Comparing the Safety Profiles of Vaginally Administered Misoprostol and Dinoprostone: A Retrospective Pharmacovigilance Study

Summary

This study compares the safety profiles of vaginally administered misoprostol and dinoprostone using FAERS data from 2004 to 2023.

Abstract

Misoprostol and dinoprostone are the most commonly used agents for cervical ripening during labour induction. However, comparative safety data remain limited, particularly regarding rare adverse events and off-label use. Data were obtained from the FDA Adverse Event Reporting System (FAERS) database for the period from the first quarter of 2004 to the fourth quarter of 2023. Adverse event (AE) reports involving vaginal administration of misoprostol and dinoprostone were extracted, followed by deduplication and exclusion of cases without a specified route of administration. A total of 3,925 misoprostol-related and 1,191 dinoprostone-related AEs were included for analysis. Clinical characteristics were then compared between the two groups. Pharmacovigilance signal detection was performed at both the system organ class (SOC) and preferred term (PT) levels using disproportionality and Bayesian approaches, including reporting odds ratios (RORs), proportional reporting ratios (PRRs), information components (ICs), and empirical Bayesian geometric means (EBGMs). Distinct safety profiles were observed between the two agents. Dinoprostone was primarily associated with pregnancy-related complications, including stronger signals for uterine rupture and postpartum haemorrhage. In contrast, misoprostol was more frequently associated with pregnancy termination-related events, including incomplete abortion, as well as gastrointestinal adverse effects such as abdominal pain. Misoprostol also demonstrated a stronger signal for off-label use. These findings suggest that vaginally administered misoprostol and dinoprostone exhibit different safety profiles, which may inform clinical decision-making during labour induction by highlighting potential risks associated with each agent. However, because FAERS is a spontaneous reporting system subject to underreporting, reporting bias, and the inability to establish causality, the results should be interpreted with caution. Further prospective studies are warranted to validate these safety observations.

Introduction

Labour induction plays a crucial role in childbirth management, particularly in cases where labour needs to be initiated. The promotion of cervical ripening is essential to ensuring a smooth delivery process¹. Insufficient cervical ripening can lead to prolonged labour, increasing the risk of maternal and neonatal complications. Therefore, the use of appropriate pharmacological agents to facilitate cervical ripening enhances both the safety and efficiency of labour induction². However, existing induction methods and pharmacological agents exhibit significant variations in efficacy and safety³, nec....

Protocol

This research used publicly available data and did not involve animal or human subjects. Therefore, ethical approval was not required.

Data source
This retrospective chart review study utilised publicly available AE reports from the FAERS database to perform a comparative analysis of AEs associated with the vaginal administration of misoprostol and dinoprostone. As a global reporting system for drug-related AEs, the FAERS database serves as a crucial resource for regulatory agencies and researchers in monitoring and evaluating drug safety in real-world settings. For this analysis, comprehensive data on vaginally adminis....

Results

Descriptive analysis
Based on FAERS data from the first quarter of 2004 to the fourth quarter of 2023, a total of 1,567 AE reports related to misoprostol and 388 AE reports related to dinoprostone were included after deduplication and exclusion of cases without specified vaginal administration.

The temporal trend illustrated in Figure 3 shows a significant phase-specific fluctuation in AE reports for misoprostol. Between 2004 and 2007, the num.......

Discussion

This study, based on data analysis from the FAERS database, compared the AE profiles of misoprostol and dinoprostone when administered via the vaginal route. The results revealed significant differences in the association of AEs between the two drugs. These findings support the hypothesis that misoprostol and dinoprostone exhibit distinct AE profiles and help address the limited availability of large-scale real-world comparative safety data for these commonly used cervical ripening agents. However, the observed .......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
FAERS dataset (2004-2023)	U.S. FDA	www.fda.gov/drugs/drug-approvals-and-databases/fda-adverse-event-reporting-system-faers-database	Public database used to extract AE reports for misoprostol and dinoprostone.
faersR package	N/A	www.bioconductor.org/packages/faers	faersR package used for FAERS-based disproportionality and Bayesian signal detection analyses, including ROR, PRR, IC, and EBGM metrics
R software (version 4.5.1)	R Foundation for Statistical Computing	RRID:SCR_001905	Statistical computing environment used for all analyses.