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Health Canada advisory on domperidone
Should I avoid prescribing domperidone to women to increase milk production?
Pina Bozzo Gideon Koren MD FRCPC FACMT Shinya Ito MD FRCPC
I often prescribe domperidone to women as a galactagogue starting at a dose of 30 mg and increasing
the dose as needed. In March of this year, Health Canada released an advisory warning of domperidone use and
abnormal heart rhythms and sudden cardiac death. Should I cap doses at 30 mg or stop prescribing domperidone all
together to these women?
The Health Canada warning is based on 2 studies. The results of the studies are not directly applicable to
breastfeeding and should not change the way you normally manage otherwise healthy breastfeeding women.
Avis de Santé Canada sur la dompéridone
Devrais-je éviter de prescrire de la dompéridone aux femmes pour augmenter la production de lait?
Je prescris souvent de la dompéridone aux femmes comme galactagogue, en commençant par une dose
de 30 mg et en augmentant cette dose au besoin. En mars cette année, Santé Canada a publié une mise en garde
concernant l’utilisation de la dompéridone et les risques d’anomalies graves du rythme cardiaque et de mort subite.
Devrais-je limiter les doses à 30 mg ou arrêter complètement de prescrire de la dompéridone à ces femmes?
L’avis de Santé Canada se fonde sur 2 études. Les résultats de ces études ne sont pas directement
applicables à l’allaitement maternel et ne devraient pas changer la façon dont vous prenez normalement en charge
les femmes autrement en bonne santé qui allaitent.
omperidone is a dopamine antagonist with anti- infants). Only minimal amounts of domperidone are
emetic and gastroprokinetic properties.1 It is indi-
excreted into breast milk (less than 0.1% of the mater-
cated for the symptomatic management of upper
nal weight-adjusted dose), and side effects in breastfed
gastrointestinal motility disorders and gastrointestinal
infants have not been reported.3,6-8 Therefore, when
symptoms associated with the use of dopamine agonist
nonpharmacologic treatments fail or are inadequate,
Breastfeeding is recommended for all infants, with
very few exceptions, as there are many benefits for
Health Canada advisory
the developing child, including evidence for improved
In March 2012 Health Canada released an advisory to
cognitive development, reduced incidence of infec-
health care professionals and to the public warning of
tion, and less risk of sudden infant death syndrome.2
possible serious side effects associated with the use
Further, there is evidence of benefits for the mother,
of domperidone.9,10 The warning was based on 2 stud-
such as reduced incidence of reproductive cancers.3
ies reporting an association of domperidone with seri-
Some women, however, experience insufficient breast
ous abnormal heart rhythms and sudden cardiac death
milk production. Domperidone has been demon-
strated to induce and maintain lactation by increas-
In the first study, a nested case-control study by
ing prolactin levels.4 A recent systematic review and
Johannes et al,11 domperidone use was associated with
meta-analysis by Motherisk demonstrated a statisti-
an increased risk of serious ventricular arrhythmia (SVA)
cally significant increase of 74.7% (95% CI 54.6 to 94.9,
and SCD when compared with nonusers (adjusted odds
< .001) in daily milk production following treatment
ratio [AOR] 1.59, 95% CI 1.28 to 1.98). The average age
with domperidone and found no maternal safety issues
for the cohort was 79.4 years (range 20 to 95, median
when compared with placebo.5 At present, some inter-
age 82); when stratified by age and sex, individuals
vention trials are under way to define the appropriate
younger than age 60 years and women did not have
dose in specific populations (eg, mothers of preterm
increased risk from domperidone exposure (OR [95% CI]
952 Canadian Family Physician
• Le Médecin de famille canadien
| Vol 58: september • septembre 2012
1.10 [0.35 to 3.47] and 1.25 [0.93 to 1.67], respectively).11
2. Health Canada. Nutrition for healthy term infants. Statement of the Joint
Working Group: Canadian Paediatric Society, Dietitians of Canada, and Health
In the second study, a case-control analysis by van
. Ottawa, ON: Health Canada; 2005. Available from: www.hc-sc.
