Generic Name: Piroxicam
Class: Other Nonsteroidal Anti-inflammatory Agents
VA Class: MS120
Chemical Name: 4-Hydroxy-2-methyl-N2-pyridinyl-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide
Molecular Formula: C15H13N3O4S
CAS Number: 36322-90-4
- Cardiovascular Risk
Possible increased risk of serious (sometimes fatal) cardiovascular thrombotic events (e.g., MI, stroke).1 Risk may increase with duration of use.1 Individuals with cardiovascular disease or risk factors for cardiovascular disease may be at increased risk.1 (See Cardiovascular Effects under Cautions.)
Contraindicated for the treatment of pain in the setting of CABG surgery.1
- GI Risk
Increased risk of serious (sometimes fatal) GI events (e.g., bleeding, ulceration, perforation of the stomach or intestine).1 Serious GI events can occur at any time and may not be preceded by warning signs and symptoms.1 Geriatric individuals are at greater risk for serious GI events.1 (See GI Effects under Cautions.)
Uses for Feldene
Consider potential benefits and risks of piroxicam therapy as well as alternative therapies before initiating therapy with the drug.1 Use lowest possible effective dosage and shortest duration of therapy consistent with patient's treatment goals.1
Symptomatic treatment of rheumatoid arthritis and osteoarthritis.1
Feldene Dosage and Administration
Consider potential benefits and risks of piroxicam therapy as well as alternative therapies before initiating therapy with the drug.1
To minimize the potential risk of adverse cardiovascular and/or GI events, use lowest effective dosage and shortest duration of therapy consistent with patient's treatment goals.1 Adjust dosage based on individual requirements and response; attempt to titrate to lowest effective dosage.1
Osteoarthritis or Rheumatoid ArthritisOral
Dosage reduction may be required.1
Cautions for Feldene
Known hypersensitivity to piroxicam or any ingredient in the formulation. 1
History of asthma, urticaria, or other sensitivity reaction precipitated by aspirin or other NSAIAs.1
Treatment of perioperative pain in the setting of CABG surgery.1
Selective COX-2 inhibitors have been associated with increased risk of cardiovascular events (e.g., MI, stroke) in certain situations.112 Several prototypical NSAIAs also have been associated with increased risk of cardiovascular events.115 116 117 Current evidence (based on limited data from observational studies) suggests that use of piroxicam is not associated with increased cardiovascular risk.115
Use NSAIAs with caution and careful monitoring (e.g., monitor for development of cardiovascular events), and at the lowest effective dose for the shortest duration necessary.1
Short-term use to relieve acute pain, especially at low dosages, does not appear to be associated with increased risk of serious cardiovascular events (except immediately following CABG surgery).112
No consistent evidence that concomitant use of low-dose aspirin mitigates the increased risk of serious adverse cardiovascular events associated with NSAIAs.1 (See Specific Drugs under Interactions.)
Hypertension and worsening of preexisting hypertension reported; either event may contribute to the increased incidence of cardiovascular events.1 Use with caution in patients with hypertension; monitor BP.1 Impaired response to certain diuretics may occur.1 (See Specific Drugs under Interactions.)
Serious GI toxicity (e.g., bleeding, ulceration, perforation) can occur with or without warning symptoms; increased risk in those with a history of GI bleeding or ulceration, geriatric patients, smokers, those with alcohol dependence, and those in poor general health.1 94 102 109
For patients at high risk for complications from NSAIA-induced GI ulceration (e.g., bleeding, perforation), consider concomitant use of misoprostol;16 47 68 94 102 alternatively, consider concomitant use of a proton-pump inhibitor (e.g., omeprazole)16 68 94 or use of an NSAIA that is a selective inhibitor of COX-2 (e.g., celecoxib).16
Direct renal injury, including renal papillary necrosis, reported in patients receiving long-term NSAIA therapy.1
Potential for overt renal decompensation.1 31 48 49 50 65 Increased risk of renal toxicity in patients with renal or hepatic impairment or heart failure, in geriatric patients, in patients with volume depletion, and in those receiving a diuretic, ACE inhibitor, or angiotensin II receptor antagonist.1 31 48 65 114 (See Renal Impairment under Cautions.)
