aprepitant and Gastroparesis

There are few effective treatments for nausea and other symptoms in patients with gastroparesis and related syndromes. We performed a randomized trial of the ability of the neurokinin-1 receptor antagonist aprepitant to reduce symptoms in patients with chronic nausea and vomiting caused by gastroparesis or gastroparesis-like syndrome.. We conducted a 4-week multicenter, double-masked trial of 126 patients with at least moderate symptoms of chronic nausea and vomiting of presumed gastric origin for a minimum of 6 months. Patients were randomly assigned to groups given oral aprepitant (125 mg/day, n = 63) or placebo (n = 63). The primary outcome from the intention-to-treat analysis was reduction in nausea, defined as a decrease of 25 mm or more, or absolute level below 25 mm, on a daily patient-reported 0-to-100 visual analog scale (VAS) of nausea severity. We calculated relative risks of nausea improvement using stratified Cochran-Mental-Haenszel analysis.. Aprepitant did not reduce symptoms of nausea, based on the primary outcome measure (46% reduction in the VAS score in the aprepitant group vs 40% reduction in the placebo group; relative risk, 1.2; 95% CI, 0.8-1.7) (P = .43). However, patients in the aprepitant group had significant changes in secondary outcomes such as reduction in symptom severity (measured by the 0-5 Gastroparesis Clinical Symptom Index) for nausea (1.8 vs 1.0; P = .005), vomiting (1.6 vs 0.5; P = .001), and overall symptoms (1.3 vs 0.7; P = .001). Adverse events, predominantly mild or moderate in severity grade, were more common in aprepitant (22 of 63 patients, 35% vs 11 of 63, 17% in the placebo group) (P = .04).. In a randomized trial of patients with chronic nausea and vomiting caused by gastroparesis or gastroparesis-like syndrome, aprepitant did not reduce the severity of nausea when reduction in VAS score was used as the primary outcome. However, aprepitant had varying effects on secondary outcomes of symptom improvement. These findings support the need to identify appropriate patient outcomes for trials of therapies for gastroparesis, including potential additional trials for aprepitant. ClinicalTrials.gov no: NCT01149369.

Topics: Adult; Antiemetics; Aprepitant; Chronic Disease; Double-Blind Method; Female; Gastroparesis; Humans; Male; Middle Aged; Morpholines; Nausea; Treatment Outcome; Vomiting

Topics: Alemtuzumab; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Busulfan; Cyclosporine; Gastroparesis; Hematopoietic Stem Cell Transplantation; Humans; Infant; Lymphohistiocytosis, Hemophagocytic; Male; Methotrexate; Nausea; Unrelated Donors; Vidarabine; Vomiting

People with gastroparesis who develop treatment-resistant (refractory) disease pose a difficult challenge, especially in the setting of end-stage renal disease (ESRD) or post pancreas transplant. Aprepitant (a neurokinin-receptor antagonist) is licensed for the short-term treatment of chemotherapy-induced nausea. There is lack of information on its long-term efficacy and safety in people with diabetic gastroparesis.. Case 1 was 73-year-old man with Type 2 diabetes of 25 years' duration and ESRD requiring dialysis. He was referred to our unit as his severe symptoms of gastroparesis had failed to respond to multiple medications and resulted in frequent hospital admissions. Aprepitant, which can be used in ESRD, resulted in significant improvement in his symptoms of nausea and vomiting within weeks, and he remained on this long term (18 months) with continued benefits and had no further gastroparesis-related hospital admissions. Case 2 was a 44-year-old man with Type 1 diabetes of 41 years' duration with a history of severe hypoglycaemic events that required a pancreas transplant. Despite normoglycaemia, his symptoms of gastroparesis persisted and failed to respond to multiple medications and frequent botulinum toxin injections. He was commenced on aprepitant with significant improvement in symptoms and has remained on treatment for 12 months with sustained benefits.. We describe two cases in which long-term aprepitant treatment proved effective in alleviating severe symptoms of gastroparesis that had failed to respond to conventional first-line medical treatments. Our cases highlight the need for novel treatments for managing refractory diabetic gastroparesis.

