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ROCKLATAN ® (netarsudil and latanoprost ophthalmic solution) 0.02%/0.005%, for topical oph- thalmic use BRIEF SUMMARY OF FULL PRESCRIBING INFORMATION INDICATIONS AND USAGE. ROCKLATAN (netarsudil and latanoprost ophthalmic solution) 0.02%/0.005% is a fi xed dose combination of a Rho kinase inhibitor and a prostaglandin F2α analogue indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glauco- ma or ocular hypertension. CONTRAINDICATIONS. None. WARNINGS AND PRECAUTIONS. Pigmentation—ROCKLATAN contains latanoprost which has been reported to cause changes to pigmented tissues. The most frequently reported changes have been increased pigmentation of the iris, periorbital tissue (eyelid), and eyelashes. Pigmentation is ex- pected to increase as long as latanoprost is administered. The pigmentation change is due to increased melanin content in the melanocytes rather than to an increase in the number of melanocytes. After discontinuation of latanoprost, pigmentation of the iris is likely to be permanent, while pigmentation of the periorbital tissue and eyelash changes have been reported to be reversible in some patients. Pa- tients who receive treatment should be informed of the possibility of increased pigmentation. Beyond 5 years the eff ects of increased pigmentation are not known. Iris color change may not be noticeable for several months to years. Typically, the brown pigmentation around the pupil spreads concentrically towards the periphery of the iris and the entire iris or parts of the iris become more brownish. Neither nevi nor freckles of the iris appear to be aff ected by treatment. While treatment with ROCKLATAN can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly [see Patient Counseling Information in the Full Prescribing Information]. Eyelash Changes—ROCKLATAN contains latanoprost which may gradually change eyelashes and vellus hair in the treated eye; these changes include increased length, thickness, pigmentation, the number of lashes or hairs, and misdirected growth of eyelashes. Eyelash changes are usually reversible upon discontinuation of treatment [see Patient Counseling Information in the Full Prescribing Information]. Intraocular In- fl ammation—ROCKLATAN contains latanoprost which should be used with caution in patients with a history of intraocular infl ammation (iritis/uveitis) and should generally not be used in patients with active intraocular infl ammation because it may exacerbate infl ammation. Macular Edema—Mac- ular edema, including cystoid macular edema, has been reported during treatment with latanoprost. ROCKLATAN should be used with caution in aphakic patients, in pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular edema. Herpetic Kerati- tis—Reactivation of Herpes Simplex keratitis has been reported during treatment with latanoprost. ROCKLATAN should be used with caution in patients with a history of herpetic keratitis. ROCKLATAN should be avoided in cases of active herpes simplex keratitis because it may exacerbate infl ammation. Bacterial Keratitis—There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products. These containers had been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface [see Patient Counseling Information in the Full Prescribing Information]. Use with Contact Lenses— Contact lenses should be removed prior to the administration of ROCKLATAN and may be reinserted 15 minutes after administration. ADVERSE REACTIONS 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 refl ect the rates observed in clinical practice. The most common ocular adverse reaction observed in controlled clinical studies with ROCKLATAN was conjunctival hyperemia which was report- ed in 59% of patients. Five percent of patients discontinued therapy due to conjunctival hyperemia. Other common ocular adverse reactions reported were: instillation site pain (20%), corneal verticillata (15%), and conjunctival hemorrhage (11%). Eye pruritus, visual acuity reduced, increased lacrimation, instillation site discomfort, and blurred vision were reported in 5-8% of patients. Other adverse reactions that have been reported with the individual components and not listed above include: Netarsudil 0.02%: Instillation site erythema, corneal staining, increased lacrimation, and erythema of eyelid. Latanoprost 0.005%: Foreign body sensation, punctate keratitis, burning and stinging, itching, increased pigmentation of the iris, excessive tearing, eyelid discomfort, dry eye, eye pain, eyelid margin crusting, erythema of the eyelid, upper respiratory tract infection/ nasopharyngitis/infl uenza, photophobia, eyelid edema, myalgia/arthralgia/back pain, and rash/ allergic reactions. DRUG INTERACTIONS In vitro drug interaction studies have shown that precipitation can occur when eye drops containing