VIZZ- aceclidine solution/ drops
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anum Ijaz M.B.B.S., M.D.[2]
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Overview
VIZZ- aceclidine solution/ drops is a cholinergic muscarinic agonist that is FDA approved for the treatment of presbyopia in adults.. Common adverse reactions include instillation site irritation, dim vision, and headache..
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Presbyopia
FDA-Labeled Indication
- VIZZ is indicated for the treatment of presbyopia in adults.
Dosing Information
Recommended Dosage
- Instill one drop in each eye, wait 2 minutes and instill a second drop in each eye once daily from the same single-dose vial.
Administration Instructions
- Contact lenses should be removed prior to the instillation of VIZZ and may be reinserted 10 minutes after instillation.
- If more than one topical ophthalmic product is being used, the products should be administered at least 5 minutes apart.
- To open vial, twist off top.
- Discard the opened single-dose vial after use.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of VIZZ- aceclidine solution/ drops in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of VIZZ- aceclidine solution/ drops in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding VIZZ- aceclidine solution/ drops FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of VIZZ- aceclidine solution/ drops in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of VIZZ- aceclidine solution/ drops in pediatric patients.
Contraindications
None.
Warnings
Blurred Vision
- Miotics may cause accommodative spasm.
- Do not drive or operate machinery if vision is not clear (e.g., blurred vision).
- Patients may experience temporary dim or dark vision.
- Exercise caution in night driving and other hazardous activities in poor illumination.
Risk of Retinal Tear/Detachment
- Rare cases of retinal tear and detachment have been reported with miotics when used in susceptible individuals and those with pre-existing retinal disease.
- Examination of the retina is advised in all patients prior to the initiation of treatment with VIZZ.
- Patients should be advised to seek immediate care with sudden onset of flashing lights, floaters, or vision loss.
Iritis
- Sequelae of ocular inflammation, i.e., adhesions (synechiae) between the iris and the lens, may be exacerbated with miotic use in patients with a known history of iritis.
Hypersensitivity
- VIZZ is not recommended for use in patients with a known hypersensitivity to aceclidine or any other ingredient in VIZZ.
Use with Contact Lenses
- Contact lenses should be removed prior to the instillation of VIZZ and may be reinserted 10 minutes after instillation.
Potential for Eye Injury or Contamination
- To prevent eye injury or contamination, care should be taken to avoid touching the single-dose vial to the eye or to any other surface.
Adverse Reactions
Clinical Trials Experience
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.
- VIZZ dosed once daily was evaluated for safety and efficacy in 466 participants with presbyopia in 2 randomized, double-masked, controlled phase 3 studies for 42 days (CLARITY-1, NCT05656027 and CLARITY-2, NCT05728944).
- VIZZ dosed once daily was also evaluated for long term safety in 217 participants with presbyopia in a separate randomized, double-masked, controlled phase 3 study (CLARITY-3, NCT05753189) for a 6-month duration.
- The most common reported adverse reactions of participants were instillation site irritation (20%), dim vision (16%), and headache (13%).
- Adverse reactions reported in > 5% of participants were conjunctival hyperemia (8%) and ocular hyperemia (7%).
- The majority of adverse reactions were mild, transient, and self-resolving.
Postmarketing Experience
There is limited information regarding VIZZ- aceclidine solution/ drops Postmarketing Experience in the drug label.
Drug Interactions
There is limited information regarding VIZZ- aceclidine solution/ drops Drug Interactions in the drug label.
Use in Specific Populations
Pregnancy
Risk Summary
- There are no adequate and well controlled studies of VIZZ administration in pregnant women to inform a drug associated risk.
- In animal reproduction studies, oral administration of aceclidine to pregnant rats and rabbits throughout organogenesis and lactation did not produce adverse maternal, fetal or neonatal effects at clinically relevant doses.
Data
Animal Data
- In embryofetal development studies, oral administration of aceclidine to pregnant rats and rabbits throughout organogenesis produced no maternal toxicity, skeletal anomalies, nor reduction in fetal body weight at 1.5 mg/kg/day (approximately 110-fold and 70-fold the human plasma exposure to the metabolite, 3-quinuclidinol, in rats and rabbits, respectively, at the MRHOD, assuming administration of 2 drops/eye/day).
- In a pre-/postnatal development study in rats, oral administration of aceclidine during organogenesis through lactation produced no adverse maternal, fetal, or neonatal effects at doses up to 1.5 mg/kg/day (approximately 110-fold higher than the MHOD based on body surface area, assuming administration of 2 drops/eye/day).
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of VIZZ- aceclidine solution/ drops in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of VIZZ- aceclidine solution/ drops during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of VIZZ- aceclidine solution/ drops in women who are nursing.
Pediatric Use
Presbyopia does not occur in the pediatric population.
Geriatic Use
- No overall differences in safety or effectiveness of VIZZ have been observed between patients 65 years of age and older and younger adult patients.
