Methotrexate Aspirin

Methotrexate Aspirin, phenylbutazone, probenecid Delayed excretion Increased toxicity. 

Cardiovascular Keep doses of NSAIDs and glucocorticoids low, consider initiation of folic acid to reduce homocysteine level elevations induced by methotrexate, consider initiation of low-dose aspirin and/or HMG-CoA reductase inhibitors (statins), and encourage smokers to discontinue tobacco use and assist with the development of a tobacco-cessation plan.11,12... 

Drugs that may be affected by aspirin include ACE inhibitors, acetazolamide, anticoagulants, anticonvulsants (hydantoins, valproic acid), beta blockers, diuretics, methotrexate, NSAIDs, oral hypoglycemics, and uricosuric agents (probenecid, sulfinpyrazone). 

Drugs that may affect aspirin include activated charcoal, ammonium chloride, ascorbic acid or methionine, antacids and urinary alkalinizers, carbonic anhydrase inhibitors, corticosteroids, and nizatidine. Drugs that may be affected by aspirin include alcohol, ACE inhibitors, anticoagulants (oral), beta-adrenergic blockers, heparin, loop diuretics, methotrexate, nitroglycerin, NSAIDs, probenecid and sulfinpyrazone, spironolactone, sulfonylureas and exogenous insulin, and valproic acid. 

Concomitant therapy - Aspirin, NSAIDs, and/or low-dose steroids may be continued, although the possibility of increased toxicity with concomitant use of NSAIDs, including salicylates, has not been fully explored. Steroids may be reduced gradually in patients who respond to methotrexate. Combined use of methotrexate with... 

For a displacement interaction to become clinically important, a second mechanism usually operates sodium valproate can cause phenytoin toxicity because it both displaces phenytoin from its binding site on plasma albumin and inhibits its metabolism. Similarly aspirin and probenecid (and possibly other nonsteroidal anti-inflammatory drugs) displace the folic acid antagonist methotrexate from its protein-binding site and reduce its rate of active secretion by the renal tubules the result is serious methotrexate toxicity. 

Interference with active transport. Organic acids are passed from the blood into the urine by active transport across the renal tubular epithelium. Penicillin is mostly excreted in this way. Probenecid, an organic acid that competes successfully with penicillin for this transport system, may be used to prolong the action of penicillin when repeated administration is impracticable, e.g. in sexually transmitted diseases, where compliance is notoriously poor. Interference with renal excretion of methotrexate by aspirin, of zidovudine by probenecid and of digoxin by quinidine, contribute to the potentially harmful interactions with these combinations. 

Aspirin displaces methotrexate from its binding sites and also inhibits its renal tubular elimination, so that the dosage of concurrently used methotrexate should be reduced (except once-a-week low-dose treatment in rheumatoid arthritis) (110). 

Aspirin and methotrexate compete for renal tubular secretion, and aspirin alters the systemic and renal clearances of intravenous methotrexate (131). However, the clinical relevance of this interaction is not clear. In one study, aspirin (mean dose 4.5 g) in 12 patients did not cause more toxicity than other NSAIDs taken by 22 other patients (132). 

Stewart CF, Fleming RA, Germain BE, Seleznick MJ, Evans WE. Aspirin alters methotrexate disposition in rheumatoid arthritis patients. Arthritis Rheum 1991 34(12) 1514-20. 

Rooney TW, Furst DE, Koehnke R, Burmeister L. Aspirin is not associated with more toxicity than other nonsteroidal antiinflammatory drugs in patients with rheumatoid arthritis treated with methotrexate. J Rheumatol 1993 20(8) 1297-302. 

Concomitant use of heparin and oral anticoagulants can increase the risk for bleeding due to the antiplatelet effect of aspirin. In addition, use with alcohol can increase the risk of Gl bleeding. / spirin displaces a number of drugs (e.g., tolbutamide, nonsteroidal anti-inflammatory drugs [NSAIDs], methotrexate, phenytoin, and probenecid) from protein binding sites in the blood. Corticosteroid use can reduce serum salicylate levels by increasing the clearance of aspirin. 

Clinically important, potentially hazardous interactions with aspirin, ciprofloxacin, doxycycline, hypoglycemics, lomefloxacin, lymecycline, methotrexate, minocycline, tetracycline, warfarin... 

Clinically important, potentially hazardous interactions with albendazole, aminoglutethimide, aspirin, bexarotene, carbamazepine, cyclophosphamide, dasatinib, diuretics, ephedrine, imatinib, itraconazole, lapatinib, live vaccines, lopinavir, methotrexate, phenobarbital, phenytoin, praziquantel, primidone, rifampicin, rifampin, temsirolimus, warfarin... 

Clinically important, potentially hazardous interactions with aspirin, methotrexate... 

Clinically important, potentially hazardous interactions with aldesleukin, aspirin, diflunisal, diuretics, methotrexate, NSAIDs, prednisolone, prednisone, sermorelin, tiludronate, torsemide, triamterene, urokinase... 

Clinically important, potentially hazardous interactions with aluminum, aminophylline, aspirin, chlorambucil, cimetidine, clarithromycin, cyclophosphamide, cyclosporine, dicumarol, diuretics, docetaxel, estrogens, grapefruit juice, indomethacin, influenza vaccines, itraconazole, ketoconazole, lansoprazole, live vaccines, methotrexate, montelukast, omeprazole, oral contraceptives, pancuronium, phenobarbital, phenytoin, ranitidine, rifampicin, rifampin, timolol, tolbutamide, vitamin A... 

A number of commonly used drugs are carboxylic acid derivatives. These include aspirin (pKa 3.5), the anticancer compound methotrexate (pKa 3.8, 4.8 and 5.6) and the diuretic furosemide (previously called frusemide in the UK, pKa 3.9). The structures of these compounds are shown in Figure 3.4. 

Aspirin and, to a lesser extent, ibuprofen reduce excretion of methotrexate, and can cause life-threatening rises in serum levels. Concurrent administration... 

Although there have been many reports describing how patients with EMS have been treated, results were not successful in the majority of patients. Basically, the treatment of EMS has consisted of discontinuation of L-tryp-tophan and administration of corticosteroids, nonsteroidal anti-inflammatory drugs, and several other drugs, such as D-penicillamine and colchicine, cyclophosphamide, AZA (azathioprine), methotrexate, amitriptyline, acetaminophen, aspirin, naproxen, diphenhydramine, cyclobenzaprine, and fluoxetine.2132 56 In general, it was concluded that prednisone was helpful in the acute phase of the disease. Slow improvement was reported in 79% of the 193 patients. However, no treatment was clearly valuable in the management of the later phase of the syndrome.55... 

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