Last update March 24, 2019

Phosphorothioic tri(ethyleneamide); Tris(aziridin-1-yl)phosphine sulphide

Incompatible

Very unsafe. Contraindicated. Use of an alternative or cessation of breastfeeding. Read the Commentary.

Thiotepa and its active metabolites (TEPA, monochlorotepa and thiotepa-mercapturate) are antineoplastics with alkylating action.
Indicated in the treatment of solid tumors, ovarian, breast and bladder cancer and in conditioning treatment before a transplantation of hematopoietic stem cells.
Administration by parenteral or intramuscular route in intervals of between 1 and 4 weeks or daily for 4 days.

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

Its pharmacokinetic data (low molecular weight, low percentage of plasma protein binding, high liposolubility), makes it probable that it could pass to breastmilk in potentially significant quantities.

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).

Taking the longest published T½ of all the active metabolites as a reference, 21 hours for TEPA (ASHP 2016 p426), these 5 T½ would correspond to 4 days. Due to major side effects, it would be advisable to wait 7 T½, which would correspond to 6 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).

Alternatives

We do not have alternatives for Phosphorothioic tri(ethyleneamide); Tris(aziridin-1-yl)phosphine sulphide.

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

Phosphorothioic tri(ethyleneamide); Tris(aziridin-1-yl)phosphine sulphide is Thiotepa in Chemical name.

Is written in other languages:

Phosphorothioic tri(ethyleneamide); Tris(aziridin-1-yl)phosphine sulphide is also known as

Group

Phosphorothioic tri(ethyleneamide); Tris(aziridin-1-yl)phosphine sulphide belongs to this group or family:

Tradenames

Main tradenames from several countries containing Phosphorothioic tri(ethyleneamide); Tris(aziridin-1-yl)phosphine sulphide in its composition:

Pharmacokinetics

Variable Value Unit
Oral Bioavail. baja - poor %
Molecular weight 189 daltons
Protein Binding 10 - 30 %
VD 41 - 75 l/m2 l/Kg
1.5 - 4.1 (TEPA: 10 - 21) hours

References

  1. FDA-Adienne. Thiotepa. Drug Summary. 2017 Full text (in our servers)
  2. 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
  3. ASHP-American Society of Health-System Pharmacists. Thiotepa. AHFS Drug Information. 2016
  4. Anderson PO. Cancer Chemotherapy. Breastfeed Med. 2016 May;11:164-5. Abstract Full text (link to original source) Full text (in our servers)
  5. EMA-Adienne. Tiotepa. Ficha técnica. 2015 Full text (in our servers)
  6. Urbaniak C, McMillan A, Angelini M, Gloor GB, Sumarah M, Burton JP, Reid G. Effect of chemotherapy on the microbiota and metabolome of human milk, a case report. Microbiome. 2014 Jul 11;2:24. Abstract Full text (link to original source) Full text (in our servers)
  7. 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

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