FDA Approves Phentolamine Ophthalmic Solution for Pharmacologically-Induced Mydriasis

Published on: 

According to the approval, the percentage of study eyes returning to ≤0.2 mm from baseline pupil diameter was statistically significantly greater in the phentolamine ophthalmic solution group than placebo.

The US Food and Drug Administration (FDA) has approved phentolamine ophthalmic solution (RYZUMVI) 0.75% for the treatment of pharmacologically-induced mydriasis produced by adrenergic agonists or parasympatholytic agents.1

Announced by Ocuphire Pharma and Viatris Inc. on September 27, the ophthalmic solution is expected to become commercially available in the US in the first half of 2024.

“The FDA’s approval of RYZUMVI marks a significant milestone for our eye care division and underscores Viatris’ commitment to advancing eye care and enhancing access for both eye care professionals and patients,” said Jeffery Nau, PhD, eye care division president, Viatris.

Phentolamine ophthalmic solution 0.75% is a relatively non-selective alpha-1 and alpha-2 adrenergic agnostic. Phentolamine reversibly binds to receptors of the radial iris dilator muscle and reduces pupil diameter. It directly antagonizes the mydriatic effect of an α-1 adrenergic agonist and indirectly reverses mydriasis induced by muscarinic antagonist effects on the iris sphincter muscle.

The ophthalmic solution was evaluated in the MIRA clinical trial program including more than 600 patients in the MIRA-1 phase 2b trial, the MIRA-2 and MIRA-3 phase 3 pivotal trials, and the MIRA-4 phase 3 pediatric trial.

A total of 553 participants aged 12 to 80 years with mydriasis induced by the instillation of phenylephrine or tropicamide or a combination of hydroxyamphetamine hydrobromide and tropicamide were randomized in the MIRA-2 and MIRA-3 trials. Trial investigators administered 2 drops in the study eye or 1 drop in the fellow eye of phentolamine ophthalmic solution or placebo 1 hour after the instillation of the mydriatic agent.

Analyses revealed the percentage of participants with study eyes returning to ≤0.2mm from baseline pupil diameter was statistically significantly greater (P <.01) at all time points measured from 60 minutes through 24 hours in the phentolamine ophthalmic solution group, compared with placebo, across both trials.

The efficacy of the phentolamine ophthalmic solution was similar for all age ranges, including pediatric subjects aged 3 to 17 years. Pediatric populations aged 12 to 17 years (n = 27) were treated in MIRA-2 and MIRA-3 trials and those aged 3 to 11 years (n = 11) were treated in MIRA-4.

Safety analyses showed the most common ocular adverse reactions reported in >5% of subjects were instillation site discomfort, including pain, stinging, and burning (16%) and conjunctival hyperemia (12%). It showed the only non-ocular adverse reactions reported in >5% of subjects were dysgeusia (6%).

An estimated 100 million comprehensive eye exams take place each year in the US that involve pharmacologically-induced mydriasis of the pupils, to examine the retina for routine check-ups, disease monitoring, or surgical procedures. Mydriasis can last up to 24 hours in adults and children. Side effects of the procedure can include photophobia and blurred vision, making it difficult for patients to read, work, and drive.

“Comprehensive dilated eye exams are vital for early detection of vision-compromising diseases,” Nau said. “Our hope is that by addressing patient dilation barriers, we’re empowering eye care professionals to broaden exam availability, leading to enhanced eye health outcomes.”


  1. Ocuphire Pharma and Viatris announce FDA approval of RYZUMVITM (Phentolamine Ophthalmic Solution) 0.75% eye drops for the treatment of pharmacologically-induced mydriasis produced by adrenergic agonists (e.g., phenylephrine) or parasympatholytic (e.g., tropicamide) agents. Ocuphire Pharma, Inc. September 27, 2023. Accessed September 27, 2023.
  2. Iapoce C. FDA accepts New Drug Application for NYXOL for reversal of Mydriasis. HCP Live. February 21, 2023. Accessed September 27, 2023.