Accuracy of Dose Administered to Children Using Off-Labelled or Unlicensed Oral Dosage Forms

Abstract

The pediatric population suffers from a lack of age-appropriate medicines leading to unsafe situations when off-labelled or unlicensed drugs are used. Assessing the best option to administrate medicines when manipulations are required is essential in order to improve child care. This study aimed to compare the accuracy of the administered dose provided by three dosage forms and their techniques of administration. Different techniques of administration were assessed, covering three oral dosage forms (commercially available tablets, capsules, oral suspensions) using two APIs not available in a children-adapted dosage form. Techniques of administration were simulated and administered doses were determined using HPLC-UV. Means were compared to the target dose while distributions of doses were compared between each technique. For both APIs, mean administered doses obtained with capsules and tablets were significantly different from the target dose, whereas there was no statistical difference with oral suspensions. Distributions of doses showed significant difference between the three dosage forms. This study demonstrates that manipulations of solid oral dosage forms provide dramatic underdosing leading to unsafe situations. Compounded oral suspension is the best option to avoid underdosing and dose variation. This solution should be prioritized when age-appropriate commercial medicines are not available.

Development and evaluation of an assessment of the age-appropriateness/inappropriateness of formulations used in children

“…We have previously shown that DF modification at the point of administration to achieve the required dose is common in paediatric practice [ 42 ]. However, the safety and risks in terms of dose accuracy and handling associated with this practice are often unknown [ 11 , 12 ]. This study demonstrated that manipulations of medicines used in children are performed for many reasons, including patient preference.…”

Compounded Nonsterile Preparations and FDA-Approved Commercially Available Liquid Products for Children: A North American Update

“…Many, if not most, of these dose forms provide only “close enough” dosing flexibility for individual patients. However, “close enough” often is not good enough, especially for the most vulnerable of patients [ 9 ]. In our experience, how to measure exact milligram per kilogram (mg/kg) doses from these solid orals in the in-patient setting would be problematic, considering that the pharmacies in most U.S. pediatric institutions provide a measured, ready-to-give liquid dose form for the nurse to administer for improved patient safety.…”

Opportunities for Comprehensive Medication Management (CMM) for Children with Special Healthcare Needs and Medical Complexity (CSHCN-CMC): The Methodology of a Prospective Case Series within a Collaborative Practice Agreement (CPA)

“…A recent literature review aimed to estimate the rates of pediatric off-label and unlicensed drug use [50]. Many studies reported high rates of off-label (up to 78.7%) and unlicensed (up to 35%) drug use in different pediatric patient settings [51]. The lack of clinical safety and efficacy data for the indication and age range, as well as the dose, dosage form and route of administration, places these children at increased risk for adverse events.…”