Anaphylactoid reactions reported. 1
Immediate medical intervention and discontinuance for anaphylaxis.1
Avoid in patients with aspirin triad (aspirin sensitivity, asthma, nasal polyps); caution in patients with asthma.1
Serious skin reactions (e.g., exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) reported; can occur without warning.1 Discontinue at first appearance of rash or any other sign of hypersensitivity (e.g., blisters, fever, pruritus).1
Severe reactions including jaundice, fatal fulminant hepatitis, liver necrosis, and hepatic failure (sometimes fatal) reported rarely with NSAIAs. 1
Elevations of serum ALT or AST reported.1
Monitor for symptoms and/or signs suggesting liver dysfunction; monitor abnormal liver function test results.1 Discontinue if signs or symptoms of liver disease or systemic manifestations (e.g., eosinophilia, rash) occur or if liver function test abnormalities persist or worsen.1
May inhibit platelet aggregation and prolong bleeding time. 1
Visual disturbances reported; ophthalmic evaluation recommended if visual changes occur. 1
Not a substitute for corticosteroid therapy; not effective in the management of adrenal insufficiency.1
May mask certain signs of infection.1
Obtain CBC and chemistry profile periodically during long-term use.1
Distributed into milk in humans; use not recommended.1
Safety and efficacy not established.1
Caution advised.1 Geriatric adults appear to tolerate NSAIA-induced adverse effects less well than younger individuals.96 Fatal adverse GI effects reported more frequently in geriatric patients than younger adults.96
Consider lowest effective dosage for the shortest possible duration.1
Monitor closely.1 (See Hepatic Impairment under Dosage and Administration.)
Use not recommended in patients with advanced renal disease; close monitoring of renal function advised if used.1
Common Adverse Effects
Dyspepsia, nausea, diarrhea, constipation, rash, dizziness, headache, edema, tinnitus.1
Interactions for Feldene
Pharmacokinetic interaction possible with other highly protein-bound drugs; monitor patient; dosage adjustment may be needed.1
Reduced BP response to ACE inhibitor1
Angiotensin II receptor antagonists
Reduced BP response to angiotensin II receptor antagonist118
Antacids (magnesium- or aluminum-containing)
Possible bleeding complications1
Diuretics (furosemide, thiazides)
Monitor for diuretic efficacy and renal failure1
Use with caution1
NSAIAs including aspirin: Increased risk of GI ulceration and other complications 1
Aspirin: No consistent evidence that use of low-dose aspirin mitigates the increased risk of serious cardiovascular events associated with NSAIAs112
Decreased plasma piroxicam concentrations with concomitant use of 20 mg piroxicam and 3.9 g aspirin daily 1
Concomitant use not recommended1
Thrombolytic agents (streptokinase)
Possible bleeding complications26
Use with caution26
Distributed into synovial fluid.3
Plasma Protein Binding
Advice to Patients
Importance of reading the medication guide for NSAIAs that is provided to the patient each time the drug is dispensed.1
Risk of serious cardiovascular events with long-term use.1
Risk of GI bleeding and ulceration.1
Risk of hepatotoxicity.1
Importance of notifying clinician if signs and symptoms of a cardiovascular event (chest pain, dyspnea, weakness, slurred speech) occur.1
Importance of notifying clinician if signs and symptoms of GI ulceration or bleeding, unexplained weight gain, or edema develops.1
Importance of discontinuing piroxicam and contacting clinician if rash or other signs of hypersensitivity (blisters, fever, pruritus) develop.1 Importance of seeking immediate medical attention if an anaphylactic reaction occurs.1
Importance of discontinuing therapy and contacting clinician immediately if signs and symptoms of hepatotoxicity (nausea, fatigue, lethargy, pruritus, jaundice, upper right quadrant tenderness, flu-like symptoms) occur.1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant diseases.1
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
Feldene 20MG Capsules (PFIZER U.S.): 30/$175.98 or 90/$519.98
Piroxicam 10MG Capsules (NOSTRUM LABORATORIES): 30/$77.68 or 60/$135.00
Piroxicam 20MG Capsules (NOSTRUM LABORATORIES): 30/$134.28 or 60/$254.94
AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions August 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
