Ophthalmic Anesthetics

• Ophthalmic anesthetics
• Ophthalmic Antibacterials and combination products
• Ophthalmic Anti-allergy agents
• Ophthalmic Antivirals
• Ophthalmic Corticosteroids
• Ophthalmic - Dry eye disease (DED)
• Ophthalmic - Glaucoma
• Ophthalmic Mydriatics
• Ophthalmic NSAIDs
• Fortified Ophthalmic Preparations

• ALCAINE® (proparacaine hydrochloride 0.5%)
• Akten™ (lidocaine hydrochloride) Ophthalmic Gel 3.5%
• Tetracaine Hydrochloride 0.5%

Indications: 
ALCAINE (proparacaine hydrochloride ophthalmic solution) (Proparacaine Hydrochloride) Ophthalmic Solution is indicated for topical anesthesia in ophthalmic practice. Representative ophthalmic procedures in which the preparation provides good local anesthesia include measurement of intraocular pressure (tonometry), removal of foreign bodies and sutures from the cornea, conjunctival scraping in diagnosis and gonioscopic examination; it is also indicated for use as a topical anesthetic prior to surgical operations such as cataract extraction.

Dosing:
Deep anesthesia as in cataract extraction:

Instill 1 drop every 5 to 10 minutes for 5 to 7 doses.

Removal of sutures:

Instill 1 or 2 drops 2 or 3 minutes before removal of stitches.

Removal of foreign bodies:

Instill 1 or 2 drops prior to operating.

Tonometry:

Instill 1 or 2 drops immediately before measurement.

Precautions/Warnings:
WARNINGS
For topical ophthalmic use only. Do not touch dropper tip to any surface as this may contaminate the solution. Prolonged use of a topical ocular anesthetic may produce permanent corneal opacification with accompanying loss of vision.

PRECAUTIONS
GENERAL
Proparacaine hydrochloride should be used cautiously and sparingly in patients with known allergies, cardiac disease, or hyperthyroidism. The long-term toxicity of proparacaine is unknown, prolonged use may possibly delay wound healing. Although exceedingly rare with ophthalmic application of local anesthetics, it should be borne in mind that systemic toxicity (manifested by central nervous system stimulation followed by depression) may occur. Protection of the eye from irritating chemicals, foreign bodies and rubbing during the period of anesthesia is very important. Tonometers soaked in sterilizing or detergent solutions should be thoroughly rinsed with sterile distilled water prior to use. Patients should be advised to avoid touching the eye until the anesthesia has worn off.

CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY
Long-term studies in animals have not been performed to evaluate carcinogenic potential, mutagenicity, or possible impairment oi fertility in males or females.

PREGNANCY CATEGORY C
Animal reproduction studies have not been conducted with ALCAINE (proparacaine hydrochloride ophthalmic solution) (Proparacaine Hydrochloride) Ophthalmic Solution. It is also not known whether proparacaine hydrochloride can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Proparacaine hydrochloride should be administered to a pregnant woman only if clearly needed.

NURSING MOTHERS
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when proparacaine hydrochloride is administered to a nursing woman.

PEDIATRIC USE
Controlled clinical studies have not been performed with ALCAINE (proparacaine hydrochloride ophthalmic solution) (Proparacaine Hydrochloride) Ophthalmic Solution to establish safety and effectiveness in children; however, the literature cites the use of proparacaine hydrochloride as a topical ophthalmic anesthetic agent in children.

Supplied:
HOW SUPPLIED
ALCAINE (proparacaine hydrochloride ophthalmic solution) (Proparacaine Hydrochloride) Ophthalmic Solution. 0.5% is supplied in 15 mL DROP-TAINER® dispensers.

Storage: Store at 2°-8°C. Keep refrigerated. Do not use the solution if darker than a pale yellow.

Efficacy:

CLINICAL PHARMACOLOGY
ALCAINE (proparacaine hydrochloride ophthalmic solution) Solution is a rapid acting local anesthetic suitable for ophthalmic use. The onset of anesthesia usually begins within 30 seconds and lasts a relatively short period of time. The main site of anesthetic action is the nerve cell membrane where proparacaine interferes with the large transient increase in the membrane permeability to sodium ions that is internally produced by a slight depolarization of the membrane. As the anesthetic action progressively develops in a nerve, the threshold for electrical stimulation gradually increases and the safety factor for conduction decreases; when this action is sufficiently well developed, block of conduction is produced. The exact mechanism whereby proparacaine and other local anesthetics influence the permeability of the cell membrane is unknown; however, several studies indicate that local anesthetics may limit sodium ion permeability through the lipid layer of the nerve cell membrane. This limitation prevents the fundamental change necessary for the generation of the action potential

Indications: 
Akten™ (lidocaine hydrochloride ophthalmic gel) is a local anesthetic indicated for ocular surface anesthesia during ophthalmologic procedures.

Dosing:
The recommended dose of Akten™ (lidocaine hydrochloride ophthalmic gel) is 2 drops applied to the ocular surface in the area of the planned procedure. Akten™ (lidocaine hydrochloride ophthalmic gel) may be reapplied to maintain anesthetic effect.

Precautions/Warnings:
WARNINGS
Included as part of the PRECAUTIONS section.

PRECAUTIONS
Not for Injection.
Corneal Opacification. Prolonged use of a topical ocular anesthetic may produce permanent corneal opacification and ulceration with accompanying visual loss.
NONCLINICAL TOXICOLOGY
CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY
Long-term studies in animals have not been performed to evaluate the carcinogenic potential of Akten™ (lidocaine hydrochloride ophthalmic gel) .