thimerosal are mixed with ROCKLATAN. If such drugs are used, they should be administered at least fi ve (5) minutes apart. The combined use of two or more prostaglandins or prostaglandin analogs including latanoprost ophthalmic solution 0.005% is not recommended. It has been shown that administration of these prostaglandin drug products more than once daily may decrease the IOP lowering eff ect or cause paradoxical elevations in IOP. USE IN SPECIFIC POPULATIONS Pregnancy—Risk Summary: There are no adequate and well-controlled studies of ROCKLATAN oph- thalmic solution or its pharmacologically active ingredients (netarsudil and latanoprost) in pregnant women to inform any drug associated risk. However, systemic exposure to netarsudil from ocular administration is low [see Clinical Pharmacology in the Full Prescribing Information]. Reproduction studies of latanoprost showed embryofetal lethality in rabbits. No embryofetal lethality was observed at a dose approximately 15 times higher than the recommended human ophthalmic dose (RHOD). Intravenous administration of netarsudil to pregnant rats and rabbits during organogenesis did not produce adverse embryofetal eff ects at clinically relevant systemic exposures. ROCKLATAN should be used during pregnancy only if the potential benefi t justifi es the potential risk to the fetus. Data: Animal Data. Netarsudil administered daily by intravenous injection to rats during organogenesis caused abortions and embryofetal lethality at doses ≥0.3 mg/kg/day (126-fold the plasma exposure at the RHOD, based on Cmax). The no-observed-adverse-eff ect-level (NOAEL) for embryofetal development toxicity was 0.1 mg/kg/day (40-fold the plasma exposure at the RHOD, based on Cmax). Netarsudil administered daily by intravenous injection to rabbits during organogenesis caused embryofetal lethality and decreased fetal weight at 5 mg/kg/day (1480-fold the plasma exposure at the RHOD, based on Cmax). Malformations were observed at ≥3 mg/kg/ day (1330-fold the plasma exposure at the RHOD, based on Cmax), including thoracogastroschisis, umbilical hernia and absent intermediate lung lobe. The NOAEL for embryofetal development toxicity was 0.5 mg/kg/day (214-fold the plasma exposure at the RHOD, based on Cmax). Reproduction stud- ies have been performed with latanoprost in rats and rabbits. In 4 of 16 pregnant rabbits, no viable fetuses were present at a dose that was approximately 80 times higher than the RHOD. Latanoprost did not produce embryofetal lethality in rabbits at a dose approximately 15 times higher than the RHOD. Lactation—Risk Summary: There are no data on the presence of netarsudil or latanoprost in human milk, the eff ects on the breastfed infant, or the eff ects on milk production. However, systemic exposure to netarsudil following topical ocular administration is low, and it is not known whether measurable levels of netarsudil would be present in maternal milk following topical ocular administration. The developmental and health benefi ts of breastfeeding should be considered along with the mother's clinical need for ROCKLATAN and any potential adverse eff ects on the breast-fed child from ROCKLATAN. Pediatric Use—Safety and eff ectiveness in pediatric patients have not been established. Geriatric Use—No overall diff erences in safety or eff ectiveness have been observed between elderly and other adult patients. NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment of Fertility—Carcinogenesis: Long-term studies in animals have not been performed to evaluate the carcinogenic potential of netarsudil. Latanoprost was not carcinogenic in either mice or rats when administered by oral gavage at doses of up to 170 mcg/kg/day (approximately 2800 times the RHOD) for up to 20 and 24 months, respectively. Mutagenesis: Netarsudil was not mutagenic in the Ames test, in the mouse lymphoma test, or in the in vivo rat micronucleus test. Latanoprost was not mutagenic in bacteria, in mouse lymphoma, or in mouse micronucleus tests. Chromosome aberrations were observed in vitro with human lymphocytes. Additional in vitro and in vivo studies on unscheduled DNA synthesis in rats were negative. Impairment of Fertility: Studies to evaluate the eff ects of netarsudil on male or female fertility in animals have not been performed. Latanoprost has not been found to have eff ects on male or female fertility in animal studies. For a copy of the Full Prescribing Information, please visit ROCKLATAN.com. U.S. Patent Nos.: 8,450,344; 8,394,826; 9,096,569; 9,415,043; 9,931,336; 9,993,470; 10,174,017; 10,532,993; 10,588,901 ROCKLATAN is a trademark of Aerie Pharmaceuticals, Inc. Manufactured for: Aerie Pharmaceuticals, Inc., Irvine, CA 92614, U.S.A. PI Version Date: 6/2020 © 2024 Alcon Inc. US-ROC-2400005

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