Lidocaine Hydrochloride Anhydrous

1- INDICATIONS AND USAGE AKTEN is indicated for ocular surface anesthesia during ophthalmologic procedures in adults and pediatric patients. AKTEN is an amide local anesthetic indicated for ocular surface anesthesia during ophthalmologic procedures. ( 1 )

The recommended dose of AKTEN is 2 drops applied to the ocular surface in the area of the planned procedure. AKTEN may be reapplied to maintain anesthetic effect. The recommended dose of AKTEN is 2 drops applied to the ocular surface in the area of the planned procedure. AKTEN may be reapplied to maintain anesthetic effect. ( 2 )

Ophthalmic Gel: 3.5% lidocaine hydrochloride in single-patient use tubes. Ophthalmic Gel: 3.5% lidocaine hydrochloride in single-patient-use tubes. ( 3 )

None. None. ( 4 )

5 WARNINGS AND PRECAUTIONS For Topical Ophthalmic Use: AKTEN is not for injection or intraocular administration. ( 5.1 ) Patients should not touch the eye for at least 10 to 20 minutes after using AKTEN as accidental injuries can occur due to insensitivity of the eye. ( 5.2 ) Corneal Opacification: Prolonged use of a topical ocular anesthetic may produce permanent corneal opacification and ulceration with accompanying visual loss. ( 5.2 ) For Administration by Healthcare Provider: AKTEN is not intended for patient self-administration. ( 5.3 )

5.1 For Topical Ophthalmic Use AKTEN is not for injection or intraocular administration.

5.2 Corneal Injury Due to Insensitivity Patients should not touch the eye for at least 10 to 20 minutes after using AKTEN as accidental injuries can occur due to insensitivity of the eye.

5.3 Corneal Opacification Prolonged use of a topical ocular anesthetic may produce permanent corneal opacification and ulceration with accompanying visual loss.

5.4 For Administration by Healthcare Provider AKTEN is indicated for administration under the direct supervision of a healthcare provider. AKTEN is not intended for patient self-administration.

Most common adverse reactions are conjunctival hyperemia, corneal epithelial changes, headache, and burning upon instillation. Most common adverse reactions are conjunctival hyperemia, corneal epithelial changes, headache, and burning upon instillation. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Thea Pharma Inc. at 1-833-838-4028 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. See 17 for PATIENT COUNSELING INFORMATION.

Prolonged use of a topical ocular anesthetic may produce permanent corneal opacification and ulceration with accompanying visual loss. Acute emergencies from local anesthetics are generally related to high plasma levels encountered during therapeutic use of local anesthetics or to unintended subarachnoid injection of local anesthetic solution. However, topical ocular application of AKTEN is not expected to result in systemic exposure.

8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies with AKTEN in pregnant women to inform a drug-associated risk. In animal reproduction studies, subcutaneous administration of lidocaine to pregnant rats at doses >800-fold the human dose based on body surface area did not result in adverse developmental effects. The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

8.2 Lactation Risk Summary Lidocaine is secreted in human milk. The clinical significance of this observation is unknown. Caution should be exercised when AKTEN is administered to a nursing woman.

8.4 Pediatric Use The safety and effectiveness of AKTEN for ocular surface anesthesia during ophthalmologic procedures have been established in pediatric patients. Use of AKTEN for this indication has been extrapolated from adequate and well-controlled studies in adults and studies in pediatric patients using different formulations of lidocaine.

8.5 Geriatric Use No overall clinical differences in safety or effectiveness were observed between the elderly and other adult patients.

Risk Summary There are no adequate and well-controlled studies with AKTEN in pregnant women to inform a drug-associated risk. In animal reproduction studies, subcutaneous administration of lidocaine to pregnant rats at doses >800-fold the human dose based on body surface area did not result in adverse developmental effects. The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

The safety and effectiveness of AKTEN for ocular surface anesthesia during ophthalmologic procedures have been established in pediatric patients. Use of AKTEN for this indication has been extrapolated from adequate and well-controlled studies in adults and studies in pediatric patients using different formulations of lidocaine.

