OBJECT DRUGS

• Methotrexate (Anticancer Doses, etc.)
• Pralatrexate (Folotyn)

PRECIPITANT DRUGS

NSAIDs:

• Diclofenac (Voltaren, etc.)
• Diflunisal (Dolobid)
• Etodolac (Lodine)
• Fenoprofen (Nalfon)
• Flurbiprofen (Ansaid, etc.)
• Ibuprofen (Motrin, etc.)
• Indomethacin (Indocin, etc.)
• Ketoprofen (Orudis)
• Ketorolac (Toradol, etc.)
• Meclofenamate
• Mefenamic acid
• Meloxicam (Mobic)
• Nabumetone (Relafen)
• Naproxen (Aleve, etc.)
• Oxaprozin (Daypro)
• Piroxicam (Feldene)
• Salicylates
• Sulindac (Clinoril)
• Tolmetin (Tolectin)

Comment:

In patients receiving antineoplastic doses of methotrexate, NSAIDs and full dose salicylates have been associated with methotrexate toxicity such as bone marrow suppression and GI toxicity. The risk with low-dose methotrexate (e.g., for rheumatoid arthritis) is probably much lower; indeed, NSAIDs are often used with low-dose methotrexate in this situation. Nonetheless, one should still be alert for evidence of methotrexate toxicity. A Cochrane systematic review of studies involving patients on methotrexate for arthritis found that although NSAIDs did not appear to increase the risk of methotrexate toxicity, anti-inflammatory doses of aspirin combined with methotrexate may increase the risk of hepatic and renal malfunction. Pralatrexate concentrations are increased by probenecid, so caution with other potential inhibitors of renal clearance (such as NSAIDs) is warranted.

Class 2: Use Only if Benefit Felt to Outweigh Risk

• Use Alternative: Consider acetaminophen instead of NSAIDs or salicylates. Preliminary evidence suggests that celecoxib (Celebrex) does not affect methotrexate pharmacokinetics and could be considered as an alternative. Valdecoxib (withdrawn from US market), however, may increase methotrexate serum concentrations.
• Monitor: Monitor for altered methotrexate or pralatrexate effect if a renal tubular secretion inhibitor is initiated, discontinued, or changed in dose.