CARDIAC SAFETY AND CLINICAL EFFICACY OF DOMPERIDONE USE IN GASTROPARESIS USING AN FDA APPROVED IND PROTOCOL : A PROSPECTIVE 11-YEARS STUDY

Background:Domperidone, a D2 receptor antagonist, has been in clinical use in Europe and Asia since 1974. This drug is not FDA approved in USA. There are concerns about its cardiac toxicity, including QT prolongation, Torsade’s de pointes or sudden death.
Aims:1. To determine the incidence of abnormal QT prolongation in patients on long term domperidone treatment at our institution.2.To assess the incidence of adverse cardiac events in these patients. 3. To determine the clinical efficacy of domperidone use in gastroparesis.
Methods: We prospectively enrolled patients with gastroparesis (GP), who had previously not responded to two prokinetics, to an FDA approved IND protocol of Domperidone use . Patients were excluded if they had CAD, ventricular tachycardia, atrial fibrillation; h/o Torsade’s de pointes; sinus node dysfunction; or heart block or were using antiarrhythmic medications. Patients underwent EKG at baseline, at 8 weeks and then every 6 months. Clinical assessment was performed every 2 months for one year then 6 monthly. QTcF (Fridericia) was used to assess the QTc interval. The starting dose for domperidone was 10 mg TID. It was increased as clinically indicated to a maximum of 20mg QID. In case of abnormal QTc prolongation (>450 msec male; >470 msec female, increase >60 msec from baseline) the domperidone was reduced to previous tolerated dose and the patient was evaluated by a cardiologist.
Patients were asked about chest pain and arrhythmia. Clinical response was documented by the Gastroparesis Cardinal Symptom Index (GCSI) at each clinic visit. Response was defined as a 25% decrease in the GCSI score after 8 weeks of therapy.
Results:Since October 2012, 94 patients have been consented for enrollment. 6 patients were screen failures. 3 did not take the study medicine. The median age is 52 years (17-83). 62 (73%) are white. 68 (80%) are female. 50 (59%) have idiopathic GP, 17 (20%) diabetic GP, 13 (15%) postsurgical GP. 64 patients (76%) are on 10 mg TID dosage, 15 (17%) on 20mg TID and 6 (7 %) patients on 20mg QID.
The median follow-up period is 43 weeks.In 2 patients the QTc increased >60 ms from baseline. Three patients exceeded the QTc cutoff (470/450 ms) resulting in discontinuation/dose reduction of domperidone. No MI, arrhythmia or death was reported. The median GCSI at baseline was 2.7 (1.7-3.8). At 8 weeks 45 of 69 (65%) patients met the response criterion, at 26 weeks 37 of 51 patients (71%) had a 25% reduction in GCSI and at 12 months this was seen in 25 of 37 (67%) of patients.
Conclusion: Oral domperidone use was safe in our patients, who were screened for preexisting cardiac disease or arrthymias. Asymptomatic QTc prolongation was seen in 5.1% of patients. Clinical response in gastroparesis was seen in 65% of patients with a 25% reduction in GCSI after 8 weeks and in 67% at one year.