Last update Feb. 1, 2022

σουλφασαλαζίνη

Very Low Risk

Safe. Compatible. Minimal risk for breastfeeding and infant.

Prodrug of Mesalazine: Sulfasalazine is a compound of a sulfonamide (sulfapyridine) and an anti-inflammatory (5-aminosalicylic acid, 5-ASA, or mesalazine). In the colon, bacteria break down sulfasalazine into sulfapyridine and mesalazine (Klotz 1985). Used in inflammatory bowel disease and rheumatoid arthritis. Oral and rectal administration in 2 to 4 daily doses.

No problems have been observed in infants of mothers treated with sulfasalzine (Ikram 2021, Correia 2010, Khan 1979), except for rare cases of diarrhea reported in the 80's with the use of Sulfasalazine (Nelis 1989, Branski 1986). In a review of 121 cases and 121 controls, the authors failed to observe those findings. (Moretti, 1998) (Ikram 2021, Correia 2010, Khan 1979). Plasma levels in these infants were very low. (Esbjörner 1987, Berlin 1980)

Mesalazine is badly absorbed by the intestine, serum levels are low with scant excretion into breast milk (Klotz 1993, Jenss 1990, Christensen 1994 y 1987, Miller 1993, Berlin 1980). Plasma levels in these infants were very low (Silverman 2005, Berlin 1980). Inactive metabolite N-acetyl-5-ASA was found in small amount in the milk with a relative infant dose not higher than 10%.(Silverman 2005, Jenss 1990)

It is very debatable (Sánchez 204) whether the thrombocytosis of a 4-month-old infant whose mother was in chronic treatment with mesalazine was due to mesalazine or to the sudden stopping of breastfeeding. (Barriuso 2003)

Sulfapyridine released in the large intestine is 60% absorbed with a protein-binding capacity of 90%, both being a reason for low excretion into breast milk. (Ambrosius 1987, Esbjörner 1987, Berlin 1980, Järnerot 1979, Khan 1979)

Expert consensus supports the compatibility of Mesalazine and/or its prodrugs during breastfeeding. (Sammaritano 2020 y 2014, Mahadevan 2019, 2015 y 2006, Nguyen 2016, Flint 2016, Götestam 2016, Huang 2016, McConnell 2016, Damas 2015, van der Woude 2015 y 2010, Nielsen 2014 y 2013, Schulze 2014, Hassid 2014, Yarur 2013, Selinger 2012, Makol 2011, Jain 2011, Zrour 2010, Van Assche 2010, Weber 2008, Heetun 2007, Østensen 2007 y 2006, Temprano 2005, Alstead 2002, Chin 2001, Janssen 200, Gran 1998, Connell 1996, Byron 1987)

List of WHO essential medicines 2002: Avoid if the Infant is premature or less than 1month old. Monitor the infant for side-effects (bloody diarrhea, haemolysis and jaundice). Avoid in G6PD deficient infants. (WHO 2002)

Mesalazine derivatives that not contain Sulfapyridine are recommended by some authors for use while breastfeeding (see alternative drugs). (Habal 2012, Mottet 2009 y 2007) 


See below the information of this related product:

Alternatives

  • Balsalazide ( Safe. Compatible. Minimal risk for breastfeeding and infant.)
  • Mesalazine (5-ASA) ( Safe. Compatible. Minimal risk for breastfeeding and infant.)
  • Olsalazine ( Safe. Compatible. Minimal risk for breastfeeding and infant.)

Suggestions made at e-lactancia are done by APILAM team of health professionals, and are based on updated scientific publications. It is not intended to replace the relationship you have with your doctor but to compound it. The pharmaceutical industry contraindicates breastfeeding, mistakenly and without scientific reasons, in most of the drug data sheets.

Jose Maria Paricio, Founder & President of APILAM/e-Lactancia

Your contribution is essential for this service to continue to exist. We need the generosity of people like you who believe in the benefits of breastfeeding.

Thank you for helping to protect and promote breastfeeding.

José María Paricio, founder of e-lactancia.

Other names

σουλφασαλαζίνη is Sulfasalazine in Greek.

