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Ophthalmic Compounding of Losartan

At VLS Pharmacy & New Drug Loft, we are placing increased focus on our ophthalmic compounding offerings. This type of compounding requires specialized facilities and equipment that meet United States Pharmacopeia (USP) guidelines. It may be performed for a variety of reasons, such as to remove an allergenic ingredient in a commercial medication, to minimize systemic exposure, or to directly deliver a drug to its site of action.

Many FDA-approved drugs are prescribed for off-label ophthalmic indications, but their commercially available forms are not suitable for ophthalmic administration. In this blog post, we’ll focus on losartan, which is currently only commercially available for oral administration. A 503A compounding pharmacy like VLS Pharmacy can reformulate this medication for ophthalmic delivery.

Visual impairment can occur due to a variety of reasons, including glaucoma, age-related macular degeneration, post-surgery scarring, or diabetes. Regardless of the cause, vision loss or impairment diminishes a patient’s quality of life. Traditional treatment options, like laser surgery or corneal transplantation, come with risks, but emerging research is showing that topical ophthalmic losartan can be used to treat many of these conditions.

Off-label ophthalmic indications of losartan 

Losartan, a well-known angiotensin II receptor blocker (ARB), is indicated for hypertension, left ventricular hypertrophy, and diabetic nephropathy, but its benefits have recently been shown to extend beyond these cardiovascular indications. As we continue to focus on ophthalmic compounding, this month, we turn our attention to topical ophthalmic losartan and how it is being investigated to treat various ophthalmic conditions.

Corneal scarring fibrosis

Corneal scarring may result due to trauma, surgery, or infections. Although surgery using cornea transplantation is the current standard of care for severe and permanent corneal haze and blindness, it comes with many risks, just as with any surgery. Pharmacological approaches offer another route to improve corneal haze and mild-to-moderate opacities. Topical losartan (0.1–0.8 mg/mL) has been shown to prevent myofibroblast development or induce apoptosis (1).

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A pioneer in this treatment, Steven E. Wilson, MD, has noted that topical losartan will likely be effective in treating conditions in which myofibroblasts are the cause of corneal scarring. His recent research in rabbits has also shown that combining the corticosteroid prednisolone acetate with topical losartan synergistically decreased myofibroblast-associated fibrosis after corneal alkali burn (2). 

It is critical to use topical losartan for treating fibrosis. When taken orally, it is not distributed in the cornea. 

Corneal scarring due to bacterial infections

As we noted last month, contact lens usage may lead to the contraction of Acanthamoeba keratitis, which can be treated with metronidazole. However, recalcitrant infections may take several months to cure, leading to severe corneal scarring fibrosis. A regimen of 0.8 mg/mL losartan in a balanced salt solution six times a day was shown to decrease corneal scarring fibrosis after four months of usage. It is important to note that consistent administration over several months is generally necessary to show improvements. 

Corneal scarring after refractive surgery

Haze may develop after refractive surgeries such as LASIK, with rates ranging anywhere from 2.7 percent to 5.8 percent in the literature (3). Topical losartan was used in a clinical case report to treat severe corneal haze that manifested after a LASIK procedure. After using topical losartan for 4.5 months, UDVA improved to 20/30 and CDVA improved to 20/25 in the patient’s left eye (4). A significant reduction of corneal haze was also observed, highlighting the promise of using topical losartan to treat corneal haze after LASIK procedures. 

Photorefractive keratectomy (PRK) late haze typically develops within three or four months of a PRK procedure. Although it has become much less common due to treatment with mitomycin C, a small number of patients still develop haze, a process that is mediated by myofibroblast development. As such, it may respond to topical losartan, which has been shown to decrease corneal opacity and myofibroblasts in rabbits after PRK after only one month of 50 µL topical 0.2 mg/mL losartan, six times per day (5).

Diabetic Retinopathy

Angiotensin II plays a role in the progression of diabetic retinopathy by enhancing the main events involved in its pathogenesis, including angiogenesis. ARBs like losartan have shown promising results and may be used as an adjuvant therapy for treating diabetic retinopathy and preventing vision loss in diabetic patients.

A five-year, multicenter, randomized, double-blind, placebo-controlled trial published in the New England Journal of Medicine used losartan to treat normotensive type I diabetic patients. The results showed that losartan slowed the progression of diabetic retinopathy (6). A review article suggested that losartan may treat diabetic retinopathy by inhibiting leukocyte recruitment, downregulating VEGF-mediated capillary formation, or preventing oxidative stress-induced retinal cell apoptosis (7).

Additional Ophthalmic Indications of Losartan: Emerging Research

In addition to the above indications, losartan has also been hypothesized to be suitable for other ophthalmic indications (8). 

Glaucoma

Glaucoma is the leading cause of irreversible blindness around the world and is often associated with elevated intraocular pressure (IOP). Several studies, including a small pilot study, have shown that oral administration of losartan reduces IOP in glaucomatous humans (9,10). 

Topical administration of losartan has also reduced IOP in rats (11) and also protects retinal ganglion cells and alters scleral remodeling in mice with experimental glaucoma (12). These studies suggest that topical administration of losartan may also help reduce IOP. It may also improve myofibroblast-mediated conditions, such as conjunctival bleb fibrosis and tube shunt encapsulation.

Diabetic cataracts

Diabetic patients are several times more likely to develop cataracts compared with non-diabetic patients. Although diabetic retinopathy is the most common cause of visual loss in this population, diabetes can also lead to the development of cataracts. Although there have been no human studies of losartan for treating diabetic cataracts, a murine study showed a reduction in cataract formation after topical administration of 0.5 percent wt/v losartan over a period of eight weeks (13). 

