Skip to Content
Is your RA under control? Take an assessment and find out

Ibuprofen

Pronunciation

Pronunciation

(eye byoo PROE fen)

Index Terms

  • p-Isobutylhydratropic Acid
  • Ibuprofen Lysine

Dosage Forms

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

Capsule, Oral:

Advil: 200 mg

Advil Migraine: 200 mg

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

Generic: 200 mg

Cream, External:

EnovaRX-Ibuprofen: 10% (60 g, 120 g) [contains cetearyl alcohol]

Kit, Combination:

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

Solution, Intravenous:

Caldolor: 400 mg/4 mL (4 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 Ibuprofen: 100 mg/5 mL (118 mL) [alcohol free; contains brilliant blue fcf (fd&c blue #1), fd&c red #40, polysorbate 80, sodium benzoate; grape flavor]

Childrens Ibuprofen: 100 mg/5 mL (120 mL) [alcohol free; contains butylparaben, fd&c red #40, polysorbate 80, propylene glycol, sodium benzoate; bubble-gum flavor]

Childrens Ibuprofen: 100 mg/5 mL (5 mL, 118 mL, 237 mL, 240 mL) [alcohol free; contains fd&c red #40, fd&c yellow #10 (quinoline yellow), polysorbate 80, sodium benzoate; berry flavor]

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

Childrens Ibuprofen: 40 mg/mL (15 mL) [alcohol free; berry flavor]

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

Childrens Ibuprofen: 100 mg/5 mL (118 mL) [alcohol free, gluten free; contains brilliant blue fcf (fd&c blue #1), fd&c red #40, polysorbate 80, sodium benzoate; grape flavor]

Childrens Motrin: 40 mg/mL (15 mL) [berry flavor]

Childrens Motrin: 100 mg/5 mL (120 mL) [alcohol free]

Childrens Motrin: 100 mg/5 mL (60 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; contains fd&c red #40, sodium benzoate]

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

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

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

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

HyVee Ibuprofen Childrens: 100 mg/5 mL (120 mL) [gluten free; contains 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 brilliant blue fcf (fd&c blue #1), fd&c red #40, polysorbate 80, sodium benzoate; grape flavor]

Ibuprofen Childrens: 100 mg/5 mL (120 mL) [alcohol free; contains butylparaben, fd&c red #40, fd&c yellow #6 (sunset yellow), polysorbate 80, propylene glycol, sodium benzoate; fruit flavor]

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

Ibuprofen Childrens: 100 mg/5 mL (120 mL) [alcohol free, gluten free; contains brilliant blue fcf (fd&c blue #1), fd&c red #40, polysorbate 80, sodium benzoate; grape flavor]

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

Infants Ibuprofen: 50 mg/1.25 mL (15 mL) [alcohol free; contains butylparaben, fd&c red #40, polysorbate 80, propylene glycol, sodium benzoate; berry flavor]

Infants Ibuprofen: 50 mg/1.25 mL (15 mL, 30 mL) [alcohol free, dye free; contains polysorbate 80, sodium benzoate; berry flavor]

Infants Ibuprofen: 50 mg/1.25 mL (15 mL) [alcohol free, gluten free; contains butylparaben, fd&c red #40, polysorbate 80, propylene glycol, sodium benzoate; berry flavor]

Motrin: 40 mg/mL (15 mL) [alcohol free, dye free; berry flavor]

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

Motrin Infants Drops: 50 mg/1.25 mL (15 mL, 30 mL) [alcohol free, dye free; contains polysorbate 80, sodium benzoate]

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

Tablet, Oral:

Addaprin: 200 mg

Advil: 200 mg

Advil Junior Strength: 100 mg

Dyspel: 200 mg

Genpril: 200 mg

I-Prin: 200 mg

IBU-200: 200 mg

Motrin IB: 200 mg

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

Motrin Junior Strength: 100 mg [scored]

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]

Childrens Motrin: 50 mg [scored; contains aspartame, fd&c yellow #6 (sunset yellow); orange flavor]

Childrens Motrin Jr Strength: 100 mg [scored; contains aspartame, brilliant blue fcf (fd&c blue #1); grape flavor]

Ibuprofen Junior Strength: 100 mg [contains aspartame, fd&c yellow #6 (sunset yellow), soybean oil, whey protein]

Motrin Junior Strength: 100 mg [contains aspartame, brilliant blue fcf (fd&c blue #1)]

Motrin Junior Strength: 100 mg [scored; contains aspartame, fd&c yellow #6 (sunset yellow); orange flavor]

Brand Names: U.S.

