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Sprix (ketorolac) Disease Interactions

There are 12 disease interactions with Sprix (ketorolac):

Major

Ketorolac (Includes Sprix) ↔ Gi Toxicity

Severe Potential Hazard, High plausibility

Applies to: Duodenitis/Gastritis, Gastrointestinal Hemorrhage, Gastrointestinal Perforation, History - Peptic Ulcer, Peptic Ulcer, Alcoholism, Colitis/Enteritis (Noninfectious), Colonic Ulceration

The use of ketorolac is contraindicated in patients with active peptic ulcers, recent gastrointestinal bleeding or perforation, or a history of peptic ulcer disease or gastrointestinal bleeding. Ketorolac is a potent nonsteroidal anti-inflammatory drug (NSAID). NSAIDs can cause gastrointestinal mucosal damage, the risk of which appears to be related to both dosage and duration of therapy. Serious GI toxicity such as bleeding, ulceration and perforation can occur at any time, with or without warning symptoms, in patients treated with ketorolac. Therapy with ketorolac should be considered and administered cautiously in patients with a history of GI inflammation or alcoholism, particularly if they are elderly and/or debilitated, since such patients may be more susceptible to the GI toxicity of NSAIDs and seem to tolerate ulceration and bleeding less well than other individuals. Close monitoring for toxicity is recommended during ketorolac therapy, which should be limited to 5 days regardless of the route of administration.

References

  1. Estes LL, Fuhs DW, Heaton AH, Butwinick CS "Gastric ulcer perforation associated with the use of injectable ketorolac." Ann Pharmacother 27 (1993): 42-3
  2. Fuller DK, Kalekas PJ "Ketorolac and gastrointestinal ulceration." Ann Pharmacother 27 (1993): 978-9
  3. Litvak KM, McEvoy GK "Ketorolac, an injectable nonnarcotic analgesic." Clin Pharm 9 (1990): 921-35
  4. Wolfe PA, Polhamus CD, Kubik C, Robinson AB, Clement DJ "Giant duodenal ulcers associated with the postoperative use of ketorolac: report of three cases." Am J Gastroenterol 89 (1994): 1110-1
  5. Wiedrick JE, Friesen EG, Garton AM, Otten NH "Upper gastrointestinal bleeding associated with oral ketorolac therapy." Ann Pharmacother 28 (1994): 1109
  6. Maliekal J, Elboim CM "Gastrointestinal complications associated with intramuscular ketorolac tromethamine therapy in the elderly." Ann Pharmacother 29 (1995): 698-701
  7. Buckley MM, Brogden RN "Ketorolac. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential." Drugs 39 (1990): 86-109
  8. Quigley EMM, Donovan JP, Livingston WC "Ketorolac-related giant gastric ulcers." Am J Gastroenterol 89 (1994): 631-2
  9. Sacanella E, Munoz F, Cardellach F, Estruch R, Miro O, Urbanomarquez A "Massive haemorrhage due to colitis secondary to nonsteroidal anti-inflammatory drugs." Postgrad Med J 72 (1996): 57-8
  10. Strom BL, Berlin JA, Kinman JL "Parenteral ketorolac and risk of gastrointestinal and operative site bleeding: a postmarketing surveillance study." JAMA 275 (1996): 376-82
  11. Singh G, Ramey DR, Morfeld D, Fries JF "Comparative toxicity of non-steroidal anti-inflammatory agents." Pharmacol Ther 62 (1994): 175-91
  12. "Product Information. Toradol (ketorolac)." Roche Laboratories, Nutley, NJ.
  13. Buchman AL, Schwartz MR "Colonic ulceration associated with the systemic use of nonsteroidal antiinflammatory medication." J Clin Gastroenterol 22 (1996): 224-6
View all 13 references
Major

Ketorolac (Includes Sprix) ↔ Platelet Aggregation Inhibition

Severe Potential Hazard, Moderate plausibility

Applies to: Bleeding, Coagulation Defect, Thrombocytopathy, Thrombocytopenia, Vitamin K Deficiency

The use of ketorolac is considered by the manufacturer to be contraindicated in patients with suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis, incomplete hemostasis, or a high risk of bleeding. Ketorolac is a potent nonsteroidal anti-inflammatory drug (NSAID). NSAIDs reversibly inhibit platelet adhesion and aggregation and may prolong bleeding time in healthy individuals. With the exception of aspirin, the platelet effects seen with most NSAIDs at usual recommended dosages are generally slight and of relatively short duration but may be more pronounced in patients with underlying hemostatic abnormalities. Thrombocytopenia has also been reported rarely during NSAID use. Therapy with NSAIDs, including ketorolac, should be administered cautiously in patients with significant active bleeding.

