Loteprednol Etabonate Ophthalmic Gel is a corticosteroid indicated for the treatment of post-operative inflammation and pain following ocular surgery.

{ "type": "p", "children": [], "text": "Loteprednol Etabonate Ophthalmic Gel is a corticosteroid indicated for the treatment of post-operative inflammation and pain following ocular surgery." }

Invert closed bottle and shake once to fill tip before instilling drops.

{ "type": "p", "children": [], "text": "Invert closed bottle and shake once to fill tip before instilling drops." }

Apply one to two drops of Loteprednol Etabonate Ophthalmic Gel into the conjunctival sac of the affected eye four times daily beginning the day after surgery and continuing throughout the first 2 weeks of the post-operative period.

{ "type": "p", "children": [], "text": "Apply one to two drops of Loteprednol Etabonate Ophthalmic Gel into the conjunctival sac of the affected eye four times daily beginning the day after surgery and continuing throughout the first 2 weeks of the post-operative period." }

Loteprednol Etabonate Ophthalmic Gel is a sterile preserved ophthalmic gel containing 5 mg of loteprednol etabonate per gram of gel.

{ "type": "p", "children": [], "text": "Loteprednol Etabonate Ophthalmic Gel is a sterile preserved ophthalmic gel containing 5 mg of loteprednol etabonate per gram of gel." }

Loteprednol Etabonate Ophthalmic Gel is contraindicated in most viral diseases of the cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, in mycobacterial infection of the eye and fungal diseases of ocular structures.

{ "type": "p", "children": [], "text": "Loteprednol Etabonate Ophthalmic Gel is contraindicated in most viral diseases of the cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, in mycobacterial infection of the eye and fungal diseases of ocular structures." }

Prolonged use of corticosteroids, including Loteprednol Etabonate Ophthalmic Gel, 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, intraocular pressure should be monitored.

Use of corticosteroids may result in posterior subcapsular cataract formation.

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 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.

Prolonged use of corticosteroids may suppress the host response and thus increase the hazard of secondary ocular infections. In acute purulent conditions of the eye, steroids may mask infection or enhance existing infection.

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).

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 cultures should be taken when appropriate.

Patients should not wear contact lenses during their course of therapy with Loteprednol Etabonate Ophthalmic Gel.

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

{ "type": "p", "children": [], "text": "Adverse reactions associated with ophthalmic steroids include elevated intraocular pressure, which may be associated with infrequent optic nerve damage, visual acuity and field defects, posterior subcapsular cataract formation, delayed wound healing and secondary ocular infection from pathogens including herpes simplex, and perforation of the globe where there is thinning of the cornea or sclera." }

The most common adverse drug reactions reported in the clinical trials (2-5%) were anterior chamber inflammation, eye pain, and foreign body sensation.

{ "type": "p", "children": [], "text": "The most common adverse drug reactions reported in the clinical trials (2-5%) were anterior chamber inflammation, eye pain, and foreign body sensation." }

Risk Summary

There are no adequate and well-controlled studies with loteprednol etabonate in pregnant women.

Loteprednol etabonate produced teratogenicity at clinically relevant doses in the rabbit and rat when administered orally during pregnancy. Loteprednol etabonate produced malformations when administered orally to pregnant rabbits at doses ≥ 1.2 times the recommended human ophthalmic dose (RHOD) and to pregnant rats at doses ≥ 30 times the RHOD. In pregnant rats receiving oral doses of loteprednol etabonate during the period equivalent to the last trimester of pregnancy through lactation in humans, survival of offspring was reduced at doses ≥ 3 times the RHOD. Maternal toxicity was observed in rats at doses ≥ 304 times the RHOD, and a maternal no observed adverse effect level (NOAEL) was established at 30 times the RHOD.

The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk in the U.S. general population of major birth defects is 2 to 4%, and of miscarriage is 15 to 20%, of clinically recognized pregnancies.

