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Sulfasalazine

Also indexed as: Azulfidine

Illustration

Sulfasalazine is a member of the sulfonamide drug family. It is used to treat people with ulcerative colitis, Crohn’s disease, and rheumatoid arthritis.

Summary of Interactions with Vitamins, Herbs, and Foods
In some cases, an herb or supplement may appear in more than one category, which may seem contradictory. For clarification, read the full article for details about the summarized interactions.

Beneficial May Be Beneficial: Depletion or interference—The medication may deplete or interfere with the absorption or function of the nutrient. Taking these nutrients may help replenish them.

Folic acid

Vitamin K*

Beneficial May Be Beneficial: Side effect reduction/prevention—Taking these supplements may help reduce the likelihood and/or severity of a potential side effect caused by the medication.

Bifidobacterium longum*

Lactobacillus acidophilus*

Lactobacillus casei*

Saccharomyces boulardii*

Saccharomyces cerevisiae*

Vitamin K*

Beneficial May Be Beneficial: Supportive interaction—Taking these supplements may support or otherwise help your medication work better.

Saccharomyces boulardii*

Avoid Avoid: Reduced drug absorption/bioavailability—Avoid these supplements when taking this medication since the supplement may decrease the absorption and/or activity of the medication in the body.

Iron

Avoid Avoid: Adverse interaction—Avoid these supplements when taking this medication because taking them together may cause undesirable or dangerous results.

PABA*

An asterisk (*) next to an item in the summary indicates that the interaction is supported only by weak, fragmentary, and/or contradictory scientific evidence.

Interactions with Dietary Supplements

Folic acid
Sulfasalazine decreases the absorption of folic acid.1 Biochemical evidence of depletion of folic acid has been reported in people taking this drug,2 although available evidence remains mixed.3 4

Folic acid is needed for the normal healthy replication of cells. Perhaps as a result, there is evidence that folic acid can reverse precancerous changes in humans.5 Ulcerative colitis, a disease commonly treated with sulfasalazine, is associated with an increased risk of colon cancer. Folate deficiency has also been linked to an increased risk for colon cancer.6 It is plausible that some of the increased risk for colon cancer in people with ulcerative colitis may be related to folate depletion caused by sulfasalazine.

Folic acid supplementation may help protect against colon cancer.7 One study found that people who have ulcerative colitis and who supplement with folic acid have a 55% lower risk of getting colon cancer, compared with ulcerative colitis patients who do not supplement with folic acid (although this dramatic association with protection did not quite reach statistical significance).8 Researchers at the University of Chicago Medical Center reported a 62% lower risk of colon cancer in folic acid supplementers.9 They suggested that the link between folic acid supplementation and protection from colon cancer may well be due to overcoming the folic acid deficiency induced by sulfasalazine.

Many doctors believe that it is important for all people taking sulfasalazine to supplement with folic acid. Folic acid in the amount of 800 mcg can be found in many multivitamins and B-complex vitamins. People wishing to supplement with more—typically 1,000 mcg per day—should consult their doctor.

Iron
Iron can bind with sulfasalazine, decreasing sulfasalazine absorption and possibly decreasing iron absorption.10 This interaction can be minimized by taking iron-containing products two hours before or after sulfasalazine.

PABA (Para-aminobenzoic acid)
PABA may interfere with the activity of sulfasalazine. PABA should not be taken with this drug until more is known.

Probiotics
A common side effect of antibiotics is diarrhea, which may be caused by the elimination of beneficial bacteria normally found in the colon. Controlled studies have shown that taking probiotic microorganisms—such as Lactobacillus casei, Lactobacillus acidophilus, Bifidobacterium longum, or Saccharomyces boulardii—helps prevent antibiotic-induced diarrhea.11

The diarrhea experienced by some people who take antibiotics also might be due to an overgrowth of the bacterium Clostridium difficile, which causes a disease known as pseudomembranous colitis. Controlled studies have shown that supplementation with harmless yeast—such as Saccharomyces boulardii12 or Saccharomyces cerevisiae (baker’s or brewer’s yeast)13 —helps prevent recurrence of this infection. In one study, taking 500 mg of Saccharomyces boulardii twice daily enhanced the effectiveness of the antibiotic vancomycin in preventing recurrent clostridium infection.14 Therefore, people taking antibiotics who later develop diarrhea might benefit from supplementing with saccharomyces organisms.