USE IN SPECIFIC POPULATIONS
PREGNANCY. PREGNANCY CATEGORY B.
Reproduction

NURSING MOTHERS
Lidocaine is secreted in human milk. The clinical significance of this observation is unknown. Although no systemic exposure is expected with administration of Akten™ (lidocaine hydrochloride ophthalmic gel) , caution should be exercised when Akten™ (lidocaine hydrochloride ophthalmic gel) is administered to a nursing woman.

PEDIATRIC USE
Safety and efficacy in pediatric patients has been extrapolated from studies in older subjects and studies in pediatric patients using different formulations of lidocaine.

GERIATRIC USE
No overall clinical differences in safety or effectiveness were observed between the elderly and other adult patients.

Supplied:
Akten™ (lidocaine hydrochloride ophthalmic gel) 3.5% is a sterile, preservative-free, single patient use ophthalmic gel preparation for topical ocular anesthesia.

DOSAGE FORMS AND STRENGTH
Akten™ (lidocaine hydrochloride ophthalmic gel) Ophthalmic Gel, 3.5% contains 35 mg per mL of lidocaine hydrochloride for topical ophthalmic administration.

STORAGE AND HANDLING
Akten™ (lidocaine hydrochloride ophthalmic gel) 3.5% is supplied as a clear gel for single patient use as follows:

5mL fill in a 10mL natural, round plastic dropper bottle

Efficacy:

CLINICAL STUDIES
The effect of Akten™ (lidocaine hydrochloride ophthalmic gel) on ocular anesthesia was studied in a multi-center, randomized, controlled, double-blind study.

A total of 209 subjects were enrolled, with 54, 51, 53, and 51 subjects randomized to the sham, Akten™ (lidocaine hydrochloride ophthalmic gel) 1.5%, Akten™ (lidocaine hydrochloride ophthalmic gel) 2.5%, and Akten™ (lidocaine hydrochloride ophthalmic gel) 3.5% groups, respectively. Ocular anesthesia was achieved within 5 minutes of anesthetic application by 47 of 51 subjects (92%) in the Akten™ (lidocaine hydrochloride ophthalmic gel) 3.5% group.

The mean time to anesthesia onset ranged from 20 seconds to 5 minutes was not affected by Akten™ (lidocaine hydrochloride ophthalmic gel) dose. The mean time to anesthesia onset was approximately 60 seconds, with a median onset time of 40 seconds for the Akten™ (lidocaine hydrochloride ophthalmic gel) 3.5% group. Among the subjects in the Akten™ (lidocaine hydrochloride ophthalmic gel) groups who achieved anesthesia within 5 minutes, approximately 90% had achieved anesthesia within 60 seconds of application.

The duration of anesthesia generally ranged from approximately 5 minutes to 30 minutes, with mean anesthesia durations of approximately 15 minutes for the Akten™ (lidocaine hydrochloride ophthalmic gel) 3.5% group.

Approximately 84% of the subjects in the Akten™ (lidocaine hydrochloride ophthalmic gel) 3.5% group experienced anesthesia for at least 5 minutes, approximately 55% of subjects experienced anesthesia for 10 minutes or longer and 27% experienced anesthesia for 15 minutes or longer. The anesthetic effect of additional applications of Akten™ (lidocaine hydrochloride ophthalmic gel) has not been evaluated.

MECHANISM OF ACTION
Akten™ (lidocaine hydrochloride ophthalmic gel) is a local anesthetic agent that stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses, thereby effecting local anesthetic action. Anesthesia generally occurs between 20 seconds to 1 minute and persists for 5 to 30 minutes.

Indications: 
For procedures in which a rapid and short-acting topical ophthalmic anesthetic is indicated such as in tonometry, gonioscopy, removal of corneal foreign bodies, conjunctival scraping for diagnostic purposes, suture removal from the cornea, other short corneal and conjunctival procedures.

CONTRAINDICATIONS:
Should not be used by the patient without physician supervision, or in those persons showing hypersensitivity to any component of this preparation. This product should never be prescribed for the patient’s own use.

Dosing:
For tonometry and other procedures of short duration, instill one or two drops just prior to evaluation. For minor surgical procedures such as foreign body or suture removal, administer one to two drops every five to ten minutes for one to three instillations. For prolonged anesthesia as in cataract extraction, instill one or two drops in the eye(s) every five to ten minutes for three to five doses.

Precautions/Warnings:
WARNINGS:
Prolonged use results in diminished duration of anesthesia and retarded healing. This may cause the drug to be used more frequently creating a “vicious circle.” Subsequent corneal infection and/or corneal opacification with accompanying permanent visual loss or corneal perforation may occur.

PRECAUTIONS:
FOR TOPICAL USE ONLY—NOT FOR INJECTION. To prevent contaminating the dropper tip and solution, care should be taken not to touch the eyelids or surrounding area with the dropper tip. Patient should be advised not to touch or rub the eye(s) until the effect of the anesthetic has worn off.

INFORMATION TO THE PATIENT:
After instillation of this product, the surface of the eye is insensitive and can be scratched without feeling it. Do not rub eye. Do not instill this product repeatedly because severe eye damage may occur.

NOTE:
DO NOT USE IF SOLUTION CONTAINS CRYSTALS, OR IS CLOUDY OR DISCOLORED.

Supplied:

Tetracaine Hydrochloride Ophthalmic Solution USP, 0.5% is supplied in a plastic bottle with a controlled drop tip in the following size:

NDC 68071-4579-5 BOX OF 15mL

STORAGE:
Storage: Store between 15°-25°C (59°-77°F). KEEP TIGHTLY CLOSED.

Efficacy:

CLINICAL PHARMACOLOGY:
Topical anesthetics stabilize the neuronal membrane and prevent the initiation and transmission of nerve impulses, thereby effecting local anesthesia. The onset of anesthesia usually begins within 30 seconds and lasts a relatively short period of time.