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Special Alerts
Ibuprofen: Unapproved Topical Products - August 2009
The U.S. Food and Drug Administration (FDA) issued information for healthcare providers and consumers regarding unapproved topical combination products containing ibuprofen. Unlike oral ibuprofen products (which are FDA-approved), topical products containing ibuprofen are not FDA-approved. Safety claims for topical products containing ibuprofen have not been reviewed by the FDA.
For information, including a list of the unapproved products, please refer to: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm179925.htm
ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Medication Safety Issues
Sound-alike/look-alike issues:
Haltran® may be confused with Halfprin®
Motrin® may be confused with Neurontin®
Pronunciation
(eye byoo PROE fen)
U.S. Brand Names
Index Terms
Generic Available
Yes: Caplet, suspension, tablet
Canadian Brand Names
Pharmacologic Category
Use: Labeled Indications
Oral: Inflammatory diseases and rheumatoid disorders including juvenile rheumatoid arthritis, mild-to-moderate pain, fever, dysmenorrhea, osteoarthritis
Injection: Ibuprofen lysine is for use in premature infants weighing between 500-1500 g and who are ?32 weeks gestational age (GA) to induce closure of a clinically-significant patent ductus arteriosus (PDA) when usual treatments are ineffective
Use: Dental
Management of pain and swelling
Use: Unlabeled/Investigational
Cystic fibrosis, gout, ankylosing spondylitis, acute migraine headache
Pregnancy Risk Factor
C
Pregnancy Considerations
Adverse events were not observed in the initial animal reproduction studies; therefore, the manufacturer classifies ibuprofen as pregnancy category C. Ibuprofen exposure during the first trimester is not strongly associated with congenital malformations; however, cardiovascular anomalies and cleft palate have been observed following NSAID exposure in some studies. The use of an NSAID in the first trimester may be associated with an increased risk of miscarriage. Nonteratogenic effects have been observed following NSAID administration during the third trimester, including myocardial degenerative changes, prenatal constriction of the ductus arteriosus, failure of the ductus arteriosus to close postnatally, and fetal tricuspid regurgitation; renal dysfunction or failure, oligohydramnios; gastrointestinal bleeding or perforation, increased risk of necrotizing enterocolitis; intracranial bleeding, platelet dysfunction with resultant bleeding; pulmonary hypertension. Because they may cause premature closure of the ductus arteriosus, use of NSAIDs late in pregnancy should be avoided (use after 31 or 32 weeks gestation is not recommended by some clinicians). The chronic use of NSAIDs in women of reproductive age may be associated with infertility that is reversible upon discontinuation of the medication. A registry is available for pregnant women exposed to autoimmune medications including ibuprofen. For additional information contact the Organization of Teratology Information Specialists, OTIS Autoimmune Diseases Study, at 877-311-8972.
Lactation
Enters breast milk/not recommended (AAP rates “compatible”)
Breast-Feeding Considerations
Based on limited data, only very small amounts of ibuprofen are excreted into breast milk. Adverse events have not been reported in nursing infants. The AAP considers ibuprofen to be "usually compatible with breast-feeding." Because there is a potential for adverse events to occur in nursing infants, the manufacturer does not recommend the use of ibuprofen while breast-feeding. Use with caution in nursing women with hypertensive disorders of pregnancy or pre-existing renal disease.
Contraindications
Hypersensitivity to ibuprofen, aspirin, other NSAIDs, or any component of the formulation; perioperative pain in the setting of coronary artery bypass graft (CABG) surgery
Ibuprofen lysine is contraindicated in preterm infants with untreated proven or suspected infection; congenital heart disease where patency of the PDA is necessary for pulmonary or systemic blood flow; bleeding (especially with active intracranial hemorrhage or GI bleed); thrombocytopenia; coagulation defects; proven or suspected necrotizing enterocolitis (NEC); significant renal dysfunction
Warnings/Precautions
Boxed warnings:
• Cardiovascular events: See “Concerns related to adverse effects” below.
• Coronary artery bypass graft surgery: See “Disease-related concerns” below.
• Gastrointestinal events: See “Concerns related to adverse effects” below.
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. Do not use in patients who experience bronchospasm, asthma, rhinitis, or urticaria with NSAID or aspirin therapy.
• Aseptic meningitis: May increase the risk of aseptic meningitis, especially in patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders.
• Bleeding/hemostasis: 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.
• Cardiovascular events: [U.S. Boxed Warning]: NSAIDs are associated with an increased risk of adverse cardiovascular thrombotic events, including MI and stroke. Risk may be increased with duration of use or pre-existing cardiovascular risk factors or disease. Carefully evaluate individual cardiovascular risk profiles prior to prescribing. Use caution with fluid retention. Avoid use in heart failure. Concurrent administration of ibuprofen, and potentially other nonselective NSAIDs, may interfere with aspirin's cardioprotective effect. 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.
• Gastrointestinal events: [U.S. Boxed Warning]: NSAIDs may increase risk of gastrointestinal irritation, inflammation, ulceration, bleeding, and perforation. These events may occur at any time during therapy and without warning. Use caution with a history of GI disease (bleeding or ulcers), concurrent therapy with aspirin, anticoagulants and/or corticosteroids, smoking, use of alcohol, the 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 ?325 mg of aspirin, a substantial increase in the risk of gastrointestinal complications (eg, ulcer) occurs; concomitant gastroprotective therapy (eg, proton pump inhibitors) is recommended (Bhatt, 2008).