1. Pfizer Laboratories. Feldene (piroxicam) capsules prescribing information. New York, NY; 2006 Mar.
2. Dahl SL, Ward JR. Pharmacology, clinical efficacy, and adverse effects of piroxicam, a new nonsteroidal anti-inflammatory agent. Pharmacotherapy. 1982; 2:80-9. [IDIS 150330] [PubMed 6765393]
3. Brogden RN, Heel RC, Speight TM et al. Piroxicam: a review of its pharmacological properties and therapeutic efficacy. Drugs. 1981; 22:165-87. [IDIS 140930] [PubMed 7021122]
4. Wiseman EH. Pharmacologic studies with a new class of nonsteroidal anti-inflammatory agents–the oxicams–with special reference to piroxicam (Feldene). Am J Med. 1982; 72(2A):2-8.
5. Conner CS. Piroxicam. Drugdex. 1983; (Mar):1-36.
6. Simon LS, Mills JA. Nonsteroidal anti-inflammatory drugs. N Engl J Med. 1980; 302:1179-85. [IDIS 113555] [PubMed 6988717]
7. Flower RJ, Moncada S, Vane JR. Drug therapy of inflammation: analgesic-antipyretics and antiinflammatory agents; drugs employed in the treatment of gout. In: Gilman AG, Goodman L, Gilman A, eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 6th ed. New York: Macmillan Publishing Company; 1980:682-93.
8. Wiseman EH. Review of preclinical studies with piroxicam: pharmacology, pharmacokinetics, and toxicology. In: O’Brien WM, Wiseman EH, eds. Royal Society of Medicine International Congress and Symposium Series. Number 1. New York: Grune & Stratton; 1978:11-23.
9. Ferreira SH, Lorenzetti BB, Correa FMA. Central and peripheral antianalgesic action of aspirin-like drugs. Eur J Pharmacol. 1978; 53:39-48. [PubMed 310771]
10. Atkinson DC, Collier HOJ. Salicylates: molecular mechanism of therapeutic action. Adv Pharmacol Chemother. 1980; 17:233-88. [PubMed 7004141]
11. Bernheim HA, Block LH, Atkins E. Fever: pathogenesis, pathophysiology, and purpose. Ann Intern Med. 1979; 91:261-70. [PubMed 223485]
12. Ishizaki T, Nomura T, Abe T. Pharmacokinetics of piroxicam, a new nonsteroidal anti-inflammatory agent, under fasting and postprandial states in man. J Pharmacokinet Biopharm. 1979; 7:369-81. [IDIS 104494] [PubMed 512843]
13. Hobbs DC, Twomey TM. Piroxicam pharmacokinetics in man: aspirin and antacid interaction studies. J Clin Pharmacol. 1979; 19:270-81. [IDIS 104479] [PubMed 89124]
14. Pitts NE. Efficacy and safety of piroxicam. Am J Med. 1982; 72(2A):77-87.
15. Abruzzo JL, Gordon GV, Meyers AR. Double-blind study comparing piroxicam and aspirin in the treatment of osteoarthritis. Am J Med. 1982; 72(2A):45-9.
16. American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis; 2002 update. Arthritis Rheum. 2002; 46:328-46. [IDIS 476480] [PubMed 11840435]
17. Willkens RF. The use of nonsteroidal anti-inflammatory agents. JAMA. 1978; 240:1632-5. [IDIS 87147] [PubMed 691156]
18. Willkens RF, Ward JR, Louie JS et al. Double-blind study comparing piroxicam and aspirin in the treatment of rheumatoid arthritis. Am J Med. 1982; 72(2A):23-6.
