China
Africa
Explore chapters and articles related to this topic
Autonomic Nervous System Disorders
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
Metoclopramide 10 mg before meals and at night. Have caution with long-term use, where domperidone up to 10 mg three times per day in adults is preferable. Nizatidine may be helpful in some patients.
Palliative Care of Gastroparesis
Published in Victor R. Preedy, Handbook of Nutrition and Diet in Palliative Care, 2019
In conjunction with the dietary modifications mentioned previously, the use of pharmacologic promotility agents (prokinetics) such as metoclopramide, domperidone and erythromycin may be used to improve symptoms and rate of gastric emptying. Metoclopramide is used as a first-line agent and has both prokinetic and anti-nausea properties. However, this medication should be used cautiously because of its potential risks and side effects of QT prolongation and extra-pyramidal manifestations (Sarosiek et al. 2016). The drug is available for use as oral, intravenous and rectal formulations. Domperidone, a dopamine antagonist, is the preferred drug if metoclopramide is not tolerated. It does not cross the blood-brain barrier so does not have neurological side effects, but has potential for cardiac toxicity. Domperidone has a quite potent anti-emetic effect. Domperidone has been shown to be effective in approximately 70% patients in a recent single-center study, but 40% of patients had significant adverse effects, and 12% of patients had to discontinue the therapy (Schey et al. 2016). This drug is not approved by the U.S. Food and Drug Administration but has been used under the investigational new drug (IND) program. Domperidone is available in many countries outside the United States.
Common problems in pregnancy
Published in Anne Lee, Sally Inch, David Finnigan, Therapeutics in Pregnancy and Lactation, 2019
Metoclopramide and domperidone are generally considered safe for use in pregnancy, although they are used less often than antihistamine or phenothiazine anti-emetics and evidence from controlled studies is lacking.13,14 Metoclopramide is associated with an increased risk of extrapyramidal reactions in young women, so it is best reserved for use when first-line agents have been ineffective.
Gastroparesis syndromes: emerging drug targets and potential therapeutic opportunities
Published in Expert Opinion on Investigational Drugs, 2023
Le Yu Naing, Matthew Heckroth, Prateek Mathur, Thomas L Abell
Metoclopramide is currently the only drug approved by the US Food and Drug Administration (FDA) for the treatment of gastroparesis. However, in 2009 a black box warning for metoclopramide and the risk of tardive dyskinesia was issued, with the risk increasing with longer duration and higher cumulative dose. Therefore, it has been advised against the use of metoclopramide for >12 weeks except for in extraordinary circumstances[23]. Domperidone is another D2 receptor antagonist for the treatment of gastroparesis. It crosses the blood-brain barrier poorly and therefore has less frequent central adverse effects than metoclopramide. However, domperidone has been associated with significant QT prolongation, arrhythmia, and sudden cardiac death. A proposed mechanism for QT prolongation with domperidone is due to the blockade of the cardiac delayed rectifier K(+) current (I(Kr)), which is encoded by human Ether-a-go-go Related Gene (hERG)[24]. Other studies have shown that it can be used chronically with no adverse cardiac effects[25]. The FDA never approved domperidone for the US market, although it is available in most other countries. However, domperidone has been available by an investigational new drug (IND) program in the US for several years. There is continuing evidence that domperidone is safe for use in GpS [26–28].
Safety considerations when managing gastro-esophageal reflux disease in infants
Published in Expert Opinion on Drug Safety, 2021
Melina Simon, Elvira Ingrid Levy, Yvan Vandenplas
The most concerning adverse effect of domperidone is prolongation of the QTc interval. In adults, oral intake of domperidone was related to an increased risk of ventricular arrythmias and sudden death [145,146]. In infants and children, there are a few reports of increased QTc duration due to domperidone. In 2005, Rocha and Barbosa reported a case of a 3 month old infants with QTc prolongation (463 ms) and intermittent cyanosis during treatment with domperidone; after stopping the drug the QTc time normalized (400 ms) [147]. After this initial report, a few studies confirmed the QTc prolongation. A prospective study in neonates (n = 34, mean GA 34.2 weeks) given 1.3 ± 0.7 mg/kg/day domperidone, noticed a prolongation of QTc time (P < 0.01, pretreatment 373.2 ± 4.8; during treatment, 387.2 ± 5.1) [148]. Consequently, QTc prolongation, however mostly asymptomatic, was reported in several studies in infants and children [149–151]. There are also a few reports on extra pyramidal effects of domperidone in older children [152,153]. Domperidone was never marketed in the USA. In Europe, the Agency of Medicines and Health Products has withdrawn the domperidone suspension for children, recommending not to use domperidone in children < 12 year or < 35 kilogram, and a warning for the use in adults [154]. Therefore, the guidelines by NASPGHAN and ESPGHAN do not recommend domperidone [9].
Current and future treatment management strategies for gastroparesis
Published in Expert Opinion on Orphan Drugs, 2019
Priyadarshini Loganathan, Mahesh Gajendran, Richard McCallum
Domperidone antagonizes peripheral D2 receptor in GI tract and increases acetylcholine release, which is the main GI excitatory neurotransmitter inducing a net prokinetic effect. It also has its effects on nausea and vomiting by blocking D2 receptor in the CTZ area. Several studies have showed significant improvement in GP symptoms compared to placebo [21,22]. In a prospective cohort (88 IDGP, 16 DMGP, and 9 post-surgical GP), patients showed an improvement in GP symptoms, including nausea, vomiting, retching, early satiety, post-prandial fullness, and upper abdominal pain (p < 0.001) [23]. Domperidone does not cross the blood brain barrier and there by does not have CNS side effects [5]. It is able to stimulate pituitary hormone release, specifically prolactin, since the pituitary is regarded as being outside the blood brain barrier. Domperidone is well absorbed in oral form with 7% excreted unchanged in feces [24]. The recommended dose of Domperidone is 10 mg before each meal and at bedtime. Systematic review of 28 trials (11 full articles and 17 abstracts), 64% of studies showed symptom improvement, and 60% showed improvement in GE, and 67% of studies showed a reduction in hospital readmissions. It was concluded that there is level 3 evidence for the efficacy of domperidone in diabetic GP, leading to a grade C recommendation [25]. Due to the cardiotoxic side effects, the intravenous formulation was discontinued [26]. Domperidone was never approved in the US based on the FDA assessment that larger clinical trials were needed.