Gender
There is no FDA guidance on the use of VIZZ- aceclidine solution/ drops with respect to specific gender populations.
Race
There is no FDA guidance on the use of VIZZ- aceclidine solution/ drops with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of VIZZ- aceclidine solution/ drops in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of VIZZ- aceclidine solution/ drops in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of VIZZ- aceclidine solution/ drops in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of VIZZ- aceclidine solution/ drops in patients who are immunocompromised.
Administration and Monitoring
Administration
Recommended Dosage
- Instill one drop in each eye, wait 2 minutes and instill a second drop in each eye once daily from the same single-dose vial.
Administration Instructions
- Contact lenses should be removed prior to the instillation of VIZZ and may be reinserted 10 minutes after instillation.
- If more than one topical ophthalmic product is being used, the products should be administered at least 5 minutes apart.
- To open vial, twist off top.
- Discard the opened single-dose vial after use.
Monitoring
Risk of Retinal Tear/Detachment
- Examination of the retina is advised in all patients prior to the initiation of treatment with VIZZ.
- Patients should be advised to seek immediate care with sudden onset of flashing lights, floaters, or vision loss.
IV Compatibility
There is limited information regarding the compatibility of VIZZ- aceclidine solution/ drops and IV administrations.
Overdosage
- Systemic toxicity following topical ocular administration of miotics is rare, but occasionally patients who are sensitive may develop increased salivation, sweating, gastrointestinal overactivity, and slowing of the pulse.
- Accidental ingestion can produce sweating, salivation, nausea, tremors, slowing of the pulse, 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.
Pharmacology
There is limited information regarding VIZZ- aceclidine solution/ drops Pharmacology in the drug label.
Mechanism of Action
- Aceclidine is a cholinergic muscarinic agonist that stimulates muscarinic receptors located on smooth muscles.
- VIZZ is a predominantly pupil selective miotic that interacts with the iris with minimal ciliary muscle stimulation.
- VIZZ causes contraction of the iris sphincter muscle, resulting in a pinhole effect that extends depth of focus to improve vision.
Structure
- VIZZ (aceclidine ophthalmic solution) 1.44% is a cholinergic muscarinic receptor agonist supplied as a sterile, clear to opalescent, colorless to slightly yellow, and viscous ophthalmic solution containing 1.75% of aceclidine hydrochloride (equivalent to 1.44% aceclidine).
The structural formula is shown as a figure in section 11 of the DailyMed label. The image must be uploaded to WikiDoc separately and inserted here.
- The chemical names for aceclidine hydrochloride are: 1) 3-Acetoxyquinuclidine Hydrochloride; 2) 3-Quinuclidinyl Acetate Hydrochloride.
- Its molecular weight is 205.68 g/mol and its molecular formula is C9H15NO2∙HCl.
- Each mL of VIZZ contains aceclidine hydrochloride 1.75% (17.82 mg) as the active ingredient.
- Inactive ingredients in the ophthalmic solution are: polysorbate 80, mannitol, hypromellose, edetate disodium dihydrate, sodium citrate dihydrate, water for injection, and may also include hydrochloric acid and/or sodium hydroxide for pH adjustment to between 4.5 and 5.5, if necessary.
- VIZZ does not contain antimicrobial preservatives.
Pharmacodynamics
There is limited information regarding VIZZ- aceclidine solution/ drops Pharmacodynamics in the drug label.
Pharmacokinetics
- Aceclidine undergoes hydrolysis in the eye to acetate and 3-quinuclidinol (3-Q) with one mole of aceclidine hydrolyzed to one mole of 3-Q.
- Pharmacokinetic studies are performed on the analysis of 3-Q, which is a metabolite formed from the hydrolysis of aceclidine.
- Systemic exposure of aceclidine hydrochloride was evaluated in 16 subjects with presbyopia following once daily VIZZ administration (one drop of VIZZ in each eye followed by a second drop in each eye two minutes later) for 8 days.
- The mean Cmax and AUC0-t values for 3-Q after Day 8 dosing were 2.114 ng/mL and 4.899 hr*ng/mL, respectively.
- There was little to no accumulation of 3-Q after repeat once daily dosing of VIZZ.
- After 8 days, the mean (SD) RAUC0-t and RCmax values were 1.189 (0.770) and 0.996 (0.314), respectively.
- T1/2 could not be estimated at any timepoint due to the limited amount of quantifiable 3-Q concentrations after ocular dosing.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis
- Long term studies in animals have not been performed to evaluate carcinogenic potential.
Mutagenesis
- Aceclidine did not show any potential to cause genetic toxicity in a series of studies that included: 1) bacterial assays (Salmonella and E. coli) for reverse gene mutations; 2) an in vitro chromosome aberration assay in cultured human peripheral blood lymphocytes; and 3) an in vivo chromosome aberration assay (micronucleus test) in mice.
