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 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. 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 Valdecoxib (withdrawn from US market), however, may increase methotrexate serum concentrations.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.