Ibuprofen

Dosage Forms

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

Capsule, Oral:

Advil: 200 mg

Advil Migraine: 200 mg

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

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

Motrin IB: 200 mg

Generic: 200 mg

Kit, Combination:

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

Kit, Oral:

IBU 600-EZS: 600 mg [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 disodium, fd&c red #40, 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 brilliant blue fcf (fd&c blue #1), edetate disodium, fd&c red #40, polysorbate 80, propylene glycol, sodium benzoate; grape flavor]

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

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

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

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

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

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

Childrens Motrin: 100 mg/5 mL (120 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]

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

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

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

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

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

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

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

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

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

Motrin Infants Drops: 50 mg/1.25 mL (15 mL) [alcohol free; contains fd&c red #40, 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

Addaprin: 200 mg [contains corn starch]

Advil: 200 mg

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

Advil Junior Strength: 100 mg

CareAll Ibuprofen: 200 mg [contains corn starch]

Dyspel: 200 mg

Genpril: 200 mg

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

I-Prin: 200 mg [DSC]

IBU: 400 mg, 600 mg, 800 mg

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

Motrin IB: 200 mg

Motrin IB: 200 mg [contains corn starch, fd&c red #40 aluminum lake, fd&c yellow #6 aluminum lake]

Motrin IB: 200 mg [contains fd&c yellow #6 (sunset yellow)]

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 aluminum lake; grape flavor]

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

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

Pharmacology

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/Pharmacodynamics

Absorption

Oral: Rapid (85%)

Distribution

V_d:

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 V_d that decreases with increasing PNA and ductal closure (Van Overmeire, 2001) and a V_d, apparent: 0.062 L/kg in 21 premature neonates (GA <32 weeks, PNA: <1 day) (Aranda 1997); a 2-compartment open model was observed

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).

Excretion

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

Onset of Action

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: 2-4 hours

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)

Duration of Action

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

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)

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)

Protein Binding

>90%; Premature infants: ~95% (Aranda 1997)

Use: Labeled Indications

Oral: Inflammatory diseases and rheumatoid disorders, mild to moderate pain, fever, dysmenorrhea, 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 (PDA): To close a clinically significant PDA in premature infants weighing between 500-1500 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, migraine, sore throat, arthritis, physical or athletic overexertion (eg, sprains/strains), menstrual pain, dental pain, minor muscle/bone/joint pain, backache, pain due to the common cold and flu

Use: Off Label

Gout, acute flarescyes

Clinical experience suggests the utility of ibuprofen as an alternative option for acute gout flares Becker 2018.

Based on the 2012 American College of Rheumatology guidelines for management of gout, NSAIDs are effective and recommended agents in the treatment of acute gout flares.

Pericarditisbyes

Data from double-blind, placebo-controlled, multicenter trials indicate that colchicine in combination with aspirin or ibuprofen significantly reduces the incidence of symptoms at 72 hours and the risk of recurrence in acute and recurrent pericarditis. Based on Brazilian Society of Cardiology guidelines for the management of myocarditis and pericarditis and European Society of Cardiology (ESC) guidelines for the management of pericardial diseases, nonsteroidal anti-inflammatory drugs (NSAIDs) (typically, aspirin or ibuprofen) in combination with colchicine are recommended as first-line treatment to manage pain and resolve inflammation in idiopathic and viral acute and recurrent pericarditis.

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): Preterm neonates: With 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.

Dosage and Administration

Dosing: Adult

Analgesia (mild to moderate pain):

Oral:

200 to 800 mg 3 to 4 times daily; usual dose: 400 mg; usual daily dose: 1,200 to 2,400 mg/day (Becker 2010; Blondell 2013; Derry 2009; Roelofs 2008); maximum: 3,200 mg/day (Blondell 2013; Derry 2009)

American Pain Society: 200 to 400 mg every 4 to 6 hours; maximum: 3,200 mg/day (APS 2016)

IV (Caldolor): 400 to 800 mg every 6 hours as needed (maximum: 3,200 mg/day). Note: Patients should be well hydrated prior to administration.

Antipyretic: IV (Caldolor): Note: Patients should be well hydrated prior to administration. Initial: 400 mg, then every 4 to 6 hours or 100 to 200 mg every 4 hours as needed (maximum: 3,200 mg/day)

Dysmenorrhea: Oral:

200 to 800 mg three to four times daily; usual daily dose: 1,200 to 2,400 mg/day; most sources did not exceed a daily dose of 2,400 mg/day and a maximum duration of 3 to 5 days (Majoribanks 2010).

