Australian Prescriber An independent Review Logo
ISSUE 2 APRIL
Letters to the Editor

Drugs and breastfeeding

  • Elizabeth Barbehenn, Molika In

Letter to the Editor

Editor, – After reading the book review of 'Drugs and breastfeeding', I looked up the US product information for metronidazole in the 2000 Physicians' Desk Reference.

The information under Carcinogenicity states that pulmonary tumours were found in all six studies done in mice including one with dosing only every fourth week; there were also malignant tumours in the liver and malignant lymphomas. In rats, there were liver and mammary tumours. And finally, the drug is genotoxic - it damages the DNA directly.

Under the heading Nursing Mothers, it says, 'because of the potential for tumorigenicity shown for metronidazole in mouse and rat studies, a decision should be made whether to discontinue nursing or to discontinue the drug'. It further states that, 'metronidazole is secreted in human milk in concentrations similar to those found in plasma'.

Based on this information, I take issue with the reviewer who says that, based on this book, she is reassured that metronidazole 'will do the baby no harm'. On the contrary, there is tremendous potential for harm and the US product information actually says not to nurse when using metronidazole. So much for the usefulness of this book!

Elizabeth Barbehenn
Research analyst
Public Citizen's Health Research Group
Washington DC, USA

 

Author's comment

Molika In, Pharmacy Department, The Royal Women's Hospital, Melbourne, comments:

Prescribing for breastfeeding women is a potentially complex decision. Clinicians are often faced with a dilemma when reading product information, as these documents tend to recommend ceasing breastfeeding whenever medications are required. Weaning a baby may, however, not be practical and immediate treatment may be required. Various resources are available and should be used by clinicians in order to make informed decisions and weigh up the risks and benefits with breastfeeding women requiring treatment.

The product information for metronidazole clearly states a potential mutagenicity and carcinogenicity association in animals but not in humans. Several studies showed this association with short treatment courses of metronidazole as not statistically significant.1,2,3 Also, the cytogenic effects occur only when there is a metabolic reduction of metronidazole, as in hypoxic tumour cells.4,5,6,7 Metronidazole has been used therapeutically for more than 40 years and its use in breastfeeding has been reviewed over two decades.8,9

Metronidazole is excreted in the breast milk, but very few cases of adverse effects have been reported and even then the correlation is questionable. Recent reports show no obvious adverse effects associated with mothers taking metronidazole while breastfeeding.10,11,12 Even more reassuring is the fact that the dose of metronidazole received by a breastfeeding infant is far lower than the dose used for treating neonates, infants or children.13

Current literature and The Royal Women's Hospital Drugs and breastfeeding guide suggests the benefits of continuing breastfeeding outweigh the theoretical potential cancer risk posed by metronidazole.10,14,15

 

References

  1. Falagas ME, Walker AM, Jick H, Ruthazer R, Griffith J, Snydman DR. Late incidence of cancer after metronidazole use: a matched metronidazole user/nonuser study. Clin Infect Dis 1998;26:384-8.
  2. Bendesky A, Menendez D, Ostrosky-Wegman P. Ismetronidazole carcinogenic? Mutat Res 2002;511:133-44.
  3. Fahrig R, Engelke M. Reinvestigation of in vivo genotoxicity studies in man. I. No induction of DNA strand breaks in peripheral lymphocytes after metronidazole therapy. Mutat Res 1997;395:215-21.
  4. Dobias L, Cerna M, Rossner P, Sram R. Genotoxicity and carcinogenicity of metronidazole. Mutat Res1994;317:177-94.
  5. Thomson MICROMEDEX. Metronidazole. Healthcare Series Vol. 123 [subscription required].
  6. Schreiber A, Krause M, Zips D, Dorfler A, Richter K, Vettermann S, et al. Effect of the hypoxic cell sensitizer isometronidazole on local control of two human squamous cell carcinomas after fractionated irradiation. Strahlenther Onkol 2004;180:375-82.
  7. Skoropad VY, Berdov BA, Zagrebin VM. Preoperative radiotherapy in combination with metronidazole for resectable gastric cancer: long-term results of a phase 2study. Eur J Surg Oncol 2003;29:166-70.
  8. Drinkwater P. Metronidazole. Aust N Z J Obstet Gynaecol1987;27:228-30.
  9. Einarson A, Ho E, Koren G. Can we use metronidazole during pregnancy and breastfeeding? Putting an end to the controversy. Can Fam Physician 2000;46:1053-4.
  10. Hale TW. Medications and mother's milk 2002. 10th ed.Amarillo, TX: Pharmasoft Publishing; 2002.
  11. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 5th ed. Baltimore, MD: Williams & Wilkins; 1998.
  12. Weiner CP, Buhimschi C. Drugs for pregnant and lactating women. New York: Churchill Livingstone; 2004.
  13. Paediatric Pharmacopoeia. 13th ed. Melbourne: Women's and Children's Health, Royal Children's Hospital; 2002.
  14. Passmore CM, McElnay JC, Rainey EA, D'Arcy PF. Metronidazole excretion in human milk and its effect on the suckling neonate. Br J Clin Pharmacol 1988;26:45-51.
  15. Bar-Oz B, Bulkowstein M, Benyamini L, Greenberg R, Soriano I, Zimmerman D, et al. Use of antibiotic and analgesic drugs during lactation. Drug Saf 2003;26:925-35.
 

The Editorial Executive Committee welcomes letters, which should be less than 250 words. Before a decision to publish is made, letters which refer to a published article may be sent to the author for a response. Any letter may be sent to an expert for comment. When letters are published, they are usually accompanied in the same issue by their responses or comments. The Committee screens out discourteous, inaccurate or libellous statements. The letters are sub-edited before publication. Authors are required to declare any conflicts of interest. The Committee's decision on publication is final.

Elizabeth Barbehenn

Research analyst Public, Citizen's Health Research Group Washington DC, USA

Molika In

Pharmacy Department, The Royal Women's Hospital, Melbourne