• Skin reactions: NSAIDs may cause serious skin adverse events including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN); discontinue use at first sign of skin rash or hypersensitivity.
Disease-related concerns:
• Asthma: Do not administer to patients with aspirin-sensitive asthma; severe bronchospasm may occur. Use caution in patients with other forms of asthma.
• Coronary artery bypass graft surgery: [U.S. Boxed Warning]: Use is contraindicated for treatment of perioperative pain 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 decreased hepatic function. Closely monitor patients with any abnormal LFT. Severe hepatic reactions (eg, fulminant hepatitis, liver failure) have occurred with NSAID use, rarely; discontinue if signs or symptoms of liver disease develop, or if systemic manifestations occur.
• Hypertension: Use with caution; may cause new-onset hypertension or worsening of existing hypertension.
• Renal impairment: 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. Patients with impaired renal function, dehydration, heart failure, liver dysfunction, 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. Not recommended for use in patients with advanced renal disease. Long-term NSAID use may result in renal papillary necrosis.
Special populations:
• Elderly: The elderly are at increased risk for adverse effects (especially peptic ulceration, CNS effects, renal toxicity) from NSAIDs even at low doses.
Dosage form specific issues:
• Injection: 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.
Other warnings/precautions:
• Self medication (OTC use): Prior to self-medication, patients should contact healthcare 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 healthcare provider if they have not had a migraine diagnosis by healthcare 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 healthcare provider if symptoms get worse, 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 4-6 half-lives prior to surgical or dental procedures.
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: Rash (3% to 9%), itching (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/cramps/distress (1% to 3%), appetite decreased (1% to 3%), constipation (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%: Acute renal failure, agranulocytosis, allergic rhinitis, alopecia, amblyopia, anaphylaxis, arrhythmia, aplastic anemia, aseptic meningitis, azotemia, blurred vision, bone marrow suppression, bronchospasm, CHF, confusion, conjunctivitis, creatinine clearance decreased, cystitis, depression, drowsiness, dry eyes, duodenal ulcer, edema, emotional lability, eosinophilia, epistaxis, erythema multiforme, gastric ulcer, gastritis, GI bleed, GI hemorrhage, GI ulceration, hallucinations, hearing decreased, hematuria, hematocrit decreased, hemoglobin decreased, hemolytic anemia, hepatitis, hypertension, inhibition of platelet aggregation, insomnia, jaundice, liver function tests abnormal, leukopenia, melena, neutropenia, palpitation, pancreatitis, peripheral neuropathy, photosensitivity, polydipsia, polyuria, Stevens-Johnson syndrome, tachycardia, thrombocytopenia, toxic amblyopia, toxic epidermal necrolysis, urticaria, vesiculobullous eruptions, vision changes
Injection:
>10%:
Cardiovascular: Intraventricular hemorrhage (29%; grade 3/4: 15%)
Dermatologic: Skin irritation (16%)
Endocrine & metabolic: Hypocalcemia (12%), hypoglycemia (12%)
Gastrointestinal: GI disorders, non NEC (22%)
Hematologic: Anemia (32%)
Respiratory: Apnea (28%), respiratory infection (19%)
Miscellaneous: Sepsis (43%)
1% to 10%:
Cardiovascular: Edema (4%)
Endocrine & metabolic: Adrenal insufficiency (7%), hypernatremia (7%)
Genitourinary: Urinary tract infection (9%)
Renal: Urea increased (7%), renal impairment (6%), creatinine increased (3%), urine output decreased (3%; small decrease reported on days 2-6 with compensatory increase in output on day 9), renal failure (1%)
Respiratory: Respiratory failure (10%), atelectasis (4%)
Frequency not defined: Abdominal distension, cholestasis, feeding problems, gastritis, GI reflux, heart failure, hyperglycemia, hypotension, ileus, infection, inguinal hernia, injection site reaction, jaundice, neutropenia, seizure, tachycardia, thrombocytopenia
Postmarketing and/or case reports: GI perforation, necrotizing enterocolitis
Metabolism/Transport Effects
Substrate (minor) of CYP2C9, 2C19; Inhibits CYP2C9 (strong)
Drug Interactions
ACE Inhibitors: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of ACE Inhibitors. Risk C: Monitor therapy
Aminoglycosides: Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants. Risk C: Monitor therapy
Angiotensin II Receptor Blockers: Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Angiotensin II Receptor Blockers. The combination of these two agents may also significantly decrease glomerular filtration and renal function. Risk C: Monitor therapy
Anticoagulants: Antiplatelet Agents may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Anticoagulants: Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Antidepressants (Tricyclic, Tertiary Amine): May enhance the antiplatelet effect of NSAID (Nonselective). Risk C: Monitor therapy
Antiplatelet Agents: May enhance the anticoagulant effect of other Antiplatelet Agents. Risk C: Monitor therapy
Antiplatelet Agents: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Antiplatelet Agents. An increased risk of bleeding may occur. Nonsteroidal Anti-Inflammatory Agents may diminish the cardioprotective effect of Antiplatelet Agents. This interaction is likely specific to aspirin, and not to other antiplatelet agents. Risk C: Monitor therapy
Beta-Blockers: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Beta-Blockers. Exceptions: Levobunolol; Metipranolol. Risk C: Monitor therapy
Bile Acid Sequestrants: May decrease the absorption of Nonsteroidal Anti-Inflammatory Agents. Risk D: 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. Risk C: Monitor therapy
Carvedilol: CYP2C9 Inhibitors (Strong) may increase the serum concentration of Carvedilol. Specifically, concentrations of the S-carvedilol enantiomer may be increased. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the adverse/toxic effect of NSAID (Nonselective). Risk C: Monitor therapy