19. Turner R, April PA, Robbins DL. Double-blind multicenter study comparing piroxicam and ibuprofen in the treatment of rheumatoid arthritis. Am J Med. 1982; 72(2A):34-8.
20. Davies J, Dixon AS. Efficacy and safety of piroxicam compared with indomethacin in the management of rheumatoid arthritis. Am J Med. 1982; 72(2A):27-30.
21. Sydnes OA. Double-blind comparison of piroxicam and naproxen in the management of rheumatoid arthritis. Am J Med. 1982; 72(2A):31-3.
22. Hart FD. Rheumatic disorders. In: Avery GS, ed. Drug treatment: principles and practice of clinical pharmacology and therapeutics. 2nd ed. New York: ADIS Press; 1980:861-2.
23. Huskisson EC. European experience with piroxicam. Am J Med. 1982; 72(2A):70-6.
24. Pitts NE, Proctor RR. Summary: efficacy and safety of piroxicam. In O’Brien WM, Wiseman EH, eds. Royal Society of Medicine International Congress and Symposium Series. Number 1. New York: Grune & Stratton; 1978:97-108.
25. Mitnick PD, Klein WJ. Piroxicam-induced renal disease. Arch Intern Med. 1984; 144:63-4. [IDIS 179965] [PubMed 6691775]
26. Hoechst-Roussel. Streptase prescribing information. Somerville, NJ; 1980 Aug.
27. Pfizer. Feldene (piroxicam): the first one-a-day agent for rheumatoid arthritis and osteoarthritis. New York. 1983 Mar.
28. Wiseman EH, Hobbs DC. Review of pharmacokinetic studies with piroxicam. Am J Med. 1982; 72(2A):9-17. [IDIS 146274] [PubMed 6800256]
29. Reimann IW, Frolich JC. Effects of diclofenac on lithium kinetics. Clin Pharmacol Ther. 1981; 30:348-52. [IDIS 137530] [PubMed 7273598]
30. Rae SA, Williams IA, English J et al. Alteration of plasma prednisolone levels by indomethacin and naproxen. Br J Clin Pharmacol. 1982; 14:459-61. [IDIS 158831] [PubMed 7126420]
31. Merck, Sharp & Dohme. Indocin, Indocin SR prescribing information. West Point, PA. 1985 Oct.
32. Syntex. Naprosyn prescribing information. Palo Alto, CA. 1983 Apr.
33. Gosselin RE, Hodge HC, Smith RP et al. Clinical toxicology of commercial products. Acute poisoning. 5th ed. Baltimore: The Williams & Wilkins Co; 1984:I-10.
34. USP DI. Vol. 1: 1984 Drug information for the health care provider. Rockville, MD: The United States Pharmacopeial Convention, Inc; 1983:896-7.
35. The United States Pharmacopeial Convention, Inc. Piroxicam. Pharmacopeial Forum. 1984; 10:4058-9.
36. D’Ambrosio GG (Pfizer Laboratories, New York): Personal communication; 1984 Mar 29, Apr 11.
37. Jacotot B. Interaction of piroxicam with oral anticoagulants. Proceedings of the IXth European Congress of Rheumatology; 1979 September 4; Wiesbaden. New York: Academy Professional Information Services; 1980:46-8.
38. Widmark PH. Piroxicam: its safety and efficacy in the treatment of acute gout. Am J Med. 1982; 72(2A):63-5. [IDIS 146285] [PubMed 7058825]
39. Weintraub M, Case K, Kroening B et al. Effects of piroxicam on platelet aggregation. Clin Pharmacol Ther. 1978; 23:134-5.
