|
This information has been developed and provided by an independent third-party source. Merck & Co., Inc. does not endorse and is not responsible for the accuracy of the content, or for practices or
standards of non-Merck sources.
Special Alerts
Ibuprofen Lysine Injection (NeoProfen®): Recall Due to Risk of Particulate Matter
August 2010
The Food and Drug Administration (FDA), in conjunction with Lundbeck Inc, has notified healthcare professionals of a nationwide voluntary recall of two lots of NeoProfen® (ibuprofen lysine) injection. The recall was initiated after the product failed to meet quality requirements due to the presence of visible particulate matter. Particulate matter in an injectable product may result in adverse events such as anaphylactic reactions or blood vessel obstruction and the potential for subsequent pulmonary emboli.
The two lots affected by the recall are the only lots currently available to prescribers. Therefore, a temporary product shortage of NeoProfen® is expected. The lots affected by the recall are 1734991 (expiration date April, 2011) and 1922319 (expiration date March, 2012).
For additional information, please refer to http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm220798.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.
Pronunciation
(eye byoo PROE fen)
Generic Available (U.S.)
Yes: Caplet, softgel capsule, suspension, tablet
Index Terms
Medication Guide
An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088647.pdf, must be dispensed with this medication.
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Use: Labeled Indications
Oral: Inflammatory diseases and rheumatoid disorders including juvenile idiopathic arthritis (JIA), mild-to-moderate pain, fever, dysmenorrhea, osteoarthritis
Ibuprofen injection (Caldolor™): Management of mild-to-moderate pain; management moderate-to-severe pain when used concurrently with an opioid analgesic; reduction of fever
Ibuprofen lysine injection (NeoProfen®): To induce closure of a clinically-significant patent ductus arteriosus (PDA) in premature infants weighing between 500-1500 g and who are ≤32 weeks gestational age (GA) 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/D ≥30 weeks gestation
Pregnancy Considerations
Adverse events were not observed in the initial animal reproduction studies; therefore, the manufacturer classifies ibuprofen as pregnancy category C (category D: ≥30 weeks gestation). NSAID 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 a NSAID close to conception 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, fetal tricuspid regurgitation, failure of the ductus arteriosus to close postnatally; renal dysfunction or failure, oligohydramnios; gastrointestinal bleeding or perforation, increased risk of necrotizing enterocolitis; intracranial bleeding (including intraventricular hemorrhage), 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). Product labeling for Caldolor™ specifically notes that use at ≥30 weeks gestation should be avoided and therefore classifies ibuprofen as pregnancy category D at this time. 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”; AAP 2001 update pending)
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. 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; history of asthma, urticaria, or allergic-type reaction to aspirin or other NSAIDs; aspirin triad (eg, bronchial asthma, aspirin intolerance, rhinitis); perioperative pain in the setting of coronary artery bypass graft (CABG) surgery
Ibuprofen lysine (NeoProfen®): 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.
• Cardiovascular events: [U.S. Boxed Warning]: NSAIDs are associated with an increased risk of adverse cardiovascular thrombotic events, including fatal 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.
• 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). Discontinue use with blurred or diminished vision and perform ophthalmologic exam. Periodically evaluate vision in all patients receiving long-term therapy.
• Gastrointestinal events: [U.S. Boxed Warning]: NSAIDs may increase risk of gastrointestinal irritation, inflammation, ulceration, bleeding, and perforation. These events can be fatal and 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 ethanol, 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).
• 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).
• Hyperkalemia: NSAID use may increase the risk of hyperkalemia, particularly in the elderly, diabetics, renal disease, and with concomitant use of other agents capable of inducing hyperkalemia (eg, ACE-inhibitors). Monitor potassium closely.
• Ophthalmic events: Blurred/diminished vision, scotomata, and changes in color vision have been reported. Discontinue therapy and refer for ophthalmologic evaluation if symptoms occur.
• 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:
• Aseptic meningitis: May increase the risk of aseptic meningitis, especially in patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders.
• 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. Response to ACE inhibitors, thiazides, or loop diuretics may be impaired with concurrent use of NSAIDs.
• 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 serious gastrointestinal events, CNS effects, renal toxicity) from NSAIDs even at low doses.
Dosage form specific issues:
• 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.