Manufacturer's labeling: Dosing in the prescribing information may not reflect current clinical practice. 400 mg every 4 hours as needed; maximum: 3,200 mg/day

Gout, acute flares (alternative agent) (off-label use): Oral: 800 mg three times daily; initiate within 24 to 48 hours of flare onset preferably; discontinue 2 to 3 days after resolution of clinical signs; usual duration: 5 to 7 days (ACR [Khanna 2012]; Becker 2018)

Osteoarthritis: Oral: 400 to 800 mg 3 to 4 times daily (maximum: 3,200 mg/day)

Rheumatoid arthritis: Oral: 400 to 800 mg 3 to 4 times daily (maximum: 3,200 mg/day)

OTC labeling:

Analgesic, antipyretic: 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: 1,200 mg/day); Duration: treatment for >10 days as an analgesic or >3 days as an antipyretic is not recommended unless directed by health care provider.

Migraine: Oral: 400 mg at onset of symptoms (maximum: 400 mg/24 hours unless directed by health care provider)

Pericarditis (off-label use): Oral: Note: Administer in combination with colchicine therapy. Concurrent gastroduodenal prophylaxis with a proton pump inhibitor has been used and is recommended (ESC [Adler 2015]; Imazio 2013; Imazio 2005). With pericarditis postmyocardial infarction, the ACCF/AHA prefers the use of aspirin (ACCF/AHA [O’Gara 2013]).

Acute pericarditis: 600 mg every 8 hours for 7 to 14 days followed by a gradual tapering of the dose by 200 to 400 mg every 1 to 2 weeks (ESC [Adler 2015])

Recurrent pericarditis: 600 mg every 8 hours (range: 1,200 to 2,400 mg) for weeks to months until complete symptom resolution followed by a gradual tapering of the dose by 200 to 400 mg every 1 to 2 weeks (ESC [Adler 2015])

Dosing: Geriatric

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

Dosing: Pediatric

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 two concentrations (ie, concentrated infant drops: 50 mg/1.25 mL and suspension: 100 mg/5 mL); precautions should be taken to verify and avoid confusion between the different concentrations; dose should be clearly presented as "mg".

Analgesic:

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

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

Oral:

Weight-directed dosing: Infants and Children <50 kg: Limited data available in infants <6 months: 4 to 10 mg/kg/dose every 6 to 8 hours; maximum single dose: 400 mg; maximum daily dose: 40 mg/kg/day (APS 2008; Berde 1990; Berde 2002; Kliegman 2011).

Fixed dosing:

Infants and Children 6 months to 11 years: 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.

Table has been converted to the following text.

Ibuprofen Dosing

Weight (preferred)^A 5.4 to 8.1 kg (12 to 17 lbs) or 6 to 11 months of age: 50 mg

Weight (preferred)^A 8.2 to 10.8 kg (18 to 23 lbs) or 12 to 23 months of age: 75 to 80 mg

Weight (preferred)^A 10.9 to 16.3 kg (24 to 35 lbs) or 2 to 3 years of age: 100 mg

Weight (preferred)^A 16.4 to 21.7 kg (36 to 47 lbs) or 4 to 5 years of age: 150 mg

Weight (preferred)^A 21.8 to 27.2 kg (48 to 59 lbs) or 6 to 8 years of age: 200 mg

Weight (preferred)^A 27.3 to 32.6 kg (60 to 71 lbs) or 9 to 10 years of age: 200 to 250 mg

Weight (preferred)^A 32.7 to 43.2 kg (72 to 95 lbs) or 11 years of age: 300 mg

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

Children ≥12 years and Adolescents: Oral: 200 mg every 4 to 6 hours as needed; if pain does not respond may increase to 400 mg; maximum daily dose: 1,200 mg/day; treatment of pain for >10 days is not recommended, unless directed by health care provider.

Antipyretic:

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

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

Oral:

Weight-directed dosing: Infants ≥6 months, Children, and Adolescents: 5 to 10 mg/kg/dose every 6 to 8 hours; maximum single dose: 400 mg; maximum daily dose: 40 mg/kg/day up to 1,200 mg, unless directed by physician; under physician supervision daily doses ≤2,400 mg may be used (Kliegman 2011; Litalien 2001; Sullivan 2011).