CycloSPORINE: Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of CycloSPORINE. Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of CycloSPORINE. Risk D: Consider therapy modification
CYP2C9 Substrates (High risk): CYP2C9 Inhibitors (Strong) may decrease the metabolism of CYP2C9 Substrates (High risk). Risk D: Consider therapy modification
Dasatinib: May enhance the anticoagulant effect of Antiplatelet Agents. Risk C: Monitor therapy
Desmopressin: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Desmopressin. Risk C: Monitor therapy
Drotrecogin Alfa: Antiplatelet Agents may enhance the adverse/toxic effect of Drotrecogin Alfa. Bleeding may occur. Risk D: Consider therapy modification
Eplerenone: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Eplerenone. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Eplerenone. Risk C: Monitor therapy
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Antiplatelet Agents. Bleeding may occur. Risk D: 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. Risk D: Consider therapy modification
HydrALAZINE: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of HydrALAZINE. Risk C: Monitor therapy
Ibritumomab: Antiplatelet Agents may enhance the adverse/toxic effect of Ibritumomab. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Risk C: Monitor therapy
Ketorolac: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination
Lithium: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Lithium. Risk D: Consider therapy modification
Loop Diuretics: Nonsteroidal Anti-Inflammatory Agents may diminish the diuretic effect of Loop Diuretics. Risk C: Monitor therapy
Methotrexate: Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Methotrexate. Risk D: Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of Antiplatelet Agents. An increased risk of bleeding may occur. Nonsteroidal Anti-Inflammatory Agents may diminish the cardioprotective effect of Antiplatelet Agents. This interaction is likely specific to aspirin, and not to other antiplatelet agents. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of other Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy
Omega-3-Acid Ethyl Esters: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Pemetrexed: NSAID (Nonselective) may increase the serum concentration of Pemetrexed. Management: Patients with mild-to-moderate renal insufficiency (CrCl 45-79 mL/minute) may use ibuprofen with caution, but should avoid other NSAIDs for 2-5 days prior to, the day of, and 2 days after pemetrexed. Risk D: Consider therapy modification
Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Antiplatelet Agents. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Risk C: Monitor therapy
Pentoxifylline: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Potassium-Sparing Diuretics: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Quinolone Antibiotics: Nonsteroidal Anti-Inflammatory Agents may enhance the neuroexcitatory and/or seizure-potentiating effect of Quinolone Antibiotics. Risk C: Monitor therapy
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. Risk D: Consider therapy modification
Salicylates: Antiplatelet Agents may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: May enhance the antiplatelet effect of NSAID (Nonselective). Risk D: Consider therapy modification
Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the antiplatelet effect of NSAID (Nonselective). Risk C: Monitor therapy
Thiazide Diuretics: Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Thiazide Diuretics. Risk C: Monitor therapy
Thrombolytic Agents: Antiplatelet Agents may enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy
Thrombolytic Agents: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Thrombolytic Agents. An increased risk of bleeding may occur. Risk C: Monitor therapy
Tositumomab and Iodine I 131 Tositumomab: Antiplatelet Agents may enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab. Specifically, the risk of bleeding-related adverse events may be increased. Risk C: Monitor therapy
Treprostinil: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Bleeding may occur. Risk C: Monitor therapy
Vancomycin: Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Vancomycin. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): NSAID (Nonselective) may enhance the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (may enhance gastric mucosal irritation).
Food: Ibuprofen peak serum levels may be decreased if taken with food.
Herb/Nutraceutical: Avoid alfalfa, anise, bilberry, bladderwrack, bromelain, cat's claw, celery, chamomile, coleus, cordyceps, dong quai, evening primrose, fenugreek, feverfew, garlic, ginger, ginkgo biloba, ginseng (American, Panax, Siberian), grapeseed, green tea, guggul, horse chestnut seed, horseradish, licorice, prickly ash, red clover, reishi, SAMe (S-adenosylmethionine), sweet clover, turmeric, white willow (all have additional antiplatelet activity).
Storage
Injection: Store at room temperature of 20°C to 25°C (68°F to 77°F). Protect from light. Following dilution, administer within 30 minutes of preparation.
Suspension, tablet: Store at room temperature of 20°C to 25°C (68°F to 77°F).
Reconstitution
Injection: Dilute with dextrose or saline to an appropriate volume.
Compatibility
Stable in dextrose, saline; incompatible with TPN solution.
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.
Pharmacodynamics/Kinetics
Onset of action: Analgesic: 30-60 minutes; Anti-inflammatory: ?7 days
Peak effect: 1-2 weeks
Duration: 4-6 hours
Absorption: Oral: Rapid (85%)
Distribution: Vd: 6.35 L; premature infants with ductal closure (highly variable between studies):
Day 3: 145-349 mL/kg
Day 5: 72-222 mL/kg
Protein binding: 90% to 99%
Metabolism: Hepatic via oxidation
Half-life elimination:
Premature infants (highly variable between studies):
Day 3: 35-51 hours
Day 5: 20-33 hours
Children 3 months to 10 years: 1.6 ± 0.7 hours
Adults: 2-4 hours; End-stage renal disease: Unchanged
Time to peak: ~1-2 hours
Excretion: Urine (primarily as metabolites; 1% as unchanged drug); some feces
Dosage
I.V.: Infants between 500-1500 g and ?32 weeks GA: Patent ductus arteriosus: 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.
