Label: LOTEPREDNOL ETABONATE suspension/ drops

Loteprednol etabonate ophthalmic suspension contains a sterile, topical anti-inflammatory corticosteroid for ophthalmic use. Loteprednol etabonate is a white to off-white crystalline powder.

Loteprednol etabonate is represented by the following structural formula:

Molecular formula: C24H31ClO7                                Molecular weight: 466.95 g/mol

Chemical name: chloromethyl 17α-[(ethoxycarbonyl)oxy]-11β-hydroxy-3-oxoandrosta-1,4-diene-17β-carboxylate.

Each mL contains:

ACTIVE: Loteprednol Etabonate, 5 mg (0.5%)

INACTIVES: Edetate Disodium, Glycerin, Povidone, Tyloxapol and Water for Injection.

Hydrochloric Acid and/or Sodium Hydroxide may be added to adjust the pH to 3.5 to 6.0. The suspension is essentially isotonic with a tonicity of 250 to 310 mOsmol/kg.

PRESERVATIVE ADDED: Benzalkonium Chloride, 0.01%.

Corticosteroids inhibit the inflammatory response to a variety of inciting agents and probably delay or slow healing. They inhibit the edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen and scar formation associated with inflammation. There is no generally accepted explanation for the mechanism of action of ocular corticosteroids. 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. Corticosteroids are capable of producing a rise in intraocular pressure.

Loteprednol etabonate is structurally similar to other corticosteroids. However, the number 20 position ketone group is absent. It is highly lipid soluble which enhances its penetration into cells. Loteprednol etabonate is synthesized through structural modifications of prednisolone-related compounds so that it will undergo a predictable transformation to an inactive metabolite. Based upon in vivo and in vitro preclinical metabolism studies, loteprednol etabonate undergoes extensive metabolism to inactive carboxylic acid metabolites.

Results from a bioavailability study in normal volunteers established that plasma levels of loteprednol etabonate and Δ1 cortienic acid etabonate (PJ 91), its primary, inactive metabolite, were below the limit of quantitation (1 ng/mL) at all sampling times. The results were obtained following the ocular administration of one drop in each eye of 0.5% loteprednol etabonate 8 times daily for 2 days or 4 times daily for 42 days. This study suggests that limited (< 1 ng/mL) systemic absorption occurs with loteprednol etabonate ophthalmic suspension.

Clinical Studies

Post-operative Inflammation: Placebo-controlled clinical studies demonstrated that loteprednol etabonate ophthalmic suspension is effective for the treatment of anterior chamber inflammation as measured by cell and flare.

Uveitis: Controlled clinical studies of patients with uveitis demonstrated that loteprednol etabonate ophthalmic suspension was less effective than prednisolone acetate 1%. Overall, 72% of patients treated with loteprednol etabonate ophthalmic suspension experienced resolution of anterior chamber cell by day 28, compared to 87% of patients treated with 1% prednisolone acetate. The incidence of patients with clinically significant increases in IOP (≥ 10 mmHg) was 1% with loteprednol etabonate ophthalmic suspension and 6% with 1% prednisolone acetate.

Giant Papillary Conjunctivitis: Placebo-controlled clinical studies demonstrated that loteprednol etabonate ophthalmic suspension was effective in reducing the signs and symptoms of giant papillary conjunctivitis after 1 week of treatment and continuing for up to 6 weeks while on treatment.

Seasonal Allergic Conjunctivitis: A placebo-controlled clinical study demonstrated that loteprednol etabonate ophthalmic suspension was effective in reducing the signs and symptoms of allergic conjunctivitis during peak periods of pollen exposure.

Loteprednol etabonate ophthalmic suspension is indicated for the treatment of steroid responsive inflammatory conditions of the palpebral and bulbar conjunctiva, cornea and anterior segment of the globe such as allergic conjunctivitis, acne rosacea, superficial punctate keratitis, herpes zoster keratitis, iritis, cyclitis, selected infective conjunctivitides, when the inherent hazard of steroid use is accepted to obtain an advisable diminution in edema and inflammation.

Loteprednol etabonate ophthalmic suspension is less effective than prednisolone acetate 1% in two 28-day controlled clinical studies in acute anterior uveitis, where 72% of patients treated with loteprednol etabonate ophthalmic suspension experienced resolution of anterior chamber cells, compared to 87% of patients treated with prednisolone acetate 1%. The incidence of patients with clinically significant increases in IOP (≥ 10 mmHg) was 1% with loteprednol etabonate ophthalmic suspension and 6% with prednisolone acetate 1%. Loteprednol etabonate ophthalmic suspension should not be used in patients who require a more potent corticosteroid for this indication.

