Use and Safety of Erythromycin and Metoclopramide in Hospitalized Infants

Abstract

Objective Prokinetic medications are used in premature infants to promote motility and decrease time to full enteral feeding. Erythromycin and metoclopramide are the most commonly used prokinetic medications in the neonatal intensive care unit (NICU), but their safety profile is not well defined. Methods We conducted a large retrospective cohort study using data from 348 NICUs managed by the Pediatrix Medical Group. All infants exposed to ≥1 dose of erythromycin, metoclopramide, or both, from a cohort of 887,910 infants discharged between 1997 and 2012 were included. We collected laboratory and clinical information while infants were exposed to erythromycin or metoclopramide and described the frequency of laboratory abnormalities and clinical adverse events. Results Metoclopramide use increased from 1997–2005 and decreased from 2005–2012, while erythromycin use remained stable. Erythromycin use was most often associated with a diagnosis of feeding problem (40%), while metoclopramide was most often associated with a diagnosis of gastroesophageal reflux (59%). The most common laboratory adverse event during exposure to erythromycin or metoclopramide was hyperkalemia (8.6/1000 infant days on erythromycin and 11.0/1000 infant days on metoclopramide). Incidence of pyloric stenosis was greater with erythromycin than with metoclopramide (10/1095, 0.9% vs. 76/19,001, 0.4%, p=0.01), but odds were not significantly increased after adjusting for covariates (odds ratio=0.52 [95% CI: 0.26, 1.02], p=0.06). More infants experienced an adverse event while treated with metoclopramide than with erythromycin (odds ratio=1.21 [95% CI: 1.03, 1.43]). Conclusion Metoclopramide was associated with increased risk of adverse events compared to erythromycin. Studies are needed to confirm safety and effectiveness of both drugs in infants.

Safety of histamine-2 receptor blockers in hospitalized VLBW infants

“…(11) In 2009, the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition published clinical practice guidelines for pediatric gastroesophageal reflux, which warned of H2 blockers’ association with NEC and presented them as inferior to proton pump inhibitors (PPIs). (19)…”

“…(19) A 2014 Cochrane review found moderate evidence to support the use of PPIs over H2 blockers in the treatment of pediatric gastroesophageal reflux, but noted the difficulty in drawing conclusions due to a lack of placebo-controlled trials, especially in infants. (20) Prokinetics previously studied in infants include erythromycin and metoclopramide, but neither are approved for this use by the Food and Drug Administration and both have serious potential side effects including pyloric stenosis and dopaminergic dysregulation.…”

“…(20) Prokinetics previously studied in infants include erythromycin and metoclopramide, but neither are approved for this use by the Food and Drug Administration and both have serious potential side effects including pyloric stenosis and dopaminergic dysregulation. (19-23)…”

Post-natal erythromycin exposure and risk of infantile hypertrophic pyloric stenosis: a systematic review and meta-analysis

“…Erythromycin is commonly indicated within the neonatal population for prophylaxis following Chlamydia trachomatis infection [18] in preventing conjunctivitis or pneumonia and in the treatment of pertussis [14]. In addition, erythromycin has also been utilised in the treatment of gastrointestinal dysmotility within this population [10].…”

Drugs Acting on the Gut: Prokinetics, Antispasmodics, Laxatives

“…Evidence for use in pediatric GER is confl icting as some studies show that there is no signifi cant improvement in symptoms and esophageal pH measurements compared to placebo while others show signifi cant improvement [ 33 , 34 ]. In the NICU setting, there may be an increased risk for adverse events compared to erythromycin [ 35 ]. Metoclopramide is used frequently to treat postoperative nausea and vomiting [ 36 ].…”