Dosing Domperidone for Milk Production by Thomas W. Hale, PhD

For years now, we have known that domperidone was a preferred galactagogue due to its limited side effect profile in breastfeeding mothers.  Compared to Reglan (metoclopramide), it does not induce extrapyramidal symptoms, stroke, or depression.However, in the past few years, there has been a clinical movement toward using higher and higher doses in patients, assuming this would stimulate higher levels of milk production.  This is because the normal instinct in clinicians is that if a little works,  more may work better.  This philosophy, however, simply does not work with prolactin release from the pituitary.The reason for concern is that domperidone in higher doses could potentially induce arrhythmias in some patients.  After all, it is a HERG (human ether-a-go-go-related gene) receptor antagonist and could potentially alter potassium levels in the myocardium, leading to arrhythmias.  The original studies in cancer patients, where domperidone was used intravenously, illustrated this point.  Interestingly,  metoclopramide is a HERG receptor antagonist as well.  It is, however, not as potent as domperidone (about 100 fold lower).

When used in breastfeeding mothers,  orally,  we know that the risk of arrhythmias is very remote to virtually nil,  but as you push the oral dose higher and higher, the risk of arrhythmias could potentially rise.    I and others have been somewhat concerned about this anecdotal use of domperidone.   So, does increasing the dose of domperidone really lead to enhanced release of prolactin,  apparently not.   The pituitary is known to store a set quantity of prolactin and is not necessarily able to produce unlimited quantities in response to higher levels of these releasing agents.

We know in many other studies that if plasma prolactin levels are already elevated,  administering various doses of domperidone or metoclopramide probably will not increase the maternal release of additional prolactin.  The plasma levels simply don’t rise.  In essence, the pituitary’s release of prolactin  has reached it maximum level, and it simply can’t respond with additional prolactin.

A colleague of mine, Dr. Ken Ilett of Australia,  just published an abstract (SHPA Abstract 2005 Kaye Davey) comparing milk production and dose of domperidone.  His data basically shows that the effect on milk production is the same whether you use 30 mg/day or 60 mg/day doses.  While his study was only in 5 women,  it illustrates the point I’m trying to make,  that higher and higher doses probably don’t lead to higher levels of plasma prolactin.

Thus,  I think we should be extremely cautious using extraordinarily high doses of domperidone in breastfeeding patients based purely on anecdotal experience of our colleagues.