Prescribing information (package insert) - ACUVUE Theravision with Ketotifen
1 INDICATIONS AND USAGE
ACUVUE® Theravision™ with Ketotifen is a daily wear, daily disposable etafilcon A drug-eluting contact lens for prevention ocular itch due to allergic conjunctivitis and correction of refractive ametropia (myopia and hyperopia) in aphakic and/or phakic patients who do not have red eye(s), are suitable for contact lens wear and do not have more than 1 D of astigmatism.
The lens contains an H1 histamine receptor antagonist for the prevention of ocular itch due to allergic conjunctivitis. The prevention of itch has been demonstrated to last through 12 hours in clinical trials; however, the lens may be worn for longer than 12 hours in a single day.
2 DOSAGE AND ADMINISTRATION
2.1 General Dosing Information
One ACUVUE® Theravision™ with Ketotifen should be inserted per eye per day. Discard lens after a single day's use. ACUVUE® Theravision™ with Ketotifen may be worn beyond twelve hours for vision correction. Lenses should be removed prior to sleeping.
The maximum daily wearing time should be determined by the Eye Care Professional based upon the patient's individual response to contact lenses. Patients tend to over wear the lenses initially. The Eye Care Professional should emphasize the importance of adhering to the initial maximum daily wearing time. Regular checkups, as determined by the Eye Care Professional, are also extremely important.
Eye drops containing benzalkonium chloride should not be used simultaneously with this product. Patients should wait 10 minutes after applying eye drop with benzalkonium chloride before inserting or reinserting lenses.
If the lens sticks (stops moving), the patient should be instructed to remove the lens. A few drops of non-preserved sterile saline solution may be applied directly to the eye to assist with removal. If non-movement of the lens continues after a few minutes, the patient should immediately consult their Eye Care Professional.
Do not use contact lens cleaning and disinfectant solutions with ACUVUE® Theravision™ with Ketotifen.
2.2 Contact Lens Fitting Information
See the ACUVUE® Theravision™ with Ketotifen Fitting Instruction Guide for professional fitting instructions and information.
3 DOSAGE FORMS AND STRENGTHS
Daily disposable etafilcon A drug-eluting contact lens with ketotifen (19 mcg per lens).
4 CONTRAINDICATIONS
4.1 Ocular Hyperemia
ACUVUE® Theravision™ with Ketotifen is contraindicated in patients with ocular hyperemia and should not be inserted into red or irritated eye(s). Remove ACUVUE Theravision with Ketotifen immediately if eye(s) becomes red or irritated.
4.2 Corneal Hypoesthesia
ACUVUE Theravision with Ketotifen is contraindicated in patients with decreased corneal sensation.
4.3 Corneal Infections
ACUVUE Theravision with Ketotifen is contraindicated in patients with any corneal infection (bacterial, fungal, protozoal or viral).
5 WARNINGS AND PRECAUTIONS
5.1 Corneal Ulcers
ACUVUE Theravision with Ketotifen should not be inserted if the patient has corneal epithelial breakdown, corneal ulceration, dry eye disease, injury or abnormality that affects the eyelids or anterior segment of the eye. Contact lens wear may worsen these conditions and lead to sight threatening complications. If a patient experiences eye discomfort, excessive tearing, vision changes, or redness of the eye, the patient should be instructed to immediately remove the lenses, and promptly contact the Eye Care Professional.
Studies have shown that when daily wear users wear their lenses overnight, the risk of ulcerative keratitis is greater than among those who do not wear them overnight. Contact lens wearers who are smokers have a higher incidence of corneal ulcers than nonsmokers.
5.2 Contact Lens-Related Complications
ACUVUE Theravision with Ketotifen should not be used to treat or prevent lens-related symptoms including irritation, discomfort or redness. ACUVUE Theravision with Ketotifen insertion could result in serious injury if a patient is experiencing these symptoms. Patients should be cautioned that proper use and care of contact lenses and lens care products are essential for the safe use of these products. If patients experience symptoms of contact lens intolerance or keratitis, the lens(es) should be IMMEDIATELY REMOVED.