  • Addaprin [OTC]
  • Advil Junior Strength [OTC]
  • Advil Migraine [OTC]
  • Advil [OTC]
  • Caldolor
  • Childrens Advil [OTC]
  • Childrens Ibuprofen [OTC]
  • Childrens Motrin Jr Strength [OTC]
  • Childrens Motrin [OTC]
  • Dyspel [OTC]
  • EnovaRX-Ibuprofen
  • Genpril [OTC]
  • HyVee Ibuprofen Childrens [OTC]
  • I-Prin [OTC]
  • IBU-200 [OTC]
  • Ibuprofen Childrens [OTC]
  • Ibuprofen Comfort Pac
  • Ibuprofen Junior Strength [OTC]
  • Infants Advil [OTC]
  • Infants Ibuprofen [OTC]
  • KS Ibuprofen [OTC]
  • Motrin IB [OTC]
  • Motrin Infants Drops [OTC]
  • Motrin Junior Strength [OTC]
  • Motrin [OTC]
  • NeoProfen
  • Provil [OTC]

Pharmacologic Category

  • Analgesic, Nonopioid
  • Nonsteroidal Anti-inflammatory Drug (NSAID), Oral
  • Nonsteroidal Anti-inflammatory Drug (NSAID), Parenteral

Pharmacology

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.

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); 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, 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: Unlabeled

Ankylosing spondylitis, cystic fibrosis, gout, acute migraine headache, migraine prophylaxis, 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]

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.

Dosing: Adult

Analgesia/pain/dysmenorrhea: Oral: 400 mg every 4 to 6 hours as needed

Analgesic: 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.

US labeling: Initial: 400 mg, then every 4 to 6 hours or 100 to 200 mg every 4 hours as needed (maximum: 3,200 mg/day).

Canadian labeling: Initial: 200 to 400 mg, then every 4 to 6 hours as needed up to 24 hours (maximum: 2,400 mg/day).

Osteoarthritis, rheumatoid arthritis: Oral:

US labeling: 400 to 800 mg 3 to 4 times daily (maximum: 3,200 mg/day).

Canadian labeling: Initial: 600 mg 2 times daily; if necessary, may increase to 600 mg 3 times daily (maximum: 1,800 mg/day). Maintenance: 600 mg once or twice daily.

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: 400 to 800 mg 3 to 4 times daily (maximum dose: 3,200 mg/day) (Imazio 2009); with pericarditis postmyocardial infarction, the ACCF/AHA prefers the use of aspirin (O’Gara 2013).

Dosing: Geriatric

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

Dosing: Pediatric

Analgesic:

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

Infants ≥6 months and Children <12 years: 10 mg/kg (maximum dose: 400 mg) 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: 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 (American Pain Society 2008; Berde 1990; Berde 2002; Kliegman 2011)

Antipyretic:

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

Infants ≥6 months and Children <12 years: 10 mg/kg (maximum dose: 400 mg) 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: 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, not to exceed maximum of 2,400 mg daily) (Litalien 2001; Sullivan 2011).

Juvenile idiopathic arthritis (JIA) (off-label use): Oral: Children and Adolescents: 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 (Giannini 1990; Kliegman 2011; Litalien 2001).

Patent ductus arteriosus: IV (ibuprofen lysine [NeoProfen]): Infants weighing between 500 to 1,500 g and ≤32 weeks' GA: Initial dose: Ibuprofen 10 mg/kg, followed by two doses of 5 mg/kg at 24 and 48 hours. Dose should be based on birth weight.

