Cardiovascular Safety Profile and Clinical Experience With High-Dose Domperidone Therapy for Nausea and Vomiting

Abstract

Abstract:Introduction:Domperidone is a dopamine receptor antagonist with peripheral prokinetic and central antiemetic properties. Prolongation of the QTc interval with chronic use of oral domperidone in standard doses has been reported in the literature. Our goal was to investigate cardiac toxicity in patients receiving 2-fold greater doses than in previous reports.Methods:A retrospective chart review was conducted of patients with nausea (N) and vomiting (V) receiving domperidone from 2009 to 2013 under an Investigational New Drug (IND) protocol. Patient demographics, indications for therapy, clinical outcomes, cardiac symptoms and electrocardiogram tracings were reviewed. Prolonged QTc was verified if >470 milliseconds in females (F) and >450 milliseconds in males (M).Results:A total of 64 patients, 44 female (37% Hispanic, 60% white, 3% African American), were taking domperidone for diabetic gastroparesis 45%; idiopathic gastroparesis 36%; chronic N&V 8%; dumping syndrome 5%; cyclic vomiting 5% and conditioned vomiting 1%. Mean duration of therapy was 8 months (range, 3 months to 4 years). Doses ranged from 40 to 120 mg/d with 90% receiving 80 to 120 mg compared with the standard dose of 40 mg. Of note, 73% of subjects benefited from treatment with reduced nausea and vomiting. Thirty-seven patients had follow-up electrocardiograms available, and they showed that the mean QTc at baseline was 424 milliseconds ± 28.4 (SD) compared with 435 milliseconds ± 27.2 (SD) at follow-up (not significant). Ten of these patients had prolonged QTc at F/U ranging from 453 to 509 milliseconds, without any cardiovascular complaints. There was no relationship between prolonged QTc and daily dose of domperidone, body mass index or age.Conclusions:Our data indicate that at very high dosing, the prokinetic/antiemetic agent domperidone has a low risk of adverse cardiovascular events while exhibiting good clinical efficacy.

Therapeutic response to domperidone in gastroparesis: A prospective study using the GCSI‐daily diary

“…Other studies have shown improvement in gastroparesis symptoms with domperidone therapy . Symptoms that have been reported as improving include nausea, vomiting, postprandial fullness, and early satiety.…”

“…There is concern about domperidone prolonging the QTc on electrocardiograms and possibly predisoposing patients to arrhythmias. In a recent study of patients taking high dose domperidone for GI symptoms, 27% were found to have QTc prolongation . However, none of these patients experienced arrhythmia.…”

“…Treatment with domperidone can occur using the FDA investigational new drug (IND) program . One potential concern with the use of domperidone is prolongation of the EKG QTc interval and cardiac arrhythmia, especially at doses above 30 mg daily . In a recent study of the therapeutic effects of domperidone 10 mg TID in 115 patients with gastroparesis, 60% of patients reported symptom improvement with only 5 subjects experiencing QTc prolongation …”

Effects of domperidone in combination with omeprazole in the treatment of chronic superficial gastritis

“…It will not produce bad effects on the central nervous system as it is difficult to enter the brain. Besides, it can selectively block dopamine 2 and mainly act on the peripheral nervous system 15. Domperidone can improve the power of digestive tract and promote gastric emptying 16.…”

Drugs Acting on the Gut: Prokinetics, Antispasmodics, Laxatives

“…Arrhythmia and sudden cardiac death have been associated with patients given IV domperidone in the setting of hypokalemia and, as a result, the IV formulation is no longer available [ 21 , 22 ]. Prolonged QTc has been associated with PO domperidone use although this may not lead to adverse events [ 23 ].…”