart J. 2017;38(44):3282-3292. doi:10.1093/eurheartj/ehx508 [PubMed 29020251]
  204. Sahu N, Roy J, Vunnam R, Golamari R, Jain R. Naproxen-induced thrombocytopenia. Proc (Bayl Univ Med Cent). 2020;33(4):653-654. doi:10.1080/08998280.2020.1798724 [PubMed 33100559]
  205. Sammaritano LR, Bermas BL, Chakravarty EE, et al. 2020 American College of Rheumatology guideline for the management of reproductive health in rheumatic and musculoskeletal diseases. Arthritis Rheumatol. 2020;72(4):529‐556. doi:10.1002/art.41191 [PubMed 32090480]
  206. Sánchez-Borges M, Capriles-Hulett A, Caballero-Fonseca F. Risk of skin reactions when using ibuprofen-based medicines. Expert Opin Drug Saf. 2005;4(5):837-848. doi:10.1517/14740338.4.5.837 [PubMed 16111447]
  207. Sanford-Driscoll M, Knodel LC. Induction of hemolytic anemia by nonsteroidal antiinflammatory drugs. Drug Intell Clin Pharm. 1986;20(12):925-934. doi:10.1177/106002808602001202 [PubMed 3545733]
  208. Santamaria JA, Cancio LC, Reed D, et al. Complete fusion of both eyelids in Stevens-Johnson Syndrome: case report. J Burn Care Res. 2021;42(5):1023-1025. doi:10.1093/jbcr/irab024 [PubMed 33528572]
  209. Schjerning O, Larsen TB, Damkier P. The impact of selective and non-selective non-steroid anti-inflammatory drugs on secondary hemostasis in healthy volunteers. Thromb Res. 2009;124(2):208-212. doi:10.1016/j.thromres.2009.01.017 [PubMed 19269020]
  210. Schjerning Olsen AM, Fosbøl EL, Lindhardsen J, et al. Duration of treatment with nonsteroidal anti-inflammatory drugs and impact on risk of death and recurrent myocardial infarction in patients with prior myocardial infarction: a nationwide cohort study. Circulation. 2011;123(20):2226-2235. doi:10.1161/CIRCULATIONAHA.110.004671. [PubMed 21555710]
  211. Schjerning Olsen AM, Gislason GH, McGettigan P, et al. Association of NSAID use with risk of bleeding and cardiovascular events in patients receiving antithrombotic therapy after myocardial infarction. JAMA. 2015;313(8):805-814. doi:10.1001/jama.2015.0809 [PubMed 25710657]
  212. Schneider V, Lévesque LE, Zhang B, Hutchinson T, Brophy JM. Association of selective and conventional nonsteroidal antiinflammatory drugs with acute renal failure: a population-based, nested case-control analysis. Am J Epidemiol. 2006;164(9):881-889. doi:10.1093/aje/kwj331 [PubMed 17005625]
  213. Schwedt TJ, Garza Ivan. Acute treatment of migraine in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed August 12, 2021.
  214. Schweitz MC, Nashel DJ, Alepa FP. Ibuprofen in the treatment of acute gouty arthritis. JAMA. 1978;239(1):34-35. [PubMed 579229]
  215. Schwenk ES. Nonopioid pharmacotherapy for acute pain in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 16, 2020.
  216. Scott CS, Retsch-Bogart GZ, Kustra RP, et al. The pharmacokinetics of ibuprofen suspension, chewable tablets, and tablets in children with cystic fibrosis. J Pediatr. 1999;134(1):58-63.
  217. Shah GM, Muhalwas KK, Winer RL. Renal papillary necrosis due to ibuprofen. Arthritis Rheum. 1981;24(9):1208-1210. doi:10.1002/art.1780240917 [PubMed 7306246]
  218. Shaikhain TA, Al-Husayni F, Elder K. Ibuprofen-induced anaphylactic shock in adult Saudi patient. Cureus. 2019;11(12):e6425. doi:10.7759/cureus.6425 [PubMed 31993263]
  219. Shehab N, Lewis CL, Streetman DD, Donn SM. Exposure to the pharmaceutical excipients benzyl alcohol and propylene glycol among critically ill neonates. Pediatr Crit Care Med. 2009;10(2):256-259. [PubMed 19188870]
  220. Shelley WB, Talanin N, Shelley ED. Polysorbate 80 hypersensitivity. Lancet. 1995;345(8980):1312-1313. [PubMed 7746084]
  221. Smith RP, Kaunitz AM. Dysmenorrhea in adult women: treatment. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 16, 2020.
