Sulfasalazine in Pregnancy and Breastfeeding

Risk Factor: BM*
Class: Immunologic agents / Antirheumatic agents

Contents of this page:

Fetal Risk Summary

Sulfasalazine is a compound composed of 5-aminosalicylic acid (5-ASA) joined to sulfapyridine by an azo-linkage (refer to Sulfonamides for a complete review of this class of agents). Sulfasalazine is used for the treatment of ulcerative colitis and Crohn's disease. Reproduction studies in rats and rabbits at doses up to 6 times the human dose revealed no impairment of fertility or fetal harm (1).

No increase in human congenital defects or newborn toxicity has been observed from its use in pregnancy (2,3,4,5,6,7,8,9,10,11 and 12). However, three reports, involving five infants (two stillborn), have described congenital malformations after exposure to this drug (13,14 and 15). It cannot be determined whether the observed defects were related to the therapy, the disease, or a combination of these or other factors: Bilateral cleft lip/palate, severe hydrocephalus, death (13) Ventricular septal defect, coarctation of aorta (14) Potter-type IIa polycystic kidney, rudimentary left uterine cornu, stillborn (first twin) (14) Potter's facies, hypoplastic lungs, absent kidneys and ureters, talipes equinovarus, stillborn (second twin) (14) Ventricular septal defect, coarctation of aorta, macrocephaly; gingival hyperplasia, small ears (both thought to be inherited) (15) Sulfasalazine and its metabolite, sulfapyridine, readily cross the placenta to the fetal circulation (6,7). Fetal concentrations are approximately the same as maternal concentrations. Placental transfer of 5-ASA is limited because only negligible amounts are absorbed from the cecum and colon, and these are rapidly excreted in the urine (16).

At birth, concentrations of sulfasalazine and sulfapyridine in 11 infants were 4.6 and 18.2 g/mL, respectively (7). Neither of these levels was sufficient to cause significant displacement of bilirubin from albumin (7). Kernicterus and severe neonatal jaundice have not been reported following maternal use of sulfasalazine, even when the drug was given up to the time of delivery (7,8). Caution is advised, however, because other sulfonamides have caused jaundice in the newborn when given near term (see Sulfonamides).

Sulfasalazine may adversely affect spermatogenesis in male patients with inflammatory bowel disease (17,18). Sperm counts and motility are both reduced and require 2 months or longer after the drug is stopped to return to normal levels (17).

[*Risk Factor D if administered near term.]

Breast Feeding Summary

Sulfapyridine is excreted into breast milk (see also Sulfonamides) (6,16,19). Milk concentrations were approximately 40%60% of maternal serum levels. One infant's urine contained 34 g/mL of the drug (1.21.6 mg/24 hours), representing about 30%40% of the total dose excreted in the milk. Unmetabolized sulfasalazine was detected in only one of the studies (milk:plasma ratio of 0.3) (6). Levels of 5-ASA were undetectable. No adverse effects were observed in the 16 nursing infants exposed in these reports (6,16,19). However, bloody diarrhea in an infant exclusively breast-fed, occurring first at 2 months of age, and then recurring 2 weeks later and persisting until 3 months of age, was attributed to the mother's sulfasalazine therapy (3 g/day) (20). The mother was a slow acetylator with a blood concentration of sulfapyridine of 42.4 g/mL (therapeutic range 2050 g/mL) (20). The acetylation phenotype of the infant was not determined, but his blood level of sulfapyridine was 5.3 g/mL. A diagnostic workup of the infant was negative. The bloody diarrhea did stop, however, 4872 hours after discontinuance of the mother's therapy. A repeat colonoscopy of the infant 1.5 months later was normal. Based on this report, the American Academy of Pediatrics classifies sulfasalazine as a drug that should be given to nursing women with caution because significant adverse effects may occur in some nursing infants (21).

