Pregnancy Loss Signal from Prostaglandin Eye Drop Use in Pregnancy: A Disproportionality Analysis Using Japanese and US Spontaneous Reporting Databases

Abstract

Background There is limited research regarding the use of glaucoma medicines during pregnancy. Prostaglandins contract uterine smooth muscle; however, it is not clear whether prostaglandin eye drops are associated with pregnancy loss in pregnant women. Objectives We conducted a pharmacovigilance study using spontaneous report databases from Japan and the USA to evaluate the association between pregnancy loss and the use of prostaglandin eye drops during pregnancy. Methods The Japanese Adverse Drug Event Report database and the Food and Drug Administration Adverse Event Reporting System were used for analysis. Disproportionality analyses and a review of individual case safety reports were conducted. Results As for prostaglandin eye drops in pregnancy-related reports, there were eight reports involving latanoprost in the Japanese Adverse Drug Event Report database and no reports of pregnant women using other prostaglandin eye drops. In the Food and Drug Administration Adverse Event Reporting System, there were 25 reports involving latanoprost, 23 involving bimatoprost, 13 involving travoprost, and three involving tafluprost. The drug safety signal was detected during latanoprost usage and pregnancy loss. In the Japanese Adverse Drug Event Report database, there were five reports of pregnancy loss related to latanoprost, with a reporting odds ratio of 12.84 (95% confidence interval 3.06–53.86), and in the Food and Drug Administration Adverse Event Reporting System, pregnancy loss was reported in 12 cases of latanoprost usage with a reporting odds ratio of 4.35 (95% confidence interval 1.98–9.54). Uterine contractions were observed as concomitant adverse events in one case. Conclusions Although a disproportionality analysis cannot determine causality, we need to keep an eye on the signal detected in this study. This signal should be validated using a causal design study.

Doxycycline use and adverse pregnancy or neonatal outcomes: A descriptive study using the United States Food and Drug Administration Adverse Event Reporting System database

“…abortions and stillbirth). 13,14 The ICSRs so obtained were further filtered using the following preferred terms: drug exposure during pregnancy; maternal drugs affecting fetus; maternal exposure during pregnancy; fetal exposure during pregnancy.…”

Potential safety signal of pregnancy loss with vascular endothelial growth factor inhibitor intraocular injection: A disproportionality analysis using the Food and Drug Administration Adverse Event Reporting System

“…Subgroup disproportionality analyses are used to control for possible bias when analyzing the relationship between drugs and pregnancy outcomes in datasets in which most reports are from non-pregnant women ( Beyer-Westendorf et al, 2020 ; Huybrechts et al, 2021 ). However, there is no established algorithm for identifying reports of pregnant women from spontaneous reporting databases ( Deepak and Stobaugh, 2014 ; Sessa et al, 2019 ; Sandberg et al, 2020 ; Sakai et al, 2022 ). To our knowledge, no regulatory authority has provided any specific guidance for such procedure.…”

“…To our knowledge, no regulatory authority has provided any specific guidance for such procedure. Because the spontaneous reporting databases do not usually contain a dedicated field to identify reports of pregnant women, measures are being taken to identify such reports using the standard MedDRA query (SMQ) ( Sessa et al, 2019 ; Sakai et al, 2022 ). Free text and author-specific keyword searches other than dictionaries have also been conducted, but their reliability is unknown ( Deepak and Stobaugh, 2014 ).…”

“…Free text and author-specific keyword searches other than dictionaries have also been conducted, but their reliability is unknown ( Deepak and Stobaugh, 2014 ). Therefore, in the current study, we used our previously described method to identify reports of pregnant women in the FAERS ( Sakai et al, 2022 ).…”

Association of Topical Prostaglandin Analogue Use With Risk of Spontaneous Abortion

“…1 A recent case-series analysis of the US Food and Drug Administration Adverse Event Reporting System database and the Japanese Adverse Drug Event Report database showed elevated reports of miscarriages with PGA use (reporting odds ratio, 4.35; 95% CI, 1.98-9.54; and reporting odds ratio, 12.84; 95% CI, 3.06-53.86, respectively). 2 The limitation of adverse reaction databases in general is reporting bias; lack of a proper control group means the true risk of any given adverse event is over-estimated. However, although these databases are limited in demonstrating a causal link, the hypothesis generated from this study, given the prescription patterns of these drugs in pregnant individuals with glaucoma, warrants serious attention.…”