Impairment of Fertility
- Oral administration of aceclidine produced no adverse effect on fertility in rats at doses up to 1.5 mg/kg/day (approximately 25 times the MRHOD based on body surface area).
Clinical Studies
- The efficacy of VIZZ for the treatment of presbyopia was demonstrated in two, randomized, double-masked, controlled studies, CLARITY-1 and CLARITY-2.
- A total of 466 participants aged 45 to 75 years old with presbyopia were randomized.
- Participants had a refractive range from -4.00 to +1.00 D sphere, with astigmatism up to 2.00 D, and a spherical equivalent no more myopic than -4.00 D.
- Both studies included participants who were post-refractive surgery and/or pseudophakic.
- Participants were instructed to instill 2 drops of VIZZ (or control) in each eye once daily, one drop in each eye followed by a second drop in each eye two minutes later.
- Participants were treated for 42 days.
- Ophthalmic efficacy assessments were conducted on Day 1, Day 15, and Day 28 of the study at various timepoints through 10 hours post dose.
- In each study, the proportion of participants gaining 3 lines or more in high contrast, distance corrected, near visual acuity (DCNVA) at 40 cm, without loss of 1 line or more (≥5 letters) of distance corrected, distance visual acuity (DCDVA) at 4 meters was statistically significantly greater in the VIZZ group compared to the control group at Day 1, Hour 3.
Table 1. Primary Efficacy Endpoint from CLARITY-1 and CLARITY-2 Studies Day 1, at 3 Hours Post Dose (FAS Population)
| CLARITY-1 | CLARITY-2 | |||||
|---|---|---|---|---|---|---|
| VIZZ N=157 | Brimonidine N=156 | p-value | VIZZ N=77 | Vehicle N=76 | p-value | |
| Proportion of participants gaining 3-lines or more in DCNVA at 40cm, without losing 1 line or more (≥5 letters) of DCDVA at 4m at Day 1, at 3 hours | 65% | 12% | p<0.01 | 71% | 8% | p<0.01 |
- Figure 1 and Figure 2 demonstrate the onset of the VIZZ effect on presbyopia, from 30 minutes post dose and lasting 10 hours.
How Supplied
Dosage Forms and Strengths
- VIZZ is a clear to opalescent and colorless to slightly yellow ophthalmic solution containing 1.44% of aceclidine in a single-dose vial.
How Supplied
- VIZZ (aceclidine ophthalmic solution) 1.44% is supplied as a sterile, clear to opalescent, colorless to slightly yellow, and viscous ophthalmic solution in configurations of 5 single-dose vials.
- VIZZ does not include antimicrobial preservatives.
- Each single-dose vial is comprised of transparent low-density polyethylene (LDPE).
- 5 single-dose vials are packaged in a foil pouch.
- VIZZ is supplied in:
| NDC Number | Description |
|---|---|
| 84226-100-11 | carton box of 25 single-dose vials (5 pouches x five vials of 0.4 mL each) |
| 84226-100-21 | carton box of 25 single-dose vials (5 pouches x five vials of 0.25 mL each) |
Storage
- Store refrigerated at 36°F to 46°F (2°C to 8°C).
- Do not freeze.
- When stored in refrigerated conditions, VIZZ can be used until the expiration date.
- Once pouch or vial(s) are removed from refrigeration, VIZZ may be stored at room temperature [up to 77°F (25°C)] but must be used within 30 days.
- Discard the opened single-dose vial after use.
- During shipment, VIZZ may be maintained at temperatures up to 104°F (40°C) for a period not exceeding 8 days.
Images
Drug Images
Package and Label Display Panel
Patient Counseling Information
Night Driving
- Advise patients that they may experience temporary dim or dark vision.
- Advise patients to exercise caution with night driving and when hazardous activities are undertaken in poor illumination.
Blurred Vision
- Temporary problems when changing focus between near and distant objects may occur.
- Advise patients not to drive or use machinery if vision is not clear (e.g., blurred vision).
When to Seek Physician Advice
- Advise patients to seek immediate medical care with sudden onset of flashing lights, floaters, or vision loss.
Contact Lens Wear
- Advise patients to remove contact lenses prior to the instillation of VIZZ.
- Wait 10 minutes after instillation before reinserting their contact lenses.
Potential for Eye Injury or Contamination
- Advise patients to avoid touching the tip of the single-dose vial to the eye or to any other surface in order to prevent eye injury or contamination.
- Advise patients to discard the opened single-dose vial and any remaining contents after use.
Concomitant Topical Ocular Therapy
- Advise patients if more than one topical ophthalmic medication is being used, the medicines should be administered at least 5 minutes apart.
Precautions with Alcohol
Alcohol-VIZZ- aceclidine solution/ drops interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding VIZZ- aceclidine solution/ drops Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding VIZZ- aceclidine solution/ drops Look-Alike Drug Names in the drug label.
Price
References
The contents of this FDA label are provided by the National Library of Medicine.