Pegaspargase

Pegaspargase is the union of a variant of asparaginase (colaspase) with polyethylene glycol (PEG) with a molecular weight 5,000 daltons and with a longer half-life than asparaginase. Like asparaginase, pegaspargase is an enzyme that breaks down the L-asparagine plasma amino acid, preventing the growth of malignant leukemia cells which, unlike normal cells, cannot synthesize it. Indicated in the treatment of acute lymphoblastic leukemia since the neonatal period. Intravenous or intramuscular administration every 14 days.

Since the last update we have not found published data on its excretion in breastmilk.

Its high molecular weight makes excretion in breastmilk very unlikely.

Its low oral bioavailability hinders transfer to infant plasma from breastmilk since, due to its protein nature, it degrades in the gastrointestinal tract, and is not absorbed, except in premature babies and the immediate neonatal period when there may be greater permeability intestinal.

Pharmacokinetics show that after 3 elimination half-lives (T½) 87.5% of the drug is eliminated from the body; after 4 T½ it is 94%, after 5 T½, 96.9%, after 6 T½, 98.4% and after 7 T½ it is 99%. From 7 T½ the plasmatic concentrations of drug in the body are negligible. In general, a period of at least five half-lives can be considered a safe waiting period before breastfeeding again. ^{(Anderson 2016)}

Assuming it can pass into breast milk and taking the longest published T½ of all the active metabolites ^{(EMA 2018)} as a reference, these 5 T½ would correspond to 30 days. Due to major side effects, it would be advisable to wait 7 T½, which would correspond to 42 days. Meanwhile, express and discard milk from the breast regularly to maintain production.

When it is possible to do so, milk detections of each patient to determine the total elimination of the drug would be the best indicator to resume breastfeeding between two cycles of chemotherapy.

During breast cancer treatment, breastfeeding must be interrupted due to potentially serious side effects for the infant. Chemotherapy does not affect milk production during or after treatment. Abrupt weaning can be psychologically traumatic for both the mother and the infant (Pistilli 2013). If the mother wishes, the production of milk can be maintained by regularly expressing milk from the breast, being able to return to breastfeeding in the periods in which no significant traces of the drug remain in the milk ^{(Anderson 2016)} or at the end of the treatment. ^{(Pistilli 2013)}

Some chemotherapeutic agents with an antibiotic effect can alter the composition of the microbiota (bacterial set or bacterial flora) of the milk and the concentration of some of its components ^{(Urbaniak 2014)}. This possibly occurs temporarily with subsequent recovery, although no harmful effects are assumed or have been reported in breastfed infants.

Women undergoing chemotherapy during pregnancy have lower rates of breastfeeding due to difficulties in breastfeeding ^{(Stopenski 2017)}, needing more support to achieve it.

Given the strong evidence that exists regarding 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 who wishes to continue with breastfeeding. ^{(Koren 2013)}

See below the information of these related products:

• Asparaginase (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.)
• Maternal Cancer (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.)