References

  1. "Product Information. Toradol (ketorolac)." Roche Laboratories, Nutley, NJ.
  2. Concannon MJ, Meng L, Welsh CF, Puckett CL "Inhibition of perioperative platelet aggregation using toradol (ketorolac)." Ann Plast Surg 30 (1993): 264-6
  3. Strom BL, Berlin JA, Kinman JL "Parenteral ketorolac and risk of gastrointestinal and operative site bleeding: a postmarketing surveillance study." JAMA 275 (1996): 376-82
  4. Litvak KM, McEvoy GK "Ketorolac, an injectable nonnarcotic analgesic." Clin Pharm 9 (1990): 921-35
  5. Thwaites BK, Nigus DB, Bouska GW, Mongan PD, Ayala EF, Merrill GA "Intravenous ketorolac tromethamine worsens platelet function during knee arthroscopy under spinal anesthesia." Anesth Analg 82 (1996): 1176-81
View all 5 references
Major

Ketorolac (Includes Sprix) ↔ Renal Dysfunction

Severe Potential Hazard, Moderate plausibility

Applies to: Congestive Heart Failure, Dehydration, Renal Dysfunction, Hyponatremia

The use of ketorolac is contraindicated in patients with advanced renal impairment or increased risk for renal failure due to volume depletion. Ketorolac is a potent nonsteroidal anti-inflammatory drug (NSAID). The use of NSAIDs may be associated with renal toxicities, including elevations in serum creatinine and BUN, tubular necrosis, glomerulitis, renal papillary necrosis, acute interstitial nephritis, nephrotic syndrome, and renal failure. In patients with prerenal conditions whose renal perfusion may be dependent on the function of renal prostaglandins, NSAIDs may precipitate overt renal decompensation via a dose-related inhibition of prostaglandin synthesis. Patients at greatest risk for this reaction include geriatric patients and those with impaired renal function, heart failure, liver dysfunction, or substantial volume and/or sodium depletion (e.g., due to diuretics). Therapy with ketorolac should be administered cautiously in such patients, and hypovolemia and hyponatremia should be corrected prior to initiating treatment. Clinical monitoring of renal function is recommended during therapy. If renal function declines or renal failure occurs, prompt discontinuation of ketorolac therapy will usually lead to recovery to the pretreatment state. Since ketorolac and its metabolites are eliminated by the kidney, a reduction to half the normal dosage with a maximum of 60 mg/day is recommended in patients with moderately impaired renal function to avoid drug accumulation.

References

  1. Quan DJ, Kayser SR "Ketorolac induced acute renal failure following a single dose." J Toxicol Clin Toxicol 32 (1994): 305-9
  2. Brocks DR, Jamali F "Clinical pharmacokinetics of ketorolac tromethamine." Clin Pharmacokinet 23 (1992): 415-27
  3. Pearce CJ, Gonzalez FM, Wallin JD "Renal failure and hyperkalemia associated with ketorolac tromethamine." Arch Intern Med 153 (1993): 1000-2
  4. Jung D, Mroszczak E, Bynum L "Pharmacokinetics of ketorolac tromethamine in humans after intravenous, intramuscular and oral administration." Eur J Clin Pharmacol 35 (1988): 423-5
  5. Perneger TV, Whelton PK, Klag MJ "Risk of kidney failure associated with the use of acetaminophen, aspirin, and nonsteroidal antiinflammatory drugs." N Engl J Med 331 (1994): 1675-9
  6. Buller GK, Perazella MA "Acute renal failure and ketorolac." Ann Intern Med 127 (1997): 493
  7. Litvak KM, McEvoy GK "Ketorolac, an injectable nonnarcotic analgesic." Clin Pharm 9 (1990): 921-35
  8. Singh G, Ramey DR, Morfeld D, Fries JF "Comparative toxicity of non-steroidal anti-inflammatory agents." Pharmacol Ther 62 (1994): 175-91
  9. Fong J, Gora ML "Reversible renal insufficiency following ketorolac therapy." Ann Pharmacother 27 (1993): 510-2
  10. Boras-Uber LA, Brackett NC Jr "Ketorolac-induced acute renal failure." Am J Med 92 (1992): 450-2
  11. Haragsim L, Dalal R, Bagga H, Bastani B "Ketorolac-induced acute renal failure and hyperkalemia: report of three cases." Am J Kidney Dis 24 (1994): 578-80
  12. Martinez JJ, Garg DC, Pages LJ, et al "Single dose pharmacokinetics of ketorolac in healthy young and renal impaired subjects." J Clin Pharmacol 27 (1987): 722
  13. Aitken HA, Burns JW, McArdle CS, Kenny GNC "Effects of ketorolac trometamol on renal function." Br J Anaesth 68 (1992): 481-5
  14. Feldman HI, Kinman JL, Berlin JA, et al. "Parenteral ketorolac: the risk for acute renal failure." Ann Intern Med 126 (1997): 193-9
  15. "Product Information. Toradol (ketorolac)." Roche Laboratories, Nutley, NJ.
  16. Buck ML, Norwood VF "Ketorolac-induced acute renal failure in a previously healthy adolescent." Pediatrics 98 (1996): 294-6
  17. Feldman HI, Kinman JL, Strom BL "Acute renal failure and ketorolac." Ann Intern Med 127 (1997): 493-4
  18. Myles PS, Power I "Does ketorolac cause postoperative renal failure: how do we assess the evidence?" Br J Anaesth 80 (1998): 420-1
  19. Mroszczak EJ, Lee FW, Combs D, Sarnquist FH, Huang BL, Wu AT, Tokes LG, Maddox ML, Cho DK "Ketorolac tromethamine absorption, distribution, metabolism, excretion, and pharmacokinetics in animals and humans." Drug Metab Dispos 15 (1987): 618-26
  20. Jung D, Mroszczak EJ, Wu A, Ling TL, Sevelius H, Bynum L "Pharmacokinetics of ketorolac and p-hydroxyketorolac following oral and intramuscular administration of ketorolac tromethamine." Pharm Res 6 (1989): 62-5
  21. Kelley M, Bastani B "Ketorolac-induced acute renal failure and hyperkalemia." Clin Nephrol 44 (1995): 276-7
  22. Jallad NS, Garg DC, Martinez JJ, Mroszczak EJ, Weidler DJ "Pharmacokinetics of single-dose oral and intramuscular ketorolac tromethamine in the young and elderly." J Clin Pharmacol 30 (1990): 76-81
View all 22 references
Major