Data

Animal Data

Embryofetal studies were conducted in pregnant rabbits administered loteprednol etabonate by oral gavage on gestation days 6 to 18, to target the period of organogenesis. Loteprednol etabonate produced fetal malformations at doses ≥ 0.1 mg/kg (1.2 times the recommended human ophthalmic dose (RHOD) based on body surface area, assuming 100% absorption). Spina bifida (including meningocele) was observed at doses ≥ 0.1 mg/kg, and exencephaly and craniofacial malformations were observed at doses ≥ 0.4 mg/kg (4.9 times the RHOD). At 3 mg/kg (36 times the RHOD), loteprednol etabonate was associated with increased incidences of abnormal left common carotid artery, limb flexures, umbilical hernia, scoliosis, and delayed ossification. Abortion and embryofetal lethality (resorption) occurred at doses ≥ 6 mg/kg (73 times the RHOD). A NOAEL for developmental toxicity was not established in this study. The NOAEL for maternal toxicity in rabbits was 3 mg/kg/day.

Embryofetal studies were conducted in pregnant rats administered loteprednol etabonate by oral gavage on gestation days 6 to 15, to target the period of organogenesis. Loteprednol etabonate produced fetal malformations, including absent innominate artery at doses ≥ 5 mg/kg (30 times the RHOD); and cleft palate, agnathia, cardiovascular defects, umbilical hernia, decreased fetal body weight and decreased skeletal ossification at doses ≥ 50 mg/kg (304 times the RHOD). Embryofetal lethality (resorption) was observed at 100 mg/kg (608 times the RHOD). The NOAEL for developmental toxicity in rats was 0.5 mg/kg (3 times the RHOD). Loteprednol etabonate was maternally toxic (reduced body weight gain) at doses of ≥ 50 mg/kg/day. The NOAEL for maternal toxicity was 5 mg/kg.

A peri-/postnatal study was conducted in rats administered loteprednol etabonate by oral gavage from gestation day 15 (start of fetal period) to postnatal day 21 (the end of lactation period). At doses ≥ 0.5 mg/kg (3 times the clinical dose), reduced survival was observed in live-born offspring. Doses ≥ 5 mg/kg (30 times the RHOD) caused umbilical hernia/incomplete gastrointestinal tract. Doses ≥ 50 mg/kg (304 times the RHOD) produced maternal toxicity (reduced body weight gain, death), decreased number of live-born offspring, decreased birth weight, and delays in postnatal development. A developmental NOAEL was not established in this study. The NOAEL for maternal toxicity was 5 mg/kg.

There are no data on the presence of loteprednol etabonate in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered, along with the mother’s clinical need for LOTEMAX and any potential adverse effects on the breastfed infant from LOTEMAX.

The safety and effectiveness of LOTEMAX have been established in the pediatric population. Use of LOTEMAX in this population is supported by evidence from adequate and well-controlled trials of LOTEMAX in adults with additional data from a safety and efficacy trial in pediatric patients from birth to 11 years of age [see Clinical Studies ( 14)].

No overall differences in safety and effectiveness have been observed between elderly and younger patients.

Loteprednol etabonate is a corticosteroid. Its chemical name is chloromethyl 17α-[(ethoxycarbonyl)oxy]-11β-hydroxy-3-oxoandrosta-1,4-diene-17β-carboxylate. Its molecular formula is C 24H 31ClO 7and its chemical structure is:

{ "type": "p", "children": [], "text": "Loteprednol etabonate is a corticosteroid. Its chemical name is chloromethyl 17α-[(ethoxycarbonyl)oxy]-11β-hydroxy-3-oxoandrosta-1,4-diene-17β-carboxylate. Its molecular formula is C\n \n 24H\n \n 31ClO\n \n 7and its chemical structure is:\n\n " }

Loteprednol Etabonate Ophthalmic Gel 0.5% contains a sterile, topical corticosteroid for ophthalmic use. Loteprednol etabonate is a white to off-white powder.

