Contents

Search

ibuprofen (Motrin, Advil, Nuprin, Rufen, NeoProfen, Caldolor)

Tradenames: Motrin, Advil, Nuprin, Rufen. Indications: - temporary relief of minor aches, pains, fever, inflammation - bursitis - dysmenorrhea - gout - rheumatic fever, rheumatic heart disease[23] - closure of patent ductus arteriosus (NeoProfen) - prevention of acute mountain sickness [22] Contraindications: - see non-steroidal anti-inflammatory agent (NSAID) Pregnancy category: B, D in 3rd trimester Dosage: 1) 200-800 mg PO TID-QID, max: 3.2 g/day 2) pediatric 5-10 mg/kg PO every 6 hours, max: 40 mg/kg/day 3) 400-800 mg IV over 30 minutes every 6 hours (pain); [18] bolus 400 mg, then 200-400 mg IV every 4-6 hours (fever) 4) prevention of acute mountain sickness [22] - 600 mg every 6 hours 6 hours prior to ascending 5) doses > 400 mg do not provide additional pain control [26] Tabs: 200, 300, 400, 600, 800 mg. Children's Motrin: (100 mg/5 mL) NeoProfen: ibuprofen lysine, intravenous form Calador: (intravenous, for hospital use only) [18]; 400 mg/4 mL single-dose vial & 800 mg/8 mL single-dose vial; must be diluted before infusion; dilute with normal saline, D5W, or Lactated Ringers to a final concentration of 4 mg/mL or less (25-fold dilution) Pharmacokinetics: 1) rapid absorption from GI tract 2) onset of action: 30 minutes 3) elimination 1/2life 2-4 hours 4) duration of action: 4-6 hours 5) metabolized by liver by cyt P450 2C9 to at least 2 inactive metabolites 6) < 1% excreted unchanged in the urine Monitor: - liver function tests periodically [21] Adverse effects: 1) common (> 10%) - rash, dizziness, abdominal cramps, heartburn, indigestion, nausea 2) less common (1-10%) - itching, tinnitus, fluid retention, headache, nervousness, vomiting 3) uncommon (< 1%) - congestive heart failure, hypertension, arrhythmias, epistaxis, confusion, hallucinations, aseptic meningitis, depression, peripheral neuropathy, urticaria, erythema multiforme, Stevens-Johnson syndrome [16], toxic epidermal necrolysis, gastritis, GI ulceration, cystitis, agranulocytosis, anemia, hemolytic anemia, bone marrow depression, leukopenia, thrombocytopenia, hepatitis, angioedema, allergic rhinitis, toxic amblyopia, blurred vision, conjunctivitis, dry eyes, decreased hearing, polyuria, shortness of breath, polydypsia, tachycardia, hot flashes, drowsiness, insomnia, acute renal failure 4) other a) gastric distress b) GI bleed - RR=2.7 relative to placebo - lowest risk of NSAIDs, excluding COX-2 inhibitors c) worsening renal insufficiency in patients with renal disease d) hyperkalemia - inhibits renin - generally occurs in combination with an ACE inhibitor or other agent that causes hyperkalemia 5) no evidence for serious adverse effects in doses < 2400 mg/day for short periods of time [24] 6) 600 mg BID may be linked to male infertility [25] Drug interactions: 1) corticosteroids increase nephrotoxicity 2) decreased anti-hypertensive effect of ACE inhibitors 3) coumadin: prolongs bleeding time 4) ibuprofen may increase plasma levels of: a) digoxin b) Li+ c) methotrexate 5) may interfere with anti-platelet activity of aspirin [10,11,12] -> take 2 hours after aspirin dose 6) any drug which inhibits cyt P450 2C9 can increase ibuprofen levels 7) any drug which induces cyt P450 2C9 can diminish ibuprofen levels Laboratory: 1) specimen: serum, plasma (EDTA) 2) methods: HPLC, GC, GC-MS 3) concentrations > 200 ug/mL may be associated with toxicity 4) 600 mg BID may increase serum LH in men [25] Mechanism of action: 1) propionic acid class NSAID 2) analgesic 3) antipyretic 4) anti-inflammatory 5) weak anti-platelet activity (weaker than naproxen) 6) peroxisome proliferator (PPAR agonist) 7) directly interacts with APP gamma secretase to inhibit formation of A-beta(1-42) in favor of A-beta(1-38) [13,14] 8) may induce compensated hypogonadism in men [25]

Interactions

drug interactions drug adverse effects of NSAIDs monitor with non steroidal anti-inflammatory agents (NSIADs)