Nsaids (Includes Sprix) ↔ Asthma

Severe Potential Hazard, High plausibility

Applies to: Asthma

Approximately 10% of patients with asthma may have aspirin-sensitive asthma, characterized by nasal polyposis, pansinusitis, eosinophilia, and precipitation of asthma and rhinitis attacks after ingestion of aspirin. The use of aspirin in these patients has been associated with severe bronchospasm and fatal anaphylactoid reactions. Since cross-sensitivity has been noted between aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), therapy with any NSAID should be avoided in asthmatic patients with a history of aspirin or other NSAID sensitivity, and administered cautiously in all patients with preexisting asthma. Prior to initiating therapy with NSAIDs, patients should be questioned about previous allergic-type reactions to these agents. Salicylate salts, salsalate, salicylamide, and acetaminophen may be appropriate alternatives in patients with a history of NSAID-induced bronchospasm, since cross-sensitivity to these agents appears to be low. However, cross-sensitivity has been demonstrated occasionally with high dosages of these agents (e.g., acetaminophen >= 1000 mg), thus it may be appropriate to initiate therapy with low dosages and increase gradually. There is some evidence suggesting that COX-2 inhibitors may be safely used in patients with aspirin-sensitive asthma, although the labeling for these products contraindicate such use. If necessary, aspirin desensitization may also be attempted in some patients under medical surveillance.