{ "type": "p", "children": [], "text": "Loteprednol Etabonate Ophthalmic Gel 0.5% contains a sterile, topical corticosteroid for ophthalmic use. Loteprednol etabonate is a white to off-white powder." }

Each gram contains:

{ "type": "p", "children": [], "text": "Each gram contains:" }

{ "type": "ul", "children": [ "Active: loteprednol etabonate 5 mg (0.5%)", "Inactives: boric acid, edetate disodium dihydrate, glycerin, polycarbophil, propylene glycol, sodium chloride, tyloxapol, water for injection, and sodium hydroxide to adjust to a pH of between 6 and 7", "Preservative: benzalkonium chloride 0.003%" ], "text": "" }

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. While glucocorticoids are known to bind to and activate the glucocorticoid receptor, the molecular mechanisms involved in glucocorticoid/glucocorticoid receptor‑dependent modulation of inflammation are not clearly established. However, corticosteroids are thought to inhibit prostaglandin production through several independent mechanisms.

Loteprednol etabonate is lipid soluble and can penetrate 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 the inactive carboxylic acid metabolites, PJ-91 and PJ-90. The systemic exposure to loteprednol etabonate following ocular administration of Loteprednol Etabonate Ophthalmic Gel has not been studied in humans.

Long-term animal studies have not been conducted to evaluate the carcinogenic potential of loteprednol etabonate. Loteprednol etabonate was not genotoxic in vitroin the Ames test, the mouse lymphoma tk assay, or in a chromosome aberration test in human lymphocytes, or in vivoin the single dose mouse micronucleus assay.

Treatment of female and male rats with doses ≥ 25 mg/kg/day of loteprednol etabonate (152 times the RHOD based on body surface area, assuming 100% absorption) prior to and during mating caused preimplantation loss and decreased the number of live fetuses/live births. The NOAEL for fertility in rats was 5 mg/kg/day (30 times the RHOD).

Adult Studies

{ "type": "p", "children": [], "text": "\nAdult Studies\n" }

In two randomized, multicenter, double-masked, parallel-group, vehicle-controlled studies in 813 subjects with post-operative inflammation, Loteprednol Etabonate Ophthalmic Gel was more effective compared to its vehicle in resolving anterior chamber inflammation and pain following cataract surgery. Primary endpoints were complete resolution of anterior chamber cells (cell count of 0) and no pain at post-operative day 8.

{ "type": "p", "children": [], "text": "In two randomized, multicenter, double-masked, parallel-group, vehicle-controlled studies in 813 subjects with post-operative inflammation, Loteprednol Etabonate Ophthalmic Gel was more effective compared to its vehicle in resolving anterior chamber inflammation and pain following cataract surgery. Primary endpoints were complete resolution of anterior chamber cells (cell count of 0) and no pain at post-operative day 8." }

In these studies, Loteprednol Etabonate Ophthalmic Gel had a statistically significant higher incidence of subjects with complete clearing of anterior chamber cells (31% vs. 14-16%) and were pain-free at post-operative day 8 (73-76% vs. 42-46%).

{ "type": "p", "children": [], "text": "In these studies, Loteprednol Etabonate Ophthalmic Gel had a statistically significant higher incidence of subjects with complete clearing of anterior chamber cells (31% vs. 14-16%) and were pain-free at post-operative day 8 (73-76% vs. 42-46%)." }

Pediatric Study

{ "type": "p", "children": [], "text": "\nPediatric Study\n" }

The safety and effectiveness of Loteprednol Etabonate Ophthalmic Gel were evaluated in a pediatric study of patients from birth to less than 11 years of age (mean age of 3 years) undergoing cataract surgery. Patients were randomized to receive either Loteprednol Etabonate Ophthalmic Gel (54 patients) or prednisolone acetate ophthalmic suspension 1% (53 patients) four times daily for 14 days. At Day 14, the percentages of patients with complete clearing of anterior chamber inflammation were 57% in the Loteprednol Etabonate Ophthalmic Gel group and 63% in the prednisolone group.

