Drug General Information (ID: DDIM8QWXJY)
Drug Name			Methotrexate		Drug Info		Meclofenamic acid		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antimetabolites				Analgesics
Structure

Mechanism of Methotrexate-Meclofenamic acid Interaction (Severity Level: Major)
Increased risk of nephrotoxicity Click to Show/Hide Mechanism Graph
Drug Name		Methotrexate				Meclofenamic acid
Mechanism		Nephrotoxicity				Nephrotoxicity
Key Mechanism Factor 1
		Factor Name		Nephrotoxicity
		Factor Description		The combination of drugs that can induce nephrotoxicity may increase the risk of kidney injury. When kidney injury occurs, the inability to remove excess urine and waste from the body can lead to high levels of urea nitrogen, creatinine, and electrolytes (such as potassium and magnesium) in the blood.
Mechanism Description		Increased risk of nephrotoxicity by the combination of Methotrexate and Meclofenamic acid

Recommended Action
Management		NSAIDs should generally not be administered prior to or concomitantly with high dosages of methotrexate, such as those used to treat osteosarcoma. Caution should be exercised when NSAIDs are administered concomitantly with lower dosages of methotrexate. Close monitoring for signs and symptoms of bone marrow suppression, nephrotoxicity, and hepatotoxicity is recommended during treatment. Patients should be advised to contact their physician if they develop stomatitis, nausea, vomiting, diarrhea, rash, anorexia, jaundice, dark urine, dry cough, shortness of breath, and/or signs and symptoms of myelosuppression such as pallor, dizziness, fatigue, lethargy, fainting, easy bruising or bleeding, fever, chills, sore throat, body aches, and other influenza-like symptoms. Patients should also be counseled to avoid any other over-the-counter NSAID products.

References
1	Schwartz JI, Agrawal NG, Wong PH, et al. "Lack of pharmacokinetic interaction between rofecoxib and methotrexate in rheumatoid arthritis patients." J Clin Pharmacol 41 (2001): 1120-30. [PMID: 11583481]
2	Tracy TS, Worster T, Bradley JD, Greene PK, Brater DC "Methotrexate disposition following concomitant administration of ketoprofen, piroxicam and flurbiprofen in patients with rheumatoid arthritis." Br J Clin Pharmacol 37 (1994): 453-6. [PMID: 8054251]
3	Vakily M, Amer F, Kukulka MJ, Andhivarothai N "Coadministration of lansoprazole and naproxen does not affect the pharmacokinetic profile of methotrexate in adult patients with rheumatoid arthritis." J Clin Pharmacol 45 (2005): 1179-86. [PMID: 16172183]