Bt Rerdadw

NAME OF MEDICINE

Domperidone base

PRESENTATION

MOTILIUM 10 mg tablets are white, circular, film-coated, biconvex tablets with m/10 imprinted on one side and JANSSEN on the other.

USES

Pharmacodynamics

Mechanism of Actions

Domperidone is a dopamine antagonist with antiemetic properties. Domperidone does not readily cross the blood-brain barrier. It seldom causes extrapyramidal side effects, but does cause a rise in prolactin levels. Its antiemetic effect may be due to a combination of peripheral (gastrokinetic) effects and antagonism of central dopamine receptors in the chemoreceptor trigger zone which lies in the area postrema and is regarded as being outside the blood-brain barrier.

It also antagonises the behavioural effects of dopamine much more effectively when administered intracerebrally than when given systemically. These findings, together with the low concentrations found in the brain, indicate a predominantly peripheral effect of domperidone on dopamine receptors.

Studies in humans have shown intravenous and oral domperidone to increase lower oesophageal pressure, improve antroduodenal motility and accelerate gastric emptying. Domperidone has no effect on gastric secretion.

Effect on QT/QTc Interval and Cardiac Electrophysiology

In accordance with ICH—E14 guidelines, a thorough QT study was performed in healthy subjects. This study included a placebo, active comparator and positive control and was conducted using recommended therapeutic doses (10 or 20 mg administered 4 times a day). This study found a maximal difference of QTc between domperidone and placebo in LS-means in the change from baseline was 3.4 msec for 20 mg domperidone administered 4 times a day on Day 4, and the 2-sided 90% CI (1.0 5.9 msec) did not exceed 10 msec. The QT prolongation observed in this study when domperidone was administered according to the recommended dosing is not clinically relevant.

CCDS Oct 2013 Page 2 of 11 MOTILIUM (131224)ADS

This lack of clinical...