Indomethacin Disease Interactions
There are 10 disease interactions with indomethacin:
- Fluid Retention
- Gi Toxicity
- Renal Toxicities
- Cns Effects
- Platelet Aggregation Inhibition
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.
- "Product Information. Voltaren (diclofenac)." Novartis Pharmaceuticals, East Hanover, NJ.
- "Product Information. Naprosyn (naproxen)." Syntex Laboratories Inc, Palo Alto, CA.
- "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn, Kalamazoo, MI.
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.
- 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
- 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
- "Product Information. Daypro (oxaprozin)." Searle, Skokie, IL.
Nonsteroidal anti-inflammatory drugs (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 develop at any time, with or without warning symptoms, and occurs in approximately 1% of patients treated for 3 to 6 months and 2% to 4% of patients treated for one year. These trends continue with longer duration of use, although short-term therapy is not without risk. While agents that selectively inhibit cyclooxygenase-2 (i.e., COX-2 inhibitors) are generally thought to be associated with a reduced risk of GI toxicity compared to conventional NSAIDs, they have not been proven risk-free. In addition, there is evidence that COX-2 inhibitors may delay healing of gastric ulcers, and likely to the same extent as traditional NSAIDs. Thus, therapy with all NSAIDs, including COX-2 inhibitors, should be prescribed cautiously in patients with a history of peptic ulcer disease and/or gastrointestinal bleeding. Patients with such a history who use NSAIDs have a greater than 10-fold increased risk for developing a GI bleed compared to patients with neither of these risk factors. Caution is also advised if NSAIDs are prescribed to patients with other risk factors such as oral corticosteroid or anticoagulant use, alcohol use, smoking, older age, and poor general health status. Particular vigilance is necessary when treating elderly (i.e., age 60 years or more) and/or debilitated patients, since they are often more susceptible to the GI toxicity of these drugs and seem to tolerate ulceration and bleeding less well than younger, healthier individuals. Whenever possible, especially if prolonged use is anticipated, treatment with non-ulcerogenic agents should be attempted first. If NSAIDS are used, patients should be treated with the lowest effective dosage for the shortest duration possible, and prophylactic therapy with a cytoprotective agent (e.g., misoprostol), histamine H2-receptor antagonist, or a proton pump inhibitor should be administered as necessary. Patients should be counseled to avoid or minimize consumption of alcohol during NSAID therapy. Three or more alcoholic drinks per day during NSAID use may increase the risk of gastrointestinal ulceration and bleeding. Patients should also be advised to promptly seek medical attention if they experience symptoms that could indicate serious GI tract ulceration or bleeding such as epigastric pain, dyspepsia, melena, and hematemesis.
- Levy M, Miller DR, Kaufman DW, Siskind V, Schwingl P, Rosenberg L, Strom B, Shapiro S "Major upper gastrointestinal tract bleeding. Relation to the use of aspirin and other nonnarcotic analgesics." Arch Intern Med 148 (1988): 281-5
- Scott B "Bleeding massive gastric ulcer on diflunisal (Dolobid) ." Br Med J 1 (1979): 489
- "Product Information. Mobic (meloxicam)" Boehringer-Ingelheim, Ridgefield, CT.
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.
- "Product Information. Indocin (indomethacin)." Merck & Co, Inc, West Point, PA.
- "Product Information. Tolectin (tolmetin)." McNeil Pharmaceutical, Raritan, NJ.
- "Product Information. Relafen (nabumetone)." SmithKline Beecham, Philadelphia, PA.
Chronic use of nonsteroidal anti-inflammatory drugs (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 pre-renal conditions whose renal perfusion may be dependent on the function of 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 NSAIDs 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, particularly in the presence of manifestations associated with mild azotemia (e.g., malaise, fatigue, loss of appetite). If renal function declines or renal failure occurs, prompt discontinuation of NSAID therapy will usually lead to recovery to the pretreatment state. NSAIDs are generally not recommended for patients with advanced renal disease due to the lack of information from controlled clinical studies regarding their use in such patients.
- Cefali EA, Poyner WJ, Sica D, Cox S "Pharmacokinetic comparison of flurbiprofen in end-stage renal disease subjects and subjects with normal renal function." J Clin Pharmacol 31 (1991): 808-14
- Beun GD, Leunissen KM, Van Breda Vriesman PJ, Van Hooff JP, Grave W "Isolated minimal change nephropathy associated with diclofenac." Br Med J (Clin Res Ed) 295 (1987): 182-3
- Shah GM, Muhalwas KK, Winer RL "Renal papillary necrosis due to ibuprofen." Arthritis Rheum 24 (1981): 1208-10
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.
<br />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.
- Fitzgerald GA, Patrono C "The coxibs, selective inhibitors of cyclooxsygenase-2." N Engl J Med 345 (2001): 433-42
- "Product Information. Vioxx (rofecoxib)." Merck & Co, Inc, West Point, PA.
- Marcus AJ, Broekman MJ, Pinsky DJ "COX inhibitors and thromboregulation." N Engl J Med 347 (2002): 1025-6
The use of indomethacin has been reported to aggravate depression or other psychiatric disturbances, epilepsy, and parkinsonism. Therapy with indomethacin should be administered cautiously in patients with a history of these conditions. If severe CNS adverse reactions develop, indomethacin should be withdrawn.
- Bishop LC, Bisset AD, Benson JI "Mania and indomethacin." J Clin Psychopharmacol 7 (1987): 203-4
- Schwartz JI, Moura RJ "Severe depersonalization and anxiety associated with indomethacin." South Med J 76 (1983): 679-80
- Tollefson GD, Garvey MJ "Indomethacin and prostaglandins: their behavioral relationships in an acute toxic psychosis." J Clin Psychopharmacol 2 (1982): 62-4
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.
- "Product Information. Relafen (nabumetone)." SmithKline Beecham, Philadelphia, PA.
- 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
- Squires JE, Mintz PD, Clark S "Tolmetin-induced hemolysis." Transfusion 25 (1985): 410-3
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.
- "Product Information. Orudis (ketoprofen)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
- Selley ML, Madsen BW, Thomas J "Protein binding of tolmetin." Clin Pharmacol Ther 24 (1978): 694-705
- 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
Nonsteroidal anti-inflammatory drugs (NSAIDs) reversibly inhibit platelet adhesion and aggregation and may prolong bleeding time in some patients. 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 should be administered cautiously in patients with significant active bleeding or a hemorrhagic diathesis, including hemostatic and/or coagulation defects associated with hemophilia, vitamin K deficiency, hypoprothrombinemia, thrombocytopenia, thrombocytopathy, or severe hepatic impairment. NSAIDs that selectively inhibit cyclooxygenase-2 (i.e., COX-2 inhibitors) do not appear to affect platelet function or bleeding time at indicated dosages and may be preferable if risk of bleeding is a concern.
- "Product Information. Relafen (nabumetone)." SmithKline Beecham, Philadelphia, PA.
- Leese PT, Hubbard RC, Karim A, Isakson PC, Yu SS, Geis GS "Effects of celecoxib, a novel cyclooxygenase-2 inhibitor, on platelet function in healthy adults: A randomized, controlled trial." J Clin Pharmacol 40 (2000): 124-32
- 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
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indomethacin drug Interactions
There are 447 drug interactions with indomethacin
indomethacin alcohol/food Interactions
There are 2 alcohol/food interactions with indomethacin
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.|
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