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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];
  • GoodSense Ibuprofen Childrens [OTC];
  • GoodSense Ibuprofen [OTC];
  • IBU;
  • IBU 600-EZS [DSC];
  • IBU-200 [OTC];
  • Ibupak;
  • Ibuprofen Childrens [OTC];
  • 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).

Abnormal uterine bleeding, nonacute

Abnormal uterine bleeding, nonacute (alternative agent) (off-label use): Note: Not indicated for management of acute abnormal bleeding (ie, excessively heavy or prolonged bleeding that requires urgent evaluation). Alternative for patients who cannot or choose not to use hormonal therapies (Ref). Dosing based on limited data and expert opinion.

Oral: 600 mg 2 to 4 times daily. Begin at menses onset and continue for 2 to 3 days or until cessation of bleeding (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). Avoid nonaspirin NSAIDs 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: 600 mg/dose; maximum daily dose: 2,400 mg/day (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; treatment of pain for >10 days is not recommended, unless directed by health care provider (Ref).

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: 600 mg/dose; maximum daily dose: 2,400 mg/day (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 to 400 mg every 4 to 6 hours as needed (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 (indigotine)]

Motrin IB: 200 mg

Generic: 200 mg

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]

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 (indigo carm) 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

Abnormal uterine bleeding, nonacute; 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): 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. Do not exceed recommended dosages 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

Caplacizumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Caplacizumab. Specifically, the risk of bleeding may be increased. Management: Avoid coadministration of caplacizumab with antiplatelets if possible. If coadministration is required, monitor closely for signs and symptoms of bleeding. Interrupt use of caplacizumab if clinically significant bleeding occurs. Risk D: Consider therapy modification

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. Risk C: Monitor therapy

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).

Avoid maternal use of NSAIDs 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 to avoid use 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 patients 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. Avoid maternal use of NSAIDs 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)
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