5.3 Chemical Exposures
If chemicals of any kind (household products, gardening solutions, laboratory chemicals, etc.) are splashed into the eyes, the patient should: FLUSH EYES IMMEDIATELY WITH WATER AND IMMEDIATELY CONTACT THE EYE CARE PROFESSIONAL OR VISIT A HOSPITAL EMERGENCY ROOM WITHOUT DELAY.
5.4 Acanthamoeba Keratitis
ACUVUE Theravision with Ketotifen should not be worn while swimming or in hot tubs. The lens should not be rinsed in water from the tap. Tap water contains many impurities that can contaminate or damage the lenses and may lead to eye infection or injury. Contact lens wear in these settings increases the risk of sight threatening eye infections from microorganisms.
5.5 Backup Spectacles
Eye Care Professionals should instruct the patient to always have a functional pair of spectacles with a current prescription available to use if the patient becomes unable to wear contact lenses, or in circumstances where contact lens wear is not advised.
5.6 Eye Protection
Patients should be advised to notify the employer of being a contact lens wearer. Some jobs may require the use of eye protection equipment or may require that the patient not wear contact lenses.
5.7 Concomitant Use of Eye Drops or Eye Medications
Eye Drops or Eye Medications containing benzalkonium chloride should not be used simultaneously with ACUVUE® Theravision™ with Ketotifen. Wait at least 10 minutes after eye drop application before inserting lenses.
6 ADVERSE REACTIONS
The following clinically significant adverse reactions are described elsewhere in the labeling:
- Ocular Hyperemia [see Contraindications (4.1)]
- Corneal Hypoesthesia [see Contraindications (4.2)]
- Corneal Infections [see Contraindications (4.3)]
- Corneal Ulcers [see Warnings and Precautions (5.1)]
- Contact Lens-Related Complications [see Warning and Precautions (5.2)]
- Chemical Exposure [see Warnings and Precautions (5.3)]
- Acanthamoeba Keratitis [see Warnings and Precautions (5.4)]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a product cannot be directly compared to rates in the clinical trials of another product and may not reflect the rates observed in practice.
The most commonly observed adverse reactions in clinical studies, occurring in ≥1% of ACUVUE® Theravision™ with Ketotifen treated eyes, were eye irritation, eye pain, and instillation site irritation.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
There are no adequate and well-controlled studies of ACUVUE® Theravison™ with Ketotifen administration in pregnant women to inform a drug-associated risk. ACUVUE® Theravison™ with Ketotifen is not absorbed systemically following ocular administration, and maternal use is not expected to result in fetal exposure to the drug. Oral administration of ketotifen fumarate to pregnant rats or rabbits did not produce teratogenicity at clinically relevant doses [see Data].
Data
Human Data
There are no human data that establish the presence or absence of drug-associated risk with the use of ACUVUE® Theravision™ with Ketotifen by pregnant women.
Animal Data
Oral administration of 45 mg/kg/day ketotifen to pregnant rabbits resulted in an increased incidence of retarded ossification of the sternebrae. This dose (normalized to body surface area) was approximately 23,000 times higher than the daily maximum recommended human ophthalmic dose (MRHOD) of 0.038 mg.
No adverse embryofetal effects were observed in rats or rabbits orally administered 100 mg/kg/day and 15 mg/kg/day, respectively, during organogenesis. These doses (normalized to body surface area) were approximately 26,000 and 7,700 times higher than the MRHOD, respectively.
An oral dose of 50 mg/kg/day ketotifen (approximately 13,000 times higher than MRHOD) administered to rats from Day 15 of pregnancy until Day 21 postpartum produced maternal toxicity, a slight increase in postnatal mortality and a slight decrease in body weight gain in offspring during the first four days post-partum.
8.2 Lactation
Risk Summary
There is no information regarding the presence or absence of ketotifen fumarate or its metabolites in human milk following use of ACUVUE® Theravision™ with Ketotifen, or on the breastfed infants and milk production. Ketotifen fumarate has been identified in breast milk in rats following oral administration. It is not known whether topical ocular administration could result in sufficient systemic absorption to produce detectable quantities in breast milk.
The development and health benefits of breastfeeding should be considered along with the mother's clinical need for ACUVUE® Theravision™ with Ketotifen and any potential adverse effects on the breast-fed child from ketotifen fumarate.