OTC labeling (analgesic, antipyretic): Oral: Note: Discontinue use and consult health care provider if no improvement within 24 hours after initiating therapy or if symptoms persist >3 days or worsen.

Infants and Children 6 months to 11 years: See table; use of weight to select dose is preferred; doses may be repeated every 6 to 8 hours (maximum: 4 doses/day)

Children ≥12 years and Adolescents: Refer to adult dosing.

Ibuprofen Dosing

Weight

(lb)

Age

Dosage

(mg)

12 to 17

6 to 11 mo

50

18 to 23

12 to 23 mo

75

24 to 35

2 to 3 y

100

36 to 47

4 to 5 y

150

48 to 59

6 to 8 y

200

60 to 71

9 to 10 y

250

72 to 95

11 y

300

Table has been converted to the following text.

Ibuprofen Dosing

Weight 12 to 17 lbs (6 to 11 months of age): 50 mg

Weight 18 to 23 lbs (12 to 23 months of age): 75 mg

Weight 24 to 35 lbs (2 to 3 years of age): 100 mg

Weight 36 to 47 lbs (4 to 5 years of age): 150 mg

Weight 48 to 59 lbs (6 to 8 years of age): 200 mg

Weight 60 to 71 lbs (9 to 10 years of age): 250 mg

Weight 72 to 95 lbs (11 years of age): 300 mg

Dosing: Renal Impairment

US labeling: There are no dosage adjustment provided in the manufacturer’s labeling; use with caution; avoid use in advanced renal disease.

Canadian labeling:

Mild impairment: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Moderate impairment:

Oral: There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.

IV: Use is contraindicated.

Severe impairment (CrCl <30 mL/minute) or deteriorating renal disease: Use is contraindicated.

KDIGO 2012 guidelines provide the following recommendations for NSAIDs:

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.

Neoprofen: If anuria or marked oliguria (urinary output <0.6 mL/kg/hour) evident at the scheduled time of the second or third dose, hold dose until renal function returns to normal. Use is contraindicated in preterm infants with significant renal impairment.

Dosing: Hepatic Impairment

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

Canadian labeling:

Mild impairment: There are no dosage adjustments provided in the manufacturer’s labeling.

Moderate impairment:

Oral: There are no dosage adjustments provided in the manufacturer’s labeling.

IV: Use is contraindicated.

Severe impairment or active hepatic disease: Use is contraindicated.

Reconstitution

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

Ibuprofen lysine injection (NeoProfen): Dilute with dextrose or saline to an appropriate volume.

Administration

Oral: Administer with food or milk.

IV:

Caldolor: For IV administration only; infuse over at least 30 minutes (adults) or 10 minutes (pediatric).

NeoProfen (ibuprofen lysine): For IV administration only; administration via umbilical arterial line has not been evaluated. Infuse over 15 minutes through 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.

Dietary Considerations

Some products may contain phenylalanine and/or potassium.

Compatibility

Ibuprofen injection (Caldolor): Stable in D5W, LR, NS.

Ibuprofen lysine injection (NeoProfen): Stable in D5W, NS; incompatible with TPN solution.

Storage

Ibuprofen injection (Caldolor): Store intact vials at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Must be diluted prior to use. Diluted solutions stable 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, 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-ASA Derivatives: Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of 5-ASA Derivatives. Monitor therapy

ACE 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 ACE Inhibitors. Monitor therapy

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: Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid. 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

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

Anticoagulants: Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Antidepressants (Tricyclic, Tertiary Amine): May enhance the antiplatelet effect of NSAID (Nonselective). Monitor therapy

Apixaban: NSAID (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

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 NSAID (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. Specifically, elevated diclofenac concentrations have been reported. Management: Consider alternatives to nonsteroidal anti-inflammatory agents (NSAIDs). Monitor for evidence of nephrotoxicity, as well as increased serum cyclosporine concentrations and systemic effects (e.g., hypertension) during concomitant therapy with NSAIDs. Consider therapy modification