References

1. Product information. Azulfidine EN-tabs. Pharmacia & Upjohn, 2000.
2. McEwan HP. Anorectal conditions in obstetric practice. Proc R Soc Med 1972;65:27981.
3. Willoughby CP, Truelove SC. Ulcerative colitis and pregnancy. Gut 1980;21:46974.
4. Levy N, Roisman I, Teodor I. Ulcerative colitis in pregnancy in Israel. Dis Colon Rectum 1981;24:3514.
5. Mogadam M, Dobbins WO III, Korelitz BI, Ahmed SW. Pregnancy in inflammatory bowel disease: effect of sulfasalazine and corticosteroids on fetal outcome. Gastroenterology 1981;80:726.
6. Azad Khan AK, Truelove SC. Placental and mammary transfer of sulphasalazine. Br Med J 1979;2:1553.
7. Jarnerot G, Into-Malmberg MB, Esbjorner E. Placental transfer of sulphasalazine and sulphapyridine and some of its metabolites. Scand J Gastroenterol 1981;16:6937.
8. Modadam M. Sulfasalazine, IBD, and pregnancy (reply). Gastroenterology 1981;81:194.
9. Fielding JF. Pregnancy and inflammatory bowel disease. J Clin Gastroenterol 1983;5:1078.
10. Sorokin JJ, Levine SM. Pregnancy and inflammatory bowel disease: a review of the literature. Obstet Gynecol 1983;62:24752.
11. Baiocco PJ, Korelitz BI. The influence of inflammatory bowel disease and its treatment on pregnancy and fetal outcome. J Clin Gastroenterol 1984;6:2116.
12. Fedorkow DM, Persaud D, Nimrod CA. Inflammatory bowel disease: a controlled study of late pregnancy outcome. Am J Obstet Gynecol 1989;160:9981001.
13. Craxi A, Pagliarello F. Possible embryotoxicity of sulfasalazine. Arch Intern Med 1980;140:1674.
14. Newman NM, Correy JF. Possible teratogenicity of sulphasalazine. Med J Aust 1983;1:5289.
15. Hoo JJ, Hadro TA, Von Behren P. Possible teratogenicity of sulfasalazine. N Engl J Med 1988;318:1128.
16. Berlin CM Jr, Yaffe SJ. Disposition of salicylazosulfapyridine (Azulfidine) and metabolites in human breast milk. Dev Pharmacol Ther 1980;1:319.
17. Toovey S, Hudson E, Hendry WF, Levi AJ. Sulphasalazine and male infertility: reversibility and possible mechanism. Gut 1981;22:44551.
18. Freeman JG, Reece VAC, Venables CW. Sulphasalazine and spermatogenesis. Digestion 1982;23:6871.
19. Jarnerot G, Into-Malmberg MB. Sulphasalazine treatment during breast feeding. Scand J Gastroenterol 1979;14:86971.
20. Branski D, Kerem E, Gross-Kieselstein E, Hurvitz H, Litt R, Abrahamov A. Bloody diarrhea-a possible complication of sulfasalazine transferred through human breast milk. J Pediatr Gastroenterol Nutr 1986;5:3167.
21. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:13750.
    
    

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Questions and Answers

Can the arthritis drug sulfasalazine cause mouth ulcers and sore mouth?,

Please see your GP about this.
If you read the leaflet in the packet it advises you to report any sore throat to your doctor.
Adverse effects lists gastrointestinal reaction.

Does anyone take this drug, Sulfasalazine?, I have been on Sulfasalazine (generic for Azulfidine) for years off and on for Ulcerative Colitis, my disease is very mild but I noticed last year that I started to get headaches and now they have got worse. Does anyone else have headaches with this drug? I appreciate your answers.

The most common side effect is nausea but often this can be controlled by a reduction in dose. Sometimes other medications may be needed. Occasionally mouth ulcers, a sore mouth or loose bowel motions may occur. Certain patients may develop a headache or slight dizziness but adjusting the dosage may bring things under control.
Please see the webpages for more details on Sulfasalazine (generic name) Azulfidine (brand name)

Arthritis, I take diclofenac, sulfasalazine and glucosamine but it's not getting any better,please help.?, I have really bad swelling on my fingers, and my wrist is really sore and weak especially in the mornings. Any advice or help would be greatly appreciated.

