Cyclophosphamide

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; Maternal Neoplasia (Unsafe. Moderate/severe adverse effects. Compatible under certain circumstances. Follow-up recommended. Use safer alternative or discontinue breastfeeding from 5 to 7 T ½ . Read Commentary.)