Ryzumvi is indicated for the treatment of pharmacologically-induced mydriasis produced by adrenergic agonists (e.g., phenylephrine) or parasympatholytic (e.g., tropicamide) agents.

Adults and pediatric patients aged 12 years or older: Instill 1 or 2 drops in each dilated eye following the completion of the ophthalmic examination or procedure. If 2 drops are instilled, the second drop should be administered 5 minutes after the first drop.

Pediatric patients aged 3 to 11 years: Instill 1 drop in each dilated eye following the completion of the ophthalmic examination or procedure.

One single-patient-use vial can be used to dose each dilated eye. Discard the single-patient-use vial immediately after use.

Ophthalmic solution: clear and colorless solution containing phentolamine 0.75% in a single-patient-use vial.

None.

No deaths due to acute poisoning with phentolamine have been reported. Overdosage with parenterally administered phentolamine is characterized chiefly by cardiovascular disturbances, such as arrhythmias, tachycardia, hypotension, and possibly shock. In addition, the following might occur: excitation, headache, sweating, visual disturbances, nausea, vomiting, diarrhea, or hypoglycemia. There is no specific antidote; treatment consists of appropriate monitoring and supportive care. Substantial decreases in blood pressure or other evidence of shock-like conditions should be treated vigorously and promptly.

Ryzumvi (phentolamine ophthalmic solution) 0.75% is a sterile, clear and colorless solution for topical ophthalmic use containing 1% phentolamine mesylate (equivalent to 0.75% phentolamine). The product does not contain an anti-microbial preservative. The chemical name of phentolamine mesylate is 3-[[(4,5-dihydro-1H-imidazol-2-yl)methyl](4-methylphenyl)amino]phenol; methanesulfonic acid (parent phentolamine: [3-[[(4,5-dihydro-1H-imidazol-2-yl)methyl](4-methylphenyl)amino]phenol]) and the molecular formula is C18H23N3O4S (parent C17H19N3O). The molecular weight of phentolamine mesylate is 377.46 and the chemical structure is:

Each mL of Ryzumvi contains phentolamine mesylate 10 mg as the active ingredient (equivalent to 7.5 mg phentolamine as the free base). Inactive ingredients are: mannitol, sodium acetate trihydrate, and water for injection. Hydrochloric acid and/or sodium hydroxide are added to adjust pH (4.5 to 5.5), and the solution is overlaid with nitrogen.

The efficacy of Ryzumvi for the reversal of mydriasis was demonstrated in two, randomized, double-masked, vehicle-controlled trials; MIRA-2 (NCT#04620213) and MIRA-3 (NCT#05134974). A total of 553 subjects, aged 12 to 80 years, who had mydriasis induced by instillation of phenylephrine or tropicamide or a combination of hydroxyamphetamine hydrobromide and tropicamide (Paremyd) were randomized. Subjects with light and dark irides were included in both trials. Two drops (study eye) or one drop (fellow eye) of Ryzumvi or placebo (vehicle) were administered one hour after instillation of the mydriatic agent. The percentage of subjects with study eyes returning to ≤0.2 mm from baseline pupil diameter was statistically significantly greater (p<0.01) at all time points measured from 60 minutes through 24 hours in the Ryzumvi group compared with the placebo (vehicle) group across both of the MIRA-2 and MIRA-3 trials (see Figure 1).

Figure 1. Percentage of subjects with study eyes returning to ≤0.2 mm from baseline pupil diameter by time point in the MIRA-2 and MIRA-3 Trials

The efficacy of MIRA-2 and MIRA-3 also showed that the change from maximum pupil dilation in study eyes and fellow eyes was statistically significantly different between the Ryzumvi-treated group and the placebo-treated group at all time points from 60 minutes through 24 hours post-treatment (p<0.01). Pupil size at 24 hours was 1 mm smaller than baseline. These results were consistent regardless of whether phenylephrine or tropicamide/Paremyd were used as mydriatic agents (Figure 2, Figure 3; respectively).

Figure 2: Pupil Dilation by Time Point with Phenylephrine as Mydriatic Agent in MIRA-2 and MIRA-3 Trials (mITT population)

Figure 3: Pupil Dilation by Time Point with Tropicamide or Paremyd as Mydriatic Agent in MIRA-2 and MIRA-3 trials (mITT Population)

The efficacy of Ryzumvi was similar for all age ranges including pediatric subjects aged 3 to 17 years. Pediatric subjects aged 12 to 17 years (n=27) were treated in MIRA-2 and MIRA-3 and pediatric subjects, aged 3 to 11 years (n=11) were treated in MIRA-4, (NCT#05223478).

Ryzumvi (phentolamine ophthalmic solution) 0.75% is supplied as a sterile, clear, and colorless solution for topical ophthalmic use contained in a translucent, low-density polyethylene, single-patient-use vial with a 0.31 mL fill. One strip of 5 single-patient-use vials is packaged into a foil pouch, with 6 foil pouches in a carton. One single-patient-use vial should be dispensed for each patient, and it can be used to dose both eyes.

Carton of 30 single-patient-use vials – NDC-83368-075-30

Storage and Handling:

Store refrigerated at 2°C to 8°C (36°F to 46°F), not to exceed the expiration date printed on the carton and pouch. Protect from freezing.

After opening the foil pouch, the product may be stored at 25ºC (68°F to 77ºF) and should be used within 14 days, not to exceed the expiration date printed on the vial. The single-patient-use vial once opened should be discarded immediately after use.

Distributed by:
Ocuphire Pharma, Inc.
Farmington Hills, MI 48335

Marketed by:
Oyster Point Pharma, Inc., a Viatris company
Princeton, NJ 08540

NDC: 83368-075-30     Rx Only

Ryzumvi™
(phentolamine
ophthalmic solution) 0.75%

FOR TOPICAL USE IN THE EYES

Sterile

Contents: 6 pouches containing 5 single-patient-use vials each

Dosage: See Prescribing Information.

Active: Each ml contains phentolamine mesylate 10 mg (equivalent to 7.5 mg phentolamine as the free base); Inactive: Mannitol USP, Sodium Acetate Trihydrate USP, Purified Water for Injection USP. Either Hydrochloric Acid USP or Sodium Hydroxide USP.

Storage: Store refrigerated at 2°c to 8°C (36°F to 46°F), not to exceed the expiration date printed on the carton and pouch. Protect from freezing. After opening the foil pouch, the product may be stored at 25°C (68°F to 77°F) and should be used within 14 days, not to exceed the expiration date printed on the vial.

The single-patient-use vial once opened should be discarded immediately after use. Does not contain an anti-microbial preservative.

Distributed by:
Ocuphire Pharma, Inc.
Farmington Hills, Ml 48335

Marketed by:
Oyster Point Pharma, Inc.,
a Viatris company
Princeton, NJ 08540