References

  1. Stevenson DD, Simon RA "Lack of cross-reactivity between rofecoxib and aspirin in aspirin-sensitive patients with asthma." J Allerg Clin Immunol 108 (2001): 47-51
  2. "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn, Kalamazoo, MI.
  3. "Product Information. Naprosyn (naproxen)." Syntex Laboratories Inc, Palo Alto, CA.
  4. Stevenson DD, Hougham AJ, Schrank PJ, Goldlust MB, Wilson RR "Salsalate cross-sensitivity in aspirin-sensitive patients with asthma." J Allergy Clin Immunol 86 (1990): 749-58
  5. "Product Information. Voltaren (diclofenac)." Novartis Pharmaceuticals, East Hanover, NJ.
  6. Fauci AS, Braunwald E, Isselbacher KJ, Wilson JD, Martin JB, Kasper DL, Hauser SL, Longo DL, eds. "Harrison's Principles of Internal Medicine. 14th ed." New York, NY: McGraw-Hill Health Professionals Division (1998):
  7. "Product Information. Clinoril (sulindac)." Merck & Co, Inc, West Point, PA.
  8. "Product Information. Feldene (piroxicam)." Pfizer US Pharmaceuticals, New York, NY.
  9. Lewis RV "Severe asthma after naproxen." Lancet 05/30/87 (1987): 1270
  10. Carmona MJ, Blanca M, Garcia A, Fernandez S, Burgos F, Miranda A, Vega JM, Garcia J "Intolerance to piroxicam in patients with adverse reactions to nonsteroidal antiinflammatory drugs." J Allergy Clin Immunol 90 (1992): 873-9
  11. Israel E, Fischer AR, Rosenberg MA, Lilly CM, Callery JC, Shapiro J, Cohn J, Rubin P, Drazen JM "The pivotal role of 5-lipoxygenase products in the reaction of aspirin-sensitive asthmatics to aspirin." Am Rev Respir Dis 148 (1993): 1447-51
  12. Haddow GR, Riley E, Isaacs R, McSharry R "Ketorolac, nasal polyposis, and bronchial asthma: a cause for concern." Anesth Analg 76 (1993): 420-2
  13. Settipane RA, Stevenson DD "Cross sensitivity with acetaminophen in aspirin-sensitive subjects with asthma." J Allergy Clin Immunol 84 (1989): 26-33
  14. "Product Information. Mobic (meloxicam)" Boehringer-Ingelheim, Ridgefield, CT.
  15. Cohen RD, Bateman ED, Potgieter PD "Near-fatal bronchospasm in an asthmatic patient following ingestion of flurbiprofen. A case report." S Afr Med J 61 (1982): 803
  16. "Product Information. Bextra (valdecoxib)." Pharmacia Corporation, Peapack, NJ.
  17. Schreuder G "Ketoprofen: possible idiosyncratic acute bronchospasm." Med J Aust 152 (1990): 332-3
  18. "Product Information. Ansaid (flurbiprofen)." Pharmacia and Upjohn, Kalamazoo, MI.
  19. Dahlen B, Szczeklik A, Murray HH "Celecoxib in patients with asthma and aspirin intolerance." N Engl J Med 344 (2000): 142
  20. "Product Information. Indocin (indomethacin)." Merck & Co, Inc, West Point, PA.
  21. Ayres JG, Fleming DM, Whittington RM "Asthma death due to ibuprofen." Lancet 05/09/87 (1987): 1082
  22. "Product Information. Daypro (oxaprozin)." Searle, Skokie, IL.
  23. "Product Information. Vioxx (rofecoxib)." Merck & Co, Inc, West Point, PA.
  24. Shapiro N "Acute angioedema after ketorolac ingestion - report of case." J Oral Maxillofac Surg 52 (1994): 626-7
  25. Lee TH "Mechanism of aspirin sensitivity." Am Rev Respir Dis 145 (1992): s34-6
  26. "Product Information. Celebrex (celecoxib)." Searle, Chicago, IL.
  27. Szczeklik A, Stevenson DD "Aspirin-induced asthma: Advances in pathogenesis and management." J Allerg Clin Immunol 104 (1999): 5-13
  28. Salberg DJ, Simon MR "Severe asthma induced by naproxen: a case report and review of the literature." Ann Allergy 45 (1980): 372-5
  29. "Product Information. Tolectin (tolmetin)." McNeil Pharmaceutical, Raritan, NJ.
  30. "Product Information. Relafen (nabumetone)." SmithKline Beecham, Philadelphia, PA.
  31. Nasser SMS, Lee TH "Aspirin-induced early and late asthmatic responses." Clin Exp Allergy 25 (1995): 1-3
  32. Chan TY "Severe asthma attacks precipitated by NSAIDs." Ann Pharmacother 29 (1995): 199
  33. Zikowski D, Hord AH, Haddox JD, Glascock J "Ketorolac-induced bronchospasm." Anesth Analg 76 (1993): 417-9
  34. "Product Information. Orudis (ketoprofen)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  35. Lee TH "Mechanism of bronchospasm in aspirin-sensitive asthma." Am Rev Respir Dis 148 (1993): 1442-3
  36. "Product Information. Nalfon (fenoprofen)." Xspire Pharma, Ridgeland, MS.
  37. Woessner KM, Simon RA, Stevenson DD "The safety of celecoxib in patients with aspirin-sensitive asthma." Arthritis Rheum 46 (2002): 2201-6
  38. "Product Information. Lodine (etodolac)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
View all 38 references
Major

Nsaids (Includes Sprix) ↔ Fluid Retention

Severe Potential Hazard, Moderate plausibility

Applies to: Congestive Heart Failure, Hypertension, Fluid Retention

Fluid retention and edema have been reported in association with the use of nonsteroidal anti-inflammatory drugs (NSAIDs). Therapy with NSAIDs should be administered cautiously in patients with preexisting fluid retention, hypertension, or a history of heart failure. Blood pressure and cardiovascular status should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.