Fixed dosing:

Infants and Children 6 months to 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 for >3 days is not recommended unless directed by health care provider.

Table has been converted to the following text.

Weight (preferred)^A 5.4 to 8.1 kg (12 to 17 lbs) or 6 to 11 months of age: 50 mg

Weight (preferred)^A 8.2 to 10.8 kg (18 to 23 lbs) or 12 to 23 months of age: 75 to 80 mg

Weight (preferred)^A 10.9 to 16.3 kg (24 to 35 lbs) or 2 to 3 years of age: 100 mg

Weight (preferred)^A 16.4 to 21.7 kg (36 to 47 lbs) or 4 to 5 years of age: 150 mg

Weight (preferred)^A 21.8 to 27.2 kg (48 to 59 lbs) or 6 to 8 years of age: 200 mg

Weight (preferred)^A 27.3 to 32.6 kg (60 to 71 lbs) or 9 to 10 years of age: 200 to 250 mg

Weight (preferred)^A 32.7 to 43.2 kg (72 to 95 lbs) or 11 years of age: 300 mg

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

Children ≥12 years and Adolescents: Oral: 200 mg every 4 to 6 hours as needed; if fever does not respond may increase to 400 mg; maximum daily dose: 1,200 mg/day; treatment of fever >3 days is not recommended, unless directed by health care provider.

Cystic fibrosis, mild disease (to slow lung disease progression): Limited data available: Children and Adolescents 6 to 17 years with FEV₁ >60% predicted (Mogayzel 2013): 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 old with mild lung disease were observed to have greatest benefit; (Konstan 1995). 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 (Konstan 2007). 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 (Litalien 2001; Scott 1999).

Juvenile idiopathic arthritis (JIA): Children and Adolescents: 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 milder disease may be treated with 20 mg/kg/day; patients with more severe disease may require up to 50 mg/kg/day; maximum single dose: 800 mg; maximum daily dose: 2,400 mg/day (Giannini 1990; Kliegman 2011; Litalien 2001).

Reconstitution

Ibuprofen injection (Caldolor): Vials must be diluted prior to use. Dilute with D5W, NS or LR to a final concentration ≤4 mg/mL.

Administration

Oral: Administer with food or milk.

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

Dietary Considerations

Some products may contain phenylalanine and/or potassium.

Storage

Ibuprofen injection (Caldolor): Store intact vials and ready-to-use bags at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Vials must be diluted prior to use. Diluted solutions are stable in D5W, LR, or NS for 24 hours at 20°C to 25°C (68°F to 77°F).

Ibuprofen lysine injection (NeoProfen): Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Protect from light. Store vials in carton until use. After first withdrawal from vial, discard remaining solution (preservative free). Following dilution in D5W or NS, use within 30 minutes.

Suspension: Store at 15°C to 30°C (59°F to 86°F).

Tablet: Store at 20°C to 25°C (68°F to 77°F).

Drug Interactions

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

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

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

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. 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. 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. Management: Monitor renal function periodically in patients receiving aliskiren and any nonsteroidal anti-inflammatory agent. Patients at elevated risk of renal dysfunction include those who are elderly, are volume depleted, or have pre-existing renal dysfunction. Monitor therapy

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

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

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

Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Exceptions: Bemiparin; Enoxaparin; Heparin. 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. 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. 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. Consider therapy modification

Beta-Blockers: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Beta-Blockers. Exceptions: Levobunolol; Metipranolol. Monitor therapy

Bile Acid Sequestrants: May decrease the absorption of Nonsteroidal Anti-Inflammatory Agents. Consider therapy modification

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. Monitor therapy

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

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

Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. 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. 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. Monitor therapy

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

Dexibuprofen: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Dexibuprofen. Avoid combination

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

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

Diclofenac (Systemic): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Management: Seek alternatives to the combined use of diclofenac with other nonsteroidal anti-inflammatory agents (NSAIDs). Avoid the use of diclofenac/misoprostol with other NSAIDs. Consider therapy modification

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

Drospirenone: Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Drospirenone. 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. 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. 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. 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. Monitor therapy

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

Felbinac: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Monitor therapy

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

Glucosamine: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Haloperidol: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Haloperidol. Specifically including drowsiness and confusion. 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. 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. Consider therapy modification