40. Pomberg O. Comparison of piroxicam with indomethacin in ankylosing spondylitis: a double-blind crossover trial. Am J Med. 1982; 72(2A):58-62. [IDIS 146284] [PubMed 7058824]
41. Cash HC, Humpston D, Kasap HS. Feldene in the symptomatic treatment of primary dysmenorrhoea. Practitioner. 1982; 226:1338-41. [IDIS 158943] [PubMed 7050953]
42. Abramson S, Edelson H, Kaplan H et al. The neutrophil in rheumatoid arthritis: its role and the inhibition of its activation by nonsteroidal antiinflammatory drugs. Semin Arthritis Rheum. 1983; 13(Suppl 1):148-52. [PubMed 6312608]
43. Ostensen M. Piroxicam in human breast milk. Eur J Clin Pharmacol. 1983; 25:829-30. [IDIS 181122] [PubMed 6662182]
44. Stefanini M, Claustro LZ, Mulkey P. Bleeding tendency possibly related to increased plasma antithrombin III activity in patient treated with piroxicam. South Med J. 1984; 77:633-4. [IDIS 185553] [PubMed 6609435]
45. Martin RL, McSweeney GW, Schneider J. Fatal pemphigus vulgaris in a patient taking piroxicam. N Engl J Med. 1983; 309:795-6. [IDIS 175915] [PubMed 6888461]
46. MacDougall LG, Taylor-Smith A, Rothberg AD et al. Piroxicam poisoning in a 2-year-old child. South Afr Med J. 1984; 66:31-3.
47. Lanza Fl, and the Ad Hoc Committee on Practice Parameters of the American College of Gastroenterology. A guideline for the treatment and prevention of NSAID-induced ulcers. Am J Gastroenterol. 1998; 93:2037-46. [IDIS 417402] [PubMed 9820370]
48. The Upjohn Company. Motrin prescribing information. Kalamazoo, MI; 1985 Jul.
49. Clive DM, Stoff JS. Renal syndromes associated with nonsteroidal anti-inflammatory agents. N Engl J Med. 1984; 310:563-72. [IDIS 181748] [PubMed 6363936]
50. Adams DH, Michael J, Bacon PA et al. Non-steroidal anti-inflammatory drugs and renal failure. Lancet. 1986; 1:57-9. [IDIS 209841] [PubMed 2867313]
51. Fok KH, George PJM, Vicary FR. Peptic ulcers induced by piroxicam. BMJ. 1985; 290:117. [IDIS 195297] [PubMed 3917708]
52. Morgan AG. Peptic ulcers induced by piroxicam. BMJ. 1985; 290:564. [PubMed 3918675]
53. Emery P, Grahame R. Peptic ulcers induced by piroxicam. BMJ. 1985; 290:564. [PubMed 3918675]
54. Emery P, Grahame R. Gastrointestinal blood loss and piroxicam. Lancet. 1982; 1:1302-3. [IDIS 151182] [PubMed 6123039]
55. Laake K, Kjeldaas L, Borchgrevink CF. Side-effects of piroxicam (Feldene): a one-year material of 103 reports from Norway. Acta Med Scand. 1984; 215:81-3. [IDIS 181874] [PubMed 6695566]
56. Paulus HE. FDA Arthritis Advisory Committee Meeting: postmarketing surveillance of nonsteroidal antiinflammatory drugs. Arthritis Rheum. 1985; 28:1168-9. [IDIS 208792] [PubMed 4052129]
57. Settipane GA. Adverse reactions to aspirin and other drugs. Arch Intern Med. 1981; 141:328-32. [IDIS 142745] [PubMed 7008734]
58. Weinberger M. Analgesic sensitivity in children with asthma. Pediatrics. 1978; 62(Suppl):910-5. [IDIS 118712] [PubMed 103067]
59. Settipane GA. Aspirin and allergic diseases: a review. Am J Med. 1983; 74(Suppl):102-9. [IDIS 171763] [PubMed 6344621]
60. VanArsdel PP Jr. Aspirin idiosyncracy and tolerance. J Allergy Clin Immunol. 1984; 73:431-3. [IDIS 183975] [PubMed 6423718]