Is written in other languages:

σουλφασαλαζίνη is also known as

Pharmacokinetics

Variable Value Unit
Oral Bioavail. SSZ: 15; 5ASA: 10-30 %
Molecular weight 398 daltons
Protein Binding 99.3 %
VD 0.1 l/Kg
pKa 3.23 -
Tmax 6 hours
7.6 (5 - 10) hours
M/P ratio 0.1 - 0.2 -
Theoretical Dose 0.3 mg/Kg/d
Relative Dose 0.9 (0.3 - 2.7) %
Ped.Relat.Dose 0.4 - 0.8 %

References

  1. Ikram N, Eudy A, Clowse MEB. Breastfeeding in women with rheumatic diseases. Lupus Sci Med. 2021 Apr;8(1). pii: e000491. Abstract Full text (link to original source)
  2. Pfizer. Sulfasalazine (Salazopyrin). Drug Summary. 2020 Full text (in our servers)
  3. Sammaritano LR, Bermas BL, Chakravarty EE, Chambers C, Clowse MEB, Lockshin MD, Marder W, Guyatt G, Branch DW, Buyon J, Christopher-Stine L, Crow-Hercher R, Cush J, Druzin M, Kavanaugh A, Laskin CA, Plante L, Salmon J, Simard J, Somers EC, Steen V, Tedeschi SK, et al. 2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases. Arthritis Rheumatol. 2020 Apr;72(4):529-556. Abstract Full text (link to original source)
  4. AEMPS. Sulfasalazina. Ficha técnica. 2019 Full text (in our servers)
  5. Mahadevan U, Robinson C, Bernasko N, Boland B, Chambers C, Dubinsky M, Friedman S, Kane S, Manthey J, Sauberan J, Stone J, Jain R. Inflammatory Bowel Disease in Pregnancy Clinical Care Pathway: A Report From the American Gastroenterological Association IBD Parenthood Project Working Group. Gastroenterology. 2019 Apr;156(5):1508-1524. Abstract
  6. Nguyen GC, Seow CH, Maxwell C, Huang V, Leung Y, Jones J, Leontiadis GI, Tse F, Mahadevan U, van der Woude CJ; IBD in Pregnancy Consensus Group. The Toronto Consensus Statements for the Management of Inflammatory Bowel Disease in Pregnancy. Gastroenterology. 2016 Mar;150(3):734-757.e1. Abstract Full text (link to original source) Full text (in our servers)
  7. Flint J, Panchal S, Hurrell A, van de Venne M, Gayed M, Schreiber K, Arthanari S, Cunningham J, Flanders L, Moore L, Crossley A, Purushotham N, Desai A, Piper M, Nisar M, Khamashta M, Williams D, Gordon C, Giles I; BSR and BHPR Standards, Guidelines and Audit Working Group. BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding-Part I: standard and biologic disease modifying anti-rheumatic drugs and corticosteroids. Rheumatology (Oxford). 2016 Sep;55(9):1693-7. Abstract Full text (link to original source) Full text (in our servers)
  8. Huang VW, Chang HJ, Kroeker KI, Goodman KJ, Hegadoren KM, Dieleman LA, Fedorak RN. Management of Inflammatory Bowel Disease during Pregnancy and Breastfeeding Varies Widely: A Need for Further Education. Can J Gastroenterol Hepatol. 2016;2016:6193275. Epub 2016 Sep 20. Abstract Full text (link to original source) Full text (in our servers)
  9. Götestam Skorpen C, Hoeltzenbein M, Tincani A, Fischer-Betz R, Elefant E, Chambers C, da Silva J, Nelson-Piercy C, Cetin I, Costedoat-Chalumeau N, Dolhain R, Förger F, Khamashta M, Ruiz-Irastorza G, Zink A, Vencovsky J, Cutolo M, Caeyers N, Zumbühl C, Østensen M. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis. 2016 May;75(5):795-810. Abstract Full text (link to original source) Full text (in our servers)
  10. McConnell RA, Mahadevan U. Pregnancy and the Patient with Inflammatory Bowel Disease: Fertility, Treatment, Delivery, and Complications. Gastroenterol Clin North Am. 2016 Abstract
  11. IARC - WHO. International Agency for research on Cancer. Some Drugs and Herbal Products. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans Volume 108. 2016 Full text (link to original source)
