Medication in Lactation: Domperidone

From the office of the Medical Health Officer.

The January 2007 MedEffect CARN newsletter reported on domperidone and heart rate and rhythm disorders in Canada (summary below.)

Your breastfeeding mothers taking domperidone because frequent nursing with good latch was not enough to increase or maintain their breastmilk supply may ask you questions about this.

The initial 2004 US FDA warning on domperidone was well summarized by da Silva and Knoppert in the CMAJ. They pointed out that the FDA warning was based on an increased risk of cardiac arrhythmia and sudden death in patients with malignant disease receiving high-dose intravenous domperidone concurrently with chemotherapy. All patients whose serum potassium was measured had low levels (between 2.0 and 3.3 mmol/L). They advised that domperidone at antiemetic doses (10-20 mg orally three to four times daily) should continue to be considered for lactating women with decreased milk supply unresponsive to non-pharmacologic measures, including counselling, relaxation techniques, and mechanical expression. (Emphasis ours.) Patients should be warned of the risk of life-threatening cardiac arrhythmias with high doses of domperidone, and women with known cardiac disease should not take domperidone at all.

Reliable & Low Cost / Free Sources of Information on Medications and Lactation:

• Medications and Mother’s Milk (Hale, T.W.)
• Dr. Hale’s website
• Searches through LactMed and MOTHERISK
• Drugs in Pregnancy and Lactation (Briggs, Freeman, Yaffe) is available in some Fraser Health maternity wards and hospital pharmacies.

Summary of CARN report:
From Jan. 1, 1985, to Aug. 15, 2006, nine reports were received of heart rate and rhythm disorders in patients (2 mo. - 74 years old, median 45 years) on domperidone. Eight were on domperidone for motility disorders and diabetic gastroparesis. Two had QT prolongation, four had Torsade de Pointes, and three had atrial fibrillation, ventricular tachycardia, bradycardia and palpitations. Most were on multiple concomitant medications and had complex medical histories. Domperidone has been reported to induce QTc prolongation and Torsade de Pointes. Non-drug-related factors linked to QT prolongation include being female, being elderly, or having bradycardia, cardiac disease, and/or electrolyte disturbance. Domperidone is metabolized via cytochrome P450 3A4, which is markedly inhibited by ketoconazole, and inhibited by macrolides, HIV protease inhibitors, SSRI antidepressants, and grapefruit juice. Combined use of multiple drugs that prolong the QTc interval can also increase risk of Torsade de Pointes.