{ "type": "p", "children": [], "text": "The safety and effectiveness of Loteprednol Etabonate Ophthalmic Gel were evaluated in a pediatric study of patients from birth to less than 11 years of age (mean age of 3 years) undergoing cataract surgery. Patients were randomized to receive either Loteprednol Etabonate Ophthalmic Gel (54 patients) or prednisolone acetate ophthalmic suspension 1% (53 patients) four times daily for 14 days. At Day 14, the percentages of patients with complete clearing of anterior chamber inflammation were 57% in the Loteprednol Etabonate Ophthalmic Gel group and 63% in the prednisolone group." }

Loteprednol Etabonate Ophthalmic Gel 0.5% is a sterile ophthalmic gel supplied in a white low density polyethylene plastic bottle with a white controlled drop tip and a pink polypropylene cap in the following size:

{ "type": "p", "children": [], "text": "Loteprednol Etabonate Ophthalmic Gel 0.5% is a sterile ophthalmic gel supplied in a white low density polyethylene plastic bottle with a white controlled drop tip and a pink polypropylene cap in the following size:" }

{ "type": "ul", "children": [ "NDC 82260-508-01 5 g in a 10 mL bottle" ], "text": "" }

Storage:Store upright at 15ºC to 25ºC (59ºF to 77ºF).

{ "type": "p", "children": [], "text": "\nStorage:Store upright at 15ºC to 25ºC (59ºF to 77ºF).\n\n " }

Administration

{ "type": "p", "children": [], "text": "\nAdministration\n" }

Invert closed bottle and shake once to fill tip before instilling drops.

{ "type": "p", "children": [], "text": "Invert closed bottle and shake once to fill tip before instilling drops." }

Risk of Contamination

{ "type": "p", "children": [], "text": "\nRisk of Contamination\n" }

Advise patients not to allow the dropper tip to touch any surface, as this may contaminate the gel.

{ "type": "p", "children": [], "text": "Advise patients not to allow the dropper tip to touch any surface, as this may contaminate the gel." }

Contact Lens Wear

{ "type": "p", "children": [], "text": "\nContact Lens Wear\n" }

Advise patients not to wear contact lenses when using Loteprednol Etabonate Ophthalmic Gel.

{ "type": "p", "children": [], "text": "Advise patients not to wear contact lenses when using Loteprednol Etabonate Ophthalmic Gel." }

Risk of Secondary Infection

{ "type": "p", "children": [], "text": "\nRisk of Secondary Infection\n" }

Advise the patient to consult a physician if pain develops, redness, itching or inflammation becomes aggravated.

{ "type": "p", "children": [], "text": "Advise the patient to consult a physician if pain develops, redness, itching or inflammation becomes aggravated." }

Distributed by: Bausch & Lomb Americas Inc. Bridgewater, NJ 08807 USA Manufactured by: Bausch & Lomb Incorporated Tampa, FL 33637 USA

{ "type": "p", "children": [], "text": "\nDistributed by:\n Bausch & Lomb Americas Inc. \n Bridgewater, NJ 08807 USA \n \n\nManufactured by:\n Bausch & Lomb Incorporated \n Tampa, FL 33637 USA \n \n" }

© 2023 Bausch & Lomb Incorporated or its affiliates

{ "type": "p", "children": [], "text": "© 2023 Bausch & Lomb Incorporated or its affiliates \n \n" }

9590103 Folded 9590003 Flat

{ "type": "p", "children": [], "text": "9590103 Folded \n 9590003 Flat\n " }

NDC82260-508-01

{ "type": "p", "children": [], "text": "\nNDC82260-508-01\n\n " }

Loteprednol Etabonate Ophthalmic Gel 0.5% (Sterile) FOR OPHTHALMIC USE ONLY

{ "type": "p", "children": [], "text": "\nLoteprednol\n\nEtabonate\n\nOphthalmic Gel\n\n0.5%\n (Sterile) \n \n\nFOR OPHTHALMIC USE ONLY\n" }

EYE IMAGE

{ "type": "p", "children": [], "text": "\nEYE IMAGE\n" }

Rx only 5 g

{ "type": "p", "children": [], "text": "\nRx only 5 g\n" }

BAUSCH + LOMB

{ "type": "p", "children": [], "text": "\nBAUSCH + LOMB\n" }

9589803

{ "type": "p", "children": [], "text": "9589803" }

EYSUVIS is a corticosteroid indicated for the short-term (up to two weeks) treatment of the signs and symptoms of dry eye disease.