References

  1. "Product Information. Orudis (ketoprofen)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  2. Heerdink ER, Leufkens HG, Herings RM, Ottervanger JP, Stricker BH, Bakker A "NSAIDs associated with increased risk of congestive heart failure in elderly patients taking diuretics." Arch Intern Med 158 (1998): 1108-12
  3. Johnson AG, Nguyen TV, Day RO "Do nonsteroidal anti-inflammatory drugs affect blood pressure? A meta-analysis." Ann Intern Med 121 (1994): 289-300
  4. "Product Information. Nalfon (fenoprofen)." Xspire Pharma, Ridgeland, MS.
  5. "Product Information. Anaprox (naproxen)." Roche Laboratories, Nutley, NJ.
  6. "Product Information. Feldene (piroxicam)." Pfizer US Pharmaceuticals, New York, NY.
  7. Agnholt J, Andreasen F "The effect of ibuprofen therapy on water and electrolyte balance." Acta Med Scand 212 (1982): 65-9
  8. "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn, Kalamazoo, MI.
  9. Lewis RV, Toner JM, Jackson PR, Ramsay LE "Effects of indomethacin and sulindac on blood pressure of hypertensive patients." Br Med J 292 (1986): 934-5
  10. "Product Information. Lodine (etodolac)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  11. "Product Information. Celebrex (celecoxib)." Searle, Chicago, IL.
  12. "Product Information. Mobic (meloxicam)" Boehringer-Ingelheim, Ridgefield, CT.
  13. "Product Information. Daypro (oxaprozin)." Searle, Skokie, IL.
  14. Gurwitz JH, Everitt DE, Monane M, et al "The impact of ibuprofen on the efficacy of antihypertensive treatment with hydrochlorothiazide in elderly persons." J Gerontol A Biol Sci Med Sci 51 (1996): m74-9
  15. "Product Information. Ansaid (flurbiprofen)." Pharmacia and Upjohn, Kalamazoo, MI.
  16. "Product Information. Naprosyn (naproxen)." Syntex Laboratories Inc, Palo Alto, CA.
  17. Heynen G "Toleration and safety of piroxicam." Eur J Rheumatol Inflamm 8 (1987): 86-93
  18. "Product Information. Vioxx (rofecoxib)." Merck & Co, Inc, West Point, PA.
  19. Van Den Ouweland FA, Gribnau FW, Meyboom RH "Congestive heart failure due to nonsteroidal anti-inflammatory drugs in the elderly." Age Ageing 17 (1988): 8-16
  20. Easton PA, Koval A "Hypertensive reaction with sulindac." Can Med Assoc J 122 (1980): 1273-4
  21. Brooks CD, Linet OI, Schellenberg D, Turner LF, Defesche CL, Teoh KW, Johnson JH, Assenzo JR "Clinical safety of flurbiprofen." J Clin Pharmacol 30 (1990): 342-51
  22. Petersson I, Nilsson G, Hansson B-G, Hedner T "Water intoxication associated with non-steroidal anti-inflammatory drug therapy." Acta Med Scand 221 (1987): 221-3
  23. Buckley MM, Brogden RN "Ketorolac. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential." Drugs 39 (1990): 86-109
  24. "Product Information. Tolectin (tolmetin)." McNeil Pharmaceutical, Raritan, NJ.
  25. "Product Information. Relafen (nabumetone)." SmithKline Beecham, Philadelphia, PA.
  26. "Product Information. Bextra (valdecoxib)." Pharmacia Corporation, Peapack, NJ.
  27. Willkens RF "Worldwide clinical safety experience with diclofenac." Semin Arthritis Rheum 2 Suppl 1 (1985): 105-10
  28. "Product Information. Clinoril (sulindac)." Merck & Co, Inc, West Point, PA.
  29. "Product Information. Indocin (indomethacin)." Merck & Co, Inc, West Point, PA.
View all 29 references
Major

Nsaids (Includes Sprix) ↔ Rash

Severe Potential Hazard, High plausibility

Applies to: Dermatitis - Drug-Induced

Severe, potentially fatal dermatologic reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and other exfoliative dermatitis have been associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs). These events may occur without warning. Patients should be advised to discontinue the NSAID and seek medical attention promptly at the first sign of rash, blisters, fever, itching, or any other sign of hypersensitivity.

References

  1. "Product Information. Indocin (indomethacin)." Merck & Co, Inc, West Point, PA.
  2. "Product Information. Relafen (nabumetone)." SmithKline Beecham, Philadelphia, PA.
  3. "Product Information. Tolectin (tolmetin)." McNeil Pharmaceutical, Raritan, NJ.
  4. "Product Information. Voltaren (diclofenac)." Novartis Pharmaceuticals, East Hanover, NJ.
  5. "Product Information. Mobic (meloxicam)" Boehringer-Ingelheim, Ridgefield, CT.
  6. "Product Information. Feldene (piroxicam)." Pfizer US Pharmaceuticals, New York, NY.
  7. "Product Information. Ansaid (flurbiprofen)." Pharmacia and Upjohn, Kalamazoo, MI.
  8. "Product Information. Clinoril (sulindac)." Merck & Co, Inc, West Point, PA.
  9. "Product Information. Celebrex (celecoxib)." Searle, Chicago, IL.
  10. "Product Information. Daypro (oxaprozin)." Searle, Skokie, IL.
  11. Friedman B, Orlet HK, Still JM, Law E "Toxic epidermal necrolysis due to administration of celecoxib (Celebrex)." South Med J 95 (2002): 1213-4
  12. "Product Information. Naprosyn (naproxen)." Syntex Laboratories Inc, Palo Alto, CA.
  13. "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn, Kalamazoo, MI.
  14. "Product Information. Orudis (ketoprofen)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  15. "Product Information. Lodine (etodolac)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  16. "Product Information. Nalfon (fenoprofen)." Xspire Pharma, Ridgeland, MS.
View all 16 references
Major

Nsaids (Includes Sprix) ↔ Thrombosis

Severe Potential Hazard, High plausibility

Applies to: Cerebrovascular Insufficiency, History - Cerebrovascular Disease, History - Myocardial Infarction, Ischemic Heart Disease

The use of nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with an increased risk of cardiovascular thrombotic events such as myocardial infarction and stroke, which can be fatal. The risk may increase with duration of use. Clinical trials of several cyclooxygenase-2 (COX-2) selective and nonselective NSAIDs of up to three years duration have supported this association. Although not all NSAIDs have been studied, investigators believe it may be a class effect, and that the risk may be similar for all NSAIDs, both COX-2 selective and nonselective. Therapy with NSAIDs should be administered cautiously in patients with a history of cardiovascular or cerebrovascular disease. Patients should be treated with the lowest effective dosage for the shortest duration necessary. Appropriate antiplatelet therapy should be administered to patients requiring cardioprotection. However, there is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious cardiovascular thrombotic events associated with NSAID use, while the risk of serious GI events is increased. Patients should be advised to promptly seek medical attention if they experience symptoms that could indicate a cardiovascular thrombotic event such as chest pain, shortness of breath, weakness, and slurring of speech.

NSAIDs are contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery. Two large clinical trials of a COX-2 inhibitor for the treatment of pain in the first 10 to 14 days following CABG surgery found an increased incidence of myocardial infarction and stroke.

References

  1. Fitzgerald GA, Patrono C "The coxibs, selective inhibitors of cyclooxsygenase-2." N Engl J Med 345 (2001): 433-42
  2. Marcus AJ, Broekman MJ, Pinsky DJ "COX inhibitors and thromboregulation." N Engl J Med 347 (2002): 1025-6
  3. "Product Information. Vioxx (rofecoxib)." Merck & Co, Inc, West Point, PA.
  4. Mukherjee D, Nissen SE, Topol EJ "Risk of cardiovascular events associated with selective COX-2 inhibitors." JAMA 286 (2001): 954-9
  5. Bombardier C, Laine L, Reicin A, et al. "Comparison of upper gastrointestinal toxicity of refecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group." N Engl J Med 343 (2000): 1520-8
  6. Silverstein FE, Faich G, Goldstein JL, et al. "Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthtitis and rheumatoid arthritis. The CLASS Study: a randomized controlled trial." JAMA 284 (2000): 1247-55
View all 6 references
Moderate

Nsaids (Includes Sprix) ↔ Anemia

Moderate Potential Hazard, Moderate plausibility

Applies to: Anemia, Bleeding

Dose-dependent decreases in serum hemoglobin and hematocrit have been observed in patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs). Anemia has been reported occasionally. The mechanism may involve NSAID-induced fluid retention or gastrointestinal blood loss, or an incompletely described effect on erythropoiesis. The decreases in hemoglobin concentration tend to be slight with average doses but may exceed 1 g/dL when large doses are given, such as those used to treat osteoarthritis or rheumatoid arthritis. Although these effects are generally not clinically important in otherwise healthy individuals, they may be relevant in patients with preexisting anemia or substantial blood loss. Therapy with NSAIDs should be administered cautiously in patients with or predisposed to anemia. Clinical monitoring of hematopoietic function may be appropriate, particularly during chronic therapy.