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: Ibuprofen (Caldolor™): Abdominal pain, anemia, BUN increased, cough, dizziness, dyspepsia, edema, flatulence, headache, hemorrhage, hypokalemia, hypernatremia, hypertension, nausea, neutropenia, pruritus, urinary retention, vomiting
Injection: Ibuprofen lysine (NeoProfen®):
>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: 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. 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: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Angiotensin II Receptor Blockers. The combination of these two agents may also significantly decrease glomerular filtration and renal function. Risk C: Monitor therapy
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
Collagenase (Systemic): Antiplatelet Agents may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the adverse/toxic effect of 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
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). Risk D: Consider therapy modification
Dasatinib: May enhance the anticoagulant effect of Antiplatelet Agents. Risk C: Monitor therapy
Deferasirox: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Risk C: Monitor therapy
Desmopressin: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Desmopressin. Risk C: Monitor therapy
Digoxin: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Digoxin. Risk C: Monitor therapy
Drotrecogin Alfa: Antiplatelet Agents may enhance the adverse/toxic effect of Drotrecogin Alfa. Bleeding may occur. Management: When possible, avoid use of drotrecogin within 7 days of use of any IIb/IIIa antagonists, higher dose aspirin (more than 650 mg/day), or use of other antiplatelet agents. 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
Glucosamine: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Haloperidol: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Haloperidol. Specifically including drowsiness and confusion. 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. 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. 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
Ketorolac (Nasal): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination
Ketorolac (Systemic): 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
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. 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. Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration 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). NSAID (Nonselective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Consider using alternative analgesics, when appropriate, and/or addition of an gastroprotective agent. Monitor patients closely for signs/symptoms of bleeding, and for evidence of diminished SSRI effectiveness with concurrent use. Risk D: Consider therapy modification
Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the antiplatelet effect of NSAID (Nonselective). Risk C: 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. Risk D: Consider therapy modification
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 increase the serum concentration 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
Voriconazole: May increase the serum concentration of Ibuprofen. Specifically, concentrations of the S-(+)-ibuprofen enantiomer may be increased. Risk C: Monitor therapy
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
Ibuprofen injection (Caldolor™): Store intact vials at room temperature of 20°C to 25°C (68°F to 77°F). Must be diluted prior to use. Diluted solutions stable for 24 hours at room temperature.
Ibuprofen lysine injection (NeoProfen®): 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.
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.
Compatibility
Ibuprofen injection (Caldolor™): Stable in dextrose, saline, and lactated Ringer's
Ibuprofen lysine injection (NeoProfen®): 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: Oral: Analgesic: 30-60 minutes; Anti-inflammatory: ≤7 days
Duration: Oral: 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: Oral: ~1-2 hours
Excretion: Urine (primarily as metabolites; 1% as unchanged drug); some feces
Dosage
I.V.:
Neonates: Ibuprofen lysine (NeoProfen®): 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.
Adults (Caldolor™): Note: Patients should be well hydrated prior to administration
Analgesic: 400-800 mg every 6 hours as needed (maximum: 3.2 g/day)
Antipyretic: Initial: 400 mg, then every 4-6 hours or 100-200 mg every 4 hours as needed (maximum: 3.2 g/day)
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 idiopathic arthritis (JIA): 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 concentration 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.
Caldolor™: For I.V. administration only; must be diluted to a final concentration of ≤4 mg/mL prior to administration; infuse over at least 30 minutes
NeoProfen® (ibuprofen lysine): 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.
Administration: I.V. Detail
Caldolor™: pH: 7.4
NeoProfen®: pH: 7.0
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; with long-term therapy, periodic ophthalmic exams; signs of infection (ibuprofen lysine)
Reference Range
Plasma concentrations >200 mcg/mL may be associated with severe toxicity
PDA: Minimum effective concentration: 10-12 mg/L
Test Interactions
May interfere with urine detection of PCP, cannabinoids, and barbiturates (false-positives)
Dietary Considerations
Should be taken with food. Some products may contain phenylalanine and/or potassium.
Patient Education
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 prescriber. Take with food or milk. Do not use alcohol. Maintain adequate hydration, unless instructed to restrict fluid intake. You may experience nausea, vomiting, or gastric discomfort. 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.
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 prostaglandin-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.
Ibuprofen, prescription dose of 800 mg 3 times daily, significantly diminishes the antiplatelet effects of low-dose aspirin (baby) in healthy volunteers. Diclofenac (Systemic), 50 mg 3 times daily, did not interfere with the antiplatelet effects of low-dose aspirin (baby) in healthy volunteers. Ibuprofen, and possibly other nonselective NSAIDs, may reduce the cardioprotective effects of aspirin. It seems prudent to avoid regular, frequent use of ibuprofen in patients receiving aspirin for its cardioprotective effects. Alternative analgesics (eg, acetaminophen) or prescription diclofenac in place of prescription ibuprofen may be a safer choice.
