Last update May 11, 2019

3,4-Dihydro-3-methyl-4-oxoimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide

Limited compatibility

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.

It is a prodrug of MTIC, the active metabolite of dacarbazine, which acts as an alkylating agent and is used in the treatment of malignant melanomas and gliomas.
It is administered orally or intravenously every 24 hours for 5 days in cycles every 28 days. In the treatment of glioblastoma multiforme it is administered in an initial phase together with radiotherapy daily for 42 days.

Since the last update we have not found any published data on its excretion in breast milk.

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 (xxx hours) as a reference, these 5 T½ would correspond to 9 hours. Due to major side effects, it would be advisable to wait 7 T½, which would correspond to 13 hours. 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 the treatment of cancer, breastfeeding should be interrupted temporarily 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 this related product:

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

Alternatives

We do not have alternatives for 3,4-Dihydro-3-methyl-4-oxoimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide .

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

3,4-Dihydro-3-methyl-4-oxoimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide is Temozolomide in Chemical name.

Is written in other languages:

3,4-Dihydro-3-methyl-4-oxoimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide is also known as

Group

3,4-Dihydro-3-methyl-4-oxoimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide belongs to this group or family:

Tradenames

Main tradenames from several countries containing 3,4-Dihydro-3-methyl-4-oxoimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide in its composition:

Pharmacokinetics

Variable Value Unit
Oral Bioavail. 100 %
Molecular weight 194 daltons
Protein Binding 10 - 20 %
VD 0.4 l/Kg
pKa 10.5 -
Tmax 0.5 - 1.5 hours
1.8 hours

References

  1. 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
  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. FDA-MSD. Temozolomide. Drug Summary. 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. EMA-MSD. Temozolomida Ficha técnica. 2009 Full text (in our servers)

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