Safety of Lubiprostone in Pediatric Patients With Functional Constipation

Abstract

Objectives: Pediatric functional constipation (PFC) affects up to 30% of children. Current treatments often do not sustain symptomatic relief. Lubiprostone is a locally acting chloride channel activator that promotes fluid secretion into the small bowel without affecting serum electrolyte concentrations. We assessed the safety/tolerability of oral lubiprostone as treatment for PFC in a 24-week study. Methods: This phase 3 open-label safety trial conducted from April-November 2016 at 13 US sites included patients (ages 6–17 years) diagnosed with PFC (Rome III criteria). Patients <50 and ≥50 kg received lubiprostone 12 or 24 mcg twice daily, respectively, for 24 weeks. Safety endpoints included incidence of treatment-emergent adverse events (TEAEs) and changes from baseline in clinical laboratory parameters and vital signs. Results: Overall, 87 patients receiving lubiprostone, 64.3% (36/56) in the 12-mcg group and 54.8% (17/31) in the 24-mcg group, completed the study. Of 12 TEAEs leading to discontinuation, only upper abdominal pain occurred in >1 patient. TEAEs were mostly mild in intensity, with gastrointestinal disorders (diarrhea, vomiting) most frequently reported. No safety concerns were found in vital signs, abbreviated physical examinations, and laboratory tests. Subgroup analyses assessed an impact of age, sex, and race categories on TEAEs and treatment-related adverse events. Mean investigators’ assessments of treatment effectiveness (scale of 0–4) for lubiprostone 12- and 24-mcg groups, respectively, were 2.8 and 2.9 at week 12, and 2.7 and 2.2 at week 24. Conclusions: Lubiprostone was well tolerated in the pediatric population. The incidence of TEAEs was comparable to that observed in previous clinical trials and in adults.

An Update of Pharmacological Management in Children with Functional Constipation

“…Another multicenter open-label trial investigated the safety of lubiprostone in children with FC aged 6–17 years (mean age 10.3 years). In line with the other trials, the drug was well tolerated in children [ 83 ]. Side effects of lubiprostone are generally minor and include nausea, vomiting, abdominal pain, and diarrhea [ 82 ].…”

“…Children were allocated to a dosage of 12 µg once a day, 12 µg twice a day, or 24 µg once a day, depending on their weight. None of the studies reported any difference between the dosages for efficacy and safety [81][82][83].…”

Efficacy of lubiprostone for functional constipation treatment in adolescents and children: Randomized controlled trial

“…However, data regarding its role in childhood and pediatric patients are limited. [10][11][12] The current study showed that lubiprostone was superior to conventional laxatives in terms of improving SBM and BSF. In the current study, the clinical response was significantly higher in the lubiprostone group (91.4%) than in the conventional laxatives group (34.3%).…”

“…Upper abdominal pain was the only TRAE leading to discontinuation (of 12 patients in total) that occurred in >1 patient. 12 Diarrhea and vomiting were the most frequent (≥3% of patients). They reported no difference between different doses of lubiprostone as regards TARE.…”

Ефективність Корекції Дієтичного Харчування Дітей Із Функціональними Захворюваннями Шлунково-Кишкового Тракту Харчовими Продуктами Для Спеціальних Медичних Цілей

“…Серед функціональних розладів ШКТ у дітей найбільш часто зустрічаються функціональна диспепсія (ФД) та синдром подразненого кишечника (СПК), які у багатьох випадках поєднуються між собою [1][2][3]. Серед таких причин виникнення функціональних розладів травного тракту, як дисбактеріоз, порушення імунного захисту мукозної оболонки, вісцеральна гіперчутливість, дисрегуляція впливу центральної нервової системи на моторну функцію, важливою є нераціональне харчування дитини [4][5][6]. Корекція раціону є дієвим методом профілактики і лікування не лише функціональних хвороб органів травлення, а й хронічних захворювань у майбутньому [7][8][9].…”