Introduction

Pediatric gastroesophageal reflux disease (GERD) is common. Proton pump inhibitors have a well-established record of efficacy and safety in the treatment of acid-related disorders, including GERD, in adults and are widely considered the mainstay of therapy. two most commonly used PPIs, lansoprazole and omeprazole, have more than tripled in this population.

Aim

To evaluate the pharmacology, efficacy, and tolerability of lansoprazole in adolescents with GERD

Patient Profile

• 63 adolescents (12 to 17 years old) with symptomatic, endoscopically and/or histologically proven GERD

Method

Study Design

• Multicenter, double-blind randomized two-arm trial
• Lansoprazole 15 mg or 30 mg once daily was administered for a 5-day treatment period

Endpoints

• Pharmacokinetic parameters: the maximal observed plasma concentration (Cmax), the time to reach the maximal observed plasma concentration (Tmax) and 24-hour intragastric pH
• Reflux symptom relief
• Symptom severity, percentage of days and nights with heartburn/other predominant GERD symptom and overall symptom relief (rating of 1: better, 0: no change, and -1: worse)
• Safety endpoints: number and percentage of patients reporting adverse events, and the relationship to study medication

Results

Efficacy

• Lansoprazole achieved a T(max) of 1.6 hours with 15 mg dose and 1.7 hours with 30 mg dose; dose-proportional increases in C(max) were observed
• Age, weight, and gender had no significant effect on T(max) or C(max); a small drop in the elimination rate constantwas seen with increase in age (P = 0.0358)
• Lansoprazole significantly increased mean 24-hour intragastric pH from pretreatment levels (from 2.7 to 3.8 with 15 mg dose, P = 0.013; from 2.8 to 3.9 with 30 mg dose; P = 0.026)
• Lansoprazole significantly improved the reflux symptoms from baseline, based on daily diary data and physician-elicited GI symptom assessment (69% with 15 mg; 74% with 30 mg) after 5 days of treatment (Figure 1)
• Lansoprazole exhibited reductions from baseline in the percentage of days (from 86% to 78% with 15 mg dose) and/or nights (from 17% to 0% with 15 mg dose) with heartburn or other predominant GERD symptom and decreased symptom severity
• It reduced the percentage of days antacids were used, by approximately 50% in both dose groups; also the average number of antacid tablets used per day decreased from 1.8 to 1.05 in the 15 mg group and 0.63 in the 30 mg group
• In patients with heartburn at baseline, lansoprazole significantly reduced the severity of heartburn (P = 0.021 for 15 mg dose; P = 0.012 for 30 mg dose)
• An improvement in heartburn was achieved in 56% of the patients in the lansoprazole 15 mg group and 70% of the patients in the 30 mg group

Figure 1: Effect of lansoprazole treatment on reflux symptoms

Safety 

• Lansoprazole 15 mg and 30 mg doses were frequently associated with side effects of pharyngitis and headache, respectively, among the adolescents
• Five patients experienced adverse events considered to be possibly treatment-related
• One patient with a history of environmental allergies experienced a mild allergic reaction after 3 days of treatment with lansoprazole 15 mg
• Among those treated with lansoprazole 30 mg, 4 patients each reported one occurrence of pain, diarrhea, dizziness, and rash

Conclusion

Lansoprazole 15 mg or 30 mg once daily for 5 days produced significant increase in intragastric pH, effectively relieved symptoms of reflux disease, and was well tolerated in adolescents with GERD

J Pediatr Gastroenterol Nutr. 2002; 35(4): S327-35