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Management: Avoid combination when possible. If used, monitor more closely for evidence of bleeding. Discontinue herbal products with anticoagulant or antiplatelet actions 2 weeks prior to surgical, dental, or invasive procedures. Consider therapy modification

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Bleeding may occur. Management: Concomitant treatment with these agents should generally be avoided. If used concomitantly, increased diligence in monitoring for adverse effects (eg, bleeding, bruising, altered mental status due to CNS bleeds) must be employed. Consider therapy modification

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

Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. 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. Consider therapy modification

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

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

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

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

Lithium: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Lithium. 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. Consider therapy modification

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

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

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

Methotrexate: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Methotrexate. Management: Alternative anti-inflammatory therapy should be considered whenever possible, especially if the patient is receiving higher, antineoplastic doses of methotrexate. Consider therapy modification

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

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

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

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

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

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

Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective). Avoid combination

Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. 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. Management: Avoid concurrent use of nonsteroidal antiinflammatory drugs (NSAIDs) with omacetaxine in patients with a platelet count of less than 50,000/uL. Avoid combination

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

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

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. 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. Monitor therapy

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

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

Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. 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. 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: Closely monitor for increased pralatrexate serum levels and/or toxicity if used concomitantly with an NSAID. Monitor for decreased pralatrexate serum levels with NSAID discontinuation. Monitor therapy

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

Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. 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). 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. 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. 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). Exceptions: Choline Magnesium Trisalicylate. Consider therapy modification

Salicylates: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Monitor therapy

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. Consider therapy modification

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

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

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

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

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. Consider therapy modification

Tenoxicam: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. 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. Monitor therapy

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

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

Tricyclic Antidepressants (Tertiary Amine): May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Monitor therapy

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

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

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

Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. 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. Consider therapy modification

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

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

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

Test Interactions

May interfere with urine detection of phencyclidine (false-positives) (Marchei 2007). May lead to false-positive aldosterone/renin ratio (ARR) (Funder 2016).

Adverse Reactions

Oral:

>10%:

Hematologic & oncologic: Decreased hemoglobin (7% to 23%)

Hepatic: Increased serum alanine aminotransferase (≤15%), increased serum aspartate aminotransferase (≤15%)

1% to 10%:

Cardiovascular: Edema

Central nervous system: Dizziness (3% to 9%), headache, nervousness

Dermatologic: Skin rash (3% to 9%), maculopapular rash, pruritus

Endocrine & metabolic: Fluid retention

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

Hematologic & oncologic: Anemia, prolonged bleeding time

Hepatic: Increased liver enzymes

Otic: Tinnitus (<3%)

Renal: Renal function abnormality

Frequency not defined:

Cardiovascular: Hypertension, syncope, tachycardia

Central nervous system: Anxiety, malaise, vertigo

Dermatologic: Diaphoresis, ecchymoses

Endocrine & metabolic: Weight changes

Gastrointestinal: Duodenitis, esophagitis, glossitis, hematemesis, rectal hemorrhage, stomatitis

Genitourinary: Dysuria, oliguria, proteinuria

Hematologic & oncologic: Leukopenia

Infection: Infection, sepsis

Neuromuscular & skeletal: Asthenia, tremor

Renal: Interstitial nephritis

Respiratory: Asthma, dyspnea

<1%, postmarketing, and/or case reports: Abnormal dreams, abnormal hepatic function tests, acidosis, acute renal failure, agranulocytosis, alopecia, amblyopia, anaphylactoid shock, anaphylaxis, anemia, angioedema, aplastic anemia, apnea, aseptic meningitis, auditory impairment, azotemia, blurred vision, bronchospasm, cardiac arrhythmia, cardiac failure, cataract, cerebrovascular accident, change in appetite, chills, coma, confusion, conjunctivitis, cystitis, decreased creatinine clearance, decreased hematocrit, depression, diplopia, DRESS syndrome (Koca 2016; Roales-Gómez 2014), drowsiness, duodenal ulcer, emotional lability, eosinophilia, epistaxis, eructation, erythema multiforme, exfoliative dermatitis, fever, gastric ulcer, gastritis, gastrointestinal hemorrhage, gastrointestinal perforation, gastrointestinal ulcer, gingival ulceration, glomerulonephritis, gynecomastia, hallucination, hearing loss, heavy menstrual bleeding, hematuria, hemolytic anemia, hemorrhage, Henoch-Schonlein purpura, hepatic failure, hepatic necrosis, hepatitis, hepatorenal syndrome, hepatotoxicity (idiosyncratic) (Chalasani 2014), hyperglycemia, hypoglycemia, hypotension, increased serum creatinine, insomnia, jaundice, lymphadenopathy, melena, myocardial infarction, neutropenia, nonthrombocytopenic purpura, occult blood in stools, optic neuritis, palpitations, pancreatitis, pancytopenia, paresthesia, pneumonia, polyuria, pseudotumor cerebri, renal papillary necrosis, renal tubular necrosis, respiratory depression, rhinitis, scotoma, seizure, serum sickness, sinus bradycardia, sinus tachycardia, skin photosensitivity, Stevens-Johnson syndrome, systemic lupus erythematosus, thrombocytopenia, thrombosis, toxic epidermal necrolysis, urticaria, vasculitis, vesiculobullous dermatitis, vision color changes, vision loss, xerophthalmia, xerostomia

