Last update March 24, 2019

4′-Demethylepipodophyllotoxin 9-[4,6-O-(R)-ethylidene-β-d-glucopyranoside]; (5S,5aR,8aS,9R)-9-(4,6-O-Ethylidene-β-d-glucopyranosyloxy)-5,8,8a,9-tetrahydro-5-(4-hydroxy-3,5-dimethoxyphenyl)-isobenzofuro[5,6-f][1,3]benzodioxol-6(5aH)-one

Incompatible

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

Derived from podophyllotoxin, it is an inhibitor of mitosis. There is a high risk of serious side effects such as myelotoxicity (AEMPS 2015, Bristol MS 2010).
Indicated in certain leukemias, lung neoplasms and others; it is generally associated with other chemotherapeutic agents.
Intravenous or oral administration: 3 to 4 cycles of daily intravenous or several oral doses for 3 to 5 days followed by a 10 to 20 day break (AEMPS 2015, Bristol MS 2010).

Its high percentage of protein binding would explain the limited transfer to breastmilk (Azuno 1995). Due to its short half-life (T½), levels were undetectable in milk at 24 hours (Azuno 1995). The mother referred to in this publication (Azuno 1995), who also took mitoxantrone (T½ 1 to 9 days) and cytarabine (T½ 1 to 3 hours), waited 3 weeks before breastfeeding again; the infant did not present any problems in a follow-up at 16 months.

Given its serious side effects, it is prudent to interrupt breastfeeding during the period when the drug is still in the mother's body.

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

It is known from pharmacokinetics 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 plasma concentrations of the 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).

Expert authors recommend waiting 3 days (about 6 T½) after the last dose to resume breastfeeding. Meanwhile, express and discard milk from the breast regularly (Hale 2017 p.353, Pistilli 2013).

Some chemotherapeutic agents with antibiotic effects can alter the composition of the microbiota (bacterial cluster 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 expected nor have been reported in breastfed infants.

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:

  • Cytarabine (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.)
  • Mitoxantrone Hydrochloride (Very unsafe. Contraindicated. Use of an alternative or cessation of breastfeeding. Read the Commentary.)

Alternatives

We do not have alternatives for 4′-Demethylepipodophyllotoxin 9-[4,6-O-(R)-ethylidene-β-d-glucopyranoside]; (5S,5aR,8aS,9R)-9-(4,6-O-Ethylidene-β-d-glucopyranosyloxy)-5,8,8a,9-tetrahydro-5-(4-hydroxy-3,5-dimethoxyphenyl)-isobenzofuro[5,6-f][1,3]benzodioxol-6(5aH)-one.

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

4′-Demethylepipodophyllotoxin 9-[4,6-O-(R)-ethylidene-β-d-glucopyranoside]; (5S,5aR,8aS,9R)-9-(4,6-O-Ethylidene-β-d-glucopyranosyloxy)-5,8,8a,9-tetrahydro-5-(4-hydroxy-3,5-dimethoxyphenyl)-isobenzofuro[5,6-f][1,3]benzodioxol-6(5aH)-one is Etoposide in Chemical name.

Is written in other languages:

Group

4′-Demethylepipodophyllotoxin 9-[4,6-O-(R)-ethylidene-β-d-glucopyranoside]; (5S,5aR,8aS,9R)-9-(4,6-O-Ethylidene-β-d-glucopyranosyloxy)-5,8,8a,9-tetrahydro-5-(4-hydroxy-3,5-dimethoxyphenyl)-isobenzofuro[5,6-f][1,3]benzodioxol-6(5aH)-one belongs to this group or family:

Tradenames

Main tradenames from several countries containing 4′-Demethylepipodophyllotoxin 9-[4,6-O-(R)-ethylidene-β-d-glucopyranoside]; (5S,5aR,8aS,9R)-9-(4,6-O-Ethylidene-β-d-glucopyranosyloxy)-5,8,8a,9-tetrahydro-5-(4-hydroxy-3,5-dimethoxyphenyl)-isobenzofuro[5,6-f][1,3]benzodioxol-6(5aH)-one in its composition:

Pharmacokinetics

Variable Value Unit
Oral Bioavail. 55 (17 - 74) %
Molecular weight 589 daltons
Protein Binding 97 - 98 %
VD 0.25 - 0.41 l/Kg
pKa 9.33 -
Tmax 1 (0.5 - 2) hours
4 - 11.5 hours
Theoretical Dose 0.09 - 0.12 mg/Kg/d
Relative Dose ≅ 6 %

References

  1. Hale TW, Rowe HE. Medications & Mothers' Milk. A Manual of Lactation Pharmacology. Springer Publishing Company. 2017
  2. Anderson PO. Cancer Chemotherapy. Breastfeed Med. 2016 May;11:164-5. Abstract Full text (link to original source) Full text (in our servers)
  3. AEMPS. Etoposido. Ficha técnica. 2015 Full text (in our servers)
  4. 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)
  5. 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
  6. 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)
  7. Bristol MS. Etoposide (oral Vepesid). Drug Summary. 2010 Full text (in our servers)
  8. Azuno Y, Kaku K, Fujita N, Okubo M, Kaneko T, Matsumoto N. Mitoxantrone and etoposide in breast milk. Am J Hematol. 1995 Abstract

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