Clobetasol Propionate

BYQLOVI is indicated for the treatment of post-operative inflammation and pain following ocular surgery. BYQLOVI is a corticosteroid indicated for the treatment of post- operative inflammation and pain following ocular surgery. ( 1 )

Ophthalmic suspension containing clobetasol propionate 0.05% (0.5 mg/mL). Ophthalmic suspension containing clobetasol propionate 0.05%. ( 3 )

BYQLOVI is contraindicated in most active viral diseases of the cornea and conjunctiva, including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, and also in mycobacterial infection of the eye and fungal diseases of ocular structures. BYQLOVI is contraindicated in most active viral diseases of the cornea and conjunctiva, including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, and also in mycobacterial infection of the eye and fungal diseases of ocular structures. ( 4 )

Intraocular Pressure (IOP) Increase : Prolonged use of corticosteroids may result in glaucoma with damage to the optic nerve, defects in visual acuity and fields of vision. Steroids should be used with caution in the presence of glaucoma. If this product is used for 10 days or longer, IOP should be monitored. ( 5.1 ) Cataracts : Prolonged use of corticosteroids may result in posterior subcapsular cataract formation. ( 5.2 ) Delayed Healing : The use of steroids after cataract surgery may delay healing and increase the incidence of bleb formation. ( 5.3 ) Corneal and Scleral Melting : In those diseases causing thinning of the cornea or sclera, perforations have been known to occur with the use of topical steroids. The initial prescription and renewal of the medication order should be made by a physician only after examination of the patient with the aid of magnification, such as slit lamp biomicroscopy, and where appropriate, fluorescein staining. ( 5.4 ) Bacterial Infections : Prolonged use of corticosteroids may suppress the host response and thus increase the hazard of secondary ocular infections. In acute purulent conditions, steroids may mask infection or enhance existing infection. If signs and symptoms fail to improve after 2 days, the patient should be reevaluated. ( 5.5 ) Viral Infections : Employment of a corticosteroid medication in the treatment of patients with a history of herpes simplex requires great caution. Use of ocular steroids may prolong the course and may exacerbate the severity of many viral infections of the eye (including herpes simplex). ( 5.6 ) Fungal Infections : Fungal infections of the cornea are particularly prone to develop coincidentally with long-term local steroid application. Fungus invasion must be considered in any persistent corneal ulceration where a steroid has been used or is in use. Fungal culture should be taken when appropriate. ( 5.7 )

5.1 Intraocular Pressure (IOP) Increase Prolonged use of corticosteroids may result in glaucoma with damage to the optic nerve, defects in visual acuity and fields of vision. Steroids should be used with caution in the presence of glaucoma. If BYQLOVI is used for 10 days or longer, IOP should be monitored.

5.2 Cataracts Prolonged use of corticosteroids may result in posterior subcapsular cataract formation.

5.3 Delayed Healing The use of corticosteroids after cataract surgery may delay healing and increase the incidence of bleb formation.

5.4 Corneal and Scleral Melting In those diseases causing thinning of the cornea or sclera, perforations have been known to occur with the use of topical corticosteroids. The initial prescription and renewal of the medication order should be made by a physician only after examination of the patient with the aid of magnification, such as slit lamp biomicroscopy, and where appropriate, fluorescein staining.

5.5 Bacterial Infections Prolonged use of corticosteroids may suppress the host response and thus increase the hazard of secondary ocular infections. In acute purulent conditions, steroids may mask infection or enhance existing infection. If signs and symptoms fail to improve after 2 days, the patient should be reevaluated.

5.6 Viral Infections Employment of a corticosteroid medication in the treatment of patients with a history of herpes simplex requires great caution. Use of ocular corticosteroids may prolong the course and may exacerbate the severity of many viral infections of the eye (including herpes simplex).

5.7 Fungal Infections Fungal infections of the cornea are particularly prone to develop coincidentally with long- term local corticosteroid application. Fungus invasion must be considered in any persistent corneal ulceration where a corticosteroid has been used or is in use. Fungal culture should be taken when appropriate.

