Domperidone

Products

Domperidone is commercially available as film-coated tablets, lingual tablets, and as a suspension (Motilium, generics). It was synthesized in 1974 and has been approved in many countries since 1979.

Structure and properties

Domperidone (C22H24ClN5O2, Mr = 425.9 g/mol) exists as a white powder that is practically insoluble in water. It is a benzimidazole derivative and has structural similarity to butyrphenones such as haloperidol, which, like domperidone, was developed at Janssen.

Effects

Domperidone (ATC A03FA03) has antidopaminergic properties with high affinity for the D2 receptor and exerts antiemetic effects outside the blood–brain barrier in the chemoreceptor trigger zone against nausea and vomiting. Dopamine inhibits gastric motility, promotes satiety, and induces nausea and stomach pain. By blocking the effects of dopamine, domperidone acts prokinetically, promoting gastric motility, accelerating gastric emptying, increasing lower esophageal sphincter pressure, and promoting esophageal motility.

Indications

For the treatment of nausea and vomiting.

Dosage

According to the professional information. The drug is usually taken up to a maximum of three times daily 15 to 30 minutes before meals. The duration of therapy should be kept as short as possible.

Contraindications

  • Hypersensitivity
  • Prolactinoma
  • QT interval prolongation and associated risk factors.
  • Concurrent use of strong CYP3A4 inhibitors, which prolong the QT interval.
  • If stimulation of gastric motility could be dangerous.
  • Liver dysfunction

Full precautions can be found in the drug label.

Interactions

Domperidone is inactivated by CYP3A4 (intestinal and hepatic first-pass metabolism), resulting in a reduction in bioavailability. CYP3A4 inhibitors may increase plasma concentrations. This is problematic because domperidone can prolong the QT interval, causing cardiac arrhythmias. For this reason, concomitant administration with potent CYP3A4 inhibitors such as azole antifungals or macrolides is contraindicated. Anticholinergics may reduce the effect of domperidone. Antacids and antisecretory drugs decrease the bioavailability of domperidone when administered concomitantly. Domperidone may affect the absorption of other drugs because it affects gastric motility.

Adverse effects

As a dopamine antagonist, domperidone, like the neuroleptics and metoclopramide, has the potential for numerous adverse effects in the central nervous system. However, these are not observed in practice because domperidone does not cross the blood–brain barrier. It is also partially inactivated in the liver and has a high affinity for the gastrointestinal tract. Domperidone may prolong the QT interval and rarely cause cardiac arrhythmias. Domperidone may rarely increase prolactin levels, leading to enlargement of the mammary gland, breast pain, lactation, disruption and absence of menstruation. Other common adverse effects include: