Sudden Death in Cancer Patient on High-Dose Domperidone

Joss, R; Goldhirsch, Aron; Brunner, K.; Rl, Galeazzi

doi:10.1016/s0140-6736(82)92016-5

Cited by 61 publications

(24 citation statements)

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“…Due to reports of cardiac arrythmia and sudden death in cancer patients treated with intravenous domperidone indicated as an antiemetic (33,(46)(47)(48), the US FDA banned the use of the drug in July 2004 even as a lactation enhancer (28,42). In Canada, Domperidone is approved for the treatment of upper gastric motility.…”

Section: Domperidonementioning

confidence: 99%

Safety and Efficacy of Galactogogues: Substances that Induce, Maintain and Increase Breast Milk Production

Zuppa¹,

Sindico²,

Orchi³

et al. 2010

J Pharm Pharm Sci

167

168

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Poor production of breast milk is the most frequent cause of breast lactation failure. Often, physician prescribe medications or other substances to solve this problem. The use of galactogogues should be limited to those situations in which reduced milk production from treatable causes has been excluded. One of the most frequent indication for the use of galactogogues is the diminution of milk production in mothers using indirect lactation, particularly in the case of preterm birth. The objective of this review is to analyze to the literature relating to the principal drugs used as galactogogues (metoclopramide, domperidone, chlorpromazine, sulpiride, oxytocin, growth hormone, thyrotrophin releasing hormone, medroxyprogesterone). Have been also analyzed galactogogues based on herbs and other natural substances (fenugreek, galega and milk thistle). We have evaluated their mechanism of action, transfer to maternal milk, effectiveness and potential side effects for mother and infant, suggested doses for galactogogic effect, and recommendation for breastfeeding.

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Section: Domperidonementioning

confidence: 99%

Safety and Efficacy of Galactogogues: Substances that Induce, Maintain and Increase Breast Milk Production

Zuppa¹,

Sindico²,

Orchi³

et al. 2010

J Pharm Pharm Sci

167

168

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“…There are several reports of cardiotoxic effects (ventricular arrythmias, cardiac arrest, sudden death) after intravenous treatment with domperidone in humans [7][8][9][10][11][12] . Drolet et al [13] found that HERG currents expressed in CHO cells were blocked by domperidone with a halfmaximally inhibitory concentration (IC 50 value) of 162 nmol/l and that 100 nmol/l domperidone prolonged the action potential duration in ventricular myocytes from guinea pigs.…”

Section: Introductionmentioning

confidence: 99%

Comparison of the Effects of Metoclopramide and Domperidone on HERG Channels

Claassen

Zünkler²

2005

Pharmacology

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Torsades de pointes (TdP) is a potentially fatal form of ventricular arrhythmia that occurs under conditions where cardiac repolarization is delayed (as indicated by prolonged QT intervals from electrocardiographic recordings). A likely mechanism for QT prolongation and TdP is blockade of the rapid component of the cardiac delayed rectifier K⁺ current (I_Kr), which is encoded by HERG (human ether-a-go-go-related gene). The gastroprokinetic agent cisapride is a potent blocker of HERG currents and serious cardiac arrhythmias and deaths from TdP and ventricular fibrillation have been reported in patients taking cisapride. The aim of the present study was to compare 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. Both domperidone and metoclopramide concentration-dependently blocked HERG currents, and the following values were calculated for IC₅₀ (the concentrations causing half-maximal inhibition) and n (the Hill coefficient): 57.0 nmol/l and 0.99 for domperidone, 5.4 µmol/l and 0.95 for metoclopramide. The observation that the extent of block of HERG currents by domperidone increased at more positive membrane potentials whereas block of HERG currents by metoclopramide displayed a smaller degree of voltage dependency seems to indicate that domperidone and metoclopramide have distinct binding sites on HERG channels. In conclusion, the potency for block of HERG currents is about 100-fold lower for metoclopramide when compared to domperidone.

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“…However, serious doubts have arisen about the safety of this agent, with one death (Joss et al, 1982) and several cases of potentially fatal cardiac arrhythmias (Roussak et al , 1984) being reported after its use. In all cases these incidents have been associated with hypokalaemia, excessive domperidone dosage or both of these factors.…”

Section: Introductionmentioning

confidence: 99%

Cardiac Arrhythmias during Cytotoxic Chemotherapy: Role of Domperidone

Osborne¹,

Ml²,

et al. 1985

Human Toxicology

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1 Four patients receiving platinum-containing chemotherapy were treated with domperidone (20 mg) by slow intravenous injection followed by a continuous infusion for 24 h at a dose of 10 mg 24 h-1 kg-1. Cardiac monitoring and plasma potassium and domperidone concentration measurements were performed. Severe cardiac arrhythmias occurred in two patients. 2 A control group of 14 patients treated with similar chemotherapy, without domperidone, also underwent cardiac and plasma potassium monitoring. No significant arrhythmias were seen. 3 The electrophysiologic effects of domperidone are discussed. 4 It is concluded that treatment with intravenous domperidone is associated with the occurrence of cardiac arrhythmias.

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Sudden Death in Cancer Patient on High-Dose Domperidone

Cited by 61 publications

References 1 publication

Safety and Efficacy of Galactogogues: Substances that Induce, Maintain and Increase Breast Milk Production

Safety and Efficacy of Galactogogues: Substances that Induce, Maintain and Increase Breast Milk Production

Comparison of the Effects of Metoclopramide and Domperidone on HERG Channels

Cardiac Arrhythmias during Cytotoxic Chemotherapy: Role of Domperidone

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