Treatment with antibiotics also commonly leads to an overgrowth of yeast (Candida albicans) in the vagina (candida vaginitis) and the intestines (sometimes referred to as “dysbiosis”). Controlled studies have shown that Lactobacillus acidophilus might prevent candida vaginitis.15

Vitamin K
Several cases of excessive bleeding have been reported in people who take antibiotics.16 17 18 19 This side effect may be the result of reduced vitamin K activity and/or reduced vitamin K production by bacteria in the colon. One study showed that people who had taken broad-spectrum antibiotics had lower liver concentrations of vitamin K2 (menaquinone), though vitamin K1 (phylloquinone) levels remained normal.20 Several antibiotics appear to exert a strong effect on vitamin K activity, while others may not have any effect. Therefore, one should refer to a specific antibiotic for information on whether it interacts with vitamin K. Doctors of natural medicine sometimes recommend vitamin K supplementation to people taking antibiotics. Additional research is needed to determine whether the amount of vitamin K1 found in some multivitamins is sufficient to prevent antibiotic-induced bleeding. Moreover, most multivitamins do not contain vitamin K.

Interactions with Foods and Other Compounds

Food
Sulfasalazine is best taken after meals, and it is important to swallow the tablets whole to avoid inactivation by stomach acid.21

References:

1. Longstreth GF, Green R. Folate status in patients receiving maintenance doses of sulfasalazine. Arch Intern Med 1983;143:902–4.

2. Halsted CH, Gandhi G, Tamura T. Sulfasalazine inhibits the absorption of folates in ulcerative colitis. N Engl J Med 1981;305:1513–7.

3. Swinson CM, Perry J, Lumb M, Levi AJ. Role of sulphasalazine in the aetiology of folate deficiency in ulcerative colitis. Gut 1981;22:456–61.

4. Longstreth GF, Green R. Folate levels in inflammatory bowel disease. N Engl J Med 1982;306:1488 [letter].

5. Heimburger DC, Alexander B, Birch R, et al. Improvement in bronchial squamous metaplasia in smokers treated with folate and vitamin B12. JAMA 1988;259:1525–30.

6. Ma J, Stampfer MJ, Giovannucci E, et al. Methylenetetrahydrofolate reductase polymorphism, dietary interactions, and risk of colorectal cancer. Cancer Res 1997;57:1098–102.

7. Mason JB. Folate and colonic carcinogenesis: Searching for a mechanistic understanding. J Nutr Biochem 1994;5:170–5.

8. Lashner BA, Provencher KS, Seidner DL, et al. The effect of folic acid supplementation on the risk for cancer or dysplasia in ulcerative colitis. Gastroenterology 1997;112:29–32.

9. Lashner BA, Heidenreich PA, Su GL, et al. Effect of folate supplementation on the incidence of dysplasia and cancer in chronic ulcerative colitis. Gastroenterology 1989;97:255–9.

10. Dukes GE Jr, Duncan BS. Inflammatory bowel disease. In Applied Therapeutics: The Clinical Use of Drugs, 6th ed. Vancouver, WA: Applied Therapeutics, 1995, 24–7.

11. Elmer GW, Surawicz CM, McFarland LV. Biotherapeutic agents. A neglected modality for the treatment and prevention of selected intestinal and vaginal infections. JAMA 1996;275:870–6 [review].

12. Elmer GW, Surawicz CM, McFarland LV. Biotherapeutic agents. A neglected modality for the treatment and prevention of selected intestinal and vaginal infections. JAMA 1996;275:870–6 [review].

13. Schellenberg D, Bonington A, Champion CM, et al. Treatment of Clostridium difficile diarrhoea with brewer’s yeast. Lancet 1994;343:171–2.

14. Surawicz CM, Elmer GW, Speelman P, et al. Prevention of antibiotic-associated diarrhea by Saccharomyces boulardii: A prospective study. Gastroenterol 1989;96:981–8.

15. Elmer GW, Surawicz CM, McFarland LV. Biotherapeutic agents. A neglected modality for the treatment and prevention of selected intestinal and vaginal infections. JAMA 1996;275:870–6 [review].

16. Suzuki K, Fukushima T, Meguro K, et al. Intracranial hemorrhage in an infant owing to vitamin K deficiency despite prophylaxis. Childs Nerv Syst 1999;15:292–4.

17. Huilgol VR, Markus SL, Vakil NB. Antibiotic-induced iatrogenic hemobilia. Am J Gastroenterol 1997;92:706–7.

18. Bandrowsky T, Vorono AA, Borris TJ, Marcantoni HW. Amoxicllin-related postextraction bleeding in an anticoagulated patient with tranexamic acid rinses. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996;82:610–2.

19. Kaiser CW, McAuliffe JD, Barth RJ, Lynch JA. Hypoprothrombinemia and hemorrhage in a surgical patient treated with cefotetan. Arch Surg 1991;126:524–5.

20. Conly J, Stein K. Reduction of vitamin K2 concentration in human liver associated with the use of broad spectrum antimicrobials. Clin Invest Med 1994;17:531–9.

21. Threlkeld DS, ed. Gastrointestinal Drugs, Sulfasalazine. In Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Sep 1997, 326e–6h.

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