Methotrexate with NSAIDs

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... 

The most recent treatment paradigm calls for earher, more aggressive treatment of rheumatoid arthritis. DMARDs are frequently employed along with NSAIDs in the initial treatment of the disease. The COX-2 inhibitors are often used because they are less likely to cause serious GI toxicity than are the nonspecihc COX inhibitors. The usual DMARD of choice for patients with mild rheumatoid arthritis is hydroxychloroquine or sulfasalazine methotrexate is used for those with moderate to serious disease. Other DMARDs are used if these agents are poorly tolerated or do not produce suf-hcient response. Combination therapy of methotrexate and another agent is also used to treat disease that is not responsive to individual DMARDs. 

E. Treatment guidelines suggest the use of DMARDs early in the course of rheumatoid arthritis to slow the joint deterioration associated with the disease. Methotrexate is the DMARD of choice for people with moderate to severe forms of rheumatoid arthritis. Although NSAIDs can decrease methotrexate clearance, NSAIDs can be safely used with the low doses of methotrexate used in the therapy of rheumatoid arthritis. Methotrexate is highly teratogenic and should not be used by women who are or may become pregnant. 

METHOTREXATE ANALGESICS-NSAIDs t methotrexate levels, with reports of toxicity, with ibuprofen, indome-tacin and possibly diclofenac, flurbiprofen, ketoprofen and naproxen Uncertain postulated that an NSAID-induced 1 in renal perfusion may have an effect Consider using an alternative NSAID... 

Cytotoxics renal tubular excretion of methotrexate is reduced by competition with NSAIDs, with risk of methotrexate toxicity (low-dose methotrexate given weekly avoids this hazard). 

Clinically important, potentially hazardous interactions with cyclosporine, lithium, methotrexate, mifepristone, NSAIDs, quinolones, salicylates... 

Disease-modifying antirheumatic drugs (DMARDs) are thought to slow disease progression and may be started with NSAIDs at the time of initial diagnosis, especially if symptoms are severe. Hydroxychloroquine is often recommended for mild arthritis and methotrexate (MTX) for moderate to severe RA. Other DMARDs (see Table VI-1-3) are used less frequently, sometimes in combination regimens for refractory cases. 

A preliminary report of a study in 87 patients receiving long-term treatment with methotrexate (mean weekly dose 8.19 mg), most of whom were also taking unspecified NSAIDs, found that the majority (72%) experienced no untoward effects and in the rest adverse effects were only relatively mild. The concurrent use of methotrexate and NSAIDs in more than 450 patients with psoriatic arthritis or rheumatoid arthritis was said to be without clinical interaction problems. ... 

A literature review of interactions between methotrexate and NSAIDs found that low-dose methotrexate pharmacokinetics were unaltered by NSAIDs, with the exception of salicylates. ... 

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... 

The most potentially serious drug interactions include the concomitant use of NSAIDs with lithium, warfarin, oral hypoglycemics, high-dose methotrexate, antihypertensives, angiotensin-converting enzyme inhibitors, fi-blockers, and diuretics. 

Unexpectedly severe (sometimes fatal) bone marrow suppression, aplastic anemia, and Gl toxicity have occurred with coadministration of methotrexate (usually in high dosage) along with some NSAIDs (see Precautions. Drug Interactions). 

Methotrexate clearance can be decreased by the coadministration of NSAIDs however, this not usually a problem with the low doses of methotrexate used to treat arthritis. Methotrexate can be displaced from plasma protein binding sites by phenylbutazone, pheny-toin, sulfonylureas, and sulfonamides and certain other antibiotics. The antifolate effects of methotrexate are additive with those of other folate-inhibitory drugs, such as trimethoprim. 

Therapy for SEE is both complex and, in many instances, disappointing for both patient and practitioner. Management of the systemic signs and symptoms may not improve the ocular manifestations of the disease. The most common therapy for the arthritic and cardiac complications is NSAID use. Hydroxychloroquine and chloroquine are particularly effective in treating the discoid rash associated with the disease. In some cases oral steroids are used either alone or in combination with other immunosuppressive agents. Methotrexate can effectively reduce the need for systemic steroids in the treatment of mild to moderate SEE. Cyclophosphamide and... 

Te use of NSAIDS and other anti-inflammatory therapies are similar to those used in other autoimmune arthritic disorders. Corticosteroid injections for severe pain and inflammation at specific joints are standard therapy. For severe forms of the disease immunomodulating anti-rheumatic drugs such as methotrexate and sulfasalazine are effective. As with other similar disorders, the biologic TNF a inhibitors are currently prescribed for severe Reiter s syndrome. 

Significant hematological abnormalities occur in 10-24% of patients who take methotrexate. Mild to moderate leukopenia is the most frequent, followed by thrombocytopenia. Isolated thrombocytopenia and anemia are uncommon (SEDA-22, 416) (36). In a retrospective study in 315 patients, 13 had thrombocytopenia, two of whom also had pancytopenia (37). Thrombocytopenia correlated with the weekly dosage of methotrexate administered on the same day as NSAIDs, and methotrexate was safely reintroduced in patients who developed thrombocytopenia as a result of concomitant administration of... 

Low-dose methotrexate is usually not regarded as nephrotoxic, and one report of nephrotic syndrome with minimal change disease on renal biopsy should be regarded with caution, since there was recovery after glucocorticoid treatment and withdrawal of concomitant NSAIDs (SEDA-22, 416). 

However, renal toxicity occurs with high-dose methotrexate and more likely to occur with concomitant administration of other nephrotoxic agents, such as aminoglycosides, cephalosporins, NSAIDs, and diuretics (60). 

Interactions of NSAIDs with methotrexate have been reviewed (SEDA-20, 89). Severe toxicity has been attributed to different dosages of methotrexate in concomitant use with several NSAIDs. The mechanisms are unclear. Both methotrexate and the NSAIDs are secreted by the organic acid secretory pathway in the kidney and both are... 

Methotrexate is often prescribed for the management of rheumatoid arthritis, and some NSAIDs have been reported to interact with it, causing increased plasma methotrexate concentrations, associated with impaired renal function. The safety of concurrent rofecoxib and oral methotrexate has been studied for 3 weeks in 25 patients with rheumatoid arthritis (7). Rofecoxib 12.5-50 mg/day had no effect on the plasma concentrations or renal clearance of methotrexate, but supratherapeutic doses of rofecoxib (75 and 250 mg) caused a significant increase in the plasma methotrexate AUC and reduced its renal clearance. 

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 acenocoumarol, anagrelide, anticoagulants, bismuth, boswellia, calcium hydroxylapatite, capsicum, cholestyramine, desvenlafaxine, devil s claw, dexamethasone, dexibuprofen, dicumarol, etodolac, evening primrose, flunisolide, ginkgo biloba, ginseng, heparin, ibuprofen, indomethacin, ketoprofen, ketorolac, lumiracoxib, methotrexate, methylprednisolone, nilutamide, NSAIDs, phellodendron, prednisone, resveratrol, reteplase, rivaroxaban, sermorelin, sulfites, tirofiban, triamcinolone, urokinase, valdecoxib, valproic acid, verapamil, warfarin... 

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