Yuvezzi Drug Information

YUVEZZI™ is indicated for the treatment of presbyopia in adults. YUVEZZI is a combination of carbachol, a cholinergic agonist, and brimonidine, an alpha-adrenergic receptor agonist, indicated for the treatment of presbyopia in adults.

Recommended Dosage

The recommended dosage of YUVEZZI is one drop in each eye once daily.

Administration Instructions Remove contact lenses prior to instillation of

YUVEZZI. Wait 10 minutes after dosing before reinserting contact lenses. If more than one topical ophthalmic medication is being used, the medicines must be administered at least 5 minutes apart. One single-dose vial can be used to dose both eyes.

Discard the open single-dose vial and any remaining contents immediately after use.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. YUVEZZI was evaluated in 536 patients with presbyopia in two randomized, double-masked, controlled studies. BRIO™ I (NCT05270863) was a single-dose crossover study in which 178 patients received YUVEZZI. BRIO II (NCT05135286) included 358 patients who received YUVEZZI in the long-term safety portion of the study (up to 12 months duration, including a 6-month open-label extension). Adverse reactions reported in > 5% to 7% of participants were eye pain upon instillation and visual impairment.

Adverse reactions reported in > 10% to 16% of participants were eye irritation upon instillation and headache. The majority of adverse events were mild, transient, and self-resolving.

Antihypertensives/Cardiac Glycosides

Because brimonidine tartrate, a component of YUVEZZI, may reduce blood pressure, caution in using drugs such as antihypertensives and/or cardiac glycosides with YUVEZZI is advised.

CNS Depressants

Although specific drug interaction studies have not been conducted with YUVEZZI, the possibility of an additive or potentiating effect with central nervous system (CNS) depressants (alcohol, opiates, barbiturates, sedatives, or anesthetics) should be considered.

Tricyclic Antidepressants Tricyclic antidepressants have been reported to blunt the hypotensive effect

of systemic clonidine. It is not known whether the concurrent use of these agents with YUVEZZI in humans can lead to resulting interference with pupil constriction effects. Caution is advised in patients taking tricyclic antidepressants, which can affect the metabolism and uptake of circulating amines.

Monoamine Oxidase Inhibitors Monoamine oxidase (MAO) inhibitors may theoretically interfere with the

metabolism of brimonidine tartrate and potentially result in an increased systemic side effect such as hypotension. Caution is advised in patients taking MAO inhibitors which can affect the metabolism and uptake of circulating amines.

Pregnancy Risk Summary There are no adequate and well-controlled studies of YUVEZZI administration in pregnant women to inform a drug-associated risk. Topical ocular administration of YUVEZZI to pregnant rats throughout organogenesis did not produce adverse effects up to 3 times the maximum recommended human ocular dose (MRHOD). Topical ocular administration of YUVEZZI to pregnant rabbits throughout organogenesis at approximately 3 times the MRHOD resulted in maternal toxicity with no effect on the fetus, including reduced maternal food consumption, body weight change, and related moribundity in 2/25 animals during the dosing period. Body weight and food consumption effects recovered after the dosing stopped ( see Data ). Because animal reproductive studies are not always predictive of human response, YUVEZZI should be administered during pregnancy only if the potential benefit justifies the potential risk to the pregnant mother and fetus.

The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk in the U.S. general population of major birth defects is 2 to 4%, and of miscarriage is 15 to 20%, of clinically recognized pregnancies. Data Human Data No adequate and well-controlled trials of YUVEZZI have been conducted in pregnant women.

Animal Data YUVEZZI was not teratogenic in embryofetal development studies when given by topical ocular administration to pregnant rats or rabbits throughout organogenesis at dose levels up to approximately 3 times the MRHOD of 1.815 mg/day carbachol and 0.066 mg/day brimonidine tartrate based on body surface area scaling. Topical ocular administration of YUVEZZI to pregnant rats on gestation days (GD) 6 to 17 at dose levels of up to 0.224 mg/day carbachol and 0.008 mg/day brimonidine tartrate (approximately 3 times the MRHOD, based on body surface area) produced no maternal toxicity or embryofetal effects. Topical ocular administration of YUVEZZI to pregnant rabbits on GD 7 to 19 at the dose level of 1.12 mg/day carbachol and 0.04 mg/day brimonidine tartrate (approximately 3 times the MRHOD, based on body surface area scaling) led to maternal toxicity with no embryofetal effects.

Maternal findings included significantly reduced food consumption (41%) and body weight change (-87%), with related moribundity in 2/25 animals during the dosing period, compared with the vehicle control group. Body weight and food consumption effects resolved after a 10-day recovery period.

Pediatric Use Presbyopia does not occur in the pediatric population.

is contraindicated in patients with known hypersensitivity to the active ingredients or to any of the excipients. Hypersensitivity.

Systemic toxicity following topical ocular administration of carbachol is rare, but patients who are sensitive may occasionally develop sweating and gastrointestinal overactivity. Accidental ingestion can produce sweating, salivation, nausea, and a decrease in blood pressure. In moderate overdosage, spontaneous recovery is to be expected and is aided by intravenous fluids to compensate for dehydration.

For patients demonstrating severe poisoning, use atropine, the pharmacologic antagonist to carbachol. Very limited information exists on accidental ingestion of brimonidine in adults; the only adverse reaction reported to date has been hypotension. Treatment of an oral overdose includes supportive and symptomatic therapy; a patent airway should be maintained.