Североамериканское и Европейское общества детских гастроэнтерологов, гепатологов и нутрициологов обновили совместные клинические рекомендации 2009 года по диагностике и лечению гастроэзофагеальной рефлюксной болезни ГЭРБ у детей. Новые клинические рекомендации ориентированы на повседневную практику, как детских гастроэнтерологов, так и врачей первичного звена, когда специалисты-гастроэнтерологи недоступны. В документе даются отдельно рекомендации по диагностике и лечению ГЭРБ у детей грудного возраста (до 1 года) и более старших (1-18 лет) детей.
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5. Pharmacological treatment
5.11 We suggest not to use domperidone in the treatment of GERD in infants and children.
Domperidone Versus Placebo
The search identified 2 studies comparing domperidone and placebo(230,231). De Loore et al investigated infants and children with a clinical diagnosis of GER, defined by the presence of vomiting after a meal(230), while Carroccio et al evaluated symptomatic infants and children with GERD confirmed by pH- metry(231). Based upon the results of De Loore et al in which 47 infants and children were randomized to a 2-week double-blind trial comparing domperidone, metoclopramide or placebo, domperidone led to significant improvement in the percentage of patients vomiting at the end of the treatment period compared with placebo (P < 0.001). Carroccio et al, randomized patients to domperidone alone, domperidone with 2 different antacids or placebo and found that domperidone, when paired with antacids, reduced GERD symptoms (though not assessed as required to be included for analysis as an outcome measure in the current guideline) as well as pH-metry variables compared with placebo(230). Both studies reported no side effects. Quality of evidence was very low(230,231).
In conclusion, it is uncertain whether the use of domperidone reduces visible regurgitation/vomiting as signs and symptoms in infants and children with GER compared with placebo. It is uncertain whether the use of domperidone for the reduction of signs and symptoms in infants and children with GER(D) leads to more side-effects compared with placebo.
– Safety of domperidone and metoclopramide:
Domperidone and metoclopramide are antidopaminergic agents that facilitate gastric emptying. Over the last 5 years, 1 meta-analysis has been completed on the safety of metoclopramide that reviewed 108 (57 prospective) studies(234). The most common adverse effects were extrapyramidal symptoms (9%; 95% CI 5%–17%), diarrhea (6%; 95% CI 4%–9%), and sedation (multiple-dose studies: 6%; 95% CI 3–12). Dysrhythmia, respiratory distress/arrest, neuroleptic malignant syndrome, and tardive dyskinesia were rarely associated with metoclopramide use. Its therapeutic dosage is very close to the toxic dosage resulting in a very narrow safe dosing range. In some countries, regulatory agencies have removed it from the market because of its side effects and in 2013, the European Medicines Agency released a statement that the risk of neurological adverse for metoclopramide outweighed the benefit when taken for a prolonged amount of time at a high dose. A similar warning was made by the Food and Drug Administration in 2009, and Health Canada issued a statement in 2015 declaring that metoclopramide is contraindicated in infants <1 year of age due to its side-effects. As with metoclopramide, the side effect concerns relative to medication efficacy with domperidone are significant. The most concerning and significant adverse event related to its use is prolongation of the QTc interval, an event that has been reported in 1 out of 5 pediatric studies although there are conflicting results among studies and heterogeneity among study populations(235). Domperidone also has been associated with extrapyramidal central nervous system side effects, which preclude its routine use(212,236–239). In 2014, the Medicine and Healthcare products Regulatory Authority (MHRA) released a statement that there was a small risk of adverse cardiac events (specifically serious ventricular arrhythmia and sudden cardiac death) with the use of domperidone. Domperidone is not available in the United States and Health Canada has issued a warning related to its use in 2012 because of the risk of sudden death. The working group was therefore concerned that these agents should only be considered for use following specialist advice and as a last-line therapy. Insufficient evidence of clinical efficacy exists to justify routine use of either metoclopramide or domperidone for GERD, and these agents should thus not be regarded as an initial treatment for GERD in infants and children.
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