Proton Pump Inhibitor Use in Infants: FDA Reviewer Experience

Division of Gastroenterology and Inborn Errors Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993-0002, USA.
Journal of pediatric gastroenterology and nutrition (Impact Factor: 2.63). 09/2011; 54(1):8-14. DOI: 10.1097/MPG.0b013e31823890b4
Source: PubMed


The Food and Drug Administration has completed its review of 4 clinical trials evaluating the use of proton pump inhibitors (PPIs) in infants (ages 1 month to <12 months) for the treatment of gastroesophageal reflux disease (GERD). An Advisory Committee meeting was held in November 2010 to discuss the potential reasons why PPI use in these trials failed to show a benefit in infants with GERD, and directions for future study. The present review summarizes the findings from the clinical trials. Potential mechanisms for the failed clinical trials are discussed. The safety of long-term use is also discussed. As a result of our analysis and review, the authors agree with the Advisory Committee members that PPIs should not be administered to treat the symptoms of GERD in the otherwise healthy infant without the evidence of acid-induced disease.

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    • "Proton pump inhibitors (PPIs) such as omeprazole (OME) are nowadays the most common drugs used for the treatment of various gastric disorders (Phillips, Metzler, Huckfeldt, & Olsen, 1998; Tofil, Benner, Fuller, & Winkler, 2008). They have been approved in children (Chen et al., 2012; Lang, 2008; Tolia & Boyer, 2008), even though they are often the subject of revision especially for the use in new-borns (Khoshoo, Edell, Thompson, & Rubin, 2007). OME dosage for the treatment of GERD in children is fixed at 0.7–1.0 "
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    ABSTRACT: The treatment of gastro-esophageal reflux disease (GERD) shows several issues among paediatric patients. This work aims to the formulation of enteric alginate beads loaded with omeprazole (OME) allowing age- and weight-related personalized dosages in children. OME was entrapped in SBA-15 mesoporous compound, characterized and loaded into alginate beads by prilling at different OME and alginate concentrations. The beads resulted of homogeneous size, spherical morphology and very consistent in drug loading and distribution. Formulations demonstrated limited swelling and release (about 10%) in simulated gastric fluid (SGF) after 2 h and a prolonged release in simulated intestinal fluid (SIF), till 6 h, due to a mixed diffusion-case II transport mechanism. The beads were superior to the market product, which showed lower release in SGF but immediate dissolution in SIF. The high alginate beads uniformity and release properties make them a potential novel tool for a personalized treatment of GERD in children.
    Carbohydrate Polymers 11/2015; 133:464-472. DOI:10.1016/j.carbpol.2015.07.064 · 4.07 Impact Factor
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    • "This has resulted in widespread inappropriate diagnosis and treatment of gastro-oesphageal reflux disease (GORD), lactose intolerance, and food allergy in crying babies in the first three to four months of life [16] [51] [52]. Despite the ongoing popularity of these diagnoses, anti-secretory medications have been shown to be no more effective than placebo [53] [54], and the mucosal inflammation of acid-peptic or allergic oesophagitis is very rarely demonstrated in crying babies in the first three or four months [55] [56]. Complicated maternal elimination diets are popular amongst breastfeeding mothers. "
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    ABSTRACT: Although problem crying in the first three to four months of life is usually self-limiting, it is not a trivial condition. Early intervention is important, yet families receive conflicting advice from health professionals. The past decade has seen significant advances in neuroscience, lactation science, and developmental psychology, including new insights into the significance of developmentally sensitive windows. We propose a neurobiological model to explain the mechanisms of cry-fuss problems in the first months of life, and the mechanisms which underlie effective intervention, with a view to facilitating research collaboration and consistency of advice across health disciplines. We hypothesise that crying in the first three to four neurodevelopmentally sensitive months signals activation of the hypothalamic-pituitary-adrenal axis and adrenergic neuronal circuitry in response to perceptions of discomfort or threat. Susceptible infants may be conditioned by early stress, for example, by unidentified feeding difficulties, into a sensitised stress response, which usually settles at three to four months of age with neurodevelopmental maturity. Bouts of prolonged and unsoothable crying result from positive feedback loops in the hypothalamic-pituitary-adrenal and adrenergic systems. Importantly, epigenetic modulation of the infant's limbic neuronal circuitry may explain correlations between regulatory problems in the first months of life, and behavioural problems including feeding problems in later childhood.
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    ABSTRACT: To prospectively evaluate the effects of oral domperidone on the QTc interval in infants. Infants (0-1 year) with a diagnosis of gastro-oesophageal reflux (GOR) disease were included. A 12-lead electrocardiography (ECG) was performed in all infants at baseline and 1 h after the intake of domperidone after 7-14 days; the corrected QTc interval was calculated by one investigator (MV) according to Bazett's formula. Forty-five infants were enrolled in this study. The mean gestational age was of 38.6 weeks (35.5-42.0), and the mean age at the start of domperidone was 75.3 days (19-218 days). No statistically significant difference in corrected QTc was observed between baseline and the second ECG (0.389 ± 0.02 vs. 0.397 ± 0.31; p 0.130)). A trend was observed regarding gender: Although there was no difference in QTc change in girls (p 0.622), there was a strong trend in boys (p 0.051). Two infants (both boys) had a clinically significant QTc prolongation (> 460 msec) without symptoms. The Spearman correlation test showed no relation between the QTc change and age (r: -0.05822; p 0.7284). There was no relation between domperidone dosage and QTc change. Overall, the group-analysis showed no statistical significant difference in QTc duration induced by domperidone. However, 2/45 (4.4%) infants had a prolonged QTc interval (> 460 msec) induced by domperidone. As a consequence, QTc measurement should be recommended in routine in infants when domperidone is started.
    Acta Paediatrica 01/2012; 101(5):494-6. DOI:10.1111/j.1651-2227.2012.02593.x · 1.67 Impact Factor
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