Hi there hun! I have chronic psoriatic arthritis. I spent over 8 years on sulphazalazine if anything it caused damage on my stomach which I am suffering with now and the difladenac did not help matters either. Get referred to a rheumatologist who knows what they are talking about! Have physio and hydro. Try looking at your diet too and try little exercises. Also have an electric blanket at bed time to warm you. Have a shower am and pm to warm those stiff joints up. I am 27 and have had this since I was 11. Also try hot and cold treatment, if your joints are warm and swollen try putting some frozen peas on in a towel and if joints are cold add heat, like a water bottle in a towel. I was a volunteer for Arthritis Care and ran a local branch for The Arthritis Research Campaign, if I can help let me know as I have loads of leaflets etc or visit www.arc.org.uk for more info. Get well soon and merry christmas!

How does sulfasalazine measure up to other 5-ASA drugs such as Asacol and Colazal for Ulcerative Colitis?, I am a 23 year old male who was diagnosed with UC 8 years ago and have gone through a variety of treatments. Originally I was prescribed Asacol as well as a large dose of prednisone. I eventually went into remission and came off the steroid, but continued to take Asacol as my maintenance drug. Remission lasted for 3 or 4 years.

My symptoms started reoccurring and progressively worsened for a while, and I found that while on Asacol they were actually worse. I also know that some common side effects of Asacol are similar to the actually symptoms of UC. I had more frequent stools, increased urgency and increased bleeding.

I tried Colazal as well, but I experienced nausea and again, increased urgency. At this point I was frequently having embarrasing accidents. When I was not on medication, but kept to some natural remedies that I also take, I did not experience this as badly.

My GI doc, however, wants me to try sulfasalazine rather than stay off everything... any advice / input?

hi jacob, I have crohn's disease, a type of IBD like UC. I have had it since the age of 12.

Ask your GI about the newer treatments for UC b/c the 5ASA meds don't seem to last long on some patients plus they tend to cause nausea as well.

If he doesn't listen to you, then get another opinion. You the ability to hire/fire your doctors at any time so don't feel guilty. A pt. should feel comfortable discussing their concerns during their appt. and be able to work as a team w/his physician to get the UC in remission.

Remicade has been approved for colitis as well as a few others. Can't remember the names but if you go to the Crohn's & Colitis Foundation of America website, they have all the latest treatments listed. You can call their hotline or chat online w/a medical professional M-F 9 am - 5pm (EST) 1-888-my-gut-pain.

I hope this helps. I can totally relate to what you are going through. I went through symptoms when I was in my 20s so I talked w/my GI and he worked w/me to find a treatment that agreed w/me, thus, fewer side effects & I was able to be on it for a long time until my white cell count dropped. Then he found another medication and I haven't had any trouble since.

Happy New Year.

what drug is this? or where can i find out? IC SULFASALAZINE?,

sulfasalazine (sul·fa·sal·a·zine) (sul”fə-sal´ə-zēn) [USP] an antibacterial sulfonamide used orally or rectally in the prophylaxis and treatment of inflammatory bowel disease, and orally as a disease-modifying antirheumatic drug in the treatment of rheumatoid arthritis.

What complications can OTC sleep aids cause for people on prescription medication?, I am thinking of taking an over-the-counter sleep aid, but I have a daily prescription of Sulfasalazine. I previously took small doses of Lorazepam under medical supervision for insomnia, and I didn't have any problems with that. What kind of complications, if any, can I expect if I take an OTC sleep aid with my prescription?

If the only medication you are taking is sulfasalazine an OTC sleep medication (diphenhydramine/benadryl)should have no interaction. If you are not having any pain, plain old benadryl should do the trick. Make sure you have several hours to sleep or you might feel fuzzy/hung over. I am assuming no other med conditions/allergies....good luck.

Will taking Enbrel for psoriatic arthritis also ease the symptoms of Osteoarthritis?, I have both types and am currently on Sulfasalazine, but considering Enbrel.

I have OsteoArthritis and Rhuematoid Arthritis. My Doctor has me on "methotrexate" which has really helped my Pain and stiff joints alot.