Domperidone was synthesized in 1974 as an antipsychotic drug with strong anti-emetic effects and minimal central nervous system effects. It is used globally to treat nausea and vomiting and increase breast milk production. Domperidone is more effective than metoclopramide for treating gastroparesis with fewer side effects due to not crossing the blood brain barrier. However, in vitro studies show domperidone can inhibit the hERG potassium channel associated with long QT syndrome and increased risk of arrhythmias. A meta-analysis found a significant association between domperidone use and ventricular arrhythmias or cardiac arrest. However, other studies have found no adverse effects. Future studies are needed comparing risks of

1. Domperidone Toxicity

2. feel free !

3. History of Discovery
1974 – Domperidone synthesized at Janssen
Pharmaceutica (Belgium) following the research on
antipsychotic drugs. Janssen pharmacologists
discovered that some of antipsychotic drugs had a
significant effect on dopamine receptors in the
central chemoreceptor trigger zone that regulated
vomiting and started searching for a dopamine
antagonist that would not pass the blood–brain
barrier, thereby being free of the extrapyramidal
side effects that were associated with drugs of this
type. This led to the discovery of domperidone as a
strong anti-emetic with minimal central effects.
Domperidone was first marketed 1978 with the
brand name (Motilium®).

4. Domperidone ueses
Domperidone is a prokinetic drug used globally for
relieving nausea and vomiting in several countries,
including Australia, Canada, and Thailand . Even
though domperidone is not approved in the USA
and Europe.
One off-label use (i.e. non-approved) is breast milk
production (i.e. galactogogue or lactagogue).

5. Domperidone VS metoclopramide
domperidone is more effective than
metoclopramide (primperan®) of gastroparesis.
Domperidone is associated with fewer central
nervous system side effects (e.g. somnolence and
mental activity reduction) than metoclopramide
because domperidone does not readily cross the
blood-brain barrier.

6. BUT,

7. Arrhythmia?!

8. BUT WHY ? (MOT)
In vitro studies suggest that domperidone binds to cardiac
hERG (human ether-a-go-go-related gene) proteins; It is a
gene(KCNH2) that codes for a protein known as Kv11.1,
the alpha subunit of a potassium ion channel; which is
important for cardiac repolarization and action potential
(phase2:4). Dysfunction (e.g. by inhibition ) of hERG leads
to long QT-interval syndrome which increases the risk of
ventricular arrhythmias and sudden cardiac death(arrest)
especially in patients with cardiac ischemia.

9. N.B: QT interval on ECG
(from ventricular
depolarization to
ventricular
repolarization )

10. Contradictive studies
However, there are other studies that found the
opposite conclusion. There is one systematic
review and one meta-analysis of the efficacy of
domperidone as a galactagogue in which no
adverse events occurred among the maternal or
neonatal groups.

11. Studies limitations (Further research ! )
Exposure misclassification;
In many countries, domperidone is an OTC drug used for symptomatic
relief which can be discontinued by patients at any time, so the exposure
could be overestimated. The number of patients exposed to domperidone
could be higher than reported by the studies.
This meta-analysis is not applicable to some populations,
especially breastfeeding women and neonates, as the majority of
volunteers were older males and elderly; Therefore studies in
breastfeeding populations failed to detect any significant cardiotoxicity
associated with domperidone.

12. Studies limitations (Further research ! )
In addition, future studies should compare the
adverse effects associated with domperidone with the
adverse effects associated with other prokinetic agents,
especially metoclopramide, to evaluate the risk-benefit
ratio of the use of domperidone.
As well, in the future, larger randomized trials should be
performed among more diverse populations.

13. Conclusion & Recommendations
domperidone use is significantly associated with
ventricular arrhythmia or cardiac arrest; so warnings
are put out by Health Canada and the FDA to limit its
use.
domperidone use in older populations should be
discouraged to avoid exaggeration of heart problems.

15. References
Leelakanok N. Domperidone and Risk of Ventricular Arrhythmia
and Cardiac Death : A Systematic Review and Meta-analysis. Clin
Drug Investig. 2016;36(2):97-107. doi:10.1007/s40261-015-0360-0.

16. By
Ahmed Gamal Khadr
Supervisor: Dr / Maged Wasfy
Department of pharmacology and toxicology,
Damanhour Pharmacy college