Antipsychotic drugs can increase pituitary prolactin secretion and breast milk production through dopamine antagonism, but the gastrointestinal motility drugs metoclopramide and domperidone are most commonly used off label as galactagogues. Metoclopramide and domperidone block dopamine D2 receptors in the anterior pituitary and, in a limited number of clinical trials, they have had modest efficacy over placebo in initiating and maintaining lactation.2 The best chance for efficacy is if the galactagogue is started within three weeks of delivery.3
The safe duration of galactagogue therapy is controversial. Although increased prolactin can be detected within eight hours of the first dose, about two weeks is required for the breast changes required to sustain milk production. Current recommendations of 10–14 days are based on a limited number of controlled studies and the limited number of longer term controlled clinical trials.
Metoclopramide
Metoclopramide is a centrally acting drug. It can increase milk supply by 66–100% within 2–5 days in total daily doses of 30–45 mg. While the relative dose in milk ranges from 4.7–14.3%, adverse outcomes in infants have not been reported.4 However:
- effects are dose dependent, with a threshold of 10 mg
- doses need to be administered regularly three times a day
- only 50–85% of women with low milk supply will respond
- maternal adverse effects include diarrhoea and depression
- there is a theoretical risk of extrapyramidal adverse effects in the baby
- if metoclopramide is discontinued rapidly, there can be a significant rebound decline in milk supply.
Domperidone
Domperidone is a peripheral dopamine antagonist. At doses of 10–20 mg three times daily it has comparable efficacy to metoclopramide.4 Little domperidone passes into milk (relative infant dose 0.01–0.04%), so the risk of extrapyramidal effects in the baby is less than with metoclopramide.4
In 2004, the US Food and Drug Administration (FDA) issued an alert that domperidone could cause cardiac arrhythmias. This was in response to its illegal importation into the USA by breastfeeding mothers. The data related to historical cases of high-dose, intravenous use in sick patients receiving cancer chemotherapy. Two case control studies using oral domperidone in a general population supported this rare association. However, only three probable case reports in lactating women have been received by the FDA in postmarketing surveillance.5 Concomitant use of moderate or strong inhibitors of cytochrome P450 3A4 such as ketoconazole can increase plasma concentrations of domperidone and therefore the risk of QT prolongation.
In 2013, the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency recommended that the daily oral dose be restricted to a maximum of 30 mg and that domperidone not be used for longer than one week. It is therefore important that women being offered domperidone as a galactagogue have tried non-pharmacological strategies first. They need to be aware of the very low risk of QT prolongation and weigh this against the benefits of breastfeeding.
Complementary medicines
Herb-derived galactagogues have been used for centuries in folk medicine to augment lactation. These plants contain lipophilic, pharmacologically active constituents which, if taken in sufficient quantity, can pass into the breast milk. While there are generally few adverse effects (Table), there is limited evidence of efficacy. Most of the supporting evidence is based on case reports, or historical use.