Drug Reference
Carbachol
Choline esters
Rx only
Fact box
- Therapeutic class
- Choline esters
- Habit forming
- No
- Availability
- Prescription (Rx)
Brand names
Isopto CarbacholMiostatYuvezzi
Available as
10 MG/ML · Ophthalmic Solution0.25 MG/ML · Injectable Solution1 MG/ML · Ophthalmic Solution1.5 ML · Injection15 MG/ML · Ophthalmic Solution30 MG/ML · Ophthalmic Solution
FDA label sections are from openFDA and may not reflect the most recent labeling — confirm against the current DailyMed label.
Uses
1 INDICATIONS AND USAGE 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. ( 1 )
How it works
12.1 Mechanism of Action The proposed mechanism of action of this fixed-dose combination of carbachol and brimonidine in presbyopia is pupillary constriction and the creation of a pinhole effect that improves near visual acuity and depth of focus. Carbachol is a cholinergic agent which produces constriction of the iris sphincter and ciliary body. Brimonidine tartrate, an alpha-adrenergic agonist, blocks contraction of the iris dilator muscle and relaxes tonic contraction of the ciliary muscle, enhancing selectivity for the pupil and increasing bioavailability of carbachol in the aqueous humor.
How to use / dosing
2 DOSAGE AND ADMINISTRATION Instill one drop in each eye once daily. ( 2.1 ) 2.1 Recommended Dosage The recommended dosage of YUVEZZI is one drop in each eye once daily. 2.2 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.
Side effects
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in labeling: Hypersensitivity [see Contraindications (4) ] Most common adverse reactions (incidence >5%) are eye pain upon instillation, visual impairment, eye irritation upon instillation, and headache. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Visus Therapeutics, Inc., at 1-888-735-0821 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 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.
Safety advice
Conservative summary derived from FDA labeling — defaults to “consult your doctor” unless the label is explicit. Not a substitute for your clinician’s advice.
PregnancyUnsafe
8.1 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 r
BreastfeedingConsult your doctor
…8.2 Lactation Risk Summary There is no information regarding the presence of carbachol and brimonidine tartrate in human milk, the effects on the breastfed infants, or the effects on milk production to…
AlcoholConsult your doctor
…potentiating effect with central nervous system (CNS) depressants (alcohol, opiates, barbiturates, sedatives, or anesthetics) should be considered.…
DrivingConsult your doctor
…AND PRECAUTIONS Blurred Vision : Advise patients not to drive or operate machinery if vision is not clear (e.g., blurred vision).…
KidneyNo information
No specific information in the FDA label.
LiverNo information
No specific information in the FDA label.
Warnings & precautions
5 WARNINGS AND PRECAUTIONS Blurred Vision : Advise patients not to drive or operate machinery if vision is not clear (e.g., blurred vision). Exercise caution in night driving and other hazardous activities in poor illumination. ( 5.1 ) Risk of Retinal Detachment : Rare cases of retinal tear and detachment have been reported with miotics. Individuals with preexisting retinal disease are at increased risk. Therefore, examination of the retina is advised in all patients prior to initiation of therapy. Patients should be advised to seek immediate medical care with sudden onset of flashes of lights, floaters, or vision loss. ( 5.2 ) Iritis : Caution is advised in patients with iritis. ( 5.3 ) Potentiation of Vascular Insufficiency : Use with caution in patients with depression, cerebral or coronary insufficiency, Raynaud's phenomenon, orthostatic hypotension, or thromboangiitis obliterans. ( 5.4 ) 5.1 Blurred Vision Miotics may cause accommodative spasm. Advise patients to not drive or operate machinery if vision is not clear (e.g., blurred vision). In addition, patients may experience temporary dim or dark vision with miotics. Advise patients to exercise caution in night driving and other hazardous activities in poor illumination. 5.2 Risk of Retinal Detachment Rare cases of retinal tear and detachment have been reported with miotics. Individuals with pre-existing retinal disease are at increased risk. Examination of the retina is advised in all patients prior to the initiation of therapy. Advise patients to seek immediate medical care with sudden onset of flashes of lights, floaters, or vision loss. 5.3 Iritis Sequelae of ocular inflammation, i.e., adhesions (synechiae) between the iris and the lens, may be exacerbated with miotic use, therefore, YUVEZZI is not recommended to be used when iritis is present. 5.4 Potentiation of Vascular Insufficiency YUVEZZI may potentiate syndromes associated with vascular insufficiency. YUVEZZI should be used with caution in patients with depression, cerebral or coronary insufficiency, Raynaud's phenomenon, orthostatic hypotension, or thromboangiitis obliterans. 5.5 Potential for Eye Injury or Contamination To prevent eye injury or contamination, avoid touching the single-dose vial to the eye, eyelids, or to any other surface.
Contraindications
4 CONTRAINDICATIONS YUVEZZI is contraindicated in patients with known hypersensitivity to the active ingredients or to any of the excipients. Hypersensitivity. ( 4 )
Pediatric use
8.4 Pediatric Use Presbyopia does not occur in the pediatric population.
⚑ About half of pediatric medication use is off-label and not described in FDA labels — absence of pediatric information does not mean a medicine is unused or unsafe in children. Confirm with your clinician.
Interactions (label text — not an interaction checker)
7 DRUG INTERACTIONS Antihypertensives/cardiac glycosides may lower blood pressure. ( 7.1 ) Use with CNS depressants may result in an additive or potentiating effect. ( 7.2 ) Tricyclic antidepressants may potentially blunt the hypotensive effect of systemic clonidine. ( 7.3 ) Monoamine oxidase inhibitors may result in increased hypotension. ( 7.4 ) 7.1 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. 7.2 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. 7.3 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. 7.4 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.
Overdose
10 OVERDOSAGE 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.
Current FDA labels (DailyMed)
Authoritative sources
Reference only — not clinical advice. Verify against current FDA labeling and consult a licensed provider. About half of pediatric drug use is off-label and is not reflected in FDA labels; absence of pediatric information does not mean a medicine is unused or unsafe in children.