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

AKTEN (lidocaine hydrochloride ophthalmic gel) 3.5% contains lidocaine hydrochloride, an amide local anesthetic, as a sterile ophthalmic gel for topical ophthalmic use. AKTEN does not contain an anti-microbial preservative. Lidocaine hydrochloride is designated chemically as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl) monohydrochloride with a molecular formula of C 14 H 22 N 2 O ∙ HCl and molecular weight of 270.8. The structural formula of the active ingredient is: Each mL of AKTEN contains 35 mg of lidocaine hydrochloride as the active ingredient. Inactive ingredients: hypromellose, sodium chloride, and water for injection. The pH may be adjusted to 5.5 to 7.5 with hydrochloric acid and/or sodium hydroxide. AKTEN does not contain an anti-microbial preservative. Chemical Structure

12.1 Mechanism of Action Lidocaine hydrochloride is an amide 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.

12.3 Pharmacokinetics Lidocaine may be absorbed following topical administration to mucous membranes. Its rate and extent of absorption depend upon various factors such as concentration, the specific site of application, viscosity of the agent, and duration of exposure. The plasma binding of lidocaine is dependent on drug concentration, and the fraction bound decreases with increasing concentration. At concentrations of 1 to 4 mcg of free base per mL, 60 to 80 percent of lidocaine is protein bound. Binding is also dependent on the plasma concentration of the alpha-1-acid glycoprotein. Lidocaine is metabolized rapidly by the liver, and metabolites and unchanged drug are excreted by the kidneys. Biotransformation includes oxidative N- dealkylation, ring hydroxylation, cleavage of the amide linkage, and conjugation. N-dealkylation, a major pathway of biotransformation, yields the metabolites monoethylglycinexylidide and glycinexylidide. The pharmacologic/toxicologic actions of these metabolites are similar to, but less potent than, those of lidocaine. Approximately 90% of lidocaine administered is excreted in the form of various metabolites, and less than 10% is excreted unchanged. The primary metabolite in urine is a conjugate of 4-hydroxy-2, 6-dimethylaniline. Studies of lidocaine metabolism following intravenous bolus injections have shown that the elimination half-life of this agent is typically 1.5 to 2 hours. Because of the rate at which lidocaine is metabolized, any condition that affects liver function may alter lidocaine kinetics. The half-life may be prolonged twofold or more in patients with liver dysfunction. Renal dysfunction does not affect lidocaine kinetics but may increase the accumulation of metabolites.

Lidocaine hydrochloride is an amide 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.

Lidocaine may be absorbed following topical administration to mucous membranes. Its rate and extent of absorption depend upon various factors such as concentration, the specific site of application, viscosity of the agent, and duration of exposure. The plasma binding of lidocaine is dependent on drug concentration, and the fraction bound decreases with increasing concentration. At concentrations of 1 to 4 mcg of free base per mL, 60 to 80 percent of lidocaine is protein bound. Binding is also dependent on the plasma concentration of the alpha-1-acid glycoprotein. Lidocaine is metabolized rapidly by the liver, and metabolites and unchanged drug are excreted by the kidneys. Biotransformation includes oxidative N- dealkylation, ring hydroxylation, cleavage of the amide linkage, and conjugation. N-dealkylation, a major pathway of biotransformation, yields the metabolites monoethylglycinexylidide and glycinexylidide. The pharmacologic/toxicologic actions of these metabolites are similar to, but less potent than, those of lidocaine. Approximately 90% of lidocaine administered is excreted in the form of various metabolites, and less than 10% is excreted unchanged. The primary metabolite in urine is a conjugate of 4-hydroxy-2, 6-dimethylaniline. Studies of lidocaine metabolism following intravenous bolus injections have shown that the elimination half-life of this agent is typically 1.5 to 2 hours. Because of the rate at which lidocaine is metabolized, any condition that affects liver function may alter lidocaine kinetics. The half-life may be prolonged twofold or more in patients with liver dysfunction. Renal dysfunction does not affect lidocaine kinetics but may increase the accumulation of metabolites.

, Mutagenesis, Impairment of Fertility Long-term studies in animals have not been performed to evaluate the carcinogenic potential of AKTEN .

Storage Store at 15°C to 25°C (59°F to 77°F). Keep single-patient-use tubes closed and protected from light in the original carton until ready for use. Discard after use.