  222. Solomon DF. NSAIDs: therapeutic use and variability of response in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 28, 2022.
  223. Solomon DH, Husni ME, Libby PA, et al. The risk of major NSAID toxicity with celecoxib, ibuprofen, or naproxen: a secondary analysis of the PRECISION trial. Am J Med. 2017 Dec;130(12):1415-1422.e4. doi:10.1016/j.amjmed.2017.06.028 [PubMed 28756267]
  224. Steinhubl SR. The Use of Anti-Inflammatory Analgesics in the Patient With Cardiovascular Disease: What a Pain. J Am Coll Cardiol. 2005;45(8):1302-1303. [PubMed 15837266]
  225. Sternlieb P, Robinson RM. Stevens-Johnson syndrome plus toxic hepatitis due to ibuprofen. N Y State J Med. 1978;78(8):1239-1243. [PubMed 276660]
  226. Strom BL, Carson JL, Schinnar R, Snyder ES, Shaw M, Lundin FE Jr. Nonsteroidal anti-inflammatory drugs and neutropenia. Arch Intern Med. 1993;153(18):2119-2124. [PubMed 8379803]
  227. Sullivan JE, Farrar HC; Section on Clinical Pharmacology and Therapeutics; Committee on Drugs. Fever and antipyretic use in children. Pediatrics. 2011;127(3):580-587. [PubMed 21357332]
  228. Szeto CC, Sugano K, Wang JG, et al. Non-steroidal anti-inflammatory drug (NSAID) therapy in patients with hypertension, cardiovascular, renal or gastrointestinal comorbidities: joint APAGE/APLAR/APSDE/APSH/APSN/PoA recommendations. Gut. 2020;69(4):617-629. doi:10.1136/gutjnl-2019-319300 [PubMed 31937550]
  229. Teva-Profen (ibuprofen) [product monograph]. Toronto, Ontario, Canada: Teva Canada Limited; January 2022.
  230. Thomas RL, Parker GC, Van Overmeire B, Aranda JV. A meta-analysis of ibuprofen versus indomethacin for closure of patent ductus arteriosus. Eur J Pediatr. 2005;164(3):135-140. doi:10.1007/s00431-004-1596-5 [PubMed 15717178]
  231. Thorell A, MacCormick AD, Awad S, et al. Guidelines for perioperative care in bariatric surgery: Enhanced Recovery After Surgery (ERAS) Society recommendations. World J Surg. 2016;40(9):2065-2083. doi:10.1007/s00268-016-3492-3 [PubMed 26943657]
  232. US Food and Drug Administration (FDA). FDA recommends avoiding use of NSAIDs in pregnancy at 20 weeks or later because they can result in low amniotic fluid. https://www.fda.gov/drugs/drug-safety-and-availability/fda-recommends-avoiding-use-nsaids-pregnancy-20-weeks-or-later-because-they-can-result-low-amniotic. Published October 15, 2020. Accessed October 20, 2020.
  233. Vadivel N, Trikudanathan S, Singh AK. Analgesic nephropathy. Kidney Int. 2007;72(4):517-520. doi:10.1038/sj.ki.5002251 [PubMed 17410098]
  234. van Casteren DS, van den Brink AM, Terwindt GM. Migraine and other headache disorders in pregnancy. Handb Clin Neurol. 2020;172:187-199. doi:10.1016/B978-0-444-64240-0.00011-8 [PubMed 32768088]
  235. Van Overmeire B. Common clinical and practical questions on the use of intravenous ibuprofen lysine for the treatment of patent ductus arteriosus. J Pediatr Pharmacol Ther. 2007;12:194-206.