Noord et al,12 current domperidone use was associated
php#a1. Accessed 2012 Apr 5.
with increased risk of SCD (unadjusted OR 3.72, 95%
3. Dermer A. A well-kept secret: breastfeeding’s benefits to mothers. New
CI 1.72 to 8.08), but the AOR was not significant. When
2001;18(4):124-7. Available from: www.llli.org/nb/
nbjulaug01p124.html. Accessed 2012 Apr 5.
the authors further focused on publicly insured patients,
4. Petraglia F, De Leo V, Sardelli V, Pieroni ML, D’Antona N, Genazzani AR.
which included 7 SCD cases with current domperidone
Domperidone in defective and insufficient lactation. Eur J Obstet Gynecol Reprod Biol
use, the AOR became significant (AOR 4.17, 95% CI 1.33
5. Osadchy A, Moretti ME, Koren G. Effect of domperidone on insufficient lacta-
to 13.1). Investigators were unable to demonstrate an
tion in puerperal women: a systematic review and meta-analysis of random-ized controlled trials. Obstet Gynecol Int
2012;2012:642893. Epub 2012 Feb 7.
effect of domperidone on SVA owing to an absence
6. Jantarasaengaram S, Sreewapa P. Effects of domperidone on augmentation
of exposed cases. When stratified by daily dose, doses
of lactation following cesarean delivery at full term. Int J Gynaecol Obstet
above 30 mg/d were associated with higher risk of SCD
7. Hofmeyr GJ, Van Iddekinge B, Blott JA. Domperidone: secretion in breast milk
(AOR 11.4, 95% CI 1.99 to 65.2). This association, how-
and effect on puerperal prolactin levels. Br J Obstet Gynaecol
8. Da Silva OP, Knoppert DC, Angelini MM, Forret PA. Effect of domperidone on
ever, was based on only 4 individuals exposed to dom-
milk production in mothers of premature newborns: a randomized, double-
peridone who experienced SCD. Also of importance, the
blind, placebo-controlled trial. CMAJ
9. Health Canada. Domperidone maleate—association with serious abnormal
average (SD) age of the cohort of SCD cases (n = 1304)
heart rhythms and sudden death (cardiac arrest)—for health care professionals.
was 72.5 (14.1) years. Clearly, the populations in these
Ottawa, ON: Health Canada; 2012. Available from: http://hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/_2012/domperidone_hpc-cps-eng.
studies are distinct from healthy breastfeeding women.12
Finally, in both studies, the data on the cases and
10. Health Canada. Domperidone maleate—association with serious abnormal
heart rhythms and sudden death (cardiac arrest)—for the public.
controls were retrieved from databases. These data-
Health Canada; 2012. Available from: http://hc-sc.gc.ca/dhp-mps/medeff/
bases have some limitations. One of the main limita-
tions is that the researchers were only able to examine
11. Johannes CB, Varas-Lorenzo C, McQuay LJ, Midkiff KD, Fife D. Risk of seri-
if a prescription for domperidone was filled. Whether
ous ventricular arrhythmia and sudden cardiac death in a cohort of users of domperidone: a nested case-control study. Pharmacoepidemiol Drug Saf
or not the individual took the medication was not con-
firmed.11,12 Also, in the Netherlands, where the second
12. Van Noord C, Dieleman JP, van Herpen G, Verhamme K, Sturkenboom MC.
Domperidone and ventricular arrhythmia or sudden cardiac death: a population-
study was conducted, domperidone is available over the
based case-control study in the Netherlands. Drug Saf
counter; therefore, all exposures to domperidone might not have been captured.12
Owing to the demographic characteristics of the popu-
Motherisk questions are prepared by the
Children in Toronto, Ont. Ms Bozzo
is Assistant Director, Dr Koren
is Director, and
papers would not directly apply to healthy women of
is a member of the Motherisk Program. Dr Koren is supported by the
childbearing age. Nonetheless, caution is advised when
Research Leadership for Better Pharmacotherapy during Pregnancy and Lactation.
prescribing domperidone with other drugs that prolong
He holds the Ivey Chair in Molecular Toxicology in the Department of Medicine at
the QT interval or with those that interfere with dom-
the University of Western Ontario in London.
peridone metabolism, or for women who have underly-
Do you have questions about the effects of drugs, chemicals, radiation, or
infections in women who are pregnant or breastfeeding? We invite you to submit
them to the Motherisk Program by fax at 416 813-7562; they will be addressed in
future Motherisk Updates
Published Motherisk Updates
are available on the Canadian Family Physician
[product monograph]. Toronto, ON: Teva Canada Ltd; 2012.
) and also on the Motherisk website (www.motherisk.org
Vol 58: september • septembre 2012
| Canadian Family Physician
• Le Médecin de famille canadien 953
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