Injection: Ibuprofen (Caldolor):

>10%:

Central nervous system: Headache (12%; children: ≥2%)

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

Gastrointestinal: Vomiting (22%; children: ≥2%), flatulence (16%)

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

Hepatic: Increased serum alanine aminotransferase (≤15%), increased serum aspartate aminotransferase (≤15%)

Infection: Bacteremia (13%)

1% to 10%:

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

Central nervous system: Dizziness (4% to 6%), infusion-site pain (children: ≥2%)

Endocrine & metabolic: Hypoalbuminemia (10%), hypernatremia (7% to 10%), increased lactate dehydrogenase (7% to 10%)

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

Genitourinary: Urinary retention (5%)

Hematologic & oncologic: Hemorrhage (10%), thrombocythemia (3% to 10%), wound hemorrhage (3%), decreased hemoglobin (2% to 3%)

Renal: Increased blood urea nitrogen (10%)

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

Frequency not defined:

Dermatologic: Exfoliative dermatitis, skin rash, Stevens-Johnson syndrome, toxic epidermal necrolysis

Hypersensitivity: Hypersensitivity reaction

<1%, postmarketing, and/or case reports: Abdominal pain, anaphylaxis, cerebrovascular accident, esophageal perforation, gastrointestinal hemorrhage, gastrointestinal inflammation, gastrointestinal tract perforation, gastrointestinal ulcer, hepatotoxicity (idiosyncratic) (Chalasani 2014), myocardial infarction, nasal congestion, thrombosis

Injection: Ibuprofen lysine (NeoProfen):

>10%:

Central nervous system: Intraventricular hemorrhage (29%)

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

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

Gastrointestinal: Enterocolitis (22%)

Hematologic & oncologic: Anemia (32%)

Infection: Sepsis (43%)

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

1% to 10%:

Cardiovascular: Edema (4%)

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

Genitourinary: Urinary tract infection (9%), decreased urine output (3%)

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

Respiratory: Respiratory failure (10%), atelectasis (4%)

Frequency not defined:

Cardiovascular: Cardiac failure, hypotension, tachycardia

Central nervous system: Seizure

Endocrine & metabolic: Hyperglycemia

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

Genitourinary: Oliguria

Hematologic & oncologic: Neutropenia, prolonged bleeding time, thrombocytopenia

Hepatic: Jaundice

Infection: Infection

Local: Injection site reaction

Renal: Renal failure syndrome

Miscellaneous: Reduced intake of food/fluids

<1%, postmarketing, and/or case reports: Gastrointestinal perforation, hepatotoxicity (idiosyncratic) (Chalasani 2014), necrotizing enterocolitis, pulmonary hypertension

