Domperidone

Review
In: Drugs and Lactation Database (LactMed®) [Internet]. Bethesda (MD): National Institute of Child Health and Human Development; 2006.
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Excerpt

Domperidone is not approved for marketing in the United States by the U.S. Food and Drug Administration (FDA), but is available in other countries. Domperidone may also be available from some compounding pharmacies and via the internet in the US. The quality of such products cannot be assured, and the FDA has warned against their use.[1]

Data available from 4 small studies on the excretion of domperidone into breastmilk are somewhat inconsistent, but infants would probably receive less than 0.1% of the maternal weight-adjusted dosage, even at high maternal doses. No adverse effects have been found in a limited number of published cases of breastfed infants whose mothers were taking domperidone.

Domperidone is sometimes used as a galactogogue to increase milk supply.[2,3] and has been used in induced lactation by adoptive and transgender women.[4-9] Galactogogues should never replace evaluation and counseling on modifiable factors that affect milk production.[10,11] Most mothers who are provided instruction in good breastfeeding technique and breastfeed frequently are unlikely to obtain much additional benefit from domperidone. Several meta-analyses of domperidone use as a galactogogue in mothers of preterm infants concluded that domperidone can increase milk production acutely in the range of 90 to 94 mL daily.[3,12,13] Other reviewers concluded that improvement of breastfeeding practices seems more effective and safer than off-label use of domperidone.[14,15] One retrospective study found that breastmilk feeding rates at discharge remained consistently lower in very preterm (<32 weeks gestation) infants of women dispensed domperidone than those who were not prescribed domperidone.[16]

Domperidone has no officially established dosage for increasing milk supply. Most published studies have used domperidone in a dosage of 10 mg 3 times daily for 4 to 10 days. Two small studies found no statistically significant additional increase in milk output with a dosage of 20 mg 3 times daily compared to a dosage of 10 mg 3 times and that women who failed to respond to the low dosage did not respond to the higher dosage.[17,18] Dosages greater than 30 mg daily may increase the risk of arrhythmias and sudden cardiac death in patients receiving domperidone,[19] although some feel that the risk is less in nursing mothers because of their relatively younger age.[20] Large database retrospective cohort studies in Canada found an increase in the risk of cardiac arrhythmias and sudden cardiac death, but some confounders make the results subject to question.[21,22] In one case, domperidone use uncovered congenital long QT syndrome in a woman who developed loss of consciousness, behavioral arrest, and jerking while taking domperidone.[23] Mothers with a history of cardiac arrhythmias should not receive domperidone and all mothers should be advised to stop taking domperidone and seek immediate medical attention if they experience signs or symptoms of an abnormal heart rate or rhythm while taking domperidone, including dizziness, palpitations, syncope or seizures.[19]

Maternal side effects of domperidone reported in galactogogue studies and cases reported to the FDA include dry mouth, headache, dizziness, nausea, abdominal cramping, diarrhea, palpitations malaise, and shortness of breath. Some of these were more frequent with dosages greater than with 30 mg daily.[17,18,24-26] Surveys of women taking domperidone for lactation enhancement found gastrointestinal symptoms, breast engorgement, weight gain, headache, dizziness, irritability, dry mouth and fatigue were the most common side effects reported.[27-29] One mother taking domperidone 20 mg three times daily as a galactogogue for feeding her adoptive daughter developed obsessional thoughts with adjustment disorder. This manifested as thoughts of killing her daughter. Stopping domperidone and instituting duloxetine therapy resulted in remission over a 10-month period.[30]

Canadian health authorities found an association between the abrupt discontinuation or tapering of domperidone used for lactation stimulation and the development of psychiatric adverse events.[31] Canadian labeling warns against use of domperidone doses greater than 30 mg daily for longer than 4 weeks. Drug withdrawal symptoms consisting of insomnia, anxiety, and tachycardia were reported in a woman taking 80 mg of domperidone daily for 8 months as a galactogogue who abruptly tapered the dosage over 3 days.[32] Another mother took domperidone 10 mg three times daily for 10 months as a galactagogue and stopped abruptly. After discontinuation, she experienced severe insomnia, severe anxiety, severe cognitive problems and depression.[33] A third postpartum woman began domperidone 90 mg daily, increasing to 160 mg daily to increase her milk supply. Because her milk supply did not improve, she stopped nursing at 14 weeks and began to taper the domperidone dosage by 10 mg every 3 to 4 days. Seven days after discontinuing domperidone, she began experiencing insomnia, rigors, severe psychomotor agitation, and panic attacks. She restarted the drug at 90 mg daily and tapered the dose by 10 mg daily each week. At a dose of 20 mg daily, the same symptoms recurred. She required sertraline, clonazepam and reinstitution of domperidone at 40 mg daily, slowly tapering the dose over 8 weeks. Three months were required to fully resolve her symptoms.[34] In a fourth case, a mother took domperidone 20 mg four times daily for 9 months to stimulate breastmilk production. She stopped breastfeeding and domperidone at that time. Two weeks later, she presented with insomnia, anxiety, nausea, headaches and palpitations. The drug was restarted at a dosage of 20 mg three times daily and began to taper the daily dosage by 10 mg every week, but after one week she complained of insomnia. Tapering was reduced to 5 mg every week, but whenever she stopped the drug, symptoms returned. She was able to discontinue domperidone after tapering the daily dosage by 2.5 mg weekly over 10 months.[35] A fifth case of a mother with a history of bipolar disorder and major depression developed severe anxiety, a recurrence of depression and obsessive-compulsive disorder 6 days after abruptly discontinuing domperidone 120 mg daily that she was taking as a galactogogue. Three days later, she restarted domperidone 120 mg daily and tapered her daily dose by 10 mg at weekly intervals. She took no other medications. Two weeks after discontinuing domperidone, she had signs of only mild mood disorder.[36] Three patients were reported to have severe symptoms of withdrawal (depression, reemergence of obsessive-compulsive disorder and major depressive disorder, insomnia, anxiety, irritability, poor concentration, loss of libido, lack of energy, suicidality, hot flashes, night sweats, hair thinning, and dry eyes nausea, vomiting, diarrhea and decreased appetite) after stopping domperidone as a galactogogue. Dosages ranged from 90 to 150 mg daily for 5 to 32 weeks. Dosages required a slow hyperbolic tapering over a period of several months to fully discontinue the drug.[37]

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