Dabigatran Etexilate: NSAID (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. 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

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

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: NSAID (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

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

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

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. 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: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab. 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

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

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

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

NSAID (COX-2 Inhibitor): Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of NSAID (COX-2 Inhibitor). 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

PEMEtrexed: NSAID (Nonselective) may increase the serum concentration of PEMEtrexed. Management: Patients with mild-to-moderate renal insufficiency (estimated creatinine clearance 45-79 mL/min) should avoid NSAIDs for 2-5 days prior to, the day of, and 2 days after pemetrexed. 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

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

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

Rivaroxaban: NSAID (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: NSAID (Nonselective) may enhance the adverse/toxic effect of Salicylates. An increased risk of bleeding may be associated with use of this combination. NSAID (Nonselective) may diminish the cardioprotective effect of Salicylates. Salicylates may decrease the serum concentration of NSAID (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 NSAID (Nonselective). NSAID (Nonselective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Consider using alternative analgesics, when appropriate, and/or addition of a gastroprotective agent. Monitor patients closely for signs/symptoms of bleeding, and for evidence of diminished SSRI effectiveness with concurrent use. Consider therapy modification

Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the antiplatelet effect of NSAID (Nonselective). Monitor therapy

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

Tositumomab and Iodine I 131 Tositumomab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab. Specifically, the risk of bleeding-related adverse events may be increased. Monitor therapy

Treprostinil: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Bleeding may occur. 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): NSAID (Nonselective) may enhance the anticoagulant effect of Vitamin K Antagonists. Consider therapy modification

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

Test Interactions

May interfere with urine detection of phencyclidine, cannabinoids, and barbiturates (false-positives) (Marchei 2007; Rollins 1990)

Adverse Reactions

Oral:

1% to 10%:

Cardiovascular: Edema (1% to 3%)

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

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

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

Gastrointestinal: Epigastric pain (3% to 9%), heartburn (3% to 9%), nausea (3% to 9%), abdominal pain (1% to 3%), constipation (1% to 3%), decreased appetite (1% to 3%), diarrhea (1% to 3%), dyspepsia (1% to 3%), flatulence (1% to 3%), vomiting (1% to 3%)

Otic: Tinnitus (3% to 9%)

<1% (Limited to important or life-threatening): Abnormal hepatic function tests, acute renal failure, agranulocytosis, allergic rhinitis, alopecia, amblyopia, anaphylaxis, aplastic anemia, aseptic meningitis, azotemia, blurred vision, bone marrow depression, bronchospasm, cardiac arrhythmia, cardiac failure, confusion, conjunctivitis, cystitis, decreased creatinine clearance, decreased hematocrit, decreased hemoglobin, decreased platelet aggregation, depression, drowsiness, dry eye syndrome, duodenal ulcer, emotional lability, eosinophilia, epistaxis, erythema multiforme, gastric ulcer, gastritis, gastrointestinal hemorrhage, gastrointestinal ulcer, hallucination, hearing loss, hematuria, hemolytic anemia, hepatitis, hepatotoxicity (idiosyncratic) (Chalasani 2014), hypertension, insomnia, jaundice, leukopenia, melena, neutropenia, palpitations, pancreatitis, peripheral neuropathy, polydipsia, polyuria, skin photosensitivity, Stevens-Johnson syndrome, tachycardia, thrombocytopenia, toxic amblyopia, toxic epidermal necrolysis, urticaria, vesiculobullous dermatitis, vision changes

Injection: Ibuprofen (Caldolor): Frequency not defined.