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactoid reactions: Even in patients without prior exposure anaphylactoid reactions may occur; patients with "aspirin triad" (bronchial asthma, aspirin intolerance, rhinitis) may be at increased risk. Contraindicated in patients who experience bronchospasm, asthma, rhinitis, or urticaria with nonsteroidal anti-inflammatory drug (NSAID) or aspirin therapy.
• Cardiovascular events: [US Boxed Warning]: NSAIDs cause an increased risk of serious (and potentially fatal) adverse cardiovascular thrombotic events, including fatal MI and stroke. Risk may occur early during treatment and may increase with duration of use. Relative risk appears to be similar in those with and without known cardiovascular disease or risk factors for cardiovascular disease; however, absolute incidence of cardiovascular events (which may occur early during treatment) was higher in patients with known cardiovascular disease or risk factors. New-onset hypertension or exacerbation of hypertension may occur (NSAIDS may also impair response to ACE inhibitors, thiazide diuretics, or loop diuretics); may contribute to cardiovascular events; monitor blood pressure; use with caution in patients with hypertension. May cause sodium and fluid retention; use with caution in patients with edema. Avoid use in heart failure (ACCF/AHA [Yancy 2013]). Avoid use in patients with a recent MI unless benefits outweigh risk of cardiovascular thrombotic events. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of cardiovascular events; alternate therapies should be considered for patients at high risk.
• 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).
• Gastrointestinal events: [US Boxed Warning]: NSAIDs cause an increased risk of serious gastrointestinal inflammation, ulceration, bleeding, and perforation (may be fatal); elderly patients and patients with history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events. These events may occur at any time during therapy and without warning. Avoid use in patients with active GI bleeding. In patients with a history of acute lower GI bleeding, avoid use of non-aspirin NSAIDs, especially if due to angioectasia or diverticulosis (Strate 2016). Use caution with a history of GI ulcers, concurrent therapy known to increase the risk of GI bleeding (eg, aspirin, anticoagulants and/or corticosteroids, selective serotonin reuptake inhibitors), advanced hepatic disease, coagulopathy, smoking, use of alcohol, or in elderly or debilitated patients. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of GI adverse events; alternate therapies should be considered for patients at high risk. When used concomitantly with aspirin, a substantial increase in the risk of gastrointestinal complications (eg, ulcer) occurs; concomitant gastroprotective therapy (eg, proton pump inhibitors) is recommended (Bhatt 2008).
• Hematologic effects: Platelet adhesion and aggregation may be decreased; may prolong bleeding time; patients with coagulation disorders or who are receiving anticoagulants should be monitored closely. Anemia may occur; patients on long-term NSAID therapy should be monitored for anemia. Rarely, NSAID use has been associated with potentially severe blood dyscrasias (eg, agranulocytosis, thrombocytopenia, aplastic anemia).
• Hepatic effects: Transaminase elevations have been reported with use; closely monitor patients with any abnormal LFT. Rare (sometimes fatal) severe hepatic reactions (eg, fulminant hepatitis, liver necrosis, hepatic failure) have occurred with NSAID use; discontinue immediately if signs or symptoms of hepatic disease develop or if systemic manifestations occur.
• Hyperkalemia: NSAID use may increase the risk of hyperkalemia, particularly in the elderly, diabetics, 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.
• Renal effects: NSAID use may compromise existing renal function; dose-dependent decreases in prostaglandin synthesis may result from NSAID use, reducing renal blood flow which may cause renal decompensation (usually reversible). Patients with impaired renal function, dehydration, hypovolemia, heart failure, hepatic impairment, those taking diuretics and ACE inhibitors, and the elderly are at greater risk of renal toxicity. Rehydrate patient before starting therapy; monitor renal function closely. Long-term NSAID use may result in renal papillary necrosis and other renal injury.
• Skin reactions: NSAIDs may cause potentially fatal serious skin adverse events including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN); may occur without warning; discontinue use at first sign of skin rash (or any other hypersensitivity).

Disease-related concerns:

• Aseptic meningitis: May increase the risk of aseptic meningitis, especially in patients with systemic lupus erythematosus (SLE) 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 2013). Short-term use of celecoxib or IV ketorolac is recommended as part of a multimodal pain management strategy for postoperative pain (Chou 2016; Horsley 2019; Thorell 2016).
• Coronary artery bypass graft surgery: [US Boxed Warning]: Use is contraindicated in the setting of coronary artery bypass graft (CABG) surgery. Risk of MI and stroke may be increased with use following CABG surgery.
• Hepatic impairment: Use with caution in patients with hepatic impairment; patients with advanced hepatic disease are at an increased risk of GI bleeding with NSAIDs.
• Renal impairment: Avoid use in patients with advanced renal disease; discontinue use with persistent or worsening abnormal renal function tests. Use of ibuprofen lysine (NeoProfen) is contraindicated in preterm infants with significant renal impairment.