  236. Van Overmeire B, Smets K, Lecoutere D, et al. A comparison of ibuprofen and indomethacin for closure of patent ductus arteriosus. N Engl J Med. 2000;343(10):674-681. [PubMed 10974130]
  237. Van Overmeire B. The Use of Ibuprofen in Neonates in the Treatment of Patent Ductus Arteriosus. Int J Clin Pract Suppl. 2003;(135):23-27. [PubMed 12723743]
  238. Van Overmeire B, Touw D, Schepens PJ, et al. Ibuprofen Pharmacokinetics in Preterm Infants With Patent Ductus Arteriosus. Clin Pharmacol Ther. 2001;70(4):336-343. [PubMed 11673749]
  239. Villanueva M, Heckenberger R, Palmér M, Schrör K. Stereospecific and non-stereospecific effects of ibuprofen on human platelet and polymorphonuclear leukocyte functions. Agents Actions Suppl. 1992;37:162-170. doi:10.1007/978-3-0348-7262-1_22 [PubMed 1321554]
  240. Walter K, Dilger C. Ibuprofen in Human Milk. Br J Clin Pharmacol. 1997;44(2):211-212. [PubMed 9278216]
  241. Warner TD, Giuliano F, Vojnovic I, Bukasa A, Mitchell JA, Vane JR. Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: a full in vitro analysis. Proc Natl Acad Sci U S A. 1999;96(13):7563-7568. doi:10.1073/pnas.96.13.7563 [PubMed 10377455]
  242. Whelton A. Nephrotoxicity of nonsteroidal anti-inflammatory drugs: physiologic foundations and clinical implications. Am J Med. 1999;106(5B):13S-24S. doi:10.1016/s0002-9343(99)00113-8 [PubMed 10390124]
  243. White AA, Stevenson DD. Aspirin-exacerbated respiratory disease. N Engl J Med. 2018;379(11):1060-1070. doi:10.1056/NEJMra1712125 [PubMed 30207919]
  244. World Health Organization (WHO). Breastfeeding and maternal medication, recommendations for drugs in the eleventh WHO model list of essential drugs. 2002. http://www.who.int/maternal_child_adolescent/documents/55732/en/
  245. Worthington I, Pringsheim T, Gawel MJ, et al; Canadian Headache Society Acute Migraine Treatment Guideline Development Group. Canadian Headache Society guideline: acute drug therapy for migraine headache. Can J Neurol Sci. 2013;40(5)(suppl 3):S1-S80. [PubMed 23968886]
  246. Wynn RL. Update on Nonprescription Pain Relievers for Dental Pain. Gen Dent. 2004;52(2):94-98. [PubMed 15101300]
  247. Yancy CW, Jessup M, Bozkurt B, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013;128(16):e240-e327. [PubMed 23741058]
  248. Yeomans ND, Graham DY, Husni ME, et al. Randomised clinical trial: gastrointestinal events in arthritis patients treated with celecoxib, ibuprofen or naproxen in the PRECISION trial. Aliment Pharmacol Ther. 2018;47(11):1453-1463. doi:10.1111/apt.14610 [PubMed 29667211]
  249. Yesudian PD, Penny M, Azurdia RM, King CM. Ibuprofen-induced acute generalized exanthematous pustulosis. Int J Dermatol. 2004;43(3):208-210. doi:10.1111/j.1365-4632.2004.01860.x [PubMed 15009394]
  250. Yeung T, Shahroor M, Jain A, Weisz D, Jasani B. Efficacy and safety of high versus standard dose ibuprofen for patent ductus arteriosus treatment in preterm infants: A systematic review and meta-analysis. J Neonatal Perinatal Med. 2022;15(3):501-510. doi:10.3233/NPM-210968 [PubMed 35404294]
  251. Zar T, Graeber C, Perazella MA. Recognition, treatment, and prevention of propylene glycol toxicity. Semin Dial. 2007;20(3):217-219. [PubMed 17555487]
  252. Zhan M, Doerfler RM, Xie D, et al. Association of opioids and nonsteroidal anti-inflammatory drugs with outcomes in CKD: findings from the CRIC (Chronic Renal Insufficiency Cohort) study. Am J Kidney Dis. 2020;76(2):184-193. doi:10.1053/j.ajkd.2019.12.010 [PubMed 32317121]
  253. Ziesenitz VC, Zutter A, Erb TO, van den Anker JN. Efficacy and safety of ibuprofen in infants aged between 3 and 6 months. Paediatr Drugs. 2017;19(4):277-290. doi:10.1007/s40272-017-0235-3 [PubMed 28516288]
  254. Zipser RD, Hoefs JC, Speckart PF, Zia PK, Horton R. Prostaglandins: modulators of renal function and pressor resistance in chronic liver disease. J Clin Endocrinol Metab. 1979;48(6):895-900. doi:10.1210/jcem-48-6-895 [PubMed 447795]
Topic 8547 Version 842.0