1228 Cardiac Safety and Clinical Efficacy of High Dose Domperidone for Long-Term Treatment of Gastroparesis

Abstract

INTRODUCTION: Domperidone (D), a dopamine 2 receptor antagonist, is an effective anti-emetic that acts at the chemoreceptor trigger zone and only minimally crosses the blood brain barrier while also exerting prokinetic effects on the stomach and proximal small bowel. D is not approved in the USA. Recommended dosing worldwide is 30 mg/day and due to scattered reports of cardio toxicity ECG monitoring is recommended. Our goal was to explore the cardiac safety and clinical efficacy of long-term use of D, titrated as high as 120 mg/day, in patients not responding or unable to tolerate other therapies for gastroparesis (GP). METHODS: From our database we identified 19 patients without preexisting cardiac diagnoses, 85% F, mean age 47 (range 27-74), 50% white, 42% Hispanic, who received a high dose D per FDA/IND approved protocol. Baseline GP symptoms were assessed and then monitored for changes during treatment using a physician administered IRB-approved questionnaire which recorded the GP symptoms of nausea, vomiting, early satiety and abdominal pain, which were graded for severity (0-absent to 4-extremely severe) and compared to baseline values. Patients had to be improved symptomatically by ≥50% to be considered responders. Adverse cardiac events were recorded, and follow up ECGs (average 2 repeat ECGs per patient (range 1-7) focused on prolonged QTc intervals (>450 ms in M, >470 ms in F). RESULTS: The mean duration of D therapy was 31 months (range 3-96) median time of 17 months. The average dose of D was 80 mg/day (range of 40-120), while 3 (15%) of GP patients recieved 120 mg/day. No patients had serious cardiac adverse events. Two (F) patients had prolonged QTc of 491 ms and 482 ms requiring discontinuation of D and 4 reported heart palpitations or chest pain unrelated to prolonged QTc, and continued the medication. 78% of patients met criteria for treatment response with overall mean symptoms improvement of 71% (range 30-100) compared to pre-D scores. Vomiting was the most improved symptom. CONCLUSION: Long-term treatment with high doses of D resulted in significant improvement of GP symptoms in patients previously refractory to other medical therapies. There were no adverse cardiac events reported, and only asymptomatic QTc prolongation was recorded in 11% of patients. These data emphasize both the safety and efficacy of high dose D in the treatment of symptomatic GP.