Indications:
● Delayed gastric emptying of functional origin with gastro-oesophageal reflux and/or dyspepsia.
● Control of nausea and vomiting of central or local origin.
● As an anti-emetic in patients receiving cytostatic and radiation therapy.
● Facilitates radiological examination of the upper gastrointestinal tract.
Pharmacology:
Mechanism of Action:
Domperidone is a dopamine-receptor blocking agent. Its action on the dopamine-receptors in the chemo-emetic trigger zone produces an anti-emetic effect. Domperidone does not cross the blood-brain barrier to any appreciable degree and so exerts relatively little effect on cerebral dopaminergic receptors. Domperidone has been shown to increase the duration of antral and duodenal contractions, to increase the gastric emptying.
Pharmacokinetics:
Absorption: Domperidone is rapidly absorbed, with peak plasma concentrations approximately 1 hour after oral administration. The absolute bio-availability of oral domperidone is low (approximately 15%) due to first-pass hepatic and intestinal metabolism.
Protein Binding: Domperidone is 91 - 93% bound to plasma proteins.The plasma half-life after a single oral dose is 7 - 9 hours in healthy subjects but is prolonged in patients with severe renal insufficiency.
Metabolism: Domperidone undergoes rapid and extensive hepatic metabolism by hydroxylation and N-dealkylation. In vitro metabolism experiments with diagnostic inhibitors revealed that CYP3A4 is a major form of cytochrome P-450 involved in the N-dealkylation of domperidone, whereas CYP3A4, CYP1A2 and CYP2E1 are involved in domperidone aromatic hydroxylation.
Elimination: Urinary and faecal excretion amount to 31% and 66% of the oral dose, respectively. The proportion of drug, excreted unchanged is small (approximately 1% of urinary and 10% of faecal excretion).
Drug interactions:
● Concomitant administration of anti-cholinergic drugs may inhibit the anti-dyspeptic effects of domperidome.
● Anti-muscarinic agents and opioid analgesics may antagonise the effect of domperidome.
● Domperidone suppresses the peripheral effects (digestive disorders, nausea and vomiting) of dopaminergic agonists.
● Since Domperidone has gastro-kinetic effects, it could influence the absorption of concomitant orally administered medicines, particularly those with sustained release or enteric coated formulations.
● Antacids and anti-secretory agents lower the oral bioavailability of domperidone. They should be taken after meals and not before meals, i.e. they should not be taken simultaneously with Domperidone.
● The main metabolic pathway of domperidone is through CYP3A4. In vitro data suggests that the concomitant use of drugs that significantly inhibit this enzyme may result in increased plasma levels of domperidone. Examples of CYP3A4 inhibitors include the following: azole antifungals, macrolide antibiotics, HIV protease inhibitors, nefazodone.
Side Effects:
● Allergic reactions, such as rash or urticaria.
● Abdominal cramps.
● Dystonic reactions (extrapyramidal phenomena).
● Where the blood brain barrier is not fully developed (mainly in young babies) or is impaired, the possible occurrence of neurological side-effects cannot be totally excluded.
Contraindications:
● Contra-indicated in patients with known sensitivity to domperidone.
● Should not be used whenever stimulation of gastric motility is to be avoided or could be harmful, e.g. in the presence of gastro-intestinal haemorrhage, obstruction or perforation.
● Contra-indicated in patients with a prolactin releasing pituitary tumour (prolactinoma).
● The safety of use during pregnancy and lactation has not been established.
Precautions:
● Domperidome Tablet should be used with caution in patients with renal impairment or in those at risk of fluid retention.
● The dosing frequency should be reduced to once or twice daily, depending on the severity of impairment, and the dose may need to be reduced. Patients on prolonged therapy should be reviewed regularly.
● Since domperidone is highly metabolised in the liver, it should be used with caution in patients with hepatic impairment (and in the elderly).