Last update July 16, 2022

L01AA01

High Risk

Poorly safe. Evaluate carefully. Use safer alternative or interrupt breastfeeding 3 to 7 T ½ (elimination half-lives). Read the Comment.

Cyclophosphamide, together with its active metabolites, aldophosphamide, acrolein and nitrogenated mustard, is an antineoplastic from the group of nitrogen mustards with very marked immunosuppressive properties.

Cyclophosphamide is excreted in breast milk (Wiernik 1971) in very low amount (Damoiseaux 2022, Fierro 2019, Codacci 2019), but in two studies, breastfed infants developed neutropenia, thrombocytopenia, and anemia. (Durodola 1979, Amato 1977)

A mother with non-Hodgkin's lymphoma treated with 4 cycles of 21 days of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone expressed and discarded milk the first 10 days of each cycle (3 T1/2 vincristine) and breastfed the next 10 days before of the next treatment, without problems for the infant. (Hersey 2020)

It is known via Pharmacokinetics that after 3 elimination half-lives (T½) 87.5% of the drug is eliminated from the body; after 4 T½ 94%, after 5 T½ 96.9%, after 6 T½ 98.4% and after 7 T½ 99%. Plasma drug concentrations in the body are negligible after 7 T½. In general, a period of al least five half-lives may be considered a safe waiting period before returning to breastfeeding. (Anderson 2016)

Taking the longest published T½ of all the active metabolites as a reference, these 5 T½ would correspond to 60 hours. Due to major side effects, it would be advisable to wait 7 T½, which would correspond to 84 hours. Meanwhile, express and discard milk from the breast regularly to maintain production. 

Expert authors recommend waiting 72 hours after the last dose (6 T½) to restart breastfeeding. (Hale, Damoiseaux 2022, Johnson 2020). Other authors suggest 6 weeks. (Codacci 2019)

When possible, detection in breast milk of each patient to determine the total elimination of the drug would be the best indicator for resuming breastfeeding between two rounds of chemotherapy.

Other authors, given the variability in interindividual pharmacokinetics, potential pharmacokinetic changes with co-administration with other medication and its serious side effects, believe that it is prudent not to breastfeed during treatment. (Anderson 2016, Götestam 2016, Grunewald 2015, Pistilli 2013, Østensen 2006, WHO 2002, Pediatrics 2001)

Women undergoing chemotherapy during pregnancy have lower rates of breastfeeding because they experience difficulties in breastfeeding (Stopenski 2017), needing more support to achieve it.

Given the strong evidence that exists on the benefits of breastfeeding for the development of babies and the health of mothers, it is advisable to evaluate the risk-benefit of any maternal treatment, including chemotherapy, individually advising each mother that wishes to continue with breastfeeding. (Koren 2013)


See below the information of this related product:

  • Maternal Cancer ( Poorly safe. Evaluate carefully. Use safer alternative or interrupt breastfeeding 3 to 7 T ½ (elimination half-lives). Read the Comment.)

Alternatives

We do not have alternatives for L01AA01.

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

L01AA01 is Cyclophosphamide in ATC Code/s.

Is written in other languages:

Group

L01AA01 belongs to this group or family:

Tradenames

Main tradenames from several countries containing L01AA01 in its composition:

Pharmacokinetics

Variable Value Unit
Oral Bioavail. 75 %
Molecular weight 261 daltons
Protein Binding 13 - 20 %
VD 0.4 - 0.7 l/Kg
Tmax 3 - 5 hours
7.5 (3 - 12) hours
Theoretical Dose 0.47 - 2.27 mg/Kg/d
Relative Dose 0.9 - 4.8 %