8.3 Pediatric Use
The safety and efficacy of ACUVUE® Theravision™ with Ketotifen in pediatric patients below the age of 11 years has not been established.
8.4 Geriatric Use
Clinical studies of etafilcon A with ketotifen did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
11 DESCRIPTION
ACUVUE® Theravision™ with Ketotifen is a sterile, soft (hydrophilic), spherical daily wear, daily disposable etafilcon A drug-eluting contact lens containing ketotifen, an H1 receptor antagonist, for topical administration to the eyes.
Ketotifen fumarate is a white to brownish-yellow, fine crystalline powder. The buffered packaging solution of ACUVUE® Theravision™ with Ketotifen has a pH range of 6.6 to 7.3 and an osmolality of not more than 460 mOsm/Kg. This product does not contain an antimicrobial preservative.
Contains:
Active: ketotifen 19 mcg equivalent to 43 mcg ketotifen fumarate per lens
Inactives: boric acid, calcium hydroxide, pentetic acid, sodium chloride, sodium borate, and water.
Chemical Name: 4,9-Dihydro-4-(1-methyl-4-piperidylidene)-10H-benzo[4,5]cyclohepta[1,2-b] thiophen-10-one fumarate (1:1).
Structural Formula:
| Molecular formula of C19H19NOS∙C4H4O4 (C19H19NOS as free base) |
| Molecular weight of 425.50 g/mol (309.43 g/mol as the free base) |
The contact lens material (etafilcon A) is a copolymer of 2-hydroxyethyl methacrylate and methacrylic acid cross-linked with 1, 1, 1-trimethylol propane trimethacrylate and ethylene glycol dimethacrylate. ACUVUE® Theravision™ with Ketotifen contact lenses are tinted blue using blue 2-hydroxyethyl methacrylate to make the lenses more visible for handling.
Physical/Optical Properties of the Lens:
| Refractive Index: | 1.40 |
| Visible Light Transmission: | 90% minimum |
| Ultraviolet Light Tranmission: (316 nm to 380 nm) UVA | 30% maximum |
| Ultraviolet Light Tranmission: (280 nm to 315 nm) UVB | 5% maximum |
| Surface Character: | Hydrophilic |
| Water Content: | 59% |
| Oxygen Permeability: | 21.4 × 10-11(cm2/sec) (mL O2/mL × mmHg) at 35°C (boundary corrected, edge corrected) |
Dimensional Properties of the Lens:
| Diameter: | 14.2 mm |
| Center Thickness: | Minus Lens - varies with power (e.g. -4.00D: 0.084 mm) |
| Plus Lens - varies with power (e.g. +4.00D: 0.190 mm) | |
| Base Curve: | 8.5 mm and 9.0 mm |
| Power: | -0.50D to -10.00D (in 0.25D increments) |
| -10.50D to -12.00D (in 0.50D increments) | |
| +0.50D to +6.00D (in 0.25D increments) |
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Device Component
In its hydrated state, the lens when placed on the cornea, acts as a refracting medium to focus light rays on the retina to correct refractive ametropia for as long as the lens is worn (up to 24 hours while awake).
Drug Component
Ketotifen fumarate, a benzocycloheptathiophene derivative, is a H1 receptor antagonist that stabilizes mast cells and prevents eosinophil accumulation. This action prevents the onset of ocular allergic itch allowing for continued lens wear during episodes of allergen exposure and has been demonstrated to last through 12 hours.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis
No information is available on the carcinogenic potential of ketotifen fumarate.
Mutagenesis
Ketotifen fumarate was determined to be non-mutagenic in a battery of in vitro and in vivo mutagenicity assays including: Ames test, in vitro chromosomal aberration test with V79 Chinese hamster cells, in vivo micronucleus assay in mouse, and mouse dominant lethal test. In addition, extracts of etafilcon A with ketotifen (19 mcg/lens) prepared in 0.9% sodium chloride or dimethyl sulfoxide were shown to be non-mutagenic in the Ames test.
Impairment of Fertility
Treatment of male rats with oral doses of ketotifen >10 mg/kg/day (approximately 2,600 times the MRHOD) for 70 days prior to mating resulted in mortality and a decrease in fertility. Treatment with ketotifen did not impair fertility in female rats receiving up to 50 mg/kg/day of ketotifen orally (approximately 13,000 times the MRHOD) for 15 days prior to mating.
