MOA

Why the VYZULTA dual mechanism of action may be
an option for your glaucoma patients

Only VYZULTA releases latanoprost acid and nitric oxide to reduce IOP1-3
  • Studies have shown that there are lower levels of nitric oxide markers in the eyes of patients with POAG4-6
  • Nitric oxide deficiency may play a role in trabecular contraction and elevated IOP5

Aqueous humor outflow happens through 2 pathways2:

The trabecular meshwork

  • The eye's primary outflow pathway
  • Made up of the trabecular meshwork and Schlemm’s canal7-9

The uveoscleral pathway

  • The remaining aqueous humor exits the eye through this secondary pathway, called the uveoscleral pathway7,9

Both outflow pathways are important in the regulation of IOP, slowing the progression of glaucoma and delaying the onset of ocular hypertension10


Once metabolized, VYZULTA increases outflow through both the uveoscleral pathway and the trabecular meshwork2


VYZULTA expands the trabecular meshwork and targets the uveoscleral pathway to decrease IOP1,2,10,15-17

INDICATION

VYZULTA® (latanoprostene bunod ophthalmic solution), 0.024% is indicated for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension.

IMPORTANT SAFETY INFORMATION 
  • Increased pigmentation of the iris and periorbital tissue (eyelid) can occur. Iris pigmentation is likely to be permanent
  • Gradual changes to eyelashes, including increased length, increased thickness, and number of eyelashes, may occur. These changes are usually reversible upon treatment discontinuation
  • Use with caution in patients with a history of intraocular inflammation (iritis/uveitis). VYZULTA should generally not be used in patients with active intraocular inflammation
  • Macular edema, including cystoid macular edema, has been reported during treatment with prostaglandin analogs. Use with caution in aphakic patients, in pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular edema
  • There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products that were inadvertently contaminated by patients
  • Contact lenses should be removed prior to the administration of VYZULTA and may be reinserted 15 minutes after administration
  • Most common ocular adverse reactions with incidence ≥2% are conjunctival hyperemia (6%), eye irritation (4%), eye pain (3%), and instillation site pain (2%)
1. Cavet ME, Vollmer TR, Harrington KL, VanDerMeid K, Richardson ME. Regulation of endothelin-1–induced trabecular meshwork cell contractility by latanoprostene bunod. Invest Ophthalmol Vis Sci. 2015;56(6):4108-4116.
2. VYZULTA Prescribing Information. Bausch & Lomb Incorporated.
3. Krauss AH, Impagnatiello F, Toris CB, et al. Ocular hypotensive activity of BOL-303259-X, a nitric oxide donating prostaglandin F2α agonist, in preclinical models. Exp Eye Res. 2011;93:250-255.
4. Doganay S, Evereklioglu C, Turkoz Y, et al. Decreased nitric oxide production in primary open-angle glaucoma. Eur J Ophthalmol. 2002;11:44-48.
5. Nathanson JA, McKee M. Alterations of ocular nitric oxide synthase in human glaucoma. Ophthalmol Vis Sci. 1995;36:1774-1784.
6. Galassi F, Renieri G, Sodi A, et al. Nitric oxide proxies and ocular perfusion pressure in primary open angle glaucoma. J Ophthalmol. 2004;88:757-760.
7. Braunger BM, Fuchshofer R, Tamm ER. The aqueous humor outflow pathways in glaucoma: a unifying concept of disease mechanisms and causative treatment. Eur J Pharm Biopharm. 2015;95(Pt B):173-181.
8. Tamm ER, Braunger BM, Fuchshofer R. Intraocular pressure and the mechanisms involved in resistance of the aqueous humor flow in the trabecular meshwork outflow pathways. Prog Mol Biol Transl Sci. 2015;134:301-314.
9. Winkler NS, Fautsch MP. Effects of prostaglandin analogues on aqueous humor outflow pathways. J Ocul Pharmacol Ther. 2014;30(2-3):102-109.
10. Cavet ME, DeCory HH. The role of nitric oxide in the intraocular pressure lowering efficacy of latanoprostene bunod: review of nonclinical studies. J Ocul Pharmacol Ther. 2018;34(1-2):52-60. DOI:10.1089/jop.2016.0188.
11. Weinreb RN, Khaw PT. Primary open-angle glaucoma. Lancet. 2004;363:1711-1720.
12. Cavet ME, Vittitow JL, Impagnatiello F, et al. Nitric oxide (NO): an emerging target for the treatment of glaucoma. Invest Ophthalmol Vis Sci. 2014;55:5005-5015.
13. Buys ES, Potter LR, Pasquale LR, Ksander BR. Regulation of intraocular pressure by soluble and membrane guanylate cyclases and their role in glaucoma. Front Mol Neurosci. 2014;7:1-15.
14. Schneemann A, Dijkstra BG, van den Berg TJ, Kamphuis W, Hoyng PFJ. Nitric oxide/guanylate cyclase pathways and flow in anterior segment perfusion. Graefe’s Arch Clin Exp Ophthalmol. 2002;240:936-941.
15. Wareham LK, Buys ES, Sappington RM. The nitric oxide-guanylate cyclase pathway and glaucoma. Nitric Oxide. 2018;77:75-87. DOI/10.1016/j.niox.2018.04.010.
16. Stamer DW, Ascott TS. Current understanding of conventional outflow dysfunction in glaucoma. Curr Opin Ophthalmol. 2012;23:135-143. DOI:10.1097/ICU.0b013e32834ff23e.
17. Kaufman PL. Enhancing trabecular outflow by disrupting the actin cytoskeleton, increasing uveoscleral outflow with prostaglandins, and understanding the pathophysiology of presbyopia interrogating Mother Nature: asking why, asking how, recognizing the signs, following the trail. Exp Eye Res. 2008;86:3-17. DOI:10.1016/j.exer.2007.10.007.

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INDICATION

VYZULTA® (latanoprostene bunod ophthalmic solution), 0.024% is indicated for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension.

IMPORTANT SAFETY INFORMATION 
  • Increased pigmentation of the iris and periorbital tissue (eyelid) can occur. Iris pigmentation is likely to be permanent
  • Gradual changes to eyelashes, including increased length, increased thickness, and number of eyelashes, may occur. These changes are usually reversible upon treatment discontinuation