  12. van der Woude CJ, Ardizzone S, Bengtson MB, Fiorino G, Fraser G, Katsanos K, Kolacek S, Juillerat P, Mulders AG, Pedersen N, Selinger C, Sebastian S, Sturm A, Zelinkova Z, Magro F; European Crohn’s and Colitis Organization. The second European evidenced-based consensus on reproduction and pregnancy in inflammatory bowel disease. J Crohns Colitis. 2015 Feb;9(2):107-24. Review. Abstract Full text (link to original source) Full text (in our servers)
  13. Damas OM, Deshpande AR, Avalos DJ, Abreu MT. Treating Inflammatory Bowel Disease in Pregnancy: The Issues We Face Today. J Crohns Colitis. 2015 Oct;9(10):928-36. Abstract Full text (link to original source) Full text (in our servers)
  14. Mahadevan U, Matro R. Care of the Pregnant Patient With Inflammatory Bowel Disease. Obstet Gynecol. 2015 Aug;126(2):401-12. Abstract
  15. Nielsen OH, Maxwell C, Hendel J. IBD medications during pregnancy and lactation. Nat Rev Gastroenterol Hepatol. 2014 Feb;11(2):116-27. Abstract
  16. PDR. Sulfasalazine. Drug Summary. 2014 Full text (link to original source) Full text (in our servers)
  17. Schulze H, Esters P, Dignass A. Review article: the management of Crohn's disease and ulcerative colitis during pregnancy and lactation. Aliment Pharmacol Ther. 2014 Nov;40(9):991-1008. Abstract Full text (link to original source) Full text (in our servers)
  18. Hassid B, Mahadevan U. The use of biologic therapy in pregnancy: a gastroenterologist's perspective. Curr Opin Rheumatol. 2014 Abstract
  19. Huang VW, Habal FM. From conception to delivery: managing the pregnant inflammatory bowel disease patient. World J Gastroenterol. 2014 Abstract Full text (link to original source) Full text (in our servers)
  20. Sammaritano LR, Bermas BL. Rheumatoid arthritis medications and lactation. Curr Opin Rheumatol. 2014 Abstract
  21. Yarur A, Kane SV. Update on pregnancy and breastfeeding in the era of biologics. Dig Liver Dis. 2013 Oct;45(10):787-94. Abstract Full text (link to original source) Full text (in our servers)
  22. Nielsen OH, Maxwell C, Hendel J. IBD medications during pregnancy and lactation. Nat Rev Gastroenterol Hepatol. 2013 Abstract
  23. Selinger CP, Leong RW, Lal S. Pregnancy related issues in inflammatory bowel disease: evidence base and patients' perspective. World J Gastroenterol. 2012 Abstract Full text (link to original source) Full text (in our servers)
  24. Habal FM, Huang VW. Review article: a decision-making algorithm for the management of pregnancy in the inflammatory bowel disease patient. Aliment Pharmacol Ther. 2012 Abstract Full text (link to original source) Full text (in our servers)
  25. Jain V, Gordon C. Managing pregnancy in inflammatory rheumatological diseases. Arthritis Res Ther. 2011 Abstract Full text (link to original source)
  26. Makol A, Wright K, Amin S. Rheumatoid arthritis and pregnancy: safety considerations in pharmacological management. Drugs. 2011 Abstract
  27. Van Assche G, Dignass A, Reinisch W, van der Woude CJ, Sturm A, De Vos M, Guslandi M, Oldenburg B, Dotan I, Marteau P, Ardizzone A, Baumgart DC, D'Haens G, Gionchetti P, Portela F, Vucelic B, Söderholm J, Escher J, Koletzko S, Kolho KL, Lukas M, Mottet C, et al. The second European evidence-based Consensus on the diagnosis and management of Crohn's disease: Special situations. J Crohns Colitis. 2010 Abstract Full text (in our servers)
  28. van der Woude CJ, Kolacek S, Dotan I, Oresland T, Vermeire S, Munkholm P, Mahadevan U, Mackillop L, Dignass A; European Crohn's Colitis Organisation (ECCO). European evidenced-based consensus on reproduction in inflammatory bowel disease. J Crohns Colitis. 2010 Abstract Full text (link to original source) Full text (in our servers)