61. Stevenson DD. Diagnosis, prevention, and treatment of adverse reactions to aspirin and nonsteroidal anti-inflammatory drugs. J Allergy Clin Immunol. 1984; 74(4 Part 2):617-22. [IDIS 193318] [PubMed 6436354]
62. Stevenson DD, Mathison DA. Aspirin sensitivity in asthmatics: when may this drug be safe? Postgrad Med. 1985; 78:111-3,116-9. (IDIS 205854)
63. Pleskow WW, Stevenson DD, Mathison DA et al. Aspirin desensitization in aspirin-sensitive asthmatic patients: clinical manifestations and characterization of the refractory period. J Allergy Clin Immunol. 1982; 69(1 Part 1):11-9. [IDIS 144037] [PubMed 7054250]
64. Rossi AC, Hsu JP, Faich GA. Ulcerogenicity of piroxicam: an analysis of spontaneously reported data. BMJ. 1987; 294:147-50. [IDIS 225509] [PubMed 3109543]
65. Palmer JF. Letter sent to Wolleben J, of Pfizer Pharmaceutical regarding labeling revisions about gastrointestinal adverse reactions to Feldene (piroxicam). Rockville, MD: Food and Drug Administration, Division of Oncology and Radiopharmaceutical Drug Products. 1988 Sep.
66. Anon. Labeling revisions for NSAIDs. FDA Drug Bull. 1989; 19:3-4.
67. Searle. Cytotec (misoprostol) prescribing information. Skokie, IL; 1989 Jan.
68. Anon. Drugs for rheumatoid arthritis. Med Lett Drugs Ther. 2000; 42:57-64. [PubMed 10887424]
69. Saw KC, Quick CRG, Higgins AF. Ileocaecal perforation and bleeding are non-steroidal anti-inflammatory drugs (NSAIDs) responsible? J R Soc Med. 1990; 83:114-5.
70. Stubb S, Reitamo S. Fixed drug eruption caused by piroxicam. J Am Acad Dermatol. 1990; 22:1111-2. [PubMed 2142495]
71. Soll AH, Weinstein WM, Kurata J et al. Nonsteroidal anti-inflammatory drugs and peptic ulcer disease. Ann Intern Med. 1991; 114:307-19. [IDIS 277370] [PubMed 1987878]
72. Nonsteroidal anti-inflammatory drug interactions: Lithium. In: Hansten PD, Horn JR. Drug interactions and updates. Vancouver, WA: Applied Therapeutics, Inc; 1993:609-10.
73. Lithium/NSAIDs. In: Tatro DS, Olin BR, Hebel SK eds. Drug interaction facts. St. Louis: JB Lippincott Co; 1993(April):463.
74. Miller LG, Bowman RC, Bakht F. Sparing effect of sulindac on lithium levels. J Fam Prac. 1989; 28:592-3.
75. Stein G, Robertson M, Nadarajah J. Toxic interactions between lithium and non-steroidal anti-inflammatory drugs. Psych Med. 1988; 18:535-43.
76. Khan IH. Lithium and non-steroidal anti-inflammatory drugs. BMJ. 1991; 302:1537-8. [IDIS 282630] [PubMed 1855032]
77. Kerry RJ, Owen G, Michaelson S. Possible toxic interaction between lithium and piroxicam. Lancet. 1983; 1:418-9. [IDIS 165621] [PubMed 6130411]
78. Harrison TM, Davies DW, Norris CM. Lithium carbonate and piroxicam. Br J Psychiatry. 1986; 149:124-5. [PubMed 3096415]
79. Nadarajah J, Stein GS. Piroxicam induced lithium toxicity. Ann Rheum Dis. 1985; 44:502. [IDIS 204022] [PubMed 4026412]
80. Ciba Geigy, Ardsley, NY: Personal communication on diclofenac 28:08.04.
81. Reviewers’ comments (personal observations) on diclofenac 28:08.04.
82. Corticosteroid interactions: nonsteroidal anti-inflammatory drugs (NSAIDs). In: Hansten PD, Horn JR. Drug interactions and updates. Vancouver, WA: Applied Therapeutics, Inc; 1993:562.
