Guidance and Tools to Strengthen Pharmacovigilance for Pediatric Medicines, with a Focus on New Antiretroviral Treatment Regimens in Resource-Limited Settings

Overview

Download the New Pediatric Antiretroviral Regimen Acceptability and Tolerability Form

Introduction

Pharmacovigilance is the science and activities relating to the detection, assessment, understanding, and prevention of adverse effects or any other medicine/vaccine-related problem. It is imperative to strengthen national pharmacovigilance (PV) systems to monitor acceptability, tolerability, and adverse drug reactions (ADRs) of new pediatric medicines, including the transition to Dolutegravir (DTG) as both first- and second-line regimens for children and adolescents living with HIV (CALHIV). An ADR is an unwanted or harmful response to a medicine or combination of medicines that is unintended and occurs at doses normally used in humans. Studies reporting antiretroviral (ARV)-associated ADRs in children and adults highlight the need for an active approach to PV to ensure that drugs are not only effective but also safe. ARV-associated ADRs are diverse and can lead to poor tolerance, non-adherence to treatment, negative health outcomes, and the development of HIV-drug resistance. Signs of intolerance — such as vomiting, spitting up, or sleep disturbance — can be identified soon after a child is initiated on or switched to a new drug, while other ADRs can take months to identify. Examples of significant ARV-associated ADRs include immune reconstitution inflammatory syndrome, weight gain, hyperlipidemia, and central nervous system complications (e.g., depression, sleep disturbance, and irritability).

Global guidance and a number of tools for pediatric PV already exist and are available on the World Health Organization (WHO) website, including a Module 10 on Pharmacovigilance in the 2018 WHO Toolkit for research and development of paediatric antiretroviral drugs and formulations. There is, however, a need to provide simplified and focused guidance that aims to strengthen the capacity of health care workers (HCWs) and caregivers to actively identify, document and report, and respond to information on ARV-associated ADRs in resource-limited settings.

Goal and Objectives

This package of guidance and tools aims to support active PV of ARVs, especially pediatric DTG (pDTG), with a focus on collecting and responding to short-term data on acceptability, tolerability, and clinically symptomatic ADRs among CALHIV, followed by long-term monitoring for other significant ADRs. ART optimization plans, at both national and facility levels, should include an assessment of the acceptability and tolerability of a newly introduced ARV. Information on assessing ARV tolerance and ADRs should be enhanced in HCW training materials, and relevant elements should be included in caregiver treatment-literacy materials. HCWs play an important role in collecting facility-level PV data that can be collated and analyzed at a program level, with mechanisms to provide feedback to the end user about data trends and data quality. The use of electronic medical records is desirable, but PV practices can be adapted for use with paper-based tools as well.