RHOPRESSA Ophthalmic solution Ref.[10148] Active ingredients: Netarsudil

5.1 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 (17)].

5.2 Use with Contact Lenses

Contact lenses should be removed prior to instillation of RHOPRESSA and may be reinserted 15 minutes following its administration.

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

The most common ocular adverse reaction observed in controlled clinical studies with RHOPRESSA dosed once daily was conjunctival hyperemia which was reported in 53% of patients. Six percent of patients discontinued therapy due to conjunctival hyperemia. Other common (approximately 20%) ocular adverse reactions reported were: corneal verticillata, instillation site pain, and conjunctival hemorrhage. Instillation site erythema, corneal staining, blurred vision, increased lacrimation, erythema of eyelid, and reduced visual acuity were reported in 5-10% of patients.

Corneal Verticillata

Corneal verticillata occurred in approximately 20% of the patients in controlled clinical studies. The corneal verticillata seen in RHOPRESSA-treated patients were first noted at 4 weeks of daily dosing. This reaction did not result in any apparent visual functional changes in patients. Most corneal verticillata resolved upon discontinuation of treatment.

Risk Summary

There are no available data on RHOPRESSA use in pregnant women to inform any drug associated risk; however, systemic exposure to netarsudil from ocular administration is low [see Clinical Pharmacology (12.3)]. Intravenous administration of netarsudil to pregnant rats and rabbits during organogenesis did not produce adverse embryofetal effects at clinically relevant systemic exposures [see Data].

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 recommended human ophthalmic dose [RHOD], based on C_max). 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 C_max).

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 C_max). Malformations were observed at ≥3 mg/kg/day (1330-fold the plasma exposure at the RHOD, based on C_max), 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 C_max).

Risk Summary

There are no data on the presence of RHOPRESSA 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 [see Clinical Pharmacology (12.3)], 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 RHOPRESSA and any potential adverse effects on the breast-fed child from RHOPRESSA.

Safety and effectiveness in pediatric patients below the age of 18 years have not been established.

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