Is clozapine safe to continue during breastfeeding?

There is a paucity of information on breastfeeding and clozapine in the published literature to guide recommendations. While breastfeeding has important benefit to infants, clozapine presents unique risks. Clozapine is highly lipophilic and significant concentrations have been found in breast milk (Barnas et al. 1994). Even if the infant ingests only a small amount of clozapine in breast milk, severe neutropenia (previously known as agranulocytosis) is not a dose-dependent phenomenon (Alvir et al. 1993).

In a study of four women taking clozapine who breastfed their infants, one out of the four infants developed severe neutropenia, and another developed lethargy and drowsiness (Dev, Rosenberg, and Krupp 1994). Subsequently, there was a case report of delayed speech development in a 5-year old whose mother breastfed while on clozapine, but it was impossible to determine if the delayed speech was due to the clozapine (Mendhekar 2007).

In a consensus guideline on the use of psychotropic medication in pregnancy and the postpartum period, the British Association for Psychopharmacology considers breastfeeding a contraindication for clozapine due to the risk of agranulocytosis and seizures (McAllister-Williams et al. 2017). In the Clozapine Handbook, Drs. Meyer and Stahl conclude, “at the present time, the risk of this potentially fatal complication [agranulocytosis] appear to outweigh the multiple benefits of breastfeeding” (2019). Uguz also reached a similar conclusion in a comparative review on second generation antipsychotics during lactation (2016).

See the National Institute of Health’s LactMed database for more information about clozapine and breastfeeding.

Per the Nursing Mother section of the clozapine package insert, “Because of the potential for serious adverse reactions in nursing infants from clozapine, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother” (DailyMed – US National Library of Medicine 2020).

REFERENCES

  • Alvir JMJ, Lieberman JA, Safferman AZ, et al: Clozapine-Induced Agranulocytosis — Incidence and Risk Factors in the United States. New England Journal of Medicine 329:162-167, 1993
  • Barnas C, Bergant A, Hummer M, et al: Clozapine concentrations in maternal and fetal plasma, amniotic fluid, and breast milk. Am J Psychiatry 151:945, 1994
  • DailyMed – US National Library of Medicine. (2020). “Clozapine drug label information.”   Retrieved September 14, 2020, from https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=883b5d43-0339-7dc1-f775-93791fb9b978.
  • Dev VJ, Rosenberg T, Krupp P: Agranulocytosis and clozapine. Bmj 309:54, 1994
  • McAllister-Williams RH, Baldwin DS, Cantwell R, et al: British Association for Psychopharmacology consensus guidance on the use of psychotropic medication preconception, in pregnancy and postpartum 2017. J Psychopharmacol 31:519-552, 2017
  • Mendhekar DN: Possible delayed speech acquisition with clozapine therapy during pregnancy and lactation. J Neuropsychiatry Clin Neurosci 19:196-197, 2007
  • Meyer JM, Stahl SM (2019). The Clozapine Handbook: Stahl’s Handbooks, Cambridge University Press.
  • Uguz F: Second-Generation Antipsychotics During the Lactation Period: A Comparative Systematic Review on Infant Safety. J Clin Psychopharmacol 36:244-252, 2016
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