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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section and/or refer to product labeling for additional detail.
Medication Safety Issues
Sound-alike/look-alike issues:
Haltran® may be confused with Halfprin®
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
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
Restrictions
An FDA-approved medication guide must be distributed when dispensing an oral outpatient prescription (new or refill) where this medication is to be used without direct supervision of a healthcare provider. Medication guides are available at http://www.fda.gov/cder/Offices/ODS/medication_guides.htm.
Pregnancy Risk Factor
C/D (3rd trimester)
Lactation
Enters breast milk/use caution (AAP rates “compatible”)
Breast-Feeding Considerations
Limited data suggests minimal excretion in breast milk.
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, stroke, and new onset or worsening of pre-existing hypertension. 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, heart failure, or hypertension. 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.
• 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.
• 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.
Other warnings/precautions:
• OTC labeling: 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, or are ?60 years of age. Recommended dosages should not be exceeded, due to an increased risk of GI bleeding. 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: Itching (1% to 3%), rash (3% to 9%)
Endocrine & metabolic: Fluid retention (1% to 3%)
Gastrointestinal: Dyspepsia (1% to 3%), vomiting (1% to 3%), abdominal pain/cramps/distress (1% to 3%), heartburn (3% to 9%), nausea (3% to 9%), diarrhea (1% to 3%), constipation (1% to 3%), flatulence (1% to 3%), epigastric pain (3% to 9%), appetite decreased (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)
Respiratory: Respiratory failure (10%), atelectasis (4%)
Frequency not defined: Abdominal distension, cardiac failure, cholestasis, convulsions, feeding problems, gastritis, GI reflux, hyperglycemia, hypotension, ileus, infection, inguinal hernia, injection site reaction, jaundice, neutropenia, tachycardia, thrombocytopenia
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: Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Antidepressants (Serotonin/Norepinephrine Reuptake Inhibitor): May enhance the antiplatelet effect of NSAID (Nonselective). Risk C: Monitor therapy
Antidepressants (Tricyclic, Tertiary Amine): May enhance the antiplatelet effect of NSAID (Nonselective). 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. 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
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
Desmopressin: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Desmopressin. Risk C: Monitor therapy
Eplerenone: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Eplerenone. Risk C: Monitor therapy
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
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 other Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy
Pemetrexed: NSAID (Nonselective) may decrease the excretion of Pemetrexed. Risk D: Consider therapy modification
Probenecid: May increase the serum concentration of Nonsteroidal Anti-Inflammatory 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 antiplatelet effect of Salicylates. 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
Selective Serotonin Reuptake Inhibitors: May enhance the antiplatelet effect of NSAID (Nonselective). 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: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Thrombolytic Agents. An increased risk of bleeding may occur. 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: Store at room temperature of 15°C to 30°C (59°F to 86°F).
Tablet: Store at room temperature of 20°C to 25°C (68°F to 77°F).
Reconstitution
Dilute with dextrose or saline to an appropriate volume.
Compatibility
Stable in dextrose, saline; incompatible with TPN solution.
Mechanism of Action
Inhibits prostaglandin synthesis by decreasing the activity of the enzyme, cyclooxygenase, which results in decreased formation of prostaglandin precursors
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: 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 (1% as free 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):
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
35-47
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 35-47 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)
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): 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
35-47
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 35-47 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 (2-3 L/day of fluids) 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, appropriate monitoring of blood pressure responses should be completed and the duration of therapy, when possible, kept short. The use of NSAIDs in the treatment of patients with congestive heart failure may be associated with an increased risk for fluid accumulation and edema. May precipitate renal failure in dehydrated patients.
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 congestive 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 congestive heart failure, particularly in the elderly population. The ACC/AHA 2005 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 Dental Comment.
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, 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; grape flavor]
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]
Advil® Junior: 100 mg [contains sodium benzoate; coated tablets] [DSC]
Genpril® [DSC], I-Prin, Midol® Cramp and Body Aches, Motrin® IB, Proprinal, Ultraprin: 200 mg
Ibu®: 400 mg, 600 mg, 800 mg
Ibu-200: 200 mg
Motrin®: 400 mg, 600 mg, 800 mg [DSC]
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]
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 (Ibuprofen)
400 mg (30): $11.99
600 mg (90): $14.99
Tablets (Motrin)
600 mg (30): $17.99
References
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International Brand Names
Lexi-Comp.com
Last full review/revision September 2008
Content last modified September 2008
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