Drug General Information (ID: DDICDV670P)
Drug Name			Methotrexate		Drug Info		Nitrous oxide		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antimetabolites				Respiratory Agents
Structure

Mechanism of Methotrexate-Nitrous oxide Interaction (Severity Level: Major)
Increased risk of other adverse reactions (Unspecific) Click to Show/Hide Mechanism Graph
Drug Name		Methotrexate				Nitrous oxide
Mechanism		Methotrexate				Increase the risk of methotrexate-associated cytotoxicity
Key Mechanism Factor 1
		Factor Name		Adverse reactions
		Factor Description		An adverse reaction is an unexpected negative reaction to a medication or treatment that happens even when it's used correctly.
Mechanism Description		Increased risk of adverse reactions by the combination of Methotrexate and Nitrous oxide

Recommended Action
Management		The concomitant use of nitrous oxide anesthesia with methotrexate should be avoided. Some authorities consider the use of nitrous oxide with methotrexate to be contraindicated (CA). If concomitant use is unavoidable, patients should be closely monitored for toxicity during the postoperative period. Intravenous hydration and calcium folinate (leucovorin) are recommended to decrease the incidence of methotrexate toxicity.

References
1	Canadian Pharmacists Association "e-CPS."
2	Goldhirsch A, Gelber RD, Tattersall MN, Rudenstam CM "Methotrexate/nitrous-oxide toxic interaction in perioperative chemotherapy for early breast cancer." Lancet ii (1987): 151.[PMID: 2885607]
3	Ermens AA, Schoester M, Spijkers LJ, Lindemans J, Abels J "Toxicity of methotrexate in rats preexposed to nitrous oxide." Cancer Res 49 (1989): 6337-41.[PMID: 2804978]