GERD in Pediatric Patients 1 to 11 Years of Age

The use of rabeprazole sodium delayed-release capsules for treatment of GERD in pediatric patients 1 to 11 years of age is supported by a randomized, multicenter, double-blind clinical trial which evaluated two dose levels of rabeprazole sodium delayed-release capsules in 127 pediatric patients with endoscopic and histologic evidence of GERD prior to study treatment. Dosing was determined by body weight: Patients weighing 6.0 to 14.9 kg received either 5 or 10 mg of rabeprazole sodium delayed-release capsules daily and those weighing 15.0 kg or more received 10 or 20 mg of rabeprazole sodium delayed-release capsules daily. After 12 weeks of rabeprazole treatment, 81% of patients demonstrated esophageal mucosal healing on endoscopic assessment. In patients who had esophageal mucosal healing at 12 weeks and elected to continue for 24 more weeks of rabeprazole, 90% retained esophageal mucosal healing at 36 weeks. No prespecified formal hypothesis testing for evaluation of efficacy was conducted. The absence of a placebo group does not allow assessment of sustained efficacy through 36 weeks. There were no adverse reactions reported in this study that were not previously observed in adolescents or adults.

Symptomatic GERD in Infants 1 to 11 Months of Age

The use of rabeprazole sodium delayed-release capsules is not recommended because studies conducted do not demonstrate efficacy for the treatment of GERD in pediatric patients younger than 1 year of age.

In a randomized, multicenter, placebo-controlled withdrawal trial, infants 1 to 11 months of age with a clinical diagnosis of symptomatic GERD, or suspected or endoscopically proven GERD, were treated up to 8 weeks in two treatment periods. In the first treatment period (open-label), 344 infants received 10 mg of rabeprazole sodium delayed-release capsules for up to 3 weeks. Infants with clinical response were then eligible to enter the second treatment period, which was double-blind and randomized. Two hundred sixty-eight infants were randomized to receive either placebo or 5 mg or 10 mg rabeprazole sodium delayed-release capsules.

This study did not demonstrate efficacy based on assessment of frequency of regurgitation and weight-for-age Z-score. Adverse reactions that occurred in ≥5% of patients in any treatment group and with a higher rate than placebo included pyrexia (7%) and increased serum gastrin levels (5%). There were no adverse reactions reported in this study that were not previously observed in adolescents and adults.

Neonates <1 Month and Preterm Infants <44 Weeks Corrected Gestational Age

The use of rabeprazole sodium delayed-release capsules is not recommended for the treatment of GERD, based on the risk of prolonged acid suppression and lack of demonstrated safety and effectiveness in neonates. Based on population pharmacokinetic analysis, the median (range) for the apparent clearance (CL/F) was 1.05 L/h (0.0543 to 3.44 L/h) in neonates and 4.46 L/h (0.822 to 12.4 L/h) in patients 1 to 11 months of age following once daily administration of oral rabeprazole sodium delayed-release capsules.

Juvenile Animal Data

Studies in juvenile and young adult rats and dogs were performed. In juvenile animal studies rabeprazole sodium was administered orally to rats for up to 5 weeks and to dogs for up to 13 weeks, each commencing on Day 7 post-partum and followed by a 13-week recovery period. Rats were dosed at 5, 25, or 150 mg/kg/day and dogs were dosed at 3, 10, or 30 mg/kg/day. The data from these studies were comparable to those reported for young adult animals. Pharmacologically mediated changes, including increased serum gastrin levels and stomach changes, were observed at all dose levels in both rats and dogs. These observations were reversible over the 13-week recovery periods. Although body weights and/or crown-rump lengths were minimally decreased during dosing, no effects on the development parameters were noted in either juvenile rats or dogs.

When juvenile animals were treated for 28 days with a different PPI at doses equal to or greater than 34 times the daily oral human dose on a body surface area basis, overall growth was affected and treatment-related decreases in body weight (approximately 14%) and body weight gain, and decreases in femur weight and femur length were observed.