References

  1. Damoiseaux D, Calpe S, Rosing H, Beijnen JH, Huitema ADR, Lok C, Dorlo TPC, Amant F. Presence of Five Chemotherapeutic Drugs in Breast Milk as a Guide for the Safe Use of Chemotherapy During Breastfeeding: Results From a Case Series. Clin Pharmacol Ther. 2022 Apr 29. Consulted on July 16, 2022 Abstract
  2. Hersey AE, Giglio P, Kurt H, Tarabulsi G, Chen KK. Diffuse Large B-Cell Lymphoma During Third-Trimester Pregnancy and Lactation. Obstet Gynecol. 2020 Feb;135(2):383-386. Abstract
  3. Johnson HM, Mitchell KB; Academy of Breastfeeding Medicine.. ABM Clinical Protocol #34: Breast Cancer and Breastfeeding. Breastfeed Med. 2020 Jul;15(7):429-434. Abstract Full text (link to original source)
  4. Codacci-Pisanelli G, Honeywell RJ, Asselin N, Bellettini G, Peters GJ, Giovannetti E, Peccatori FA. Breastfeeding during R-CHOP chemotherapy: please abstain! Eur J Cancer. 2019 Sep;119:107-111. Abstract
  5. Fierro ME, Datta P, Rewers-Felkins K, Smillie CM, Bresnahan A, Baker T, Hale TW. Cyclophosphamide Use in Multiple Sclerosis: Levels Detected in Human Milk. Breastfeed Med. 2019 Mar;14(2):128-130. Abstract
  6. Hale TW, Rowe HE. Medications & Mothers' Milk. A Manual of Lactation Pharmacology. Springer Publishing Company. 2017
  7. Stopenski S, Aslam A, Zhang X, Cardonick E. After Chemotherapy Treatment for Maternal Cancer During Pregnancy, Is Breastfeeding Possible? Breastfeed Med. 2017 Mar;12:91-97. Abstract
  8. Anderson PO. Cancer Chemotherapy. Breastfeed Med. 2016 May;11:164-5. 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. Grunewald S, Jank A. New systemic agents in dermatology with respect to fertility, pregnancy, and lactation. J Dtsch Dermatol Ges. 2015 Abstract Full text (link to original source) Full text (in our servers)
  11. AEMPS. Ciclofosfamida. Ficha técnica. 2014 Full text (in our servers)
  12. Koren G, Carey N, Gagnon R, Maxwell C, Nulman I, Senikas V; Society of Obstetricians and Gynaecologists of Canada. Cancer chemotherapy and pregnancy. J Obstet Gynaecol Can. 2013 Mar;35(3):263-278. Abstract Full text (link to original source) Full text (in our servers)
  13. Pistilli B, Bellettini G, Giovannetti E, Codacci-Pisanelli G, Azim HA Jr, Benedetti G, Sarno MA, Peccatori FA. Chemotherapy, targeted agents, antiemetics and growth-factors in human milk: how should we counsel cancer patients about breastfeeding? Cancer Treat Rev. 2013 May;39(3):207-11. Abstract
  14. FDA. Cyclophosphamide. Drug Summary. 2013 Full text (in our servers)
  15. 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)
  16. Temprano KK, Bandlamudi R, Moore TL. Antirheumatic drugs in pregnancy and lactation. Semin Arthritis Rheum. 2005 Abstract
  17. 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)
  18. AAP - American Academy of Pediatrics Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics. 2001 Sep;108(3):776-89. Abstract Full text (link to original source) Full text (in our servers)
  19. 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)
  20. Moretti ME, Lee A, Ito S. Which drugs are contraindicated during breastfeeding? Practice guidelines. Can Fam Physician. 2000 Sep;46:1753-7. Review. Abstract Full text (link to original source) Full text (in our servers)
  21. Durodola JI. Administration of cyclophosphamide during late pregnancy and early lactation: a case report. J Natl Med Assoc. 1979 Feb;71(2):165-6. Abstract Full text (link to original source) Full text (in our servers)
  22. Amato D, Niblett JS. Neutropenia from cyclophosphamide in breast milk. Med J Aust. 1977 Mar 12;1(11):383-4. No abstract available. Abstract
  23. Wiernik PH, Duncan JH. Cyclophosphamide in human milk. Lancet. 1971 May 1;1(7705):912. No abstract available. Abstract

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