Rocklatan

Pregnancy

Risk Summary
There are no adequate and well-controlled studies of ROCKLATAN ophthalmic 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 ].

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 effects at clinically relevant systemic exposures. ROCKLATAN should be used during pregnancy only if the potential benefit justifies 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-effect-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 studies 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 effects on the breastfed infant, or the effects 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 benefits of breastfeeding should be considered along with the mother’s clinical need for ROCKLATAN and any potential adverse effects on the breast-fed child from ROCKLATAN.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

No overall differences in safety or effectiveness have been observed between elderly and other adult patients.

Epithelial Corneal Edema

ROCKLATAN contains netarsudil which has been associated with Epithelial corneal edema, described as honeycomb or bullous, and has been reported in some patients with pre-existing corneal stromal edema or following ocular procedures that could affect corneal endothelial function. Epithelial corneal edemal typically resolves upon discontinuation of ROCKLATAN. Advise patients to notify their physician if they experience eye pain or decreased vision while using ROCKLATAN [see Adverse Reactions and Patient Counselling Information ].

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 expected 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. Patients who receive treatment should be informed of the possibility of increased pigmentation. Beyond 5 years the effects 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 affected 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 ].

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 ].

Intraocular Inflammation

ROCKLATAN contains latanoprost which should be used with caution in patients with a history of intraocular inflammation (iritis/uveitis) and should generally not be used in patients with active intraocular inflammation because it may exacerbate inflammation.

Macular Edema

Macular 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 Keratitis

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 inflammation.

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 ].

Use with Contact Lenses

Contact lenses should be removed prior to the administration of ROCKLATAN and may be reinserted 15 minutes after administration.