Eyeworld

Distributed by Harrow Eye, LLC 102 Woodmont Blvd., Suite 610 Nashville, TN 37205 USA BRIEF SUMMARY OF PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE IHEEZO™ (chloroprocaine hydrochloride ophthalmic gel) 3% is a preservative-free ester anesthetic indicated for ocular surface anesthesia. 4 CONTRAINDICATIONS IHEEZO is contraindicated in patients with a history of hypersensitivity to any component of this preparation. 5 WARNINGS AND PRECAUTIONS 5.1 Not for Injection or Intraocular Administration IHEEZO should not be injected or intraocularly administered. 5.2 Corneal Injury Due to Insensitivity Patients should not touch the eye for at least 10 to 20 minutes after using anesthetic 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 Risk of Contamination Do not touch the dropper tip to any surface as this may contaminate the gel. 5.5 For Administration by Healthcare Provider IHEEZO is indicated for administration under the direct supervision of a healthcare provider. IHEEZO is not intended for patient self-administration. 6 ADVERSE REACTIONS 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. The data described below reflect 201 patients undergoing various surgical ocular procedures in two placebo-controlled trials (Study 1 and Study 2). Patients in Study 1 were randomized to receive a single instillation of 3 drops of IHEEZO or placebo. Patients in Study 2 were randomized to receive a single or multiple instillations of 1, 3, or 3+3 drops of IHEEZO or placebo. The most common adverse reactions in these studies (incidence greater than or equal to 5%) following IHEEZO administration were mydriasis, conjunctival hyperemia, and eye irritation. 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies of IHEEZO use in pregnant women to inform a drug-associated risk. There are no animal reproduction studies for chloroprocaine. 8.2 Lactation Risk Summary There are no data on the presence of chloroprocaine in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for IHEEZO and any potential adverse effects on the breastfed infant from IHEEZO. 8.4 Pediatric Use The safety and effectiveness of IHEEZO have not been established in pediatric patients. 8.5 Geriatric Use No overall differences in safety or effectiveness of IHEEZO have been observed between elderly and younger patients. 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Chloroprocaine, like other local anesthetics, blocks the generation and the conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, slowing the propagation of the nerve impulse, and reducing the rate of rise of the action potential. In general, the progression of anesthesia is related to the diameter, myelination, and conduction velocity of affected nerve fibers. Clinically, the order of loss of nerve function is as follows: (1) pain, (2) temperature, (3) touch, (4) proprioception, and (5) skeletal muscle tone. 12.3 Pharmacokinetics The systemic exposure to chloroprocaine following topical ocular administration of IHEEZO has not been studied. Elimination Metabolism Chloroprocaine is metabolized by plasma pseudocholinesterases and nonspecific esterases in ocular tissues. Chloroprocaine is rapidly metabolized in plasma by hydrolysis of the ester linkage by pseudocholinesterase. The hydrolysis of chloroprocaine results in the production of ß-diethylaminoethanol and 2-chloro-4-aminobenzoic acid, which inhibits the action of the sulfonamides. Excretion Chloroprocaine plasma half-life in vitro is approximately 25 seconds in adults and approximately 43 seconds in neonates. The kidney is the main excretory organ for most local anesthetics and their metabolites. Urinary excretion is affected by urinary perfusion and factors affecting urinary pH. 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Long-term studies in animals to evaluate carcinogenic potential of chloroprocaine have not been conducted. Mutagenesis 2-chloroprocaine and the main metabolite, ACBA, were negative in the in vitro bacterial reverse mutation test (Ames assay) and the in vitro chromosome aberrations assay. Impairment of Fertility Studies in animals to evaluate the impairment of fertility have not been conducted with chloroprocaine. 14 CLINICAL STUDIES 14.1 Study 1 and Study 2 Study 1 (NCT04779606) and Study 2 (NCT04753710) were randomized, double-blinded, placebo- controlled studies conducted to evaluate the efficacy, safety, and local tolerability of IHEEZO in 145 healthy volunteers. In Study 1, 85 healthy males and females were randomized in a 4:1 ratio to receive a single ocular instillation of IHEEZO (n=68) or placebo (n=17). The double-blinded treatment included an IHEEZO or a placebo dose of 3 drops instilled at 1-minute (±15 seconds) intervals in the right eye of each volunteer. The median age was 39 years (range 19 to 55 years); 59% female and 41% male. In Study 2, 60 healthy males and females were randomized (40:20) to receive single or multiple ocular instillations of an IHEEZO dose of 3 drops in the right eye. The median age was 25 years (range 18 to 59 years); 54% female and 46% male. The efficacy in Study 1 and Study 2 was determined by proportion of patients achieving full conjunctival anesthesia evaluated by conjunctival pinching 5 minutes after administration. Efficacy results of Study 1 The proportion of subjects with successful anesthesia was 90% in the IHEEZO group and 12% in the placebo group (P<0.01). The median time for the IHEEZO group achieving anesthesia was 0.67 minutes. The median duration of anesthesia was 14.3 minutes. Efficacy results of Study 2 The proportion of subjects with successful anesthesia was 95% in the IHEEZO group and 20% in the placebo group (P<0.01). The median time for the IHEEZO group achieving anesthesia was 0.67 minutes. The median duration of anesthesia was 19.3 minutes. 14.2 Study 3 Study 3 (NCT04685538) was a randomized, prospective, multicenter, active-controlled, observer- masked study conducted to evaluate the efficacy and safety of IHEEZO (n=166) versus tetracaine ophthalmic solution 0.5% (n=172) in patients undergoing cataract surgery. The primary endpoint was defined as the proportion of patients in each treatment group gaining successful anesthesia without any supplementation. On average, patients needed 1 to 1.5 minutes to obtain sufficient anesthesia to successfully perform the surgical procedure, which lasted on average 22 minutes. No patient treated with IHEEZO required supplemental treatment to complete the intended surgical procedure. 17 PATIENT COUNSELING INFORMATION Eye Care Precaution Do not touch the dropper tip to any surface as this may contaminate the gel. Advise patients that their eyes will be insensitive for up to 20 minutes due to the effect of the anesthetic, and that care should be taken to avoid accidental injuries. For Full Prescribing Information, please visit www.iheezo.com/prescribinginformation. IHEEZO ™ (chloroprocaine HCl ophthalmic gel) 3%

• Blank Page
• Blank Page (1)