Aspirin with methotrexate

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. 

Clinically important, potentially hazardous interactions with aspirin, buprenorphine, methotrexate, probenecid, salicylates... 

Aspirin i plasma protein binding of methotrexate (a relatively minor contribution to the interaction) and the renal excretion of high doses of methotrexate. Salicylates compete with methotrexate for renal elimination... 

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... 

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... 

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. 

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 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 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... 

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... 

Care needs to be taken when combining naproxen with other medications. Known adverse drug interactions can occur with aspirin, methotrexate, ACE inhibitors (for high blood pressure), furosemide, lithium, and warfarin (a blood thinner). An overdose of naproxen may cause dizziness, drowsiness, and gastrointestinal problems. High blood pressure, kidney failure, and coma may occur, but are rare. 

There is an increased risk of diarrhea in patients taking misoprostol with the m nesium-containing antacids. Sulfasalazine may increase the risk of toxicity of oral hypoglycemic dru, zidovudine, methotrexate, and phenytoin. There is an increased risk of crys-talluria when sulfasalazine is administered with medienamine. A decrease in the absorption of iron and folic acid may occur when these ents are administered with sulfasalazine. When bismuth subsalicylate is administered witli aspirin-containing dru, there is an increased risk of salicylate toxicity. There is an increased risk of toxicity of valproic acid and methotrexate and decreased effectiven s of the corticosteroids when these agents are administered with bismuth subsalicylate. 

The above compounds are the glamorous pharmaceuticals, the results of fairly recent research and mostly based on a clear idea of the enzyme systems they are supposed to influence. The most widely consumed pharmaceuticals, however, are aspirin, paracetamol (called acetaminophen in the USA) and vitamin C. These can all be bought over-the-counter. Annual world consumption is of the order of 50 000 tonnes each, an order of magnitude higher than consumption of, say, penicillin V. At the other extreme come materials such as the anti-cancer drag, methotrexate, with annual... 

Several NSAIDs, including aspirin, ibuprofen, and piroxicam, increase serum levels of methotrexate by interfering with its renal clearance. The adverse effects of methotrexate, including its hematotoxicity are predictably increased. The answer is (J). 

Risk of methotrexate toxicity when co-administered with high-dose aspirin. There is a risk of toxic effects of methotrexate, e.g. liver cirrhosis, blood dyscrasias which may be fatal, pulmonary toxicity, stomatitis. Haematopoietic suppression can occur abruptly. Other adverse effects include anorexia, dyspepsia, gastrointestinal ulceration and bleeding, and pulmonary oedema... 

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