Oral:
Children:
Antipyretic: 6 months to 12 years: Temperature <102.5°F (39°C): 5 mg/kg/dose; temperature >102.5°F: 10 mg/kg/dose given every 6-8 hours (maximum daily dose: 40 mg/kg/day)
Juvenile rheumatoid arthritis: 30-50 mg/kg/24 hours divided every 8 hours; start at lower end of dosing range and titrate upward (maximum: 2.4 g/day)
Analgesic: 4-10 mg/kg/dose every 6-8 hours
Cystic fibrosis (unlabeled use): Chronic (>4 years) twice daily dosing adjusted to maintain serum levels of 50-100 mcg/mL has been associated with slowing of disease progression in younger patients with mild lung disease
OTC labeling (analgesic, antipyretic): Note: Treatment for >10 days is not recommended unless directed by healthcare provider.
Children 6 months to 11 years: See table; use of weight to select dose is preferred; doses may be repeated every 6-8 hours (maximum: 4 doses/day)
Children ?12 years: 200 mg every 4-6 hours as needed (maximum: 1200 mg/24 hours)
Ibuprofen Dosing
Weight
(lb)
Age
Dosage
(mg)
12-17
6-11 mo
50
18-23
12-23 mo
75
24-35
2-3 y
100
36-47
4-5 y
150
48-59
6-8 y
200
60-71
9-10 y
250
72-95
11 y
300
Table has been converted to the following text.
Ibuprofen Dosing
Weight 12-17 lbs (6-11 months of age): 50 mg
Weight 18-23 lbs (12-23 months of age): 75 mg
Weight 24-35 lbs (2-3 years of age): 100 mg
Weight 36-47 lbs (4-5 years of age): 150 mg
Weight 48-59 lbs (6-8 years of age): 200 mg
Weight 60-71 lbs (9-10 years of age): 250 mg
Weight 72-95 lbs (11 years of age): 300 mg
Adults:
Inflammatory disease: 400-800 mg/dose 3-4 times/day (maximum dose: 3.2 g/day)
Analgesia/pain/fever/dysmenorrhea: 200-400 mg/dose every 4-6 hours (maximum daily dose: 1.2 g, unless directed by physician; under physician supervision daily doses ?2.4 g may be used)
OTC labeling (analgesic, antipyretic): 200 mg every 4-6 hours as needed (maximum: 1200 mg/24 hours); treatment for >10 days is not recommended unless directed by healthcare provider.
Migraine: 2 capsules at onset of symptoms (maximum: 400 mg/24 hours unless directed by healthcare provider)
Dosing adjustment/comments in renal impairment: If anuria or oliguria evident, hold dose until renal function returns to normal
Dosing adjustment/comments in severe hepatic impairment: Avoid use
Dental Usual Dosing
Analgesic/pain/fever/dysmenorrhea: Oral:
Children: 4-10 mg/kg/dose every 6-8 hours
Adults: 200-400 mg/dose every 4-6 hours (maximum daily dose: 1.2 g, unless directed by physician; under physician supervision daily doses ?2.4 g may be used)
OTC labeling (analgesic, antipyretic): Note: Treatment for >10 days is not recommended unless directed by healthcare provider. Oral:
Children 6 months to 11 years: See table; use of weight to select dose is preferred; doses may be repeated every 6-8 hours (maximum: 4 doses/day)
Children ?12 years and Adults: 200 mg every 4-6 hours as needed (maximum: 1200 mg/24 hours)
Ibuprofen Dosing
Weight
(lb)
Age
Dosage
(mg)
12-17
6-11 mo
50
18-23
12-23 mo
75
24-35
2-3 y
100
36-47
4-5 y
150
48-59
6-8 y
200
60-71
9-10 y
250
72-95
11 y
300
Table has been converted to the following text.
Ibuprofen Dosing
Weight 12-17 lbs (6-11 months of age): 50 mg
Weight 18-23 lbs (12-23 months of age): 75 mg
Weight 24-35 lbs (2-3 years of age): 100 mg
Weight 36-47 lbs (4-5 years of age): 150 mg
Weight 48-59 lbs (6-8 years of age): 200 mg
Weight 60-71 lbs (9-10 years of age): 250 mg
Weight 72-95 lbs (11 years of age): 300 mg
Administration: Oral
Administer with food.
Administration: I.V.
For I.V. 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.
Monitoring Parameters
CBC; 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; with long-term therapy, periodic ophthalmic exams
Injection: Renal function, signs of infection or bleeding, ECG
Reference Range
Plasma concentrations >200 mcg/mL may be associated with severe toxicity
PDA: Minimum effective level: 10-12 mg/L
Dietary Considerations
Should be taken with food. Chewable tablets may contain phenylalanine; amount varies by product, consult manufacturers labeling.