Cardiovascular: Edema, hypertension (10%; including exacerbation), myocardial infarction

Central nervous system: Headache (12%), dizziness (4% to 6%)

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

Endocrine & metabolic: Hypokalemia (4% to 19%), hypoalbuminemia (10%), hypernatremia (7% to 10%), changes in LDH (7%)

Gastrointestinal: vomiting (22%), flatulence (16%), diarrhea (10%), dyspepsia (1% to 4%), abdominal discomfort (≤3%), abdominal pain, nausea

Genitourinary: Urinary retention (5%), renal toxicity

Hematologic & oncologic: Anemia (4% to 36%), eosinophilia (26%), hyperproteinemia (10% to 13%), neutropenia (13%), hemorrhage (10%), thrombocythemia (3% to 10%), wound hemorrhage (3%), decreased hemoglobin (2% to 3%)

Hepatic: Increased serum ALT (≤15%), increased serum AST ( ≤15%)

Hypersensitivity: Hypersensitivity reaction

Renal: Increased blood urea nitrogen (7% to 10%)

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

<1% (Limited to important or life-threatening): Hepatotoxicity (idiosyncratic) (Chalasani 2014)

Injection: Ibuprofen lysine (NeoProfen): Frequency not always defined.

Cardiovascular: Hypotension (7% to 10%), edema (4%), cardiac failure, hypotension, tachycardia

Central nervous system: Intraventricular hemorrhage (29%), convulsions, eating disorder, seizure

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

Endocrine & metabolic: Hypocalcemia (12%), hypoglycemia (12%), adrenocortical insufficiency (7%), hypernatremia (7%), hyperglycemia

Gastrointestinal: Gastrointestinal disease (non NEC; 22%), abdominal distension, cholestasis, gastritis, gastroesophageal reflux disease, inguinal hernia, intestinal obstruction

Genitourinary: Urinary tract infection (9%), uremia (7%), decreased urine output (3%; small decrease reported on days 2 to 6 with compensatory increase in output on day 9)

Hematologic & oncologic: Anemia (32%), neutropenia, thrombocytopenia

Hepatic: Jaundice

Infection: Sepsis (43%), infection

Local: Injection site reaction

Renal: Increased blood urea nitrogen (7%), renal insufficiency (6%), increased serum creatinine (3%), renal failure (1%)

Respiratory: Apnea (28%), respiratory tract infection (19%), respiratory failure (10%), atelectasis (4%)

Miscellaneous: Sepsis (43%), reduced intake of food/fluids

<1% (Limited to important or life-threatening): Gastrointestinal perforation, hepatotoxicity (idiosyncratic) (Chalasani 2014), necrotizing enterocolitis, pulmonary hypertension

ALERT: U.S. 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.

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 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. 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). The Canadian labeling contraindicates use in patients with active GI disease (eg, peptic ulcer) or GI bleeding and inflammatory bowel disease.

• 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. The Canadian labeling contraindicates use in patients with hyperkalemia.

• 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.

• 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. The Canadian labeling contraindicates use in moderate (IV only) to severe impairment and with active hepatic disease.

• 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. The Canadian labeling contraindicates use in moderate (IV only) to severe renal impairment and with deteriorating renal disease.

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 Considerations

According to the Canadian prescribing information, use is contraindicated during the third trimester and during labor and delivery.

The chronic use of NSAIDs in women of reproductive age may be associated with infertility that is reversible upon discontinuation of the medication. 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, non-closure of the ductus arteriosus postnatally may occur and be resistant to medical management (Bermas 2014; Bloor 2013). Because they may cause premature closure of the ductus arteriosus, the use of NSAIDs late in pregnancy should be avoided. Product labeling for Caldolor specifically states use should be avoided starting at 30 weeks gestation.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience heartburn, diarrhea, constipation, or flatulence. Have patient report immediately to prescriber signs of aseptic meningitis (headache, fever, chills, severe nausea or vomiting, stiff neck, rash, sensitivity to bright lights, fatigue, or confusion), signs of abdominal ulcers (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), signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; 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), signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), signs of high potassium (abnormal heartbeat, confusion, dizziness, passing out, weakness, shortness of breath, numbness or tingling feeling), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of severe cerebrovascular disease (change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes), shortness of breath, excessive weight gain, swelling of arms or legs, angina, tachycardia, severe headache, severe dizziness, passing out, severe loss of strength and energy, tinnitus, severe nausea, vomiting, severe abdominal pain, severe back pain, vision changes, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating, and advising patients.

Hide