  29. Correia LM, Bonilha DQ, Ramos JD, Ambrogini O, Miszputen SJ. Inflammatory bowel disease and pregnancy: report of two cases treated with infliximab and a review of the literature. Eur J Gastroenterol Hepatol. 2010 Abstract
  30. Zrour-Hassen S, Jguirim M, Aouam K, Korbaa W, Younes M, Bejia I, Touzi M, Bergaoui N. [Safety of rheumatic disease drugs at childbearing age]. Therapie. 2010 Abstract
  31. Mottet C, Vader JP, Felley C, Froehlich F, Gonvers JJ, Juillerat P, Stockbrügger R, Angelucci E, Seibold F, Michetti P, Pittet V; EPACT II Study Group. Appropriate management of special situations in Crohn's disease (upper gastro-intestinal; extra-intestinal manifestations; drug safety during pregnancy and breastfeeding): Results of a multidisciplinary international expert panel-EPACT II. J Crohns Colitis. 2009 Abstract Full text (link to original source) Full text (in our servers)
  32. Weber JC, Kuhnert C. Traitements de fond des affections inflammatoires systémiques au cours de l’allaitement. [Breastfeeding and drug management in connective tissue and rheumatic diseases]. Rev Med Interne. 2008 Dec;29(12):1017-23. Abstract
  33. Østensen M, Motta M. Therapy insight: the use of antirheumatic drugs during nursing. Nat Clin Pract Rheumatol. 2007 Abstract
  34. Heetun ZS, Byrnes C, Neary P, O'Morain C. Review article: Reproduction in the patient with inflammatory bowel disease. Aliment Pharmacol Ther. 2007 Abstract Full text (link to original source) Full text (in our servers)
  35. Mottet C, Juillerat P, Pittet V, Gonvers JJ, Froehlich F, Vader JP, Michetti P, Felley C. Pregnancy and breastfeeding in patients with Crohn's disease. Digestion. 2007 Abstract
  36. Mahadevan U, Kane S. American gastroenterological association institute technical review on the use of gastrointestinal medications in pregnancy. Gastroenterology. 2006 Jul;131(1):283-311. Review. Abstract Full text (link to original source) Full text (in our servers)
  37. Østensen M, Khamashta M, Lockshin M, Parke A, Brucato A, Carp H, Doria A, Rai R, Meroni P, Cetin I, Derksen R, Branch W, Motta M, Gordon C, Ruiz-Irastorza G, Spinillo A, Friedman D, Cimaz R, Czeizel A, Piette JC, Cervera R, Levy RA, et al. Anti-inflammatory and immunosuppressive drugs and reproduction. Arthritis Res Ther. 2006 Abstract Full text (link to original source) Full text (in our servers)
  38. Temprano KK, Bandlamudi R, Moore TL. Antirheumatic drugs in pregnancy and lactation. Semin Arthritis Rheum. 2005 Abstract
  39. Silverman DA, Ford J, Shaw I, Probert CS. Is mesalazine really safe for use in breastfeeding mothers? Gut. 2005 Abstract Full text (link to original source) Full text (in our servers)
  40. Sánchez-Marín B, Grasa JM. Trombosis del seno longitudinal superior en un lactante: ¿secundaria a una exposición prolongada a mesalazina? [Thrombosis of the superior sagittal sinus in an infant: secondary to prolonged exposure to mesalazine?]. Rev Neurol. 2004 Jan 16-31;38(2):200. Spanish. (No abstract) Abstract
  41. Barriuso LM, Yoldi-Petri ME, Olaciregui O, Iceta-Lizarraga A, Goñi-Orayen C. Trombosis del seno longitudinal superior en un lactante: ¿secundaria a una exposición prolongada a mesalazina? [Thrombosis of the superior sagittal sinus in a breast fed infant: secondary to prolonged exposure to mesalazine?]. Rev Neurol. 2003 Jun 16-30;36(12):1142-4. Spanish. Abstract
  42. WHO / UNICEF. BREASTFEEDING AND MATERNAL MEDICATION Recommendations for Drugs in the Eleventh WHO Model List of Essential Drugs. Department of Child and Adolescent Health and Development (WHO/UNICEF) 2002 Full text (link to original source) Full text (in our servers)
