Label: LOTEPREDNOL ETABONATE suspension/ drops

Rx only

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

Loteprednol etabonate is represented by the following structural formula:

Chemical Name:

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

Each mL contains:

ACTIVE: Loteprednol Etabonate 2 mg (0.2%);

INACTIVES: Edetate Disodium, Glycerin, Povidone, Water for Injection and Tyloxapol. Hydrochloric Acid and/or Sodium Hydroxide may be added to adjust the pH to 5.3 - 5.6. 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 A 2inhibitory 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 A 2. 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 vivoand in vitropreclinical 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 Δ 1cortienic 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.

Clinical Studies:

In two double-masked, placebo-controlled six-week environmental studies of 268 patients with seasonal allergic conjunctivitis, loteprednol etabonate, when dosed four times per day was superior to placebo in the treatment of the signs and symptoms of seasonal allergic conjunctivitis. Loteprednol etabonate provided reduction in bulbar conjunctiva! injection and itching, beginning approximately 2 hours after instillation of the first dose and throughout the first 14 days of treatment.

Loteprednol etabonate ophthalmic suspension is indicated for the temporary relief of the signs and symptoms of seasonal allergic conjunctivitis.

Loteprednol etabonate, 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 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.

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%-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 a summation of controlled, randomized studies of individuals treated for 28 days or longer with loteprednol etabonate, the incidence of significant elevation of intraocular pressure (≥10 mmHg) 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. Among the smaller group of patients who were studied with loteprednol etabonate, the incidence of clinically significant increases in IOP (≥10 mm Hg) was 1 % (1/133) with loteprednol etabonate and 1 % (1/135) with placebo.
To report SUSPECTED ADVERSE REACTIONS, contact Sentiss at 1-855-473-6847 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

SHAKE VIGOROUSLY BEFORE USING.

One drop instilled into the affected eye(s) four times daily.

Loteprednol Etabonate Ophthalmic Suspension, 0.2% is supplied in a plastic bottle with a controlled drop tip in the following sizes:

NDC 72485-653-05      5 ml in a 5 ml bottle

NDC 72485-653-10      10 ml in a 10 ml bottle

Storage:Store upright between 15° to 25°C (59° to 77°F). DO NOT FREEZE.
DO NOT USE IF IMPRINTED NECKBAND IS NOT INTACT.
Keep out of reach of children.

Distributed by:
Armas Pharmaceuticals, Inc.
Freehold, NJ 07728 USA

Manufactured by:
Ophtapham AG Riethofstrasse 1,
Hettlingen, 8442,
Switzerland (CHE) for Sentiss

Made in Switzerland                                        Rev. 08/23

NDC 72485-653-05

Loteprednol Etabonate Ophthalmic Suspension, 0.2%

Rx only

5 mL

NDC 72485-653-10

Loteprednol Etabonate Ophthalmic Suspension, 0.2%

Rx only

10 mL