Related

cytochrome P450 2C9; cytochrome P450 BP-1; cytochrome P450 MP-4; S-mephenytoin-4-hydroxylase; limonene 6-monooxygenase; limonene 7-monooxygenase (CYP2C9, CYP2C10) peroxisome proliferator-activated receptor (PPAR)

General

non-steroidal anti-inflammatory agent (NSAID) peroxisome proliferator; PPAR agonist; PPAR gamma agonist

Properties

INHIBITS: cyclooxygenase MISC-INFO: elimination route LIVER 1/2life 2-4 HOURS therapeutic-range 10-50 UG/ML toxic-range >100 UG/ML protein-binding >99% elimination by hemodialysis - peritoneal dialysis - pregnancy-category B D <3rd trimester> safety in lactation +

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 792
  3. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  4. Medical Knowledge Self Assessment Program (MKSAP) 11, American College of Physicians, Philadelphia 1998
  5. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  6. Clinical Guide to Laboratory Tests, NW Tietz (ed) 3rd ed, WB Saunders, Philadelpha 1995
  7. Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: 220233 (subscription needed) http://www.prescribersletter.com
  8. Journal Watch 21(18):143-44, 2001
  9. Sepulveda VA
  10. Prescriber's Letter 9(2):1 2002
  11. Journal Watch 22(2):11, 2002 Catella-Lawson et al, N Engl J Med 345:1809, 2001
  12. Prescriber's Letter 10(3):15 2003
  13. Weggen S et al, Evidence that nonsteroidal anti-inflammatory drugs decrease amyloid beta 42 production by direct modulation of gamma-secretase activity. J Biol Chem. 2003 Aug 22;278(34):31831-7. Epub 2003 Jun 12. PMID: 12805356
  14. Eriksen JL et al, NSAIDs and enantiomers of flurbiprofen target gamma-secretase and lower Abeta 42 in vivo. J Clin Invest. 2003 Aug;112(3):440-9. PMID: 12897211
  15. Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
  16. Prescriber's Letter 12(4): 2005 Ibuprofen and the Risk of Stevens-Johnson Syndrome Detail-Document#: 210408 (subscription needed) http://www.prescribersletter.com
  17. Prescriber's Letter 14(2): 2007 New drugs approved by the FDA in 2006 Detail-Document#: 2302213 (subscription needed) http://www.prescribersletter.com
  18. FDA NEWS RELEASE: FDA Approves Injectable Form of Ibuprofen http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm165971.htm
  19. Prescriber's Letter 16(11): 2009 New Drug: Caldolor (Ibuprofen) Injection Detail-Document#: 251111 (subscription needed) http://www.prescribersletter.com
  20. Gonzalez ELM et al Variability among nonsteroidal antiinflammatory drugs in risk of upper gastrointestinal bleeding. Arthritis Rheum 2010 Jun; 62:1592 http://dx.doi.org/10.1002/art.27412
  21. Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Liver Function Test Scheduling Detail-Document#: 260704 (subscription needed) http://www.prescribersletter.com
  22. Lipman GS et al. Ibuprofen prevents altitude illness: A randomized controlled trial for prevention of altitude illness with nonsteroidal anti-inflammatories. Ann Emerg Med 2012 Jun; 59:484. PMID: 22440488
  23. Deprecated Reference
  24. Husten L. Fairchild DG and Sofai A editors. European Regulators Investigate Cardiovascular Safety of Ibuprofen. Physician's First Watch, June 17 2014 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org
  25. Kristensen DM, Desdoits-Lethimonier C, Mackey AL et al Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism. Proc Natl Acad Sci U S A. 2018 Jan 8. PMID: 29311296 http://www.pnas.org/content/early/2018/01/03/1715035115.full
  26. Motov S, Masoudi A, Drapkin J et al. Comparison of oral ibuprofen at three single dose regimens for treating acute pain in the emergency department: A randomized controlled trial. Ann Emerg Med 2019 Aug 2; PMID: 31383385

Component-of

activation induced cytidine deaminase/ibuprofen/pseudoephedrine caffeine/cobalamin/ibuprofen/pyridoxine/riboflavin/thiamine chlorpheniramine/ibuprofen/phenylephrine chlorpheniramine/ibuprofen/pseudoephedrine chondroitin sulfate/glucosamine 2 sulfate/ibuprofen citrate/diphenhydramine/ibuprofen diphenhydramine/ibuprofen (Advil PM) famotidine/ibuprofen (Duexis) hydrocodone/ibuprofen (Vicoprofen) ibuprofen/oxycodone (Combunox) ibuprofen/phenylephrine ibuprofen/pseudoephedrine ibuprofen/pseudoisocytidine