Drug General Information (ID: DDI12NZP4V)
  Drug Name Methotrexate Drug Info Sulfadoxine Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antimetabolites Antimalarial Agents
  Structure

 Mechanism of Methotrexate-Sulfadoxine Interaction (Severity Level: Moderate)
     Competitive binding of plasma proteins Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Methotrexate Sulfadoxine
      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 Sulfadoxine and Methotrexate due to competitive binding of plasma proteins

Recommended Action
      Management Caution is advised when methotrexate is used with sulfonamides. Complete blood counts, liver enzymes, and serum creatinine levels should be performed at baseline and periodically during treatment. Patients should be closely monitored for increased methotrexate adverse effects including nausea, vomiting, diarrhea, stomatitis, alopecia, anemia, bone marrow suppression (e.g., aplastic anemia, leukopenia, neutropenia, thrombocytopenia., pancytopenia), hepatotoxicity, and nephrotoxicity.

References
1 Bannwarth B, Pehourcq F, Schaeverbeke T, Dehais J "Clinical pharmacokinetics of low-dose pulse methotrexate in rheumatoid arthritis." Clin Pharmacokinet 30 (1996): 194-210. [PMID: 8882301]
2 Beach BJ, Woods WG, Howell SB "Influence of co-trimoxazole on methotrexate pharmacokinetics in children with acute lymphoblastic leukemia." Am J Pediatr Hematol Oncol 3 (1981): 115-9. [PMID: 6975580]
3 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
4 Ferrazzini G, Klein J, Sulh H, Chung D, Griesbrecht E, Koren G "Interaction between trimethoprim-sulfamethoxazole and methotrexate in children with leukemia." J Pediatr 117 (1990): 823-6. [PMID: 2231218]
5 Frain JB "Methotrexate toxicity in a patient receiving trimethoprim-sulfamethoxazole." J Rheumatol 14 (1987): 176-7. [PMID: 3494846]
6 Govert JA, Patton S, Fine RL "Pancytopenia from using trimethoprim and methotrexate." Ann Intern Med 117 (1992): 877-8. [PMID: 1416570]
7 Jeurissen ME, Boerbooms AM, van de Putte LB "Pancytopenia and methotrexate with trimethoprim-sulfamethoxazole." Ann Intern Med 111 (1989): 261. [PMID: 2787612]
8 Liegler DG, Henderson ES, Hahn MA, Oliverio VT "The effect of organic acids on renal clearance of methotrexate in man." Clin Pharmacol Ther 10 (1969): 849-57. [PMID: 5349626]
9 Ng HW, Macfarlane AW, Graham RM, Verbov JL "Near fatal drug interactions with methotrexate given for psoriasis." Br Med J (Clin Res Ed) 295 (1987): 752-3. [PMID: 3119023]
10 Product Information. Bactrim (trimethoprim-sulfamethoxazole). Roche Laboratories, Nutley, NJ.
11 Product Information. Rheumatrex (methotrexate). Lederle Laboratories, Wayne, NJ.
12 Product Information. Sulfadiazine (sulfadiazine). Eon Labs Manufacturing Inc, Laurelton, NY.
13 Thomas DR, Dover JS, Camp RD "Pancytopenia induced by the interaction between methotrexate and trimethoprim-sulfamethoxazole." J Am Acad Dermatol 17 (1987): 1055-6. [PMID: 3501437]
14 Thomas MH, Gutterman LA "Methotrexate toxicity in a patient receiving trimethoprim-sulfamethoxazole." J Rheumatol 13 (1986): 440-1. [PMID: 3487652]
15 Verbov JL "Methotrexate and trimethoprim-sulfamethoxazole." Clin Exp Dermatol 16 (1991): 231. [PMID: 1934583]