Patient Education
If self-administered, use exactly as directed; do not increase dose or frequency. Adverse reactions can occur with overuse. Consult your prescriber before use if you have hypertension or heart failure. Do not take longer than 3 days for fever, or 10 days for pain without consulting medical advisor. Take with food or milk. While using this medication, do not use alcohol, excessive amounts of vitamin C, or salicylate-containing foods (curry powder, prunes, raisins, tea, or licorice), other prescription or OTC medications containing aspirin or salicylate, or other NSAIDs without consulting prescriber. Maintain adequate hydration unless instructed to restrict fluid intake. You may experience nausea, vomiting, gastric discomfort (frequent mouth care, small frequent meals, chewing gum, sucking lozenges may help). GI bleeding, ulceration, or perforation can occur with or without pain. Stop taking medication and report ringing in ears; persistent cramping or stomach pain; unresolved nausea or vomiting; respiratory difficulty or shortness of breath; unusual bruising or bleeding (mouth, urine, stool); skin rash; unusual swelling of extremities; chest pain; or palpitations. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. This drug should not be used in the 3rd trimester of pregnancy. Consult prescriber if breast-feeding.
Geriatric Considerations
Elderly are a high-risk population for adverse effects from NSAIDs. As much as 60% of elderly can develop peptic ulceration and/or hemorrhage asymptomatically. The concomitant use of H2 blockers and sucralfate is not effective as prophylaxis with the exception of NSAID-induced duodenal ulcers which may be prevented by the use of ranitidine. Misoprostol and proton pump inhibitors are the only agents proven to help prevent the development of NSAID-induced ulcers. Also, concomitant disease and drug use contribute to the risk for GI adverse effects. Use lowest effective dose for shortest period possible. Consider renal function decline with age. Use of NSAIDs can compromise existing renal function especially when Clcr is ?30 mL/minute. Tinnitus may be a difficult and unreliable indication of toxicity due to age-related hearing loss or eighth cranial nerve damage. CNS adverse effects such as confusion, agitation, and hallucination are generally seen in overdose or high dose situations, but the elderly may demonstrate these adverse effects at lower doses than younger adults.
Anesthesia and Critical Care Concerns/Other Considerations
The 2002 ACCM/SCCM guidelines for analgesia (critically-ill adult) suggest that NSAIDs may be used in combination with opioids in select patients for pain management. Concern about adverse events (increased risk of renal dysfunction, altered platelet function and gastrointestinal irritation) limits its use in patients who have other underlying risks for these events.
In short-term use, NSAIDs vary considerably in their effect on blood pressure. When NSAIDs are used in patients with hypertension, monitor blood pressure response, and duration of therapy, when possible, should be kept short. The use of NSAIDs in the treatment of patients with heart failure may be associated with an increased risk for fluid accumulation and edema; may precipitate renal failure in dehydrated patients by inhibition of postglandin-mediated autoregulation. Use extreme caution or avoid concurrent use with nephrotoxic agents.
Cardiovascular Considerations
Blood Pressure: In short-term use, NSAIDs vary considerably in their effect on blood pressure. A meta-analysis (Pope, 1993) showed that indomethacin and naproxen had the largest effect on blood pressure. Other NSAIDs, including piroxicam, ibuprofen, and sulindac had less of an effect. Ibuprofen combined with captopril or losartan may attenuate the antihypertensive effects of ACE inhibition or receptor blockade on sitting or 24-hour ambulatory diastolic blood pressure. When NSAIDs are used in patients with hypertension, appropriate monitoring of blood pressure responses should be completed and the duration of therapy, when possible, kept short.
Heart Failure: The use of NSAIDs in the treatment of patients with heart failure may be associated with an increased risk for fluid accumulation and edema. One study showed that NSAID use in elderly patients had an increased risk of hospitalization for heart failure. This study gives compelling reasons to avoid or limit the use of NSAIDs in patients with heart failure, particularly in the elderly population. The ACC/AHA 2009 heart failure guidelines suggest that NSAIDs be avoided or withdrawn whenever possible in patients with current or prior symptoms of heart failure and reduced LVEF.
Risk of Cardiovascular Events: Patients at increased risk of cardiovascular adverse events include patients immediately postoperative (10-14 days) from CABG surgery, and those with existing CAD, CVD, or history of TIA. Prescribers are encouraged to use the lowest effective dose for the shortest duration of time based on individual patient treatment goals. Available evidence reviewed by the FDA does not suggest an increased risk of serious CV events when NSAIDs are given short term and in the lower doses used OTC.
Drug Interactions: Nonsteroidal anti-inflammatory agents, including ibuprofen and naproxen, may diminish the cardioprotective effect of aspirin (Catella-Lawson F, 2001; Capone ML, 2005). It is surmised that ibuprofen may exhibit greater affinity than aspirin for the COX-1 site or if dosed regularly (or prior to aspirin), it would gain access to the active site first. In either case, aspirin's inhibition of COX (irreversible) would be limited in favor of ibuprofen inhibition (reversible). Avoid regular use of NSAIDs (nonselective) if possible. If used occasionally, take 1/2 -2 hours after aspirin (immediate release) ingestion.
Dental Health: Effects on Dental Treatment
In a statement released on September 8, 2006, the FDA notified consumers and healthcare professionals that the administration of ibuprofen for pain relief to patients taking aspirin for cardioprotection may interfere with aspirin's cardiovascular benefits. The FDA states that ibuprofen can interfere with the antiplatelet effect of low-dose aspirin (81 mg/day). This could result in diminished effectiveness of aspirin as used for cardioprotection and stroke prevention. The FDA adds that although ibuprofen and aspirin can be taken together, it is recommended that consumers talk with their healthcare providers for additional information. For more information, including how to advise aspirin patients requiring ibuprofen for pain relief, see Effects on Bleeding and Dental Health Professional Considerations.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Dental Comment
Preoperative use of ibuprofen at a dose of 400-600 mg every 6 hours 24 hours before the appointment decreases postoperative edema and hastens healing time.
