Domperidone

Class: antiemetic – prokinetic, dopamine antagonist

Indications: nausea, vomiting, dyspeptic symptom complex including gastro- oesophageal reflux oesophagitis, epigastric sense of fullness, feeling of abdominal distension, upper abdominal pain, eructation (belching), flatulence and heartburn, hiccups, delayed gastric emptying

Contraindications/cautions: complete intestinal obstruction; QT prolongation; underlying cardiac disease

Adverse reactions: common: hyperprolactinaemia, breast tenderness, QT prolongation; less common: abdominal cramps, diarrhoea, dry mouth, headache, dizziness

Metabolism/clearance: metabolised by enzyme CYP3A mainly in the liver and gut. Caution in moderate to severe hepatic impairment – reduce dose

Interactions:

• increased clinical effect/toxicity of domperidone (due to increased blood concentrations) may occur with some CYP metabolising enzyme inhibitors (see above) e.g. aprepitant, clarithromycin, grapefruit juice, indinavir, itraconazole, ketoconazole, nelfinavir, ritonavir, telapravir, voriconazole
• decreased clinical effect/toxicity of domperidone (due to decreased blood concentrations) may occur with some CYP metabolising enzyme inducers (see above) e.g. carbamazepine, phenobarbitone, phenytoin, rifampicin, St John’s wort
• decreased prokinetic effect of domperidone may occur with anticholinergic drugs (e.g. amitriptyline, hyoscine)
• additive increased risk of QT interval prolongation (cardiac adverse effect which may lead to arrhythmias) with tricyclic antidepressants (e.g. amitriptyline), flecainide, erythromycin, theophylline, methotrimeprazine (levomepromazine)

Syringe driver: not available

Mechanism of action: similar to metoclopramide – blocks dopamine receptors in the upper gastrointestinal tract, chemo-receptor trigger zone (CTZ) and the CNS (penetration of BBB is negligible so minimal effect on CNS therefore less likely to cause extrapyramidal side effects than metoclopramide)

Peak: concentration: 30 to 120 minutes

Onset: of action: 30 minutes

Duration: of action: 12 to 24 hours

120 Te Puka Manaaki Pairuri o Aotearoa – Putanga Tuatahi

Notes:

• main advantage over metoclopramide is less extrapyramidal side effects but not available in injectable form
• useful in nausea and vomiting associated with gastric stasis
• the United States Federal Drug Agency has warned of domperidone induced QT interval prolongation and recommend a maximum of 30 mg in 24 hours. A risk benefit assessment should be carried out when higher doses are considered along with a baseline QT interval assessment
• bioavailability relatively poor after oral dose (12 to 18%) due to first pass metabolism in wall of GIT and liver – bioavailability nearly doubled if taken after a meal (24%)
• maximal absorption requires acid environment – H2-antagonists, PPIs and antacids all reduce absorption