References

  1. Johnson FP Jr, Hamilton HE, Liesch MR "Immune hemolytic anemia associated with sulindac." Arch Intern Med 145 (1985): 1515-6
  2. "Product Information. Celebrex (celecoxib)." Searle, Chicago, IL.
  3. "Product Information. Indocin (indomethacin)." Merck & Co, Inc, West Point, PA.
  4. "Product Information. Relafen (nabumetone)." SmithKline Beecham, Philadelphia, PA.
  5. Catalano MA "Worldwide safety experience with diclofenac." Am J Med 80 (1986): 81-7
  6. "Product Information. Lodine (etodolac)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  7. Eustace S, O'Neill T, McHale S, Molony J "Fatal aplastic anaemia following prolonged diclofenac use in an elderly patient." Ir J Med Sci 158 (1989): 217
  8. "Product Information. Ansaid (flurbiprofen)." Pharmacia and Upjohn, Kalamazoo, MI.
  9. Salom IL, Jacob G, Jallad N, Perdomo CA, Mullane JF, Weidler D "Gastrointestinal microbleeding associated with the use of etodolac, ibuprofen, indomethacin, and naproxen in normal males." J Clin Pharmacol 24 (1984): 240-6
  10. "Product Information. Bextra (valdecoxib)." Pharmacia Corporation, Peapack, NJ.
  11. "Product Information. Clinoril (sulindac)." Merck & Co, Inc, West Point, PA.
  12. Squires JE, Mintz PD, Clark S "Tolmetin-induced hemolysis." Transfusion 25 (1985): 410-3
  13. Randi ML, Tison T, Luzzatto G "Haemolytic uraemic syndrome during treatment with ketorolac trometamol." BMJ 306 (1993): 186
  14. Kornberg A, Rachmilewitz EA "Aplastic anemia after prolonged ingestion of indomethacin." Acta Haematol 67 (1982): 136-8
  15. Bernhard GC "Worldwide safety experience with nabumetone." J Rheumatol 19 (1992): 48-57
  16. Bennett L, Schlossman R, Rosenthal J, et al "Aplastic anemia and sulindac." Ann Intern Med 92 (1980): 874
  17. Ashraf M, Pearson RM, Winfield DA "Aplastic anaemia associated with fenoprofen." Br Med J 284 (1982): 1301-2
  18. Andrews R, Russell N "Aplastic anaemia associated with a non-steroidal anti-inflammatory drug: relapse after exposure to another such drug." Br Med J 301 (1990): 38
  19. Sanz MA, Martinez JA, Gomis F, Garcia-Borras JJ "Sulindac-induced bone marrow toxicity." Lancet 2 (1980): 802-3
  20. Lee SH, Fawcett V, Preece JM "Aplastic anaemia associated with piroxicam." Lancet 1 (1982): 1186
  21. Arnold R, Heimpel H "Aplastic anaemia after naproxen?" Lancet 02/09/80 (1980): 321
  22. Miller JL "Marrow aplasia and sulindac." Ann Intern Med 92 (1980): 129
  23. Hughes JA, Sudell W "Hemolytic anemia associated with naproxen." Arthritis Rheum 26 (1983): 1054
  24. Kramer MR, Levene C, Hershko C "Severe reversible autoimmune haemolytic anaemia and thrombocytopenia associated with diclofenac therapy." Scand J Haematol 36 (1986): 118-20
  25. Reitz CL, Bottomley SS "Pure red cell aplasia associated with fenoprofen." Am J Med Sci 287 (1984): 62-3
  26. "Product Information. Toradol (ketorolac)." Roche Laboratories, Nutley, NJ.
  27. "Product Information. Naprosyn (naproxen)." Syntex Laboratories Inc, Palo Alto, CA.
  28. McNeil P, MacKenzie I, Manoharan A "Naproxen-associated aplastic anaemia." Med J Aust 145 (1986): 53-5
  29. "Product Information. Tolectin (tolmetin)." McNeil Pharmaceutical, Raritan, NJ.
  30. Angeles ML, Reid ME, Yacob UA, Cash KL, Fetten JV "Sulindac-induced immune hemolytic anemia." Transfusion 34 (1994): 255-8
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  32. "Product Information. Dolobid (diflunisal)." Merck & Co, Inc, West Point, PA.
  33. Sanada M, Takai K "Aplastic anaemia associated with piroxicam." Br J Haematol 77 (1991): 256-7
  34. Brooks CD, Linet OI, Schellenberg D, Turner LF, Defesche CL, Teoh KW, Johnson JH, Assenzo JR "Clinical safety of flurbiprofen." J Clin Pharmacol 30 (1990): 342-51
  35. Schattenkirchner M "An updated safety profile of etodolac in several thousand patients." Eur J Rheumatol Inflamm 10 (1990): 56-65
  36. Gerber D "Adverse reactions of piroxicam." Drug Intell Clin Pharm 21 (1987): 707-10
  37. Lopez A, Linares M, Sanchez H, Blanquer A "Autoimmune hemolytic anemia induced by diclofenac." Ann Pharmacother 29 (1995): 787
  38. Lussier A, LeBel E "Radiochromium (chromium-51) evaluation of gastrointestinal blood loss associated with placebo, aspirin, and nabumetone." Am J Med 83 (1987): 15-8
  39. "Product Information. Vioxx (rofecoxib)." Merck & Co, Inc, West Point, PA.
  40. "Product Information. Voltaren (diclofenac)." Novartis Pharmaceuticals, East Hanover, NJ.
  41. Schattner A, Shtalrid M, Levy R, Berrebi A "Fatal aplastic anemia due to indomethacin: lymphocyte transformation tests in vitro." Isr J Med Sci 17 (1981): 433-6
  42. "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn, Kalamazoo, MI.
  43. Green D, Davies RO, Holmes GI et al "Effects of diflunisal on platelet function and fecal blood loss." Pharmacotherapy 3 (1983): s65-9
  44. "Product Information. Nalfon (fenoprofen)." Xspire Pharma, Ridgeland, MS.
  45. "Product Information. Feldene (piroxicam)." Pfizer US Pharmaceuticals, New York, NY.
  46. "Product Information. Daypro (oxaprozin)." Searle, Skokie, IL.
  47. "Product Information. Orudis (ketoprofen)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  48. Salama A, Gottsche B, Mueller-Eckhardt C "Autoantibodies and drug- or metabolite-dependent antibodies in patients with diclofenac-induced immune haemolysis." Br J Haematol 77 (1991): 546-9
  49. "Product Information. Mobic (meloxicam)" Boehringer-Ingelheim, Ridgefield, CT.
View all 49 references
Moderate