{ "type": "p", "children": [], "text": "EYSUVIS is a corticosteroid indicated for the short-term (up to two weeks) treatment of the signs and symptoms of dry eye disease." }

Instill one to two drops of EYSUVIS into each eye four times daily for up to two weeks. This product should only be renewed after examination under magnification such as a slit lamp and evaluation of the intraocular pressure. [see Warnings and Precautions (5.1) and (5.2)].

Instruct patient to wash hands well before each use. Shake for two to three seconds before using.

If the patient is using other eye drops in addition to EYSUVIS, advise the patient to wait at least 5 minutes between instillation of EYSUVIS and other eye drops.

If a dose is missed, take the missed dose when remembered.

Ophthalmic suspension containing 2.5 mg/mL of loteprednol etabonate.

{ "type": "p", "children": [], "text": "Ophthalmic suspension containing 2.5 mg/mL of loteprednol etabonate." }

EYSUVIS, 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.

{ "type": "p", "children": [], "text": "EYSUVIS, 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." }

Topical corticosteroids have been known to delay healing and cause corneal and scleral thinning. Use of topical corticosteroids in the presence of thin corneal or scleral tissue may lead to perforation. The initial prescription and each 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.

Prolonged use of corticosteroids may result in glaucoma with damage to the optic nerve, as well as defects in visual acuity and fields of vision. Corticosteroids should be used with caution in the presence of glaucoma. Renewal of the medication order should be made by a physician only after examination of the patient and evaluation of the IOP.

Use of corticosteroids may result in posterior subcapsular cataract formation.

Use of corticosteroids may suppress the host response and thus increase the hazard of secondary ocular infections. In acute purulent conditions of the eye, corticosteroids may mask infection or enhance existing infection.

Use of 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).

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 cultures should be taken when appropriate.

Do not to allow the dropper tip to touch any surface, as this may contaminate the suspension.

The preservative in EYSUVIS may be absorbed by soft contact lenses. Contact lenses should be removed prior to instillation of EYSUVIS and may be reinserted 15 minutes following administration.

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.

The most common adverse reaction observed in clinical trials with EYSUVIS was instillation site pain, which was reported in 5% of patients.

Risk Summary

There are no adequate and well controlled studies with loteprednol etabonate in pregnant women. Loteprednol etabonate produced teratogenicity at clinically relevant doses in the rabbit and rat when administered orally during pregnancy. Loteprednol etabonate produced malformations when administered orally to pregnant rabbits at doses 1.4 times the recommended human ophthalmic dose (RHOD) and to pregnant rats at doses 34 times the RHOD. In pregnant rats receiving oral doses of loteprednol etabonate during the period equivalent to the last trimester of pregnancy through lactation in humans, survival of offspring was reduced at doses 3.4 times the RHOD. Maternal toxicity was observed in rats at doses 347 times the RHOD, and a maternal no observed adverse effect level (NOAEL) was established at 34 times the RHOD.

The background risk in the U.S. general population of major birth defects is 2 to 4%, and of miscarriage is 15 to 20%, of clinically recognized pregnancies.

