Mercaptopurine use while Breastfeeding

Drugs containing Mercaptopurine: Purinethol, Purixan

Mercaptopurine Levels and Effects while Breastfeeding

Summary of Use during Lactation

Most sources consider breastfeeding to be contraindicated during maternal antineoplastic drug therapy. In the treatment of conditions such as ulcerative colitis and Crohn's disease, low doses of mercaptopurine (6-MP) for immunosuppression appear to be acceptable.[1][2][3][4][5] No active metabolites of mercaptopurine were found in the blood of breastfed infants whose mothers were taking azathioprine and no adverse effects attributable to mercaptopurine or azathioprine have been noted. See the Azathioprine record for details. Mothers with decreased activity of the enzyme that detoxifies mercaptopurine metabolites may transmit higher levels of drug to their infants in breastmilk. It might be desirable to monitor exclusively breastfed infants with a complete blood count with differential, and liver function tests if mercaptopurine is used during lactation, although some authors feel that monitoring is unnecessary.[6]

Drug Levels

Mercaptopurine is the active metabolite of azathioprine. It is further metabolized to active metabolites including 6-methylmercaptopurine, thioguanine, 6-thioguanine nucleosides (6-TGNs) and 6-methylmercaptopurine nucleosides (6-MMPN). The enzyme thiopurine methyltransferase (TPMT) is responsible for metabolism of 6-TGNs. Deficiencies in this enzyme can lead to excessive toxicity.

Maternal Levels. Mercaptopurine milk levels were measured in 2 patients receiving azathioprine following renal transplantation. In one, peak milk levels occurred 2 and 8 hours after a 75 mg oral dose and were 3.4 and 4.5 mcg/L respectively. In the other, a peak milk level of 18 mcg/L occurred 2 hours after a 25 mg oral dose. Serum levels were not measured.[7]

Four women receiving an immunomodulator to treat inflammatory bowel disease had metabolite levels measured in milk during the first 6 weeks postpartum. The abstract does not mention the specific drug and dose being taken, but the azathioprine metabolites 6-methylmercaptopurine (6-MMP) and 6-thioguanine nucleosides (6-TGNs) were measured. Although therapeutic levels were found in maternal serum, 6-MMP (<650 mcg/L) and 6-TGNs were undetectable (<123 mcg/L) in milk (time of collection not stated).[8]

Infant Levels. Four infants were breastfed (3 exclusively, 1 rarely received formula) during maternal use of azathioprine orally in dosages of 1.2 to 2.1 mg/kg daily. All of the mothers and infants had the wild type TPMT *1/*1 genotype and all of the mothers had normal enzyme activity. At 3 to 3.5 months of age, all of the infants' had undetectable blood levels of 6-TGNs and 6-MMPN.[9]

Effects in Breastfed Infants

In The Netherlands, 30 infants of mothers taking either azathioprine (n = 28) or mercaptopurine (n = 2) for inflammatory bowel disease during pregnancy and postpartum were followed at 1 to 6 years of age using a 43-item quality of life questionnaire. Of this cohort, 9 infants were breastfed for a mean of 7 months (range 3 to 13 months) No statistically significant differences were found between breastfed and formula-fed infants in any of the 12 domains of the survey.[10]

A prospective cohort study followed pregnant women with inflammatory bowel disease throughout pregnancy and for 12 months postpartum. Women were assigned to one of the following groups: unexposed (no thiopurines or anti-TNF agents); group A (azathioprine or mercaptopurine); group B (infliximab, adalimumab or certolizumab) and group AB (both a thiopurine and an anti-TNF agent). Of 1052 women enrolled in the study, 72% breastfed their infants, although the extent and duration were not stated in the abstract. A total of 264 women were exposed to a thiopurine and 59 were exposed to a thiopurine plus an anti-TNF agent. The use of a thiopurine alone was not associated with any complication in the infants and their growth and development were normal throughout the 12 months. Infants exposed to both a thiopurine and an anti-TNF agent had a 50% increase in the number of infections between 9 and 12 months of age. The relationship of this increase with breastfeeding could not be determined from the available data.[11]

Possible Effects on Lactation

Relevant published information was not found as of the revision date.

Alternate Drugs to Consider

(Immunosuppression) Cyclosporine, Tacrolimus, (Inflammatory Bowel Disease) Budesonide, Infliximab, Mesalamine, Prednisone, (Systemic Lupus Erythematosus) Hydroxychloroquine, Prednisone

References

1. Ha C, Dassopoulos T. Thiopurine therapy in inflammatory bowel disease. Expert Rev Gastroenterol Hepatol. 2010;4 :575-88. PMID: 20932143

2. van der Woude CJ, Kolacek S, Dotan I et al. European evidenced-based consensus on reproduction in inflammatory bowel disease. J Crohn's Colitis. 2010;4:493-510. PMID: 21122553

3. Van Assche G, Dignass A, Reinisch W et al. The second European evidence-based Consensus on the diagnosis and management of Crohn's disease: Special situations. J Crohns Colitis. 2010;4:63-101. PMID: 21122490

4. Hassid B, Mahadevan U. The use of biologic therapy in pregnancy: a gastroenterologist's perspective. Curr Opin Rheumatol. 2014;26:347-53. PMID: 24625373

5. Nielsen OH, Maxwell C, Hendel J. IBD medications during pregnancy and lactation. Nat Rev Gastroenterol Hepatol. 2014;11:116-27. PMID: 23897285

6. Christensen LA, Dahlerup JF, Nielsen MJ et al. Azathioprine treatment during lactation: authors' reply. Aliment Pharmacol Ther. 2009;30:91. PMID: 19566905

7. Coulam CB, Moyer TP, Jiang NS et al. Breast-feeding after renal transplantation. Transplant Proc. 1982;13:605-9. PMID: 6817481

8. Kane SV, Present DH. Metabolites to immunomodulators are not detected in breast milk . Am J Gastroenterol. 2004;99 (10 Suppl S):S246-7 Abstract 761. DOI: doi:10.1111/j.1572-0241.2004.001_1.x

9. Gardiner SJ, Gearry RB, Roberts RL, Zhang M, Barclay ML, Begg EJ. Exposure to thiopurine drugs through breast milk is low based on metabolite concentrations in mother-infant pairs. Br J Clin Pharmacol. 2006;62:453-6. PMID: 16995866

10. de Meij TG, Jharap B, Kneepkens CM et al. Long-term follow-up of children exposed intrauterine to maternal thiopurine therapy during pregnancy in females with inflammatory bowel disease. Aliment Pharmacol Ther. 2013;38:38-43. PMID: 23675854

11. Mahadevan U, Martin CF, Sandler RS et al. PIANO: a 1000 patient prospective registry of pregnancy outcomes in women with IBD exposed to immunomodulators and biologic therapy. Gastroenterology. 2012;142 (5 Suppl 1):S149. Abstract 865.

Mercaptopurine Identification

Substance Name

Mercaptopurine

CAS Registry Number

50-44-2

Drug Class

  • Antineoplastic Agents

Administrative Information

LactMed Record Number

169

Information from the National Library of Medicine's LactMed Database.

Last Revision Date

2014-07-08

Disclaimer

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