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.

Fig. 1

Data extraction of pregnancy-related reports from the Japanese Adverse Drug Event Report (JADER) database. ^†Standard MedDRA queries (SMQs): congenital, familial, and genetic disorders (20000077). ^‡Preferred terms (PTs): paternal drugs affecting the fetus (10050425), paternal exposure (10071403), paternal exposure during pregnancy (10080091), paternal exposure timing unspecified (10080092), and paternal exposure before pregnancy (10080093). MedDRA Medical Dictionary for Regulatory Activities

Fig. 2

Data extraction of pregnancy-related reports from the Japanese Adverse Drug Event Report (JADER) database. ^†Standard MedDRA queries (SMQs): congenital, familial, and genetic disorders (20000077). ^‡Preferred terms (PTs): paternal drugs affecting the fetus (10050425), paternal exposure (10071403), paternal exposure during pregnancy (10080091), paternal exposure timing unspecified (10080092), and paternal exposure before pregnancy (10080093). FAERS Food and Drug Administration Adverse Event Reporting System, MedDRA Medical Dictionary for Regulatory Activities