Interaction between
Methotrexate
and
Thiosalicylic acid
Major
Distribution
Excretion
Basic Information
| ID | DDInter1174 and DDInter2086 |
| Interaction | Salicylates may interfere with the renal elimination of methotrexate and may displace it from binding sites. |
| Management | If these agents must be used concomitantly, caution should be exercised and the patient should be monitored closely for signs and symptoms of bone marrow suppression and nephrotoxicity. Patients should be advised to report possible symptoms of toxicity including nausea, vomiting, diarrhea, stomatitis, sore throat, chills, fever, rash, unusual bruising or bleeding, jaundice, dark urine, swelling of the extremities, or shortness of breath to their physician. Patients should also be counseled to avoid any other over-the-counter salicylate products. |
| References | [1] Frenia ML, Long KS "Methotrexate and nonsteroidal antiinflamatory drug interactions." Ann Pharmacother 26 (1992): 234-7 [2] Skeith KJ, Russell AS, Jamali F, Coates J, Friedman H "Lack of significant interaction between low dose methotrexate and ibuprofen or flurbiprofen in patients with arthritis." J Rheumatol 17 (1990): 1008-10 [3] Stewart CF, Fleming RA, Germain BF, et al. "Aspirin alters methotrexate disposition in rheumatoid arthritis patients." Arthritis Rheum 34 (1991): 1514-20 [4] Stewart CF, Fleming RA, Arkin CR, Evans WE "Coadministration of naproxen and low-dose methotrexate in patients with rheumatoid arthritis." Clin Pharmacol Ther 47 (1990): 540-6 [5] Liegler DG, Henderson ES, Hahn MA, Oliverio VT "The effect of organic acids on renal clearance of methotrexate in man." Clin Pharmacol Ther 10 (1969): 849-57 [6] Ellison NM, Servi RJ "Acute renal failure and death following sequential intermediate-dose methotrexate and 5-FU: a possible adverse effect due to concomitant indomethacin administration." Cancer Treat Rep 69 (1985): 342-3 [7] Kraus A, Alarcon-Segovia D "Low dose MTX and NSAID induced "mild" renal insufficiency and severe neutropenia." J Rheumatol 18 (1991): 1274 [8] Singh RR, Malaviya AN, Pandey JN, Guleria JS "Fatal interaction between methotrexate and naproxen." Lancet 1 (1986): 1390 [9] Maiche AG "Acute renal failure due to concomitant action of methotrexate and indomethacin." Lancet 1 (1986): 1390 [10] Dixon RL, Henderson ES, Rall DP "Plasma protein binding of methotrexate and its displacement by various drugs." Fed Proc 24 (1965): 454 [11] Baker H "Intermittent high dose oral methotrexate therapy in psoriasis." Br J Dermatol 82 (1970): 65-9 [12] Mandel MA "The synergistic effect of salicylates on methotrexate toxicity." Plast Reconstr Surg 57 (1976): 733-7 [13] Taylor JR, Halprin KM "Effect of sodium salicylate and indomethacin on methotrexate-serum albumin binding." Arch Dermatol 113 (1977): 588-91 [14] Dupuis LL, Koren G, Shore A, Silverman ED, Laxer RM "Methotrexate-nonsteroidal antiinflammatory drug interaction in children with arthritis." J Rheumatol 17 (1990): 1469-73 [15] "Product Information. Methotrexate (methotrexate)." Lederle Laboratories (2002): [16] Tracy TS, Krohn K, Jones DR, Bradley JD, Hall SD, Brater DC "The effects of a salicylate, ibuprofen, and naproxen on the disposition of methotrexate in patients with rheumatoid arthritis." Eur J Clin Pharmacol 42 (1992): 121-5 |
| Alternative for Methotrexate |
L04A
|
| Alternative for Thiosalicylic acid | - |
Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.