New information from the FDA states that ibuprofen can interfere with the antiplatelet effect of low-dose aspirin (81 mg/day), potentially rendering aspirin less effective when used for cardioprotection and stroke protection. In situations where these drugs could be used concomitantly, the FDA has provided the following information.
Patients who use immediate release aspirin (not enteric-coated aspirin) and take a single dose or chronic doses of ibuprofen 400 mg, should dose the ibuprofen at least 30 minutes or longer after aspirin ingestion or more than 8 hours before aspirin ingestion to avoid attenuation of aspirin's effect.
At this time, recommendations about the timing of ibuprofen 400 mg in patients taking enteric-coated low-dose aspirin cannot be made based on available data. One study however, showed that the antiplatelet effect of enteric-coated low-dose aspirin was attenuated when ibuprofen 400 mg was dosed 2, 7, and 12 hours after aspirin (Catella-Lawson, 2001).
With occasional use of ibuprofen, there is likely to be minimal risk from any attenuation of the antiplatelet effect of low-dose aspirin, because of a long-lasting effect of aspirin on platelets.
Other over-the-counter (OTC) NSAIDs (ie, naproxen sodium and ketoprofen) should be viewed as having the potential to interfere with the antiplatelet effect of low-dose aspirin until proven otherwise. However, the FDA is unaware of any studies that have looked at the same type of interference by ketoprofen with low-dose aspirin. One study of naproxen and low-dose aspirin has suggested that naproxen may interfere with aspirin's antiplatelet activity when they are coadministered (Steinhubl, 2005). However, naproxen 500 mg administered 2 hours before or after aspirin 100 mg, did not interfere with aspirin's antiplatelet effect. The FDA stated that there is no data looking at doses of naproxen <500 mg. Naproxen OTC strength is 220 mg tablets.
Mental Health: Effects on Mental Status
Drowsiness and dizziness are common; may cause nervousness; may rarely cause insomnia, confusion, hallucinations, or depression
Mental Health: Effects on Psychiatric Treatment
May rarely cause agranulocytosis; use caution with clozapine and carbamazepine; may decrease lithium clearance resulting in an increase in serum lithium levels and potential lithium toxicity; monitor serum lithium levels
Nursing: Physical Assessment/Monitoring
Evaluate cardiac risk and potential for GI bleeding prior to prescribing this medication. Assess patient for allergic reaction to salicylates or other NSAIDs. Assess other medications patient may be taking for additive or adverse interactions. Monitor blood pressure at the beginning of therapy and periodically during use. Monitor therapeutic effectiveness and signs of adverse reactions or overdose at beginning of therapy and periodically during long-term therapy. With long-term therapy, periodic ophthalmic exams are recommended. Assess knowledge/teach patient appropriate use. Teach patient to monitor for adverse reactions, adverse reactions to report, and appropriate interventions to reduce side effects.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Caplet: 200 mg [OTC]
Advil®: 200 mg [contains sodium benzoate]
Ibu-200: 200 mg
Motrin® IB: 200 mg
Motrin® Junior: 100 mg [scored]
Capsule, liquid-filled:
Advil®: 200 mg [solubilized ibuprofen; contains potassium 20 mg]
Advil® Migraine: 200 mg [solubilized ibuprofen; contains potassium 20 mg]
Gelcap:
Advil®: 200 mg [contains coconut oil]
Injection, solution, as lysine [preservative free]:
NeoProfen®: 17.1 mg/mL (2 mL) [equivalent to ibuprofen 10 mg/mL]
Suspension, oral: 100 mg/5 mL (5 mL, 10 mL, 120 mL, 240 mL, 480 mL)
Advil® Children's: 100 mg/5 mL (120 mL) [contains sodium benzoate, sodium, propylene glycol; blue raspberry, fruit, and grape flavors]
Motrin® Children's: 100 mg/5 mL (60 mL, 120 mL) [contains sodium benzoate; berry, dye free berry, bubble gum, and grape flavors]
Suspension, oral [concentrate, drops]: 40 mg/mL (15 mL)
Advil® Infants': 40 mg/mL (15 mL) [contains sodium benzoate; fruit, grape, and white grape flavors]
Motrin® Infants': 40 mg/mL (15 mL) [contains sodium benzoate; ethanol free; berry and dye-free berry flavors]
Tablet: 200 mg [OTC], 400 mg, 600 mg, 800 mg
Addaprin: 200 mg
Advil®: 200 mg [contains sodium benzoate]
Genpril®: 200 mg [DSC]
Ibu®: 400 mg, 600 mg, 800 mg
Ibu-200: 200 mg
I-Prin: 200 mg
Midol® Cramp and Body Aches: 200 mg
Motrin® IB: 200 mg
Proprinal: 200 mg [contains sodium benzoate]
Ultraprin: 200 mg [sugar free]
Tablet, chewable:
Advil® Children's: 50 mg [contains phenylalanine 2.1 mg; grape flavors]
Advil® Junior: 100 mg [contains phenylalanine 4.2 mg; grape flavors] [DSC]
Motrin® Junior: 100 mg [contains phenylalanine 2.1 mg; grape and orange flavors]
Pricing: U.S. (www.drugstore.com)
Suspension (Ibuprofen)
100 mg/5 mL (473): $24.27
Tablets (Advil)
200 mg (100): $18.99
Tablets (Ibuprofen)
600 mg (90): $14.99
800 mg (30): $12.59
References
Berde C, Ablin A, Glazer J, et al, “American Academy of Pediatrics Report of the Subcommittee on Disease-Related Pain in Childhood Cancer,” Pediatrics, 1990, 86(5 Pt 2):818-25.
