ROCKLATAN(netarsudil and latanoprost ophthalmic solution)0.02%/0.005%, for topical ophthalmic(四)
max).
Netarsudil administered daily by intravenous injection to rabbits during organogenesis caused embryofetallethality and decreased fetal weight at 5 mg/kg/day (1480-fold the plasma exposure at the RHOD, basedon 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. TheNOAEL for embryofetal development toxicity was 0.5 mg/kg/day (214-fold the plasma exposure at theRHOD, 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 thanthe RHOD.
8.2 Lactation
Risk Summary
There are no data on the presence of netarsudil or latanoprost in human milk, the effects on the breastfedinfant, or the effects on milk production. However, systemic exposure to netarsudil following topicalocular administration is low, and it is not known whether measurable levels of netarsudil would be presentin maternal milk following topical ocular administration.
The developmental and health benefits of breastfeeding should be considered along with the mother’sclinical need for ROCKLATAN and any potential adverse effects on the breast-fed child fromROCKLATAN.
8.4 Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
8.5 Geriatric Use
No overall differences in safety or effectiveness have been observed between elderly and other adultpatients.
11. DESCRIPTION
ROCKLATAN (netarsudil and latanoprost ophthalmic solution) 0.02%/0.005% is a fixed dosecombination of a Rho kinase inhibitor and a prostaglandin F2α analogue.
The chemical name of netarsudil dimesylate is: (S)-4-(3-amino-1-(isoquinolin-6-yl-amino)-1-oxopropan-2-yl)benzyl 2,4-dimethylbenzoate dimesylate. Its molecular formula is C30H35N3O9S2 and its chemicalstructure is:
Netarsudil mesylate is a light yellow to white powder that is freely soluble in water, soluble in methanol,sparingly soluble in dimethyl formamide, and practically insoluble in dichloromethane and heptane.
The chemical name of latanoprost is: isopropyl-(Z)-7[1R,2R,3R,5S) 3,5-dihydroxy-2-[(3R)-3-hydroxy-5-phenylpentyl]cyclopentyl]-5-heptenoate. Its molecular formula is C26H40O5 and its chemical structure is:Latanoprost is a colorless to slightly yellow oil that is very soluble in acetonitrile and freely soluble inacetone, ethanol, ethyl acetate, isopropanol, methanol, and octanol. It is practically insoluble in water.
ROCKLATAN (netarsudil and latanoprost ophthalmic solution) 0.02%/0.005% is supplied as a sterile,isotonic, buffered aqueous solution of netarsudil mesylate and latanoprost with a pH of approximately 5and an osmolality of approximately 295 mOsmol/kg. Each mL of ROCKLATAN contains 0.20 mg of netarsudil (equivalent to 0.28 mg of netarsudil dimesylate) and 0.05 mg latanoprost. Benzalkoniumchloride, 0.02%, is added as a preservative. The inactive ingredients are: boric acid, mannitol, sodiumhydroxide to adjust pH, and water for injection.
12. CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
ROCKLATAN is comprised of two components: netarsudil and latanoprost. Each of these twocomponents decreases elevated IOP. Elev |
