title: Cardiovascular safety profile and clinical experience with high-dose domperidone therapy for nausea and vomiting.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Internal Medicine (AO, CJC, YG, IS, RWM), Texas Tech University Health Sciences Center, El Paso, Texas; and Department of Gastroenterology (AA), Cleveland Clinic, Weston, Florida.
authors.forename: Arleen
authors.initials: A
authors.lastname: Ortiz
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Cooper
authors.forename: Alicia
authors.initials: A
authors.lastname: Alvarez
authors.forename: Yvette
authors.initials: Y
authors.lastname: Gomez
authors.forename: Irene
authors.initials: I
authors.lastname: Sarosiek
authors.forename: Richard W
authors.initials: RW
authors.lastname: McCallum
mesh_terms: D000328:Adult; D066126:Cardiotoxicity / Q000175:diagnosis / Q000208:ethnology / Q000209:etiology; D004294:Domperidone / Q000008:administration & dosage / Q000009:adverse effects; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D004562:Electrocardiography / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D009325:Nausea / Q000188:drug therapy* / Q000208:ethnology / Q000209:etiology; D012189:Retrospective Studies; D013995:Time; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D014839:Vomiting / Q000188:drug therapy* / Q000208:ethnology / Q000209:etiology
chemical_list: D018492:Dopamine Antagonists; D004294:Domperidone
references.citation: Curr Drug Saf. 2010 Jan;5(1):44-53
references.pmid: 20210718
references.citation: Pediatr Cardiol. 2005 Sep-Oct;26(5):720-3
references.pmid: 15690231
references.citation: Clin Ther. 1998 May-Jun;20(3):438-53
references.pmid: 9663360
references.citation: Circulation. 2000 Oct 17;102(16):1883-5
references.pmid: 11034933
references.citation: Am J Gastroenterol. 2007 Sep;102(9):2036-45
references.pmid: 17488253
references.citation: Drug Saf. 2010 Nov 1;33(11):1003-14
references.pmid: 20925438
references.citation: Pharmacoepidemiol Drug Saf. 2010 Sep;19(9):881-8
references.pmid: 20652862
references.citation: Curr Drug Saf. 2010 Jul 2;5(3):257-62
references.pmid: 20394569
references.citation: Am J Gastroenterol. 1989 Sep;84(9):1069-75
references.pmid: 2773901
references.citation: Am J Gastroenterol. 1999 May;94(5):1230-4
references.pmid: 10235199
references.citation: Diabetes Ther. 2010 Aug;1(1):32-43
references.pmid: 22127672
references.citation: Annu Rev Public Health. 2009;30:151-74
references.pmid: 19705558
references.citation: Dig Dis Sci. 1985 Jan;30(1):1-9
references.pmid: 3965269
references.citation: Am J Gastroenterol. 2013 Jan;108(1):18-37; quiz 38
references.pmid: 23147521
references.citation: J Am Coll Cardiol. 2006 Jan 17;47(2):362-7
references.pmid: 16412861
references.citation: Br J Clin Pharmacol. 2012 Mar;73(3):411-21
references.pmid: 21883386
references.citation: Digestion. 1983;27(4):214-7
references.pmid: 6653921
references.citation: Autoimmun Rev. 2006 May;5(5):306-13
references.pmid: 16782554
references.citation: Ann Pharmacother. 2006 Jul-Aug;40(7-8):1456-61
references.pmid: 16849620
references.citation: J Assoc Physicians India. 2004 Aug;52:626-8
references.pmid: 15847356
references.citation: Am J Emerg Med. 2013 May;31(5):866-71
references.pmid: 23602761