14 CLINICAL STUDIES
The safety and efficacy of ACUVUE® Theravision™ with Ketotifen was assessed in two double-masked, randomized, placebo-controlled clinical conjunctival allergen challenge (CAC) studies (CR-4483 and CR-4484) and two 12-week safety studies (CR-4490 and CR-4539). Patients in these studies had allergic conjunctivitis induced by an ocular allergen challenge and refractive ametropia (myopia and hyperopia) suitable for contact lens wear without more than 1.00 D of astigmatism. A total of 244 patients (488 eyes) were evaluate in the CAC studies. A total of 491 subjects were exposed to ACUVUE® Theravision™ with Ketotifen over a period of 12 weeks in the safety studies. These four studies demonstrated that ACUVUE® Theravision™ with Ketotifen was safe and more effective than placebo (1•DAY ACUVUE®) in preventing ocular itching in patients with allergic conjunctivitis. ACUVUE® Theravision™ with Ketotifen reduced ocular itching within 3 minutes and the response was sustained for up to 12 hours after lens insertion. Visual acuity was comparable between ACUVUE® Theravision™ with Ketotifen and 1•DAY ACUVUE®.
Not all refractive powers, design configurations, or lens parameters available were tested in clinical investigation of the lenses. Therefore, when selecting an appropriate lens design, the Eye Care Professional should consider all characteristics of the lens that can affect lens performance and ocular health, including oxygen permeability, wettability, central and peripheral thickness and optic zone diameter. The potential impact of these factors on the patient's ocular health should be carefully weighed against the patient's need for refractive correction and prevention of itching associated with allergic conjunctivitis; therefore, the continuing ocular health of the patient and lens performance on the eye should be carefully monitored by the prescribing Eye Care Professional.
16 HOW SUPPLIED/STORAGE AND HANDLING
ACUVUE® Theravision™ with Ketotifen (etafilcon A drug-eluting contact lens with ketotifen) is a daily disposable contact lens, 19 mcg ketotifen per lens is supplied in a plastic blister bowl and a foil laminated lidstock containing a buffered ketotifen solution. The plastic package is marked with base curve, lens diameter, diopter (lens power), date of manufacture, expiration date and lot number.
ACUVUE® Theravision™ with Ketotifen is supplied in a 30-count carton containing 30 foil sealed blister packages containing etafilcon A contact lens with 19 mcg ketotifen (NDC 60123-019-30).
Store at 15°C to 25°C (59°F to 77°F). Protect from light. Store lenses in carton until use.
DO NOT to use if the ACUVUE® Theravision™ with Ketotifen lens sterile blister package is opened or damaged.
17 PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Fitting
See the ACUVUE® Theravision™ with Ketotifen FITTING INSTRUCTION GUIDE for professional fitting instructions and information.
Wearing Schedule (Daily Wear)
Advise patients that ACUVUE® Theravision™ with Ketotifen should not be used to treat red eye(s). Remove lens(es) immediately if the eye(s) become red or irritated.
A single ACUVUE® Theravision™ with Ketotifen should be worn in each eye per day and should be discarded upon removal each day. The lens should not be worn beyond the period recommended by an eye care professional.
Advise patients that ACUVUE® Theravision™ with Ketotifen should be removed prior to sleep.
Lens Handling and Care
Advise patients to not use if the ACUVUE® Theravision™ with Ketotifen lens sterile blister package is opened or damaged.
Advise patients to always wash and rinse hands before handling lenses.
Advise patients to avoid contaminating hands or lenses with cosmetics, lotions, soaps, creams, deodorants or sprays. Instruct patients to put in lenses prior to applying makeup.
Advise patients not to touch contact lenses if hands have any foreign materials as microscopic scratches of the lenses may occur, which can cause distorted vision and/or injury to the eye.
Instruct patients to examine the lens after opening to be sure that it is a single, moist, clean lens that is free of any nicks or tears. If the lens appears damaged, patients should be instructed NOT to use it.
Instruct patients not to use contact lens cleaning and disinfectant solutions with ACUVUE® Theravision™ with Ketotifen. Discard lens after a single day's use.
