Effect of domperidone, ondansetron, olanzapine-containing antiemetic regimen on QTC interval in patients with malignancy: a prospective, observational, single-group, assessor-blinded study

Abstract

Domperidone, ondansetron and olanzapine can prolong the QT interval. The clinical use of combinations of these drugs is not uncommon. Our study aimed to determine the presence of any QTc prolonging effect of the combination when used as antiemetic in patients receiving cancer chemotherapy. We carried out a prospective, observational study of patients with malignancy who were to receive domperidone, ondansetron and olanzapine-containing antiemetic regimen. Electrocardiograms were recorded before and during the administration of antiemetics, for three consecutive days. A blinded assessor determined the QTc interval using Bazett and Fridericia formulae. Thirty-six patients completed the study; 23 (63.9%) were females. There was a statistically significant change in QTc with time (Fridericia, χ2(4) = 15.629, p = 0.004; Bazett, χ2(4) = 15.910, p = 0.003); QTc on Day 1 was more than that during baseline (p < 0.001); these differences were significant in females (Fridericia, χ2(4) = 13.753, p = 0.008; Bazett, χ2 (4) = 13.278, p = 0.010) but not in males (Fridericia, χ2 (4) = 4.419, p = 0.352; Bazett, χ2(4) = 4.280, p = 0.369). Two female patients had an absolute QTc prolongation (Bazett correction) of > 500 ms. However, no clinically significant adverse events occurred. The findings show that QTc prolongation is a concern with olanzapine alone and in combination with domperidone and ondansetron, and needs to be investigated further.

Pilot Study on QTc Interval in Dogs Treated with Domperidone

“…Among them, diarrhea can be a self-limiting adverse side effect [ 8 ], while mammary gland hyperplasia with increased milk production and other disorders (e.g., lethargy, appetite loss, abdominal pain, and emesis) normally disappear after drug discontinuation [ 6 , 8 ]. The effect of domperidone on QT interval prolongation and possible cardiac toxicity has been extensively studied in human medicine [ 2 , 9 , 10 , 11 , 12 , 13 , 14 , 16 , 17 , 18 , 19 , 30 ], and the use of the drug has been restricted as a result by the European Medicines Agency in 2014 [ 28 ]. The possibility of a similar adverse effect in dogs has been previously pointed out [ 20 ], but it has not been investigated before this pilot study.…”

“…Nevertheless, this finding had no clinical significance, as none of the dogs showed arrhythmias or other cardiac side effects, and QTc remained within the reference range in almost all dogs. On the other hand, this finding suggests that further studies should be considered to evaluate the safety of domperidone administration in patients affected by heart diseases, electrolytic disorders, or those under treatment with drugs directly responsible for a QT interval increase or that have strong cytochrome P450 3A4 (CYP3A4) inhibitory activity [ 12 , 17 , 18 , 19 ]. For instance, some antiarrhythmic, antihistamine, antimicrobial, psychotherapeutic, and prokinetic drugs can prolong the QT interval in dogs and cats [ 20 , 34 ].…”

“…The risks of severe and potentially fatal cardiac arrythmias in association with domperidone are known in humans [ 16 ], particularly when administered at doses >30 mg/day [ 2 ]. Moreover, prolonged QT intervals have been described when domperidone was administered in patients with concurrent electrolytic disorders (e.g., hypokalemia, hypomagnesemia, hypocalcemia) and/or some risk factors (e.g., older age, female sex, sleep apnea, complete atrioventricular block, dilated cardiomyopathy, and bradycardia) [ 11 ], or in association with other drugs that directly increase the QT interval or, indirectly, compete with domperidone metabolism and elimination (cytochrome P450-3A4 inhibitors) [ 12 , 17 , 18 , 19 ].…”

Development of evidence-based indicators for the detection of drug-related problems among ovarian cancer patients

“…However, ondansetron and domperidone combination have a therapeutically superior antiemetic effect. Moreover, a combination of tramadol with domperidone or ondansetron may increase the risk of serotonin syndrome ( Kamath et al, 2021 ).…”

A dopamine antagonist, domperidone enhances the replication of an oncolytic adenovirus in human tumour cells

“…in the absence of domperidone pre-treatment (). In clinical settings, domperidone is usually orally administered to adults at a total dose of 20–80 mg per day [18, 21]. The mean peak plasma concentrations of domperidone have been shown to be less than 20 ng ml −1 (approximately 0.05 µM) following oral administration of domperidone tablets [22].…”