Drug General Information (ID: DDIO4WPIZH)
Drug Name			Doxycycline		Drug Info		Methotrexate		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antiinflammatory Agents				Antimetabolites
Structure

Mechanism of Doxycycline-Methotrexate Interaction (Severity Level: Moderate)
Competitive binding of plasma proteins Click to Show/Hide Mechanism Graph
Drug Name		Doxycycline				Methotrexate
Mechanism		Competition for plasma protein binding sites				Competition for plasma protein binding sites
Key Mechanism Factor 1
		Factor Name		Plasma protein binding
		Factor Description		Plasma protein binding refers to the degree of binding of a drug to proteins in the blood, and the lower the degree of binding, the more efficiently the drug can cross cell membranes or diffuse. Plasma protein binding alters the distribution and therapeutic characteristics of the drugs.
Mechanism Description		Increased plasma concentration of Methotrexate and Doxycycline due to competitive binding of plasma proteins

Recommended Action
Management		If these drugs must be used together, close monitoring for evidence of serious methotrexate toxicity or reduced therapeutic efficacy is recommended. If broad-spectrum antibiotic coverage is needed during high-dose methotrexate therapy, the use of an alternate anti-infective may be considered.

References
1	Canadian Pharmacists Association.
2	Cerner Multum, Inc. "Australian Product Information.".
3	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
4	Product Information. Methotrexate (methotrexate). Lederle Laboratories, Wayne, NJ.
5	Tortajada-Ituren JJ, Ordovas-Baines JP, Llopis-Salvia P, Jimenez-Torres NV "High-dose methotrexate-doxycycline interaction." Ann Pharmacother 33 (1999): 804-8. [PMID: 10466909]