# Mapping the therapeutic versatility of WHO essential medicines: a systematic analysis of off-label indications

## TL;DR

This study shows that many essential medicines are used for purposes beyond their official approvals, with varying levels of evidence and guidance.

## Contribution

The first comprehensive analysis of off-label uses across the WHO Essential Medicines List, including evidence quality and therapeutic transitions.

## Key findings

- 60% of WHO essential medicines have off-label uses, most commonly in infectious diseases and oncology.
- Most off-label uses are supported by lower-level evidence (Level C or B), with limited Level A evidence.
- 64% of off-label uses are included in clinical guidelines, but many lack specified evidence levels.

## Abstract

Off-label prescribing represents an important aspect of clinical practice globally. However, there are limited data on the extent, evidence base and guideline support of off-label indications among the World Health Organization’s essential medicines list (WHO EML), which serves as a cornerstone for healthcare systems, especially in low- and middle-income countries.

This study aimed to systematically analyse the prevalence, therapeutic distribution, quality of evidence and inclusion in clinical guidelines of off-label uses for drugs listed in the 2023 WHO EML.

We conducted a descriptive analysis of all medications on the WHO EML using UpToDate® Lexidrug™ database. For each medication, we extracted FDA-approved indications, identified off-label indications, the level of evidence supporting each off-label use (Level A, B, C, or G) and inclusion status in clinical practice guidelines. Off-label indications were categorized across 24 therapeutic systems, and system-to-system transitions from labelled to off-label uses were mapped.

Descriptive cross-sectional observational study using a structured database analysis.

Off-label prevalence among the WHO EML was 60.0%. The most frequent off-label use was observed in infectious diseases (30.5%) and oncology (25.2%). Most off-label uses were supported by Level C (32%) and Level B (30%) evidence, while only 11% were backed by Level A evidence. Notably, 64% of off-label uses were included in clinical guidelines, though many lacked associated evidence levels in Lexicomp. The majority of off-label uses remained within the same therapeutic system, with limited cross-system transitions.

This first comprehensive analysis of off-label uses across the WHO EML demonstrates widespread repurposing of essential medicines with variable evidence quality.

A study to understand how WHO essential medicines are used beyond their approved purposes as off-labeled indications. (Medicines are labeled for specific approved conditions, but off-label use means doctors also prescribe them for other health problems based on experience or evidence.)

Medicines listed by the World Health Organization (WHO) as ‘Essential Medicines’ are meant to treat specific, approved health conditions. However, in real-world practice, doctors often use these medicines for other conditions too, which is called ‘off-label use’. In our study, we looked closely at how WHO Essential Medicines are used beyond their official purposes. We grouped the different off-label uses into 24 broad health areas, such as heart diseases, infections, or mental health. We also tracked how medicines originally approved for one system (like the lungs) are being used for problems in another system (like the brain). Our findings show that many essential medicines have a wide range of uses in patient care, which could help guide future updates to essential medicine lists and treatment guidelines.