Special populations:

• Elderly: Elderly patients are at greater risk for serious GI events; use with caution.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer’s labeling.
• Ibuprofen injection (Caldolor): Must be diluted prior to administration; hemolysis can occur if not diluted.
• Ibuprofen lysine injection (NeoProfen): Hold second or third doses if urinary output is <0.6 mL/kg/hour. May alter signs of infection. May inhibit platelet aggregation; monitor for signs of bleeding. May displace bilirubin; use caution when total bilirubin is elevated. Long-term evaluations of neurodevelopment, growth, or diseases associated with prematurity following treatment have not been conducted. A second course of treatment, alternative pharmacologic therapy or surgery may be needed if the ductus arteriosus fails to close or reopens following the initial course of therapy. Avoid extravasation.
• Phenylalanine: Some products may contain phenylalanine.
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer’s labeling.
• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures and respiratory depression; use caution (AAP ["Inactive" 1997]; Zar 2007).

Other warnings/precautions:

• Self-medication (OTC use): Prior to self-medication, patients should contact health care provider if they have had recurring stomach pain or upset, ulcers, bleeding problems, high blood pressure, heart or kidney disease, other serious medical problems, are currently taking a diuretic, aspirin, anticoagulant, or are ≥60 years of age. If patients are using for migraines, they should also contact health care provider if they have not had a migraine diagnosis by health care provider, a headache that is different from usual migraine, worst headache of life, fever and neck stiffness, headache from head injury or coughing, first headache at ≥50 years of age, daily headache, or migraine requiring bed rest. Recommended dosages should not be exceeded, due to an increased risk of GI bleeding. Stop use and consult a health care provider if symptoms do not improve within first 24 hours of use (children) get worse, or newly appear, fever lasts for >3 days or pain lasts >3 days (children) and >10 days (adults). Do not give for >10 days unless instructed by healthcare provider. Consuming ≥3 alcoholic beverages/day or taking longer than recommended may increase the risk of GI bleeding.
• Surgical/dental procedures: Withhold for at least 4 to 6 half-lives prior to surgical or dental procedures.

Monitoring Parameters

CBC, chemistry profile, occult blood loss and periodic liver function tests; 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; evaluate gastrointestinal effects (abdominal pain, bleeding, dyspepsia); mental confusion, disorientation; blood pressure; periodic ophthalmic exams with long-term therapy; signs of infection (ibuprofen lysine)

Pregnancy

Pregnancy Considerations

Birth defects have been observed following in utero NSAID exposure in some studies; however, data is 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. In addition, nonclosure of the ductus arteriosus postnatally may occur and be resistant to medical management (Bermas 2014; Bloor 2013). Because NSAIDs cause premature closure of the ductus arteriosus, prescribing information for ibuprofen specifically states use should be avoided starting at 30-weeks gestation.

Use of NSAIDs can be considered for the treatment of mild rheumatoid arthritis flares in pregnant women; however, use should be minimized or avoided early and late in pregnancy (Bermas 2014; Saavedra Salinas 2015). If treatment of migraine is needed in pregnant women, ibuprofen is preferred when an NSAID is required; however, other agents are recommended as initial therapy (Amundsen 2015).

The chronic use of NSAIDs in women of reproductive age may be associated with infertility that is reversible upon discontinuation of the medication. Consider discontinuing use in women having difficulty conceiving or those undergoing investigation of fertility. The use of NSAIDs close to conception may be associated with an increased risk of miscarriage (Bloor 2013; Bermas 2014).

Patient Education

What is this drug used for?

• It is used to ease pain, swelling, and fever.
• It is used to ease painful period (menstrual) cycles.
• It is used to treat arthritis.
• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Heartburn
• Stomach pain
• Nausea
• Vomiting
• Diarrhea
• Constipation
• Passing gas

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Aseptic meningitis like headache, fever, chills, severe nausea or vomiting, stiff neck, rash, sensitivity to bright lights, fatigue, or confusion
• Abdominal ulcers like severe abdominal or back pain; black, tarry, or bloody stools; vomiting blood or vomit that looks like coffee grounds; or weight gain or abnormal swelling
• Bleeding like vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding
• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain
• High potassium like abnormal heartbeat, confusion, dizziness, passing out, weakness, shortness of breath, numbness or tingling feeling
• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin
• Severe cerebrovascular disease like change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or vision changes
• Shortness of breath
• Excessive weight gain
• Swelling of arms or legs
• Chest pain
• Fast heartbeat
• Severe headache
• Severe dizziness
• Passing out
• Severe loss of strength and energy
• Noise or ringing in the ears
• Severe back pain
• Vision changes
• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.