Safety and Effectiveness of Prucalopride in Children with Functional Constipation with and without Upper Symptoms.

INTRODUCTION: Pediatric prucalopride studies for treatment of gastrointestinal (GI) disorders have reported mixed results. We aimed to assess the safety and effectiveness of prucalopride in functional constipation (FC) with and without upper GI symptoms. METHODS: Retrospective data on patients with FC receiving combined prucalopride and conventional therapy was compared with those receiving conventional therapy alone within 12 months. Thirty patients on combined therapy and those on conventional therapy were each matched on the basis of age, gender, race, and presence of fecal soiling. Response (complete, partial, or no resolution) was compared. Similarly, response to concurrent functional upper GI symptoms (postprandial pain, bloating, weight loss, vomiting, early satiety, or nausea) and dysphagia, as well as adverse effects, were evaluated in the combined group. RESULTS: Mean age of 57 cases was 14.7 ± 4.9 years and 68% were female. Comorbidities included functional upper GI (UGI) symptoms (84%), dysphagia (12%), mood disorders (49%), and hypermobility spectrum disorder (37%). Unmatched cases reported 63% improvement to FC; response did not differ between the matched cohorts (70% versus 76.6%, p = 0.84). Cases showed a 56% improvement in functional UGI symptoms and 100% in dysphagia. Adverse effects were reported in 30%, abdominal cramps being most common. Four (7%) patients with a known mood disorder reported worsened mood, of which two endorsed suicidal ideation. CONCLUSION: Prucalopride efficaciously treated concurrent UGI symptoms and dysphagia in constipated pediatric patients and was overall well tolerated. Preexisting mood disorders seemed to worsen in a small subset of cases.

Evaluation of the safety and tolerability of intravenous undiluted levetiracetam at a pediatric institution.

STUDY OBJECTIVE: Recent studies suggest rapid administration of high-dose, undiluted levetiracetam is safe in adults; however, no information exists in pediatric patients. The purpose of this study was to evaluate the safety and tolerability of undiluted levetiracetam at a pediatric institution. DESIGN: Retrospective, single-center, cohort study. SETTING: Pediatric Academic Medical Center. PATIENTS: All patients who received high-dose >60 mg/kg (-10%) up to 4500 mg undiluted or diluted intravenous levetiracetam were included. INTERVENTION: Rapid intravenous administration of undiluted versus diluted levetiracetam. MEASUREMENTS AND MAIN RESULTS: A total of 776 levetiracetam doses were included, 358 doses administered and 418 doses wasted. The doses administered (61 undiluted and 297 diluted) accounted for a total of 252 patients (39 received undiluted, and 213 received diluted levetiracetam) (median [minimum-maximum range] age, 2 years [1 day to 32.7 years]; mean (standard deviation [SD]) weight, 20.1 kg [22.1 kg]). The incidence of hemodynamic disturbances and infusion-related reactions was not statistically significant between undiluted (24.6%) and diluted (26.3%) groups (p = 0.87). The median (interquartile range [IQR]) time difference between first-line antiseizure medication and levetiracetam administration in patients with status epilepticus was 18 min (10.5-30.5) in the undiluted group versus 36.5 min (21.8-67.3) in the diluted group (p < 0.01). Additionally, there was a significant amount of drug waste from dispensed but not administered doses of the diluted bag compared to undiluted vials (57.6% diluted vs. 18.7% undiluted, p < 0.001). CONCLUSION: Undiluted levetiracetam was not associated with an increased incidence of adverse effects compared to diluted levetiracetam in high-doses, up to 4500 mg given over 5 min in pediatric patients.

Tacrolimus interaction with dexmedetomidine--a case report.

Drugs and xenobiotics that inhibit the CYP-450 isoenzyme 3A4 are associated with increased serum tacrolimus levels. We sought to determine whether there was a temporal association between initiation of dexmedetomidine and increased serum tacrolimus levels. An interaction has not been previously documented. We reviewed tacrolimus levels and dosing in a pediatric patient aged 8 months who had undergone deceased-donor liver transplantation for biliary atresia and later required sedation with dexmedetomidine continuous infusion during the POD (212-216). Serum tacrolimus trough levels increased 4-fold from 3.4 to 13.1 ng/mL (tacrolimus regimen: 1 mg every 12 h) within 21 h of initiating dexmedetomidine. During dexmedetomidine infusion, serum tacrolimus trough levels were maintained with doses that were 25% of baseline tacrolimus dose. Tacrolimus trough levels decreased to below goal range within 30-40 h of discontinuation of dexmedetomidine. Data submitted to the U.S. Food and Drug Administration demonstrate that dexmedetomidine inhibits CYP 3A4 and may produce adequate liver concentrations that could interfere with tacrolimus metabolism. We suggest that tacrolimus levels should be carefully monitored in children receiving prolonged infusions of dexmedetomidine to avoid adverse events associated with elevated tacrolimus levels.