Is ADM Safe in Breastfeeding

I am a breastfeeding mother and i want to know if it is safe to use ADM? Is ADM safe for nursing mother and child? Does ADM extracts into breast milk? Does ADM has any long term or short term side effects on infants? Can ADM influence milk supply or can ADM decrease milk supply in lactating mothers?

ADM is a cytotoxic anthracycline antibiotic isolated from cultures of the caesium variety of Streptomyces peucetius. ADM and its active metabolite ADMol are excreted in breast milk in significant amounts and with a very high milk/plasma ratio (Pistilli 2013, Egan 1985). There are two distinct pharmaceutical forms of ADM, in the form of hydrochloride and in liposomal form, with very different pharmacokinetic profiles (Gabizon 2003). Given the variability in interindividual pharmacokinetics, potential pharmacokinetic changes with co-administration with other medication (EMA 2017, Swenson 2003) and their serious side effects (cardiotoxicity, myelotoxicity and liver toxicity) (Tacar 2013, Danesi 2002), it is prudent not to breastfeed during treatment. When possible, detection in the 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. 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 five half-lives may be considered a safe waiting period to return to breastfeeding (Anderson 2016). For ADM in hydrochloride form, with a mean elimination half-life (T½) of 30 hours, authors recommend waiting 7 to 10 days (between 5, 6 and 8 T½) after the last dose to restart breastfeeding. Meanwhile, express and discard breast milk regularly (Hale 2017 p.210). For the liposomal form with a mean T ½ of 74 hours and a wide range, this is not applicable. Some chemotherapeutics with antibiotic effects may alter the composition of the microbiota (combination of bacteria or bacterial flora) of the milk and the concentration of some of its components (Urbaniak 2014). This possibly occurs briefly with later recovery, with no harmful effects being reported in breastfed infants.

Most sources consider breastfeeding to be contraindicated during maternal antineoplastic drug therapy, especially anthracyclines such as ADM.[1] It might be possible to breastfeed safely during intermittent therapy with an appropriate period of breastfeeding abstinence; however, the high levels and persistence of ADMol in milk make defining an appropriate abstinence interval difficult. Chemotherapy may adversely affect the normal microbiome and chemical makeup of breastmilk.[2] Women who receive chemotherapy during pregnancy are more likely to have difficulty nursing their infant.

A study of adolescent males who had received chemotherapy for childhood malignancies found that having received ADM was associated with elevated serum prolactin concentrations.[5] A woman diagnosed with Hodgkin's lymphoma during the second trimester of pregnancy received 3 rounds of chemotherapy during the third trimester of pregnancy and resumed chemotherapy 4 weeks postpartum. Milk samples were collected 15 to 30 minutes before and after chemotherapy for 16 weeks after restarting. The regimen consisted of ADM 40 mg, bleomycin 16 units, vinblastine 9.6 mg and dacarbazine 600 mg, all given over a 2-hour period every 2 weeks. The microbial population and metabolic profile of her milk were compared to those of 8 healthy women who were not receiving chemotherapy. The breastmilk microbial population in the patient was markedly different from that of the healthy women, with increases in Acinetobacter sp., Xanthomonadacae and Stenotrophomonas sp. and decreases in Bifidobacterium sp. and Eubacterium sp. Marked differences were also found among numerous chemical components in the breastmilk of the treated woman, most notably DHA and inositol were decreased.[2] A telephone follow-up study was conducted on 74 women who received cancer chemotherapy at one center during the second or third trimester of pregnancy to determine if they were successful at breastfeeding postpartum. Only 34% of the women were able to exclusively breastfeed their infants, and 66% of the women reported experiencing breastfeeding difficulties. This was in comparison to a 91% breastfeeding success rate in 22 other mothers diagnosed during pregnancy, but not treated with chemotherapy. Other statistically significant correlations included: 1. mothers with breastfeeding difficulties had an average of 5.5 cycles of chemotherapy compared with 3.8 cycles among mothers who had no difficulties; and 2. mothers with breastfeeding difficulties received their first cycle of chemotherapy on average 3.4 weeks earlier in pregnancy. Of the 62 women who received a ADM-containing regimen, 39 had breastfeeding difficulties.[6]