Bhatt DL, Scheiman J, Abraham NS, et al, “ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risk of Antiplatelet Therapy and NSAID Use. A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents,” J Am Coll Cardiol, 2008, 52(18):1502-17.
Brewer EJ, “Nonsteroidal Anti-inflammatory Agents,” Arthritis Rheum, 1977, 20(2):513-25.
Brooks PM and Day RO, “Nonsteroidal Anti-inflammatory Drugs - Differences and Similarities,” N Engl J Med, 1991, 324(24):1716-25.
Capone ML, Sciulli MG, Tacconelli S, et al, “Pharmacodynamic Interaction of Naproxen With Low-Dose Aspirin in Healthy Subjects,” J Am Coll Cardiol, 2005, 45(8):1295-1301.
Castillo M, Lam, YW, Dooley MA, et al, “Disposition and Covalent Binding of Ibuprofen and its Acyl Glucuronide in the Elderly,” Clin Pharmacol Ther, 1995, 57(6):636-44.
Catella-Lawson F, Reilly MP, Kapoor SC, et al, “Cyclooxygenase Inhibitors and the Antiplatelet Effects of Aspirin,” N Engl J Med, 2001, 345(25):1809-17.
Clinch D, Banerjee AK, and Ostick G, “Absence of Abdominal Pain in Elderly Patients With Peptic Ulcer,” Age Ageing, 1984, 13(2):120-3.
Clive DM and Stoff JS, “Renal Syndromes Associated With Nonsteroidal Anti-inflammatory Drugs,” N Engl J Med, 1984, 310(9):563-72.
Conlin P, Moore T, Swartz S, et al, “Effect of Indomethacin on Blood Pressure Lowering by Captopril and Losartan in Hypertensive Patients,” Hypertension, 2000, 36(3):461-5.
Court H and Volans GN, “Poisoning After Overdose With Nonsteroidal Anti-inflammatory Drugs,” Adverse Drug React Acute Poisoning Rev, 1984, 3(1):1-21.
Cryer B, Verlin RG, Cooper SA, et al. “Double-Blind, Randomized, Parallel, Placebo-Controlled Study Of Ibuprofen Effects On Thromboxane B2 Concentrations In Aspirin-Treated Healthy Adult Volunteers,” Clin Ther, 2005, 27 (2):185-191.
Davies NM, “Clinical Pharmacokinetics of Ibuprofen. The First 30 Years,” Clin Pharmacokinet, 1998, 34(2):101-54.
Dionne RA, “New Approaches to Preventing and Treating Postoperative Pain,” J Am Dent Assoc, 1992, 123(6):26-34.
“Drugs for Pain,” Med Lett Drugs Ther, 2000, 42(1085):73-8.
Gobetti JP, “Controlling Dental Pain,” J Am Dent Assoc, 1992, 123(6):47-52.
Graham DY, “Prevention of Gastroduodenal Injury Induced by Chronic Nonsteroidal Anti-inflammatory Drug Therapy,” Gastroenterology, 1989, 96(2 Pt 2 Suppl):675-81.
Gurwitz JH, Avorn J, Ross-Degnan D, et al, “Nonsteroidal Anti-inflammatory Drug-Associated Azotemia in the Very Old,” JAMA, 1990, 264(4):471-5.
Hall AH, Smolinske SC, Conrad FL, et al, “Ibuprofen Overdose: 126 Cases,” Ann Emerg Med, 1986, 15(11):1308-13.
Hawkey CJ, Karrasch JA, Szczepañski L, et al, “Omeprazole Compared With Misoprostol for Ulcers Associated With Nonsteroidal Anti-inflammatory Drugs,” N Engl J Med, 1998, 338(11):727-34.
Heerdink ER, Leufkens HG, Herings RM, et al, “NSAIDs Associated With Increased Risk of Congestive Heart Failure in Elderly Patients Taking Diuretics,” Arch Intern Med, 1998, 158(10):1108-12.
Hoppmann RA, Peden JG, and Ober SK, “Central Nervous System Side Effects of Nonsteroidal Anti-inflammatory Drugs. Aseptic Meningitis, Psychosis, and Cognitive Dysfunction,” Arch Intern Med, 1991, 151(7):1309-13.
Hunt SA, Abraham WT, Chin MH, et al, “2009 Focused Update Incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation,” J Am Coll Cardiol, 2009, 53(15):e1-e90.
Jacobi J, Fraser GL, Coursin DB, et al, “Clinical Practice Guidelines for the Sustained Use of Sedatives and Analgesics in the Critically Ill Adult,” Crit Care Med, 2002, 30(1):119-41. Available at: http://www.sccm.org/pdf/sedatives.pdf. Accessed August 2, 2003.
Kauffman RE and Nelson MV, “Effect of Age on Ibuprofen Pharmacokinetics and Antipyretic Response,” J Pediatr, 1992, 121(6):969-73.
