Sulfasalazine and Folic Acid Concomitant Use: When and Why?

What is Sulfasalazine?

Sulfasalazine/sulphasalazine is a sulphonamide (amino salicylic acid molecule) that is approved for the treatment of active Crohn’s disease and rheumatoid arthritis, as well as the induction and management of remission in ulcerative colitis.

What is Folic Acid?

Folic Acid is also sometimes named Vitamin B9. It is man-made folate. It is considered one of the important cofactors for the enzymes involved in the synthesis of DNA and RNA. Folic acid is used to prevent and treat folic acid deficiency in megaloblastic anemia and nutritional anemias, as well as during pregnancy, infancy, and childhood. To lower the chance of neural tube abnormalities and other birth problems, folic acid is given to women who are planning to get pregnant as well as in the early months of pregnancy. It also plays an essential role as a protective factor in cancer development. Because humans are unable to produce folic acid on their own, deficits must be avoided through diet and supplementation.

Does sulfasalazine cause folate deficiency in Inflammatory Bowel Disease (IBD)?

Sulfasalazine reduces folic acid absorption and metabolism, but only rarely causes folate insufficiency in patients with inflammatory bowel disease (IBD). Even though sulfasalazine has been used to treat inflammatory bowel disease (IBD) for many years, few people have reported developing sulfasalazine-associated folate deficiency anemia. Only when there are other reasons for folate insufficiency has this condition been deemed a danger.

Does sulfasalazine cause folate deficiency in rheumatoid arthritis?

Although sulfasalazine inhibits folic acid absorption and metabolism, it only rarely causes folate insufficiency in people with inflammatory bowel disease (IBD). However, serum and red blood cell folate contents are commonly low in rheumatoid arthritis (RA), and sulfasalazine may disrupt folate metabolism.

Why do RA patients take folic acid?

Methotrexate is a drug that is prescribed by doctors to treat a variety of illnesses, particularly adult rheumatoid arthritis, cancer, and serious psoriasis.

Methotrexate, on the other hand, depletes the body of folic acid, potentially leading to folic acid deficiency. Taking folic acid with methotrexate does not reduce the effectiveness of methotrexate in treating RA. As a result, supplementing with folic acid to compensate for the folate lost while taking methotrexate helps to lessen the negative effects of folate insufficiency without interfering with RA treatment. Methotrexate can produce folate deficiency, which can have several unpleasant side effects. These negative effects, on the other hand, can often be avoided by taking folic acid.

Beverley Shea and colleagues’ Cochrane Review suggests that, given the low cost of folic acid supplements and the numerous benefits it provides, as well as the lack of evidence that it reduces methotrexate efficacy, it should be used in all rheumatoid arthritis patients who are taking or beginning to take Methotrexate.

Another study published in 2004 in the “Rheumatology” a scientific Journal of Oxford Academic proposes that all patients receiving methotrexate for the treatment of RA be given folic acid supplements on a regular basis. A dosage of 5 mg of oral folic acid should be administered the morning after the day of administration of methotrexate, is recommended.

Sulfasalazine and folic acid in pregnancy

Sulfasalazine has been proven to impede folic acid metabolism and absorption, potentially leading to folic acid insufficiency. Supplemental folic acid may be required for pregnant women receiving sulfasalazine therapy.

Plaquenil (Hydroxychloroquine) and Azulfidine (Sulfasalazine)

Rheumatoid arthritis is treated with Plaquenil (hydroxychloroquine) and Azulfidine EN-tabs (sulfasalazine delayed-release tablets).

Food sources of Folate

  • Green leafy vegetables (spinach and broccoli)
  • Sprouts and legumes
  • Organ meat (liver and kidney)
  • Peanuts
  • Peas
  • Soybeans
  • Mushrooms, Okra, and Asparagus

Sulfasalazine available brands

  • Salazine
  • Sulfine
  • Azulfidine tablets

Folic Acid available brands in the USA

  • Folic Acid Tablet (dosage 1mg/oral tab)
  • Acid injection (5mg/ml USP)
  • Folic Acid tablet (25mg)
  • Folic Acid tablet (5mg)


RA : Rheumatoid Arthritis


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