Domperidone and Risk of Ventricular Arrhythmia and Cardiac Death: A Systematic Review and Meta-analysis

Leelakanok, Nattawut; Holcombe, Andrea; Schweizer, Marin L.

doi:10.1007/s40261-015-0360-0

Cited by 72 publications

(69 citation statements)

References 39 publications

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“…As a result of the risk of QT interval prolongation and the association with ventricular tachyarrhythmia/sudden cardiac death in PD patients with preexisting cardiac disease …”

Section: Results and Conclusionmentioning

confidence: 99%

“…Midodrine provided significant benefits on measures of OH in RCTs in a mixed population of patients of which only a subgroup had PD, and there were also some significant benefits for fludrocortisone . Therefore, the practice implications for both midodrine and fludrocortisone are “ possibly useful .” Safety conclusions for domperidone have been changed to “ acceptable risk with specialized monitoring ” because domperidone may cause QT prolongation and is associated with increased risk of ventricular tachyarrhythmia and sudden cardiac death in PD patients with preexisting cardiac disease …”

Section: Results and Conclusionmentioning

confidence: 99%

“…Regarding gastrointestinal dysfunction, the EBM review covers anorexia, nausea, and vomiting associated with dopaminergic therapy such as levodopa and/or dopamine agonist treatment as well as constipation . The dopamine D2 receptor blocking agent domperidone remains “possibly useful” in this indication, although safety conclusions have been changed to “acceptable risk with specialized monitoring” because domperidone may cause potentially life‐threatening electrocardiograph changes . An alternative could be the use of trimethobenzamide, another dopamine D2 receptor blocker, which seems to reduce nausea/vomiting during the first 8 weeks of apomorphine therapy .…”

Section: Discussionmentioning

confidence: 99%

“…Safety conclusions for domperidone have been changed to "acceptable risk with specialized monitoring" because domperidone may cause QT prolongation and is associated with increased risk of ventricular tachyarrhythmia and sudden cardiac death in PD patients with preexisting cardiac disease. 96 Droxidopa, a norepinephrine prodrug, was evaluated in a high-quality trial that was originally designed to evaluate the clinical efficacy of droxidopa during an 8-week double-blind period. 27,28 Because of a preplanned interim efficacy analysis that did not demonstrate a significant difference across groups in the trial's original primary efficacy measure (ie, change in orthostatic hypotension questionnaire (OHQ) composite score), 27 the original study was stopped for futility and, subsequently, a corresponding change in the trial's primary efficacy measure was undertaken.…”

Section: New Conclusionmentioning

confidence: 99%

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Update on treatments for nonmotor symptoms of Parkinson's disease—an evidence‐based medicine review

et al. 2019

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Objective To update evidence‐based medicine recommendations for treating nonmotor symptoms in Parkinson's disease (PD). Background The International Parkinson and Movement Disorder Society Evidence‐Based Medicine Committee's recommendations for treatments of PD were first published in 2002, updated in 2011, and now updated again through December 31, 2016. Methods Level I studies testing pharmacological, surgical, or nonpharmacological interventions for the treatment of nonmotor symptoms in PD were reviewed. Criteria for inclusion and quality scoring were as previously reported. The disorders covered were a range of neuropsychiatric symptoms, autonomic dysfunction, disorders of sleep and wakefulness, pain, fatigue, impaired olfaction, and ophthalmologic dysfunction. Clinical efficacy, implications for clinical practice, and safety conclusions are reported. Results A total of 37 new studies qualified for review. There were no randomized controlled trials that met inclusion criteria for the treatment of anxiety disorders, rapid eye movement sleep behavior disorder, excessive sweating, impaired olfaction, or ophthalmologic dysfunction. We identified clinically useful or possibly useful interventions for the treatment of depression, apathy, impulse control and related disorders, dementia, psychosis, insomnia, daytime sleepiness, drooling, orthostatic hypotension, gastrointestinal dysfunction, urinary dysfunction, erectile dysfunction, fatigue, and pain. There were no clinically useful interventions identified to treat non‐dementia‐level cognitive impairment. Conclusions The evidence base for treating a range of nonmotor symptoms in PD has grown substantially in recent years. However, treatment options overall remain limited given the high prevalence and adverse impact of these disorders, so the development and testing of new treatments for nonmotor symptoms in PD remains a top priority. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

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“…As a result of the risk of QT interval prolongation and the association with ventricular tachyarrhythmia/sudden cardiac death in PD patients with preexisting cardiac disease …”

Section: Results and Conclusionmentioning

confidence: 99%

Section: Results and Conclusionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: New Conclusionmentioning

confidence: 99%

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Update on treatments for nonmotor symptoms of Parkinson's disease—an evidence‐based medicine review

et al. 2019

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“…Among the side effect profile, domperidone use is associated with an increased risk of sudden cardiac death most likely through prolongation of cardiac QT interval, thereby facilitating ventricular arrhythmias. [1415] Domperidone also causes hyperprolactinemia by blocking D2 dopaminergic receptors on the cell membrane of lactotrophs. Prolactin response to both metoclopramide and domperidone is dose related and is more in women, especially in the hyperprolactinemic state after childbirth.…”

Section: Prokinetic Agents and Serum Prolactin Levelsmentioning

confidence: 99%

Levosulpiride and serum prolactin levels

Kuchay

Mithal

2017

Indian J Endocr Metab

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Levosulpiride is the levorotatory enantiomer of sulpiride used in dyspeptic syndromes of various etiologies. The prokinetic effect of levosulpiride is mediated through the blockade of enteric inhibitory dopaminergic type 2 (D2) receptors. The antagonism of central D2 receptors leads to both therapeutic (e.g. antiemetic effect due to D2 receptor blockade in the chemoreceptor trigger zone) and adverse (including hyperprolactinemia) effects. Dopamine is the main endogenous inhibitor of prolactin synthesis and secretion in the anterior pituitary. Levosulpiride causes significant elevation of serum prolactin levels in significant number of patients. The resultant hyperprolactinemia often manifests as distressing menstrual abnormalities and galactorrhoea in females. A significant number of patients who use levosulpiride develop serum prolactin levels of > 200 ng/mL that goes against the classical textbook teaching where pituitary tumor is supposed to be the mostly likely cause. Careful drug history in patients presenting with high serum prolactin levels will be of great help in reaching the exact diagnosis and avoiding unnecessary brain imaging.

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Evaluating the Safety, Tolerability, and Disposition of Trazpiroben, a D₂/D₃ Receptor Antagonist: Phase I Single‐ and Multiple‐Ascending Dose Studies in Healthy Japanese Participants

Yamaguchi

Kudou

Okamoto³

et al. 2021

Clinical Pharm in Drug Dev

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Trazpiroben (TAK-906) is a peripherally selective dopamine D 2 /D 3 receptor antagonist being developed to treat chronic gastroparesis. This phase I, randomized, double-blind, placebo-controlled, single-and multiple-ascending dose, parallelgroup study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of trazpiroben in healthy Japanese men.Findings were compared with those from a prior US trial in healthy individuals.Overall,24 participants were enrolled into 3 cohorts (each n = 8). Per cohort, 6 participants received trazpiroben (cohort 1, 50 mg; 2, 100 mg; 3, 10 mg) once on day 1 and twice daily on days 3 through 7, and two received placebo. Trazpiroben was well tolerated, with no clinically meaningful adverse events observed.Following single-and multiple-dose administration,trazpiroben was rapidly absorbed and eliminated (mean elimination half-life, 1.89-6.45 hours; median time to maximum serum concentration [steady state], 1.00-1.25 hours). Serum prolactin increased with trazpiroben treatment (mean maximum serum concentration 93.32 ng/mL [10 mg] vs. 10.83 ng/mL [placebo]), illustrating receptor target engagement. Results reflected those from healthy US participants, indicating a lack of differences between these ethnic populations in trazpiroben disposition and safety profile.Trazpiroben may represent a promising therapy for chronic gastroparesis across different populations,with further evaluation ongoing in a phase IIb study (NCT03544229).

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Domperidone and Risk of Ventricular Arrhythmia and Cardiac Death: A Systematic Review and Meta-analysis

Cited by 72 publications

References 39 publications

Update on treatments for nonmotor symptoms of Parkinson's disease—an evidence‐based medicine review

Update on treatments for nonmotor symptoms of Parkinson's disease—an evidence‐based medicine review

Levosulpiride and serum prolactin levels

Evaluating the Safety, Tolerability, and Disposition of Trazpiroben, a D₂/D₃ Receptor Antagonist: Phase I Single‐ and Multiple‐Ascending Dose Studies in Healthy Japanese Participants

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Domperidone and Risk of Ventricular Arrhythmia and Cardiac Death: A Systematic Review and Meta-analysis

Cited by 72 publications

References 39 publications

Update on treatments for nonmotor symptoms of Parkinson's disease—an evidence‐based medicine review

Update on treatments for nonmotor symptoms of Parkinson's disease—an evidence‐based medicine review

Levosulpiride and serum prolactin levels

Evaluating the Safety, Tolerability, and Disposition of Trazpiroben, a D2/D3 Receptor Antagonist: Phase I Single‐ and Multiple‐Ascending Dose Studies in Healthy Japanese Participants

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Product

Resources

About

Evaluating the Safety, Tolerability, and Disposition of Trazpiroben, a D₂/D₃ Receptor Antagonist: Phase I Single‐ and Multiple‐Ascending Dose Studies in Healthy Japanese Participants