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. Monitor blood pressure prior to treatment and periodically throughout. Periodic ophthalmic exams are recommended.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Caplet, oral: 200 mg
Advil®: 200 mg [contains sodium benzoate]
Motrin® IB: 200 mg
Motrin® Junior: 100 mg [scored]
Capsule, liquid filled, oral:
Advil®: 200 mg [contains potassium 20 mg/capsule; solubilized ibuprofen]
Advil® Migraine: 200 mg [contains potassium 20 mg/capsule; solubilized ibuprofen]
Capsule, softgel, oral: 200 mg
Gelcap, oral:
Advil®: 200 mg [contains coconut oil]
Injection, solution:
Caldolor™: 100 mg/mL (4 mL, 8 mL)
Injection, solution, as lysine [preservative free]:
NeoProfen®: 17.1 mg/mL (2 mL) [equivalent to ibuprofen base 10 mg/mL]
Suspension, oral: 100 mg/5 mL (5 mL, 10 mL, 120 mL, 480 mL)
Advil® Children's: 100 mg/5 mL (120 mL) [contains propylene glycol, sodium 10 mg/5 mL, sodium benzoate; blue raspberry flavor]
Advil® Children's: 100 mg/5 mL (120 mL) [contains propylene glycol, sodium 3 mg/5 mL, sodium benzoate; grape flavor]
Advil® Children's: 100 mg/5 mL (120 mL) [contains sodium 3 mg/5 mL, sodium benzoate; fruit flavor]
Motrin® Children's: 100 mg/5 mL (120 mL) [dye free, ethanol free; contains sodium 2 mg/5 mL, sodium benzoate; berry flavor]
Motrin® Children's: 100 mg/5 mL (60 mL, 120 mL) [ethanol free; contains sodium 2 mg/5 mL, sodium benzoate; berry flavor]
Motrin® Children's: 100 mg/5 mL (120 mL) [ethanol free; contains sodium 2 mg/5 mL, sodium benzoate; bubblegum flavor]
Motrin® Children's: 100 mg/5 mL (120 mL) [ethanol free; contains sodium 2 mg/5 mL, sodium benzoate; grape flavor]
Motrin® Children's: 100 mg/5 mL (120 mL) [ethanol free; contains sodium 2 mg/5 mL, sodium benzoate; tropical punch flavor]
Suspension, oral [concentrate/drops]: 40 mg/mL (15 mL)
Advil® Infants': 40 mg/mL (15 mL) [contains sodium benzoate; grape flavor]
Advil® Infants': 40 mg/mL (15 mL) [dye free; contains propylene glycol, sodium benzoate; white grape flavor]
Motrin® Infants': 40 mg/mL (15 mL) [dye free, ethanol free; contains sodium benzoate; berry flavor]
Motrin® Infants': 40 mg/mL (15 mL) [ethanol free; contains sodium benzoate; berry flavor]
Tablet, oral: 200 mg, 400 mg, 600 mg, 800 mg
Addaprin: 200 mg
Advil®: 200 mg [contains sodium benzoate]
I-Prin: 200 mg
Ibu-200: 200 mg
Ibu®: 400 mg, 600 mg, 800 mg
Midol® Cramps & Body Aches: 200 mg
Motrin® IB: 200 mg
Proprinal®: 200 mg [contains sodium benzoate]
Ultraprin: 200 mg [sugar free]
Tablet, chewable, oral:
Motrin® Junior: 100 mg [contains phenylalanine 2.8 mg/tablet; grape flavor]
Motrin® Junior: 100 mg [contains phenylalanine 2.8 mg/tablet; orange flavor]
TopCare® Junior Strength: 100 mg [scored; orange flavor]
Pricing: U.S. (www.drugstore.com)
Suspension (Ibuprofen)
100 mg/5 mL (473): $27.01
Tablets (Advil)
200 mg (100): $20.63
Tablets (Ibuprofen)
400 mg (30): $11.99
600 mg (90): $14.99
800 mg (30): $12.99
References
American Academy of Pediatrics Committee on Drugs, "Transfer of Drugs and Other Chemicals Into Human Milk," Pediatrics, 2001, 108(3):776-89.
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.
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.
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.
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.
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.
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.
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.
Kauffman RE and Nelson MV, “Effect of Age on Ibuprofen Pharmacokinetics and Antipyretic Response,” J Pediatr, 1992, 121(6):969-73.
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.
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.
Marchei E, Pellegrini M, Pichini S, et al, “Are False-Positive Phencyclidine Immunoassay Instant-View Multi-Test Results Caused by Overdose Concentrations of Ibuprofen, Metamizol, and Dextromethorphan?” Ther Drug Monit, 2007, 29(5):671-3.
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.
Rollins DE, Jennison TA, and Jones G, “Investigation of Interference by Nonsteroidal Anti-Inflammatory Drugs in Urine Tests for Abused Drugs,” Clin Chem, 1990, 36(4):602-6.
Schuijt MP, Huntjens-Fleuren HW, de Metz M, et al, "The Interaction of Ibuprofen and Diclofenac With Aspirin in Healthy Volunteers," Br J Pharmacol, 2009, 157(6):931-4.
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.
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.
International Brand Names
Lexi-Comp.com
Last full review/revision May 2011
|