Advise patients that ACUVUE® Theravision™ with Ketotifen should not be worn while swimming or in hot tubs. Contact lens wear in these settings increases the risk of sight threatening eye infections from microorganisms.
If the lens sticks (stops moving), the patient should be instructed to remove the lens. A few drops of non-preserved sterile saline solution may be applied directly to the eye to assist with removal. If non-movement of the lens continues after a few minutes, the patient should immediately consult their Eye Care Professional.
Patients should be advised to notify the employer of being a contact lens wearer. Some jobs may require the use of eye protection equipment or may require that the patient not wear contact lenses.
Advise patients to avoid all harmful or irritating vapors and fumes while wearing lenses. If aerosol products, such as hair spray, are used while wearing lenses, exercise caution and keep eyes closed until the spray has settled.
Instruct patients to never use tweezers, fingernails, or other tools to remove lenses from the lens container. Instead, patients should remove ACUVUE® Theravision™ with Ketotifen from the blister container packing solution using their fingertips. Patients should not touch the lens with fingernails.
The patients should be advised to never rinse the lenses in water from the tap. Tap water contains many impurities that can contaminate or damage the lenses and may lead to eye infection or injury.
Advise patients to always dispose of lenses when removed and have spare non-medicated lenses or spectacles available.
Concomitant Use of Other Medications
Advise patients to consult with their eyecare professional before using any medicine in the eyes. Advise patients that eye drops containing benzalkonium chloride should not be used simultaneously with ACUVUE® Theravision™ with Ketotifen. Instruct patients to wait 10 minutes after eye drop application before inserting lenses.
Daily self-examination
Instruct the patient to immediately remove the lens if any eye discomfort, eye pain, eye redness or decreased vision are experienced. If the symptoms stop after lens removal, the patient should discard the lens(es) and replace with new non-medicated lens(es). ACUVUE® Theravision™ with Ketotifen should not be worn for the remainder of the day. If the problem continue after inserting a new non-medicated lens, the patient should remove the lens and IMMEDIATELY CONSULT THEIR EYE CARE PROFESSIONAL.
Emergencies
Advise the patient that if chemicals of any kind (household products, gardening solutions, laboratory chemicals, etc.) are splashed into the eyes, the patient should: FLUSH EYES IMMEDIATELY WITH TAP WATER AND IMMEDIATELY CONTACT THE EYE CARE PROFESSIONAL OR VISIT A HOSPITAL EMERGENCY ROOM WITHOUT DELAY.
Symbols Key
The following symbols may appear on the label or packaging:
| SYMBOL | DEFINITION |
|---|---|
 | Caution, Consult Instructions for Use |
 | Manufacturer |
 | Date of Manufacture |
 | Use by Date (expiration date) |
 | Batch Code |
 | Sterilized Using Steam Heat |
 | Do Not Re-Use (Single Use) |
 | Do Not Use if Package is Damaged |
 | Store Away from Direct Sunlight |
 | Indicates a Single Sterile Barrier System |
 | Authorized Representative in the European Community |
 | Medical Device in the European Community |
 | Fee Paid for Waste Management |
 | CE-mark and Identification Number of Notified Body |
 | Contains Hazardous Substances |
 | Contains a Medicinal Substance |
 | CAUTION: U.S. Federal law restricts this device to sale by or on the order of a licensed practitioner |
| CONTACT LENS | Contact Lens |
 | Lens Orientation Correct |
 | Lens Orientation Incorrect (Lens Inside Out) |
 | Package Opening Icon (Blister) |
| DIA | Diameter |
| BC | Base Curve |
| D | Diopter (Lens Power) |
Distributed by:
Johnson & Johnson Vision Care, Inc.
7500 Centurion Parkway
Jacksonville, Florida 32256, USA
www.acuvue.com
©Johnson & Johnson Vision Care, Inc. 2021
In Canada: Johnson & Johnson Vision Care, division of Johnson & Johnson, Inc.
In USA: Johnson & Johnson Vision Care, Inc.
Printed in USA
Revision date: 2/2022
Revision number: XXXXX
ACUVUE® Theravision™ is a trademark of Johnson & Johnson Vision Care, Inc.