Topics: Adult; Aged; Aprepitant; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Gastric Emptying; Gastroparesis; Humans; Kidney Failure, Chronic; Male; Morpholines; Pancreas Transplantation; Time Factors; Treatment Outcome

To report a case of refractory nausea in a patient with idiopathic gastroparesis successfully treated with aprepitant.. A 41-year-old female with idiopathic gastroparesis demonstrated by a delayed gastric emptying time experienced significant nausea, vomiting, and abdominal pain. This resulted in numerous hospital admissions and regular outpatient intravenous fluid administration. Over a 3-year period the patient had been treated with numerous agents for nausea and vomiting, including metoclopramide 10 mg 3 times daily, ondansetron 8 mg 2 times daily, and promethazine (various doses from 12.5 to 25 mg orally up to 3 times daily). No treatment tried was either tolerated or effective. As a last option before considering gastric pacing the patient was started on aprepitant 40 mg daily. The patient had a dramatic response to aprepitant and reported that her nausea had decreased significantly after 48 hours of starting the medication (2 doses). She was able to tolerate oral feeding and her need for outpatient intravenous hydration abated. Over the course of 2 months while using aprepitant her gastroparesis symptoms continued to improve. She reported no adverse effects attributable to aprepitant. After the first 2 months of aprepitant treatment, the patient was unable to continue the medication due to cost. Although her symptoms did worsen after discontinuation, they did not return to their initial severity. At 4 months after the trial of aprepitant, she continued to have improved symptoms. She claimed not to have daily nausea or vomiting, but still required high-dose promethazine and occasional outpatient intravenous fluids. At that point, she had gained 7.2 kg from the time that she had started aprepitant.. Aprepitant, a neurokinin-1 receptor antagonist, is approved in the US for nausea and vomiting associated with surgery and cancer chemotherapy. To our knowledge, this is the second reported case of its use in gastroparesis-induced nausea. Our patient reported relief of nausea and vomiting despite existing evidence showing that aprepitant has no significant effect on accelerating gastric emptying. Despite its acquisition cost, our patient avoided hospital admission and the administration of intravenous hydration, suggesting aprepitant may be cost-effective in this case.. Aprepitant may have some utility in treating refractory nausea caused by gastroparesis. This case suggests that the drug's antiemetic effect may be successfully used in areas not approved by the Food and Drug Administration. A controlled trial examining aprepitant in patients with such challenging clinical conditions may be warranted.

Topics: Abdominal Pain; Adult; Antiemetics; Aprepitant; Female; Follow-Up Studies; Gastroparesis; Humans; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Promethazine; Treatment Outcome; Vomiting

A 31-year-old woman with an 11-year history of poorly controlled type 1 diabetes mellitus was admitted with severe vomiting and ketoacidosis. The patient had been admitted to hospital on 14 occasions in the past 3 years for diabetic ketoacidosis precipitated by intractable vomiting, and she had been diagnosed with gastroparesis 2 years previously.. Assessment of the patient's response to standard treatments for diabetic gastroparesis. These approaches involved tight glycemic control that included subcutaneous insulin infusion via a pump, correction of electrolyte disturbances, use of standard antiemetic and promotility agents, somatostatin-analog treatment, intrapyloric injection of botulinum toxin, and insertion of a percutaneous jejunal feeding tube.. Severe diabetic gastroparesis refractory to standard treatments.. The neurokinin-receptor antagonist aprepitant was started and her vomiting stopped within 24 h. This treatment was successfully continued for 4 months until a gastric electrical stimulation device was inserted, which enabled aprepitant treatment to be withdrawn and the percutaneous jejunostomy feeding tube to be removed. This successful treatment led to a substantial improvement in the patient's quality of life and overall glycemic control.

Topics: Adult; Antiemetics; Aprepitant; Diabetes Mellitus, Type 1; Female; Gastroparesis; Humans; Morpholines; Treatment Outcome