Losartan Compounded Preparations Offered by New Drug Loft & VLS Pharmacy

Regardless of which indication losartan is prescribed for, our pharmacists will tailor the formulation to meet each individual patient’s specific needs by providing the specified concentration and volume.

  • Volume: 6 mL or 12 mL
  • Strength: 0.08%
  • We exclusively compound losartan 0.08% ophthalmic solution for ophthalmic use only.
  • Compounded in a sterile compounding facility that is USP chapters <795>, <797>, and <800> compliant

Why Choose VLS Pharmacy and New Drug Loft?

As we’ve shown above, losartan can be used to treat various ophthalmic conditions, including corneal scarring and retinopathy. Because the recommended treatment regimens typically last several months, it’s important to work with a compounding pharmacy that will consistently deliver safe and effective compounded losartan.

As mandated by USP, ophthalmic compounding requires specialized equipment and a sterile environment. Our expertise as a 503A pharmacy in this niche area of compounding allows us to supply adult and pediatric patients with ophthalmic compounds – whether in a hospital/surgical setting, the office, or at home. 

Our compounding pharmacists are skilled in advanced aseptic techniques, and all compounds have been independently tested by third-party facilities. With our multi-state licensure and quick turnaround, you can predictably plan patient protocols to create a safe, individualized ophthalmic treatment regimen.

Please comment below with any thoughts or questions.

Reach out to our team to learn about best practices and to partner with our experts on custom compounded medications for your patients. All medications from VLS Pharmacy and New Drug Loft are prepared in a lab that follows safety and quality standards per our status as a 503A pharmacy.

 

References

  1. Sampaio LP, Hilgert GSL, Shiju TM, Murillo SE, Santhiago MR, Wilson SE. Topical losartan inhibits corneal scarring fibrosis and collagen type IV deposition after Descemet’s membrane-endothelial excision in rabbits. Exp Eye Res. 2022;216:108940. doi:10.1016/j.exer.2022.108940
  2. Sampaio LP, Hilgert GSL, Shiju TM, Santhiago MR, Wilson SE. Topical Losartan and Corticosteroid Additively Inhibit Corneal Stromal Myofibroblast Generation and Scarring Fibrosis After Alkali Burn Injury. Transl Vis Sci Technol. 2022;11(7):9. doi:10.1167/tvst.11.7.9
  3. Moshirfar M, Wang Q, Theis J, et al. Management of Corneal Haze After Photorefractive Keratectomy. Ophthalmol Ther. 2023;12(6):2841-2862. doi:10.1007/s40123-023-00782-1
  4. Pereira-Souza AL, Ambrósio R, Bandeira F, Salomão MQ, Souza Lima A, Wilson SE. Topical Losartan for Treating Corneal Fibrosis (Haze): First Clinical Experience. J Refract Surg. 2022;38(11):741-746. doi:10.3928/1081597X-20221018-02
  5. Losartan Inhibition of Myofibroblast Generation and Late Haze (Scarring Fibrosis) After PRK in Rabbits – PubMed. Accessed April 17, 2024. https://pubmed.ncbi.nlm.nih.gov/36476304/
  6. Mauer Michael, Zinman Bernard, Gardiner Robert, et al. Renal and Retinal Effects of Enalapril and Losartan in Type 1 Diabetes. New England Journal of Medicine. 2009;361(1):40-51. doi:10.1056/NEJMoa0808400
  7. Behl T, Kotwani A. Potential of angiotensin II receptor blockers in the treatment of diabetic retinopathy. Life Sciences. 2017;176:1-9. doi:10.1016/j.lfs.2017.03.020
  8. Wilson SE. Topical Losartan: Practical Guidance for Clinical Trials in the Prevention and Treatment of Corneal Scarring Fibrosis and Other Eye Diseases and Disorders. Journal of Ocular Pharmacology and Therapeutics. 2023;39(3):191-206. doi:10.1089/jop.2022.0174
  9. Costagliola C, Verolino M, Leonarda De Rosa M, Iaccarino G, Ciancaglini M, Mastropasqua L. Effect of Oral Losartan Potassium Administration on Intraocular Pressure in Normotensive and Glaucomatous Human Subjects. Experimental Eye Research. 2000;71(2):167-171. doi:10.1006/exer.2000.0866
  10. Costagliola C, Verolino M, Iaccarino G, De Rosa ML, Ciancaglini M, Mastropasqua L. Losartan Potassium Oral Administration Decreased Intraocular Pressure in Humans. Clin Drug Investig. 1999;17(4):329-332. doi:10.2165/00044011-199917040-00009
  11. Agarwal R, Krasilnikova A, Mohamed SNL, et al. Topical Losartan Reduces IOP by Altering TM Morphology in Rats with Steroid-induced Ocular Hypertension. Indian J Physiol Pharmacol.
  12. Quigley HA, Pitha IF, Welsbie DS, et al. Losartan Treatment Protects Retinal Ganglion Cells and Alters Scleral Remodeling in Experimental Glaucoma. PLOS ONE. 2015;10(10):e0141137. doi:10.1371/journal.pone.0141137
  13. Losartan delays the progression of streptozotocin‐induced diabetic cataracts in albino rats – Shree – 2019 – Journal of Biochemical and Molecular Toxicology – Wiley Online Library. Accessed April 18, 2024. https://onlinelibrary.wiley.com/doi/10.1002/jbt.22342

 

 


 

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