VYZULTA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VYZULTA (VYZULTA).
VYZULTA (latanoprostene bunod) is a nitric oxide-donating prostaglandin F2α analog. Latanoprostene bunod is hydrolyzed by esterases in the cornea to liberate latanoprost acid and butanediol mononitrate (a nitric oxide donor). Latanoprost acid reduces intraocular pressure by increasing uveoscleral outflow via prostaglandin FP receptor agonism. The nitric oxide component activates soluble guanylate cyclase, increasing cGMP levels, which enhances trabecular outflow facility and increases conventional outflow.
| Metabolism | Latanoprostene bunod is an ester prodrug that is rapidly hydrolyzed by esterases in the cornea and plasma to latanoprost acid and butanediol mononitrate. Latanoprost acid is further metabolized primarily via beta-oxidation of the carboxylic acid chain and reduction of the double bond, with metabolites excreted renally. Butanediol mononitrate is metabolized to nitric oxide and 1,4-butanediol, which is further metabolized via alcohol dehydrogenase and aldehyde dehydrogenase. |
| Excretion | Following ocular administration, latanoprostene bunod is hydrolyzed to latanoprost acid and nitric oxide. Systemic elimination of latanoprost acid is primarily renal (88%) and fecal (7%) within 4-6 days. |
| Half-life | The terminal elimination half-life of latanoprost acid from plasma is approximately 17 minutes after topical ocular administration in humans. This short half-life limits systemic exposure. |
| Protein binding | Latanoprost acid is approximately 88% bound to human plasma proteins; albumin is the primary binding protein. |
| Volume of Distribution | The volume of distribution (Vd) for latanoprost acid is reported as 0.16 ± 0.04 L/kg, indicating distribution primarily into extracellular fluid with limited tissue binding. |
| Bioavailability | Absolute bioavailability following topical ocular administration is very low due to extensive local hydrolysis and limited systemic absorption; systemic bioavailability of latanoprost acid is approximately 0.01-0.02% of the administered dose. |
| Onset of Action | Reduction in intraocular pressure (IOP) is observed within 1-3 hours after a single topical ocular dose; peak effect occurs at 8-12 hours. |
| Duration of Action | IOP lowering is sustained for at least 24 hours following once-daily topical dosing, supporting once-daily administration. The effect persists for several days after cessation but gradually returns to baseline. |
One drop of ophthalmic solution (0.024% latanoprostene bunod) in the affected eye(s) once daily in the evening.
| Dosage form | SOLUTION/DROPS |
| Renal impairment | No dose adjustment required for renal impairment. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Safety and efficacy in pediatric patients have not been established. |
| Geriatric use | No age-related dose adjustment necessary; pharmacodynamic effects similar to younger adults. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VYZULTA (VYZULTA).
| Breastfeeding | It is not known whether latanoprostene bunod or its metabolites are excreted in human milk. In animal studies, prostaglandin analogs and their metabolites are excreted in milk. The M/P ratio is not available. Because many drugs are excreted in human milk, caution should be exercised when VYZULTA is administered to a nursing woman. Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for VYZULTA and any potential adverse effects on the breastfed child from the drug or underlying maternal condition. |
| Teratogenic Risk | There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, topical ocular administration of latanoprostene bunod to pregnant rabbits during organogenesis resulted in embryofetal lethality at doses ≥ 50 μg/kg/day (approximately 47 times the maximum recommended human dose based on body surface area) and increased post-implantation loss at 500 μg/kg/day. There was no evidence of malformations at any dose. In rats, no developmental toxicity was observed at ocular doses up to 1000 μg/kg/day (approximately 484 times the MRHD). Because animal studies cannot fully predict human response, VYZULTA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. The prostaglandin analog component may increase uterine tone and contractions; use with caution near term. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to latanoprostene bunod or any component of the formulation.","Hypersensitivity to prostaglandin analogs."]
| Precautions | ["Pigmentation: Increased iris pigmentation (may be permanent) and periorbital skin darkening reported.","Eyelash changes: Increased length, thickness, pigmentation, and number of lashes.","Inflammatory reactions: Macular edema, including cystoid macular edema, reported in aphakic or pseudophakic patients with a torn posterior lens capsule or risk factors.","Contamination: Patients should avoid touching tip of dispensing container to eye or surrounding structures to prevent ocular infections and contamination.","Use with caution in patients with intraocular inflammation (e.g., iritis/uveitis) due to potential exacerbation.","Bacterial keratitis associated with contaminated multi-dose containers reported.","May cause transient blurred vision or other visual disturbances."] |
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| Fetal Monitoring | No specific maternal or fetal monitoring is mandated beyond routine prenatal care. However, in pregnant women using VYZULTA, clinicians should monitor for signs of increased uterine contractility or preterm labor, particularly in the third trimester. Ocular hypotensive therapy should be monitored via intraocular pressure measurements as in non-pregnant patients. If used in pregnancy, periodic fetal ultrasound may be considered to assess growth and amniotic fluid volume. |
| Fertility Effects | Based on animal studies, latanoprostene bunod had no effects on mating or fertility indices in male or female rats at ocular doses up to 1000 μg/kg/day (approximately 484 times the MRHD). There are no human data on fertility effects. Theoretical concerns about prostaglandin analog effects on reproductive organs have not been observed systemically at ocular doses. |