5.8 Risk of Contamination Do not allow the dropper tip to touch any surface, as this may contaminate the ophthalmic suspension.

5.9 Contact Lens Wear BYQLOVI should not be instilled while wearing contact lenses. Remove contact lenses prior to instillation of BYQLOVI. The preservative in BYQLOVI may be absorbed by soft contact lenses. Lenses may be reinserted after 15 minutes following administration of BYQLOVI.

The following serious reactions are found elsewhere in the labeling: Intraocular Pressure (IOP) Increase [see Warnings and Precautions ( 5.1 )] Posterior Subcapsular Cataract Formation [see Warnings and Precautions ( 5.2 )] Delayed Healing [see Warnings and Precautions ( 5.3 )] Corneal and Scleral Melting [see Warnings and Precautions ( 5.4 )] Bacterial Infections [see Warnings and Precautions ( 5.5 )] Viral Infections [see Warnings and Precautions ( 5.6 )] Fungal Infections [see Warnings and Precautions ( 5.7 )] Ocular adverse reactions occurring in ≥ 1% of subjects in clinical studies who received BYQLOVI included eye inflammation (2%), corneal edema (2%), anterior chamber inflammation (2%), cystoid macular edema (2%), intraocular pressure elevation (1%), photophobia (1%) and vitreous detachment (1%). Many of these reactions may have been the consequence of the surgical procedure ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Harrow at 1-833-4HARROW(427769) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Ocular adverse reactions occurring in ≥ 1% of subjects in clinical studies who received BYQLOVI included eye inflammation (2%), corneal edema (2%), anterior chamber inflammation (2%), cystoid macular edema (2%), intraocular pressure elevation (1%), photophobia (1%) and vitreous detachment (1%). Many of these reactions may have been the consequence of the surgical procedure.

8.1 Pregnancy Risk Summary There are no adequate and well-controlled clinical studies of BYQLOVI administration in pregnant women to inform drug-associated risks. Plasma concentrations of clobetasol propionate were minimal following topical ophthalmic administration of BYQLOVI [see Clinical Pharmacology ( 12.3 )] . However, corticosteroids, including clobetasol propionate have been shown to be teratogenic and fetotoxic in laboratory animals when administered systemically at relatively low dosage levels (see Data ) . BYQLOVI should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data In embryofetal development studies in mice, clobetasol propionate was fetotoxic at the highest subcutaneous dose tested (1 mg/kg) and teratogenic at all subcutaneous dose levels tested down to 0.03 mg/kg. Abnormalities observed included cleft palate and skeletal abnormalities. These doses are approximately 98 times and 3 times, respectively, the recommended human ophthalmic dose of BYQLOVI, estimated based on body surface area and assuming 100% systemic absorption. In embryofetal development studies in rabbits, clobetasol propionate was teratogenic at subcutaneous doses of 3 and 10 μg/kg. Abnormalities seen included cleft palate, cranioschisis, and other skeletal abnormalities. These doses are approximately 1.2 times and 3.9 times, respectively, the recommended human ophthalmic dose of BYQLOVI, estimated based on body surface area and assuming 100% systemic absorption.

8.2 Lactation Risk Summary There is no information regarding the presence of clobetasol propionate in human milk, the effects on the breastfed infant, or the effects on milk production. Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. However, systemic levels of clobetasol propionate following topical ocular administration are minimal [see Clinical Pharmacology ( 12.3 )], and it is not known whether measurable levels of clobetasol propionate 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 BYQLOVI, and any potential adverse effects on the breastfed infant from BYQLOVI.

8.4 Pediatric Use The safety and effectiveness of BYQLOVI in pediatric patients have not been established.

8.5 Geriatric Use No overall differences in safety and effectiveness of BYQLOVI have been observed between patients 65 years of age and older and younger adult patients.

Like other topical corticosteroids, clobetasol propionate has anti-inflammatory, antipruritic, and vasoconstrictive properties. The mechanism of the anti-inflammatory activity of the topical steroids, in general, is unclear. However, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor, arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2.