83. Garcia Rodriguez LA, Jick H. Risk of upper gastrointestinal bleeding and perforation associated with individual non-steroidal anti-inflammatory drugs. Lancet. 1994; 343:769-72. [IDIS 328176] [PubMed 7907735]
84. Hollander D. Gastrointestinal complications of nonsteroidal anti-inflammatory drugs: prophylactic and therapeutic strategies. Am J Med. 1994; 96:274-81. [IDIS 328041] [PubMed 8154516]
85. Schubert TT, Bologna SD, Yawer N et al. Ulcer risk factors: interaction between Helicobacter pylori infection, nonsteroidal use, and age. Am J Med. 1993; 94:413-7. [IDIS 314155] [PubMed 8475935]
86. Piper JM, Ray WA, Daugherty JR et al. Corticosteroid use and peptic ulcer disease: role of nonsteroidal anti-inflammatory drugs. Ann Intern Med. 1991; 114:735-40. [IDIS 280191] [PubMed 2012355]
87. Bateman DN, Kennedy JG. Non-steroidal anti-inflammatory drugs and elderly patients: the medicine may be worse than the disease. BMJ. 1995; 310:817-8. [IDIS 345154] [PubMed 7711609]
88. Hawkey CJ. COX-2 inhibitors. Lancet. 1999; 353:307-14. [IDIS 418284] [PubMed 9929039]
89. Kurumbail RG, Stevens AM, Gierse JK et al. Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents. Nature. 1996; 384:644-8. [PubMed 8967954]
90. Riendeau D, Charleson S, Cromlish W et al. Comparison of the cyclooxygenase-1 inhibitory properties of nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors, using sensitive microsomal and platelet assays. Can J Physiol Pharmacol. 1997; 75:1088-95. [PubMed 9365818]
91. DeWitt DL, Bhattacharyya D, Lecomte M et al. The differential susceptibility of prostaglandin endoperoxide H synthases-1 and -2 to nonsteroidal anti-inflammatory drugs: aspirin derivatives as selective inhibitors. Med Chem Res. 1995; 5:325-43.
92. Cryer B, Dubois A. The advent of highly selective inhibitors of syclooxygenase—a review. Prostaglandins Other Lipid Mediators. 1998; 56:341-61. [PubMed 9990677]
93. Simon LS. Role and regulation of cyclooxygenase-2 during inflammation. Am J Med. 1999; 106(Suppl 5B):37-42S.
94. Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. N Engl J Med. 1999; 340:1888-99. [IDIS 426864] [PubMed 10369853]
95. Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and lactation. 5th ed. Baltimore, MD: Williams & Wilkins; 1998:875-6.
96. Mylan. Meclofenamate sodium capsules prescribing information. Morgantown, WV; 1998 Jun.
97. Piroxicam (Feldene) interactions: warfarin (Coumadin). In: Hansten PD, Horn JR. Drug interactions and updates. Vancouver, WA: Applied Therapeutics, Inc; 1997:440-1.
98. Furosemide (Lasix) interactions: Indomethacin (Indocin). In: Hansten PD, Horn JR. Drug interactions and updates. Vancouver, WA: Applied Therapeutics, Inc; 1997:308-9.
99. Tracy TS, Worster T, Bradley JD et al. Methotrexate disposition following concomitant administration of ketoprofen, piroxicam, and flurbiprofen in patients with rheumatoid arthritis. Br J Clin Pharmac. 1994; 37:453-6.
100. Kremer JM and Hamilton RA. The effects of nonsteroidal antiinflammatory drugs on methotrexate (MTX) pharmacokinetics: impairment of renal clearance of MTX at weekly maintenance doses but not at 7.5 mg. J Rheumatol. 1995; 22:2072-7. [IDIS 358403] [PubMed 8596147]
101. Aspirin interactions: Captopril (Capoten). In: Hansten PD, Horn JR. Drug interactions and updates. Vancouver, WA: Applied Therapeutics, Inc; 1997:62-3.
