Blood Pressure Elevation Associated with Topical Prostaglandin F2α Analogs: An Analysis of the Different Spontaneous Adverse Event Report Databases

Abstract

Topical prostaglandin F2α (PGF2α) analogs are widely used as the first line of therapy for glaucoma. Systemic PGF2α is suggested to increase blood pressure. Some ophthalmic formulations with β-receptor blocking or α-receptor stimulating actions are reported to cause systemic adverse events such as a decrease in heart rate and blood pressure. The objective of this study was to evaluate the association between topical Key words prostaglandin F2α analog; blood pressure elevation; spontaneous reporting database; adverse event; reporting odds ratio Glaucoma is a progressive, chronic condition prevalent worldwide that causes damage to the optic nerve, resulting in irreversible visual impairment and blindness. Based on the status of the internal drainage system, this condition is divided into two major subtypes i.e., open angle and angle closure.1) Reducing intraocular pressure (IOP) is one of the best ways to prevent the development of glaucoma, although there is a kind of open angle glaucoma in which optic neuropathy occurs without IOP exceeding the normal range. The approximate number of glaucoma patients was 60.5 million in 2010 and is estimated to increase to 79.6 million by 2020.2)

Confirmation of the Cardiac Safety of PGF2αReceptor Antagonist OBE022 in a First‐in‐Human Study in Healthy Subjects, Using Intensive ECG Assessments

“…An effect on cardiac function of exposure to the FP antagonists OBE002 or its parent OBE022 could be excluded despite the reported action of FP agonists on cardiac function in vitro 8,9,11,[30][31][32] and reports of blood pressure elevation in response to topical application of FP agonists. 33 This is consistent with previous clinical studies of allosteric FP antagonists that showed no QTc prolongation attributable to drug administration. 12 The predicted C max values from the concentration-response analysis model were in close agreement with the empirical data gathered in this study.…”

“…Some of the concentration–QTcF models for parent OBE002 (models both and OBE022; Table ) tended to indicate a nonsignificant negative slope. An effect on cardiac function of exposure to the FP antagonists OBE002 or its parent OBE022 could be excluded despite the reported action of FP agonists on cardiac function in vitro and reports of blood pressure elevation in response to topical application of FP agonists . This is consistent with previous clinical studies of allosteric FP antagonists that showed no QTc prolongation attributable to drug administration .…”

Pharmacokinetics, safety and tolerability of OBE022, a selective prostaglandin F2α receptor antagonist tocolytic: A first‐in‐human trial in healthy postmenopausal women

“…The prodrug was safe and well tolerated across all dosing regimens. Significant changes in vital signs were not observed in this trial, despite the previously reported blood pressure elevation in response to topical application of FP agonists [41] and the association of tocolytic medication with hypotensive effects [42,43]. After oral administration, the prodrug was readily transformed into its metabolite OBE002.…”

Evaluation of the Association between Topical Prostaglandin F2α Analogs and Asthma Using the JADER Database: Comparison with β-Blockers

“…However, some reports showed the systemic adverse events by ophthalmic formulations. 11 13) As for PGF2a formulations, a study using a diŠerent nationwide database exhibited the association between topical PGF2a analogs and blood pressure elevation, 14) which is another pharmacological action of the PGF2a. Accordingly, it is possible for topical PGF2a analogs to cause systemic adverse events such as asthma.…”