Domperidone, sold under the brand name Motilium among others, is a dopamine antagonist medication which is used to treat nausea and vomiting and certain gastrointestinal problems like gastroparesis (delayed gastric emptying). It raises the level of prolactin in the human body and is used to induce and promote breast milk production. It may be taken by mouth or rectally.
Side effects of domperidone include headache, dry mouth, abdominal cramps, diarrhea, and elevated prolactin levels. Secondary to increased prolactin levels, breast changes, milk outflow, menstrual irregularities, and hypogonadism can occur. Domperidone may also cause QT prolongation and has rarely been associated with serious cardiac complications such as sudden cardiac death. However, the risks are small and occur more with high doses. Domperidone acts as a peripherally selective antagonist of the dopamine D2 and D3 receptors. Due to its low entry into the brain, the side effects of domperidone are different from those of other dopamine receptor antagonists like metoclopramide and it produces little in the way of central nervous system adverse effects. However, domperidone can nonetheless increase prolactin levels as the pituitary gland is outside of the blood–brain barrier.
Domperidone was discovered in 1974 and was introduced for medical use in 1979. It was developed by Janssen Pharmaceutica. Domperidone is available over-the-counter in many countries, for instance in Europe and elsewhere throughout the world. It is not approved for use in the United States. However, it is available in the United States for people with severe and treatment-refractory gastrointestinal motility problems under an expanded access individual-patient investigational new drug application. An analogue of domperidone called deudomperidone is also currently under development for potential use in the United States and other countries.
Medical uses
Nausea and vomiting
There is some evidence that domperidone has antiemetic activity. It is recommended by the Canadian Headache Society for treatment of nausea associated with acute migraine.
Gastroparesis
Gastroparesis is a medical condition characterised by delayed emptying of the stomach when there is no mechanical gastric outlet obstruction. Its cause is most commonly idiopathic, a diabetic complication or a result of abdominal surgery. The condition causes nausea, vomiting, fullness after eating, early satiety (feeling full before the meal is finished), abdominal pain and bloating. Domperidone can be used to increase the transit of food through the stomach by increasing gastrointestinal peristalsis and hence to treat gastroparesis. It may be useful in idiopathic and diabetic gastroparesis. However, increased rate of gastric emptying induced by drugs like domperidone does not always correlate well with relief of symptoms.
Lactation
The hormone prolactin stimulates lactation. Dopamine, released by the hypothalamus, stops the release of prolactin from the pituitary gland. Domperidone, by acting as an anti-dopaminergic agent, results in increased prolactin secretion, and thus promotes lactation as a galactogogue. Domperidone moderately increases the volume of expressed breast milk in mothers of preterm babies where breast milk expression is inadequate, and appears to be safe for short-term use for this purpose. In the United States, domperidone is not approved for this use.
A study called the EMPOWER trial was designed to assess the effectiveness and safety of domperidone in assisting mothers of preterm babies to supply breast milk for their infants. The study randomized 90 mothers of preterm babies to receive either domperidone 10 mg orally three times daily for 28 days (Group A) or placebo 10 mg orally three times daily for 14 days followed by domperidone 10 mg orally three times daily for 14 days (Group B). Mean milk volumes at the beginning of the intervention were similar between the 2 groups. After the first 14 days, 78% of mothers receiving domperidone (Group A) achieved a 50% increase in milk volume, while 58% of mothers receiving placebo (Group B) achieved a 50% increase in milk volume.
To induce lactation, domperidone is used at a dosage of 10 to 20 mg 3 or 4 times per day by mouth. Effects may be seen within 24 hours or may not be seen for 3 or 4 days. The maximum effect occurs after 2 or 3 weeks of treatment, and the treatment period generally lasts for 3 to 8 weeks. A 2012 review shows that no studies support prophylactic use of galactagogue medications, including domperidone, at any stage of pregnancy,.