102. Singh G, Triadafilopoulos G. Epidemiology of NSAID induced gastrointestinal complications. J Rheumatol. 1999; 26(suppl 56):18-24.
103. in’t Veld BA, Ruitenberg A, Hofman A et al. Nonsteroidal antiinflammatory drugs and the risk of Alzheimer’s disease. N Engl J Med. 2001; 345:1515-21. [PubMed 11794217]
104. Breitner JCS, Zandi PP. Do nonsteroidal antiinflammatory drugs reduce the risk of Alzheimer’s disease? N Engl J Med. 2001; 345:1567-8. Editorial.
105. McGeer PL, Schulzer M, McGeer EG. Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer’s disease: a review of 17 epidemiologic studies. Neurology. 1996; 47:425-32. [IDIS 371394] [PubMed 8757015]
106. Beard CM, Waring SC, O’sBrien PC et al. Nonsteroidal anti-inflammatory drug use and Alzheimer’s disease: a case-control study in Rochester, Minnesota, 1980 through 1984. Mayo Clin Proc. 1998; 73:951-5. [IDIS 416502] [PubMed 9787743]
107. in’t Veld BA, Launer LJ, Hoes AW et al. NSAIDs and incident Alzheimer’s disease: the Rotterdam Study. Neurobiol Aging. 1998; 19:607-11. [PubMed 10192221]
108. Stewart WF, Kawas C, Corrada M et al. Risk of Alzheimer’s disease and duration of NSAID use. Neurology. 1997; 48:626-32. [IDIS 383303] [PubMed 9065537]
109. Pharmacia. Daypro (oxaprozin) caplets prescribing information. Chicago, IL; 2002 May.
110. Chan FKL, Hung LCT, Suen BY et al. Celecoxib versus diclofenac and omeprazole in reducing the risk of recurrent ulcer bleeding in patients with arthritis. N Engl J Med. 2002; 347:2104-10. [IDIS 490812] [PubMed 12501222]
111. Graham DY. NSAIDs, Helicobacter pylori, and Pandora’s box. N Engl J Med. 2002; 347:2162-4. [IDIS 490815] [PubMed 12501230]
112. Food and Drug Administration. Analysis and recommendations for agency action regarding non-steroidal anti-inflammatory drugs and cardiovascular risk. 2005 Apr 6.
113. Cush JJ. The safety of COX-2 inhibitors: deliberations from the February 16-18, 2005, FDA meeting. From the American College of Rheumatology website (). Accessed 2005 Oct 12.
114. Novartis Pharmaceuticals. Diovan (valsartan) capsules prescribing information (dated 1997 Apr). In: Physicians’ desk reference. 53rd ed. Montvale, NJ: Medical Economics Company Inc; 1999:2013-5.
115. McGettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of observational studies of selective and nonselective inhibitors of cyclooxygenase 2. JAMA. 2006; 296: 1633-44. [PubMed 16968831]
116. Kearney PM, Baigent C, Godwin J et al. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ. 2006; 332: 1302-5. [PubMed 16740558]
117. Graham DJ. COX-2 inhibitors, other NSAIDs, and cardiovascular risk; the seduction of common sense. JAMA. 2006; 296:1653-6. [PubMed 16968830]
118. Merck & Co. Clinoril (sulindac) tablets prescribing information. Whitehouse Station, NJ; 2006 Feb.
119. Chou R, Helfand M, Peterson K et al. Comparative effectiveness and safety of analgesics for osteoarthritis. Comparative effectiveness review no. 4. (Prepared by the Oregon evidence-based practice center under contract no. 290-02-0024.) . Rockville, MD: Agency for Healthcare Research and Quality. 2006 Sep. Available at: .