Nsaids (Includes Sprix) ↔ Heart Failure

Moderate Potential Hazard, Moderate plausibility

Applies to: Congestive Heart Failure

Fluid retention and edema have been observed in patients treated with NSAIDs, including some topical formulations. These drugs should be used with caution in patients with fluid retention or heart failure.

Moderate

Nsaids (Includes Sprix) ↔ Hepatotoxicity

Moderate Potential Hazard, Moderate plausibility

Applies to: Liver Disease

Borderline elevations of serum transaminases, LDH, and alkaline phosphatase have been reported in up to 15% of patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs). These abnormalities may progress, remain unchanged, or regress with continuing therapy. Notable liver enzyme elevations exceeding 3 times the upper limit of normal have been reported in approximately 1% of patients in clinical trials. In addition, rare cases of severe hepatotoxicity, including liver necrosis, hepatic failure, jaundice and fatal fulminant hepatitis, have been reported. Therapy with NSAIDs should be administered cautiously in patients with preexisting liver disease. Periodic monitoring of liver function is recommended during prolonged therapy. NSAIDs are also highly protein-bound and some are extensively metabolized by the liver. Metabolic activity and/or plasma protein binding may be altered in patients with hepatic impairment. A dosage reduction may be required in some cases.

References

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  80. Schattenkirchner M "An updated safety profile of etodolac in several thousand patients." Eur J Rheumatol Inflamm 10 (1990): 56-65
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Moderate

Nsaids (Includes Sprix) ↔ Hyperkalemia

Moderate Potential Hazard, Moderate plausibility

Applies to: Hyperkalemia, Renal Dysfunction

Increase in serum potassium concentration, including hyperkalemia, have been reported with use of NSAIDs, even in some patients without renal impairment. In patients with normal renal function, these effects have been attributed to a hyporeninemic- hypoaldosteronism state.

Moderate

Nsaids (Includes Sprix) ↔ Hypertension

Moderate Potential Hazard, Moderate plausibility

Applies to: Hypertension

NSAIDs including topicals can lead to the onset of new hypertension or worsening of preexisting hypertension, either of which can contribute to the increased incidence of cardiovascular events. Blood pressure should be monitored closely during NSAID therapy and throughout the course of therapy.

Sprix (ketorolac) drug Interactions

There are 472 drug interactions with Sprix (ketorolac)

Sprix (ketorolac) alcohol/food Interactions

There are 3 alcohol/food interactions with Sprix (ketorolac)

Drug Interaction Classification

The classifications below are a general guideline only. It is difficult to determine the relevance of a particular drug interaction to any individual given the large number of variables.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No information available.

Do not stop taking any medications without consulting your healthcare provider.

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