loteprednol etabonate 5 MG/ML Ophthalmic Suspension

INDICATIONS AND USAGE 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.

DOSAGE AND ADMINISTRATION Shake for one to two seconds before using. ( 2 ) Instill one to two drops of INVELTYS into the affected eye twice daily beginning the day after surgery and continuing throughout the first 2 weeks of the post-operative period. ( 2 ) 2.1 Dosage Information Instill one to two drops of INVELTYS into the affected eye twice daily beginning the day after surgery and continuing throughout the first 2 weeks of the post-operative period. 2.2 Administration Instructions Instruct patient to wash hands well before each use. Shake for one to two seconds before using. If the patient is using other eye drops in addition to INVELTYS , advise the patient to wait at least 5 minutes between instillation of INVELTYS and other eye drops. 2.1 Dosage Information Instill one to two drops of INVELTYS into the affected eye twice daily beginning the day after surgery and continuing throughout the first 2 weeks of the post-operative period. 2.2 Administration Instructions Instruct patient to wash hands well before each use. Shake for one to two seconds before using. If the patient is using other eye drops in addition to INVELTYS , advise the patient to wait at least 5 minutes between instillation of INVELTYS and other eye drops.

WARNINGS AND PRECAUTIONS • 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. If this product is used for 10 days or longer, IOP should be monitored even though it may be difficult in children and uncooperative patients. ( 5.1 ) • Cataracts : 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. In those diseases causing thinning of the cornea or sclera, perforations have been known to occur with the use of topical steroids. ( 5.3 ) • 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. ( 5.4 ) • 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). ( 5.5 ) • 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. ( 5.6 ) 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 this product is used for 10 days or longer, IOP should be monitored even though it may be difficult in children and uncooperative patients. 5.2 Cataracts Use of corticosteroids may result in posterior subcapsular cataract formation. 5.3 Delayed Healing The use of steroids after cataract surgery may delay healing and increase the incidence of bleb formation. 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 beyond 14 days 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 re-evaluated. 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 Risk of Contamination Do not touch the eyelid or surrounding areas with the tip of the tube. The cap should remain on the tube when not in use. 5.8 Contact Lens Wear Patients should not wear contact lenses during their course of therapy with LOTEMAX ointment. 5.9 Topical Ophthalmic Use LOTEMAX is not indicated for intraocular administration.

CONTRAINDICATIONS LOTEMAX ointment, 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. LOTEMAX ointment, 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. ( 4 )

CLINICAL PHARMACOLOGY: 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 2 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 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 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 Δ 1 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 prednisolone acetate 1%. 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.