Loteprednol etabonate ophthalmic suspension is also indicated for the treatment of post-operative inflammation following ocular surgery.

Loteprednol etabonate ophthalmic suspension, as with other ophthalmic corticosteroids, is contraindicated in most 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. Loteprednol etabonate ophthalmic suspension is also contraindicated in individuals with known or suspected hypersensitivity to any of the ingredients of this preparation and to other corticosteroids.

Prolonged use of corticosteroids may result in glaucoma with damage to the optic nerve, defects in visual acuity and fields of vision and in posterior subcapsular cataract formation. Steroids should be used with caution in the presence of glaucoma.

Prolonged use of corticosteroids may suppress the host response and thus increase the hazard of secondary ocular infections. In those diseases causing thinning of the cornea or sclera, perforations have been known to occur with the use of topical steroids. In acute purulent conditions of the eye, steroids may mask infection or enhance existing infection.

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

The use of steroids after cataract surgery may delay healing and increase the incidence of bleb formation.

Reactions associated with ophthalmic steroids include elevated intraocular pressure, which may be associated with optic nerve damage, visual acuity and field defects, posterior subcapsular cataract formation, secondary ocular infection from pathogens including herpes simplex and perforation of the globe where there is thinning of the cornea or sclera.

Ocular adverse reactions occurring in 5% to 15% of patients treated with loteprednol etabonate ophthalmic suspension (0.2% to 0.5%) in clinical studies included abnormal vision/blurring, burning on instillation, chemosis, discharge, dry eyes, epiphora, foreign body sensation, itching, injection and photophobia. Other ocular adverse reactions occurring in less than 5% of patients include conjunctivitis, corneal abnormalities, eyelid erythema, keratoconjunctivitis, ocular irritation/pain/discomfort, papillae and uveitis. Some of these events were similar to the underlying ocular disease being studied.

Non-ocular adverse reactions occurred in less than 15% of patients. These include headache, rhinitis and pharyngitis.

In controlled, randomized studies of individuals treated for 28 days or longer with loteprednol etabonate, the incidence of significant elevation of intraocular pressure (≥ 10 mm Hg) was 2% (15/901) among patients receiving loteprednol etabonate, 7% (11/164) among patients receiving 1% prednisolone acetate and 0.5% (3/583) among patients receiving placebo.

To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals LLC at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

SHAKE VIGOROUSLY BEFORE USING.

Steroid Responsive Disease Treatment: Apply one to two drops of loteprednol etabonate ophthalmic suspension into the conjunctival sac of the affected eye(s) four times daily. During the initial treatment within the first week, the dosing may be increased, up to 1 drop every hour, if necessary. Care should be taken not to discontinue therapy prematurely. If signs and symptoms fail to improve after two days, the patient should be re-evaluated (see PRECAUTIONS).

Post-Operative Inflammation: Apply one to two drops of loteprednol etabonate ophthalmic suspension into the conjunctival sac of the operated eye(s) four times daily beginning 24 hours after surgery and continuing throughout the first 2 weeks of the post-operative period.

Loteprednol Etabonate Ophthalmic Suspension, 0.5% is a sterile, white to off-white uniform suspension essentially free from foreign particles filled in 10 mL or 15 mL low density polyethylene white opaque bottle with low density polyethylene white opaque nozzle and high density polyethylene pink cap.

It is available as follows:

5 mL in 10 mL Bottle (Filled to 1/2 Capacity):                      NDC 60219-1362-1

10 mL in 15 mL Bottle (Filled to 2/3 Capacity):                    NDC 60219-1362-2

15 mL in 15 mL Bottle:                                                          NDC 60219-1362-3

Storage: Store upright between 15° to 25°C (59° to 77°F). DO NOT FREEZE.

KEEP OUT OF THE REACH OF CHILDREN.

Rx only

Manufactured by:

Amneal Pharmaceuticals Pvt. Ltd.

Ahmedabad 382213, INDIA

Distributed by:

Amneal Pharmaceuticals LLC

Bridgewater, NJ 08807

Rev. 05-2025

Version-00

NDC 60219-1362-1

Loteprednol Etabonate Ophthalmic Suspension 0.5%

Rx only

5 mL

Amneal Pharmaceuticals LLC

NDC 60219-1362-2

Loteprednol Etabonate Ophthalmic Suspension 0.5%

Rx only

10 mL

Amneal Pharmaceuticals LLC

NDC 60219-1362-3

Loteprednol Etabonate Ophthalmic Suspension 0.5%

Rx only

15 mL

Amneal Pharmaceuticals LLC