Drug Interactions between folic acid and sulfasalazine

Sulfasalazine may impair the intestinal absorption and/or metabolism of folic acid to its physiologically useful form. Folate deficiency, sometimes manifested as megaloblastic or macrocytic anemia, has been reported in patients treated chronically with sulfasalazine. However, those patients generally had inflammatory bowel disease or other risk factors for folate deficiency such as celiac disease, rheumatoid arthritis, or nutritional deficiencies. In healthy patients, the anti-folate effect of sulfasalazine is generally not associated with clinically significant hematologic changes. Data from one study suggested a dose-dependent effect. Specifically, patients with chronic colitis receiving 2 grams or more of sulfasalazine daily had lower mean red blood cell folate levels than patients taking less or nonusers of sulfasalazine (221.2 ng/mL vs 371.7 ng/mL and 330.3 ng/mL, respectively). In any case, clinicians should be mindful of the potential interaction with sulfasalazine in patients receiving folic acid supplementation. Those not responding to folic acid may require folinic acid, whose action is not inhibited by sulfasalazine.