Cardiovascular Adverse Effects of Phenylephrine Eyedrops

Abstract

IMPORTANCE Topical phenylephrine hydrochloride is routinely administered with few safety precautions, but evidence regarding its systemic safety to date is controversial. As even short-term variations in 24-hour blood pressure (BP) and heart rate (HR) can adversely affect cardiovascular health, better evidence on phenylephrine's effects on HR and BP is required.OBJECTIVE To perform a meta-analysis of available evidence regarding cardiovascular adverse effects of topical phenylephrine.DATA SOURCES PubMed, MEDLINE, and the Cochrane Database of Systematic Reviews and Clinical Trials were searched for relevant literature from January 1, 1970, to January 1, 2014, using a combination of the following search terms: topical, ocular, ophthalmic, phenylephrine, tropicamide, cardiovascular effect, side effect, blood pressure, heart rate, mydriatic, and eye drops. A total of 70 articles related to the topic were identified and all full texts were retrieved.STUDY SELECTION Randomized clinical trials reporting change in BP and HR for adults were included in this review. All studies reporting results for neonates or infants, not reporting standard deviations, or not specifying the time of measurement or the concentration of phenylephrine used were excluded.DATA EXTRACTION AND SYNTHESIS Data from randomized clinical trials that reported BP and/or HR as well as the time following administration of topical phenylephrine at which measurements were obtained by concentration of phenylephrine as a mean change and its standard deviation were extracted. Data were synthesized by concentration of phenylephrine and time of measurement following topical application using random-effects models with inverse variance weighting to account for heterogeneity across studies. MAIN OUTCOMES AND MEASURES Difference in BP and HR after topical administration of phenylephrine.RESULTS Eight RCTs with a total of 916 participants were included. Data were available for phenylephrine, 2.5%, at 20 to 30 minutes and 60 minutes or longer after administration, and neither BP nor HR changed at either time. Following application of phenylephrine, 10%, BP increased at 5 and 10 minutes (mean difference for both, +15 mm Hg; 95% CI, 11.94-18.54; P < .001) but decreased at 20 to 30 minutes and 60 minutes or longer with no changes detected against baseline. A mean increase in HR by 4.48 beats/min (95% CI, 1.09-7.88; P = .01) was present at 20 to 30 minutes following application of phenylephrine, 10%, and HR decreased by 60 minutes or longer with no changes detected compared with baseline.CONCLUSIONS AND RELEVANCE Phenylephrine, 2.5%, leads to no clinically relevant change in BP or HR, and the changes in BP and HR seen with phenylephrine, 10%, are short lived. Thus, phenylephrine, 2.5%, is safe to use in clinical routine.

High-precision piezo-ejection Ocular microdosing: Phase II Study on Local and Systemic Effects of Topical Phenylephrine

“…Absorption of topical ocular drugs into the general circulation is associated with diverse AEs that are occasionally serious [8,23,24], and PE is not exempted [25,26]. PE is similar to epinephrine/norepinephrine in chemical structure and also has cardiovascular activity.…”

“…Unintended systemic absorption of ocular PE can change blood pressure and heart rate. A systematic review of relevant randomized controlled trials indicated that these changes are only associated with PE-10% eyedrops, which transiently increase systolic blood pressure by 15 mmHg, and not the 2.5% concentration [26]. Although, these changes typically resolve within 60 min, even small alterations in blood pressure may have a negative impact on populations with predisposing comorbidities [24].…”

Systemic side effects of eye drops: a pharmacokinetic perspective

“…Nevertheless, an increased absorption even with these drugs could occur with a conjunctival hyperemia or epithelial damage to the cornea. Patients with hypertension, aneurysms, tachycardia, or cardiac disease must be treated with adequate caution 46. The use of phenylephrine 10% solution is not recommended (forbidden) for children and the elderly because of the increased risks of systemic toxicity 47,48…”

New technique to reduce systemic side effects of timolol eye drops: The tissue press method—Cross‐over clinical trial

“…[12][13][14][15][16][18][19][20][21] It would probably be reasonable to assume wider applicability for a variety of medications but currently this is unproven and would require further studies. Other ophthalmic medications, for example F I G U R E 3 Boxplot showing differences in heart rate, blood pressure, IOP, and timolol plasma levels between groups T A B L E 1 levobunolol, brimonidine, atropine, cyclopentolate, scopolamine, phenylephrine and betamethasone are also absorbed in humans after topical ocular application.…”