Keller KH, “Hypoprothrombinemia Without Hepatocellular Injury in Ibuprofen Overdose,” Clin Toxicol, 1995, 33(5):492-3.
Kim J, Gazarian M, Verjee Z, et al, “Acute Renal Insufficiency in Ibuprofen Overdose,” Pediatr Emerg Care, 1995, 11(2):107-8.
Knodel LC, “Preventing NSAID-Induced Ulcers: The Role of Misoprostol,” Consult Pharm, 1989, 4:37-41.
Konstan MW, Byard PJ, Hoppel CL, et al, “Effect of High-Dose Ibuprofen in Patients With Cystic Fibrosis,” N Engl J Med, 1995, 332(13):848-54.
Konstan MW, Krenicky JE, Finney MR, et al, “Effect of Ibuprofen on Neutrophil Migration in vivo in Cystic Fibrosis and Healthy Subjects,” J Pharmacol Exp Ther, 2003, 306(3):1086-91.
Lesko SM and Mitchell AA, “An Assessment of the Safety of Pediatric Ibuprofen. A Practitioner-Based Randomized Clinical Trial,” JAMA, 1995, 273(12):929-33.
McElwee NE, Veltri JC, Bradford DC, et al, “A Prospective, Population-Based Study of Acute Ibuprofen Overdose: Complications Are Rare and Routine Serum Levels are Not Warranted,” Ann Emerg Med, 1990, 19(6):657-62.
Mixter CG 3d, Meeker LD, and Gavin TJ, “Preemptive Pain Control in Patients Having Laparoscopic Hernia Repair: A Comparison of Ketorolac and Ibuprofen,” Arch Surg, 1998, 133(4):432-7.
Morgan TO, Anderson A, and Bertram D, “Effect of Indomethacin on Blood Pressure in Elderly People With Essential Hypertension Well Controlled on Amlodipine or Enalapril,” Am J Hypertens, 2000, 13(11):1161-7.
Olsen KM, Gurley BJ, Davis GA, et al, “Comparison of Fluid Volumes With Whole Bowel Irrigation in a Simulated Overdose of Ibuprofen,” Ann Pharmacother, 1995, 29(3):246-50.
Page J and Henry D, “Consumption of NSAIDs and the Development of Congestive Heart Failure in Elderly Patients: An Underrecognized Public Health Problem,” Arch Intern Med, 2000, 160(6):777-84.
Pearlman B, Boyatzis S, Daly C, et al, “The Analgesic Efficacy of Ibuprofen in Periodontal Surgery: A Multicentre Study,” Aust Dent J, 1997, 42(5):328-34.
Pope JE, Anderson JJ, and Felson DT, “A Meta-analysis of the Effects of Nonsteroidal Anti-inflammatory Drugs on Blood Pressure,” Arch Intern Med, 1993, 153(4):477-84.
Pounder R, “Silent Peptic Ulceration: Deadly Silence or Golden Silence?” Gastroenterology, 1989, 96(2 Pt 2 Suppl):626-31.
Smolinske SC, Hall AH, Vandenberg SA, et al, “Toxic Effects of Nonsteroid Anti-inflammatory Drugs in Overdose. An Overview of Recent Evidence on Clinical Effects and Dose-Response Relationships,” Drug Saf, 1990, 5(4):252-74.
Steinhubl SR, “The Use of Anti-Inflammatory Analgesics in the Patient With Cardiovascular Disease: What a Pain,” J Am Coll Cardiol, 2005, 45(8):1302-3.
Turturro MA, Paris PM, and Seaberg DC, “Intramuscular Ketorolac Versus Oral Ibuprofen in Acute Musculoskeletal Pain,” Ann Emerg Med, 1995, 26(2):117-20.
Vale JA and Meredith TJ, “Acute Poisoning Due to Nonsteroidal Anti-inflammatory Drugs,” Med Toxicol, 1986, 1(1):12-31.
Van Overmeire B, “The Use of Ibuprofen in Neonates in the Treatment of Patent Ductus Arteriosus,” Int J Clin Pract Suppl, 2003, (135):23-7.
Van Overmeire B, Smets K, Lecoutere D, et al, “A Comparison of Ibuprofen and Indomethacin for Closure of Patent Ductus Arteriosus,” N Engl J Med, 2000, 343(10):674-81.
Van Overmeire B, Touw D, Schepens PJ, et al, “Ibuprofen Pharmacokinetics in Preterm Infants With Patent Ductus Arteriosus,” Clin Pharmacol Ther, 2001, 70(4):336-43.
Verbeeck RK, “Pharmacokinetic Drug Interactions With Nonsteroidal Anti-inflammatory Drugs,” Clin Pharmacokinet, 1990, 19(1):44-66.
Winter L Jr, Bass E, Recant B, et al, “Analgesic Activity of Ibuprofen (Motrin®) in Postoperative Oral Surgical Pain,” Oral Surg Oral Med Oral Pathol, 1978, 45(2):159-66.
Wolfe TR, “Ibuprofen Overdose,” Am J Emerg Med, 1995, 13(3):375.
Yeomans ND, Tulassay Z, Juhasz L, et al, “A Comparison of Omeprazole With Ranitidine for Ulcers Associated With Nonsteroidal Anti-inflammatory Drugs,” N Engl J Med, 1998, 338(11):719-26.
International Brand Names
Lexi-Comp.com
Last full review/revision August 2009
Content last modified August 2009
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