  43. Alstead EM. Inflammatory bowel disease in pregnancy. Postgrad Med J. 2002 Jan;78(915):23-6. Review. Abstract
  44. Chin KG, McPherson CE 3rd, Hoffman M, Kuchta A, Mactal-Haaf C. Use of anti-infective agents during lactation: Part 2--Aminoglycosides, macrolides, quinolones, sulfonamides, trimethoprim, tetracyclines, chloramphenicol, clindamycin, and metronidazole. J Hum Lact. 2001 Feb;17(1):54-65. Abstract
  45. Janssen NM, Genta MS. The effects of immunosuppressive and anti-inflammatory medications on fertility, pregnancy, and lactation. Arch Intern Med. 2000 Abstract Full text (link to original source) Full text (in our servers)
  46. Moretti Myla Emily. Prospective follow-up of infants exposed to 5-aminosalicylic acid containing drugs through maternal milk. Thesis. Department of Pharmacology \ University of Toronto 1998 Full text (link to original source) Full text (in our servers)
  47. Gran JT, Ostensen M. Spondyloarthritides in females. Baillieres Clin Rheumatol. 1998 Abstract
  48. Connell WR. Safety of drug therapy for inflammatory bowel disease in pregnant and nursing women. Inflamm Bowel Dis. 1996 Abstract
  49. Christensen LA, Rasmussen SN, Hansen SH. Disposition of 5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid in fetal and maternal body fluids during treatment with different 5-aminosalicylic acid preparations. Acta Obstet Gynecol Scand. 1994 May;73(5):399-402. Abstract
  50. Miller LG, Hopkinson JM, Motil KJ, Corboy JE, Andersson S. Disposition of olsalazine and metabolites in breast milk. J Clin Pharmacol. 1993 Abstract
  51. Klotz U, Harings-Kaim A. Negligible excretion of 5-aminosalicylic acid in breast milk. Lancet. 1993 Abstract
  52. Ostensen M. Treatment with immunosuppressive and disease modifying drugs during pregnancy and lactation. Am J Reprod Immunol. 1992 Abstract
  53. Jenss H, Weber P, Hartmann F. 5-Aminosalicylic acid and its metabolite in breast milk during lactation. Am J Gastroenterol. 1990 Abstract
  54. Goldsmith DP. Neonatal rheumatic disorders. View of the pediatrician. Rheum Dis Clin North Am. 1989 Abstract
  55. Nelis GF. Diarrhoea due to 5-aminosalicylic acid in breast milk. Lancet. 1989 Abstract
  56. Esbjörner E, Järnerot G, Wranne L. Sulphasalazine and sulphapyridine serum levels in children to mothers treated with sulphasalazine during pregnancy and lactation. Acta Paediatr Scand. 1987 Abstract
  57. Byron MA. Treatment of rheumatic diseases. Br Med J (Clin Res Ed). 1987 Abstract Full text (link to original source) Full text (in our servers)
  58. Ambrosius Christensen L, Rasmussen SN, Hansen SH, Bondesen S, Hvidberg EF. Salazosulfapyridine and metabolites in fetal and maternal body fluids with special reference to 5-aminosalicylic acid. Acta Obstet Gynecol Scand. 1987 Abstract
  59. 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 Mar-Apr;5(2):316-7. Abstract
  60. Klotz U. Clinical pharmacokinetics of sulphasalazine, its metabolites and other prodrugs of 5-aminosalicylic acid. Clin Pharmacokinet. 1985 Abstract
  61. Berlin CM Jr, Yaffe SJ. Disposition of salicylazosulfapyridine (Azulfidine) and metabolites in human breast milk. Dev Pharmacol Ther. 1980 Abstract
  62. Khan AK, Truelove SC. Placental and mammary transfer of sulphasalazine. Br Med J. 1979 Abstract Full text (link to original source)
  63. Järnerot G, Into-Malmberg MB. Sulphasalazine treatment during breast feeding. Scand J Gastroenterol. 1979 Abstract

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