Cardiac safety concerns for domperidone, an antiemetic and prokinetic, and galactogogue medicine

@article{Doggrell2014CardiacSC,
  title={Cardiac safety concerns for domperidone, an antiemetic and prokinetic, and galactogogue medicine},
  author={Sheila Anne Doggrell and Jules C. Hancox},
  journal={Expert Opinion on Drug Safety},
  year={2014},
  volume={13},
  pages={131 - 138}
}
Introduction: Domperidone is a dopamine D2-receptor antagonist developed as an antiemetic and prokinetic agent. Oral domperidone is not approved in the United States, but it is used in many countries to treat nausea and vomiting, gastroparesis and as a galactogogue (to promote lactation). The US Food and Drug Administration (FDA) have issued a warning about the cardiac safety of domperidone. Areas covered: The authors undertook a review of the cardiac safety of oral domperidone. Expert opinion… 
Severe Proarrhythmic Potential of the Antiemetic Agents Ondansetron and Domperidone
TLDR
Both ondansetron and domperidone demonstrated a severe proarrhythmic potential and a significant prolongation of cardiac repolarization as well as a marked increase in spatial dispersion of repolarized represents the underlying electrophysiologic mechanisms.
Use of Domperidone to Increase Breast Milk Supply
  • L. Grzeskowiak
  • Medicine
    Journal of human lactation : official journal of International Lactation Consultant Association
  • 2014
TLDR
Evidence from a recent systematic review and meta-analysis demonstrated that domperidone is well tolerated by breastfeeding mothers and is associated with modest improvements in breast milk volume, which is important, as breastfeeding isassociated with significant reductions in infant morbidity and mortality, as well as providing long-term benefits for the mother, with reductions in the incidence of certain cancers.
Cardiotoxic Antiemetics Metoclopramide and Domperidone Block Cardiac Voltage-Gated Na+ Channels
TLDR
The data demonstrate that the clinically relevant cardiotoxicity of domperidone and metoclopramide corresponds to a rather potent and local anesthetic-like inhibition of cardiac Na+ channels including Nav1.5, which might be a hitherto unrecognized molecular mechanism of some cardiovascular side effects, for example, malignant arrhythmias of prokinetic and antiemetic agents.
Ghrelin Agonists as Emerging Prokinetic Agents.
  • J. Tack, M. Corsetti
  • Medicine
    Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
  • 2015
5-Hydroxytryptamine3 receptor antagonists and cardiac side effects
TLDR
The risk of cardiac adverse events (AEs) from 5-HT3-RAs is outlined, with focus on the three most commonly used, ondansetron, granisetron and palonosetron.
Effect of Chronic Domperidone Use on QT Interval
TLDR
The data suggest that domperidone can be safely prescribed at doses of 30 to 80 mg daily for the treatment of gastroparesis and is associated with QTc prolongation in only 6% of patients with no QT interval reaching the point considered to be clinically significant.
The Advantages and Disadvantages of Prokinetics
TLDR
Recently introduced, highly selective agents appear to show promise as treatments for gastrointestinal dysmotility; there seem to be no serious side-effects.
Non-Clinical Safety Pharmacology Evaluations of Trazpiroben (TAK-906), a Novel Dopamine D2/D3 Selective Receptor Antagonist for the Management of Gastroparesis
TLDR
The results suggest that trazpiroben has limited central nervous system effects and a favorable cardiac safety profile, and is being developed to treat chronic gastroparesis.
Domperidone to Treat Symptoms of Gastroparesis: Benefits and Side Effects from a Large Single-Center Cohort
TLDR
The majority of patients remaining on treatment with domperidone experienced an improvement in symptoms of gastroparesis, particularly postprandial fullness, nausea, vomiting, and stomach fullness.
Domperidone and Risk of Ventricular Arrhythmia and Cardiac Death: A Systematic Review and Meta-analysis
TLDR
Evidence from this meta-analysis suggests that current dom peridone use increases the risk of cardiac arrhythmia and sudden cardiac death by 70 %.
...
...

References

SHOWING 1-10 OF 70 REFERENCES
Domperidone: A Peripherally Acting Dopamine2-Receptor Antagonist
  • J. Barone
  • Medicine, Psychology
    The Annals of pharmacotherapy
  • 1999
TLDR
In controlled clinical trials, domperidone provided better relief of symptoms than placebo in patients with symptoms of diabetic gastroparesis and prevented the gastrointestinal and emetic adverse effects of antiparkinsonian drugs.
Domperidone: Review of Pharmacology and Clinical Applications in Gastroenterology
TLDR
The pharmacology, clinical application, and safety profile of domperidone are revisited to revisit the pharmacology and clinical application of this beneficial medication.
Domperidone Should Not Be Considered a No-Risk Alternative to Cisapride in the Treatment of Gastrointestinal Motility Disorders
TLDR
Domperidone possesses cardiac electrophysiological effects similar to those of cisapride and class III antiarrhythmic drugs, and should not be considered a no-risk alternative to cisAPride, a drug that was recently withdrawn from the US market.
Low safety index of domperidone: mechanism for increased odds ratio for sudden cardiac death
TLDR
Wide use of domperidone should best be restricted to patients in whom its benefits are proven to justify the risks, and availability without prescription and advertising as an ‘innocent’ relief is incorrect and unsafe, and needs to be reconsidered.
A comparison of controlled release metoclopramide and domperidone in the treatment of nausea and vomiting.
TLDR
Both controlled release metoclopramide and high and low dose domperidone significantly reduced symptoms of belching, flatulence, distension, heartburn, regurgitation, reflux, nausea and vomiting compared to baseline.
Comparison of the Effects of Metoclopramide and Domperidone on HERG Channels
TLDR
Compared the effects of the gastroprokinetic agents domperidone and metoclopramide on HERG channels transiently expressed in human embryonic kidney (HEK 293) cells using the whole-cell configuration of the patch-clamp technique, the potency for block of HERG currents is about 100-fold lower for metoclobramide when compared to dom peridone.
Domperidone: Limited Benefits With Significant Risk for Sudden Cardiac Death
  • L. Hondeghem
  • Medicine, Biology
    Journal of cardiovascular pharmacology
  • 2013
TLDR
Because domperidone has placebo-like benefits but is associated with increased SCD and a narrow safety margin, it should not be used in medicine.
Pharmacokinetics and Dose Proportionality of Domperidone in Healthy Volunteers
TLDR
The area under the plasma concentration‐time curve (AUC) data demonstrated bioequivalence of base and maleate tablets and Dose proportionality of domperidone was studied in 12 subjects at solution doses of 10, 20, and 40 mg, indicating linear pharmacokinetics of dom peridone over the dose range studied.
Domperidone and sudden cardiac death: How much longer should we wait?
TLDR
It is shown that domperidone has cardiac electrophysiological effects similar to those of cisapride, although the inhibitory constant for block of IKr was 10-fold lower for cisap Ride than for domperidsone, and the safety margin with this drug looks rather small.
...
...