Data

Animal Data

Embryofetal studies were conducted in pregnant rabbits administered loteprednol etabonate by oral gavage on gestation days 6 to 18, to target the period of organogenesis. Loteprednol etabonate produced fetal malformations at 0.1 mg/kg (1.4 times the recommended human ophthalmic dose (RHOD) based on body surface area, assuming 100% absorption). Spina bifida (including meningocele) was observed at 0.1 mg/kg, and exencephaly and craniofacial malformations were observed at 0.4 mg/kg (5.6 times the RHOD). At 3 mg/kg (41 times the RHOD), loteprednol etabonate was associated with increased incidences of abnormal left common carotid artery, limb flexures, umbilical hernia, scoliosis, and delayed ossification. Abortion and embryofetal lethality (resorption) occurred at 6 mg/kg (83 times the RHOD). A NOAEL for developmental toxicity was not established in this study. The NOAEL for maternal toxicity in rabbits was 3 mg/kg/day.

Embryofetal studies were conducted in pregnant rats administered loteprednol etabonate by oral gavage on gestation days 6 to 15, to target the period of organogenesis. Loteprednol etabonate produced fetal malformations, including absent innominate artery at 5 mg/kg (34 times the RHOD); and cleft palate, agnathia, cardiovascular defects, umbilical hernia, decreased fetal body weight and decreased skeletal ossification at 50 mg/kg (347 times the RHOD). Embryofetal lethality (resorption) was observed at 100 mg/kg (695 times the RHOD). The NOAEL for developmental toxicity in rats was 0.5 mg/kg (3.4 times the RHOD). Loteprednol etabonate was maternally toxic (reduced body weight gain) at 50 mg/kg/day. The NOAEL for maternal toxicity was 5 mg/kg.

A peri-/postnatal study was conducted in rats administered loteprednol etabonate by oral gavage from gestation day 15 (start of fetal period) to postnatal day 21 (the end of lactation period). At 0.5 mg/kg (3.4 times the clinical dose), reduced survival was observed in live-born offspring. Doses ≥ 5 mg/kg (34 times the RHOD) caused umbilical hernia/incomplete gastrointestinal tract. Doses ≥ 50 mg/kg (347 times the RHOD) produced maternal toxicity (reduced body weight gain, death), decreased number of live-born offspring, decreased birth weight, and delays in postnatal development. A developmental NOAEL was not established in this study. The NOAEL for maternal toxicity was 5 mg/kg.

There are no data on the presence of loteprednol etabonate in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered, along with the mother's clinical need for EYSUVIS and any potential adverse effects on the breastfed infant from EYSUVIS.

Safety and effectiveness in pediatric patients have not been established.

No overall differences in safety and effectiveness have been observed between elderly and younger adult patients.

Loteprednol etabonate is a corticosteroid. Its chemical name is chloromethyl 17α-[(ethoxycarbonyl)oxy]-11β-hydroxy-3-oxoandrosta-1,4-diene-17β-carboxylate. Its molecular formula is C24H31ClO7 and its chemical structure is:

{ "type": "p", "children": [], "text": "Loteprednol etabonate is a corticosteroid. Its chemical name is chloromethyl 17α-[(ethoxycarbonyl)oxy]-11β-hydroxy-3-oxoandrosta-1,4-diene-17β-carboxylate. Its molecular formula is C24H31ClO7 and its chemical structure is:" }

C24H31ClO7 Mol. Wt. 467.0

{ "type": "p", "children": [], "text": "\nC24H31ClO7\nMol. Wt. 467.0" }

EYSUVIS (loteprednol etabonate ophthalmic suspension) 0.25% contains a sterile, topical anti-inflammatory corticosteroid for ophthalmic use. Each mL contains:

{ "type": "p", "children": [], "text": "EYSUVIS (loteprednol etabonate ophthalmic suspension) 0.25% contains a sterile, topical anti-inflammatory corticosteroid for ophthalmic use. Each mL contains:" }

{ "type": "ul", "children": [ "ACTIVE: loteprednol etabonate 2.5 mg (0.25%)", "INACTIVES: glycerin, sodium citrate dihydrate, sodium chloride, Poloxamer 407, edetate disodium dihydrate, citric acid, and water for injection.", "PRESERVATIVE: benzalkonium chloride 0.01%" ], "text": "" }

Corticosteroids inhibit the inflammatory response to a variety of inciting agents and delay or slow healing. Corticosteroids inