• Domperidone has replaced Metoclopramide as the Galactogogue of choice in NICU

Rationale

Domperidone is a peripheral dopamine-receptor antagonist used in the treatment of dyspepsia, reflux oesophagitis, and nausea and vomiting. One of its side effects is an increase in prolactin levels ^{1, 2}.

Unlike metoclopramide that works centrally, domperidone works on peripheral dopamine receptors in the GI wall and CTZ centre of the brainstem ¹. Its effects on prolactin secretion occurs at the pituitary level (outside the blood-brain barrier) ². Domperidone is less lipid soluble, has a larger molecular weight (426), and is highly protein bound (93%) ¹, as compared to metochlopramide. Combined with the peripheral action this results in fewer central side effects such as anxiety, depression and extrapyramidal symptoms ² and less medication crossing through into breastmilk. Because domperidone crosses less freely into breastmilk (compared with metoclopramide) the possible risks to the infant are also reduced ³. There has been some concern of the possible effect of dopamine antagonists on the functional maturation of central dopamine mechanisms in newborns (identified in experiments on rats) ⁴.

Da Silva showed a milk domperidone concentration of 1.2ng/ml, after a dose of 10mg three times per day, measured on day 5 from randomly selected samples ². This is compared with 125.7ng/ml of maxalon from milk samples taken 2 hours after a dose of 10mg of metoclopramide ⁴

Efficacy

Domperidone has been approved by the American Academy of Pediatrics (AAP) for use in breastfeeding ¹ and is currently the only galactogogue that has been scientifically evaluated through a randomised, double-blind placebo-controlled trial ³. This trial by da Silva et al ² showed milk volume increased by 44.5% in the domperidone group compared with 16% in the placebo group (p<0.05). There was a steady increase in milk volume commencing 48 hours after initiation of treatment up until day 7, which was the last day of medication. This correlated with a rise in serum prolactin in the domperidone group, rising from 12.9 trial μ /L [SD7.7], measured as baseline, to 119.3 [SD97.3] μ/L of a randomly sampled blood test on day 5. The serum prolactin levels returned to baseline 3 days after treatment was ceased.

Dosage

• 10-20mgs, orally, 3-4 times per day
• A prescription for 2 weeks should be given initially and may be repeated if necessary. The medication may need to be continued for up to 8 weeks, however the long-term use of domeperidone has not been studied ¹.
• There is little evidence to guide practice as regard to when to start, how long to continue and how to wean from domperidone.

Precautions, Interactions, and Adverse Effects

• Prescribers should be aware of maternal conditions or medications that may be affected by Domperidone
• Dosage should be reduced if there are underlying maternal renal or hepatic conditions.
• Domperidone use should be avoided with antacids and antisecretory agents.
• Medications that inhibit the Cytochrome P₄₅₀ enzyme system (e.g. azole antifungals, macrolide antibiotics, HIV protease inhibitors, and nefazodone) may increase Domperidone levels.
• Rare adverse effects include headache, dizziness, abdominal cramps, dry mouth, drowsiness, and allergic reactions.

Recommendations

• Domperidone therapy to enhance lactation does not replace expressing and may not work in some cases. It should only be given if the mother has been expressing at least 6 times in 24 hours for at least 3 days. She must have had specific teaching in effective expressing techniques and positioning of the baby at the breast if possible.
• If the mother is still under obstetric or medical care, she should discuss the possible use of domperidone with her medical adviser(s).
• To ensure that adequate assistance is given to the mother, it is advisable that the mother is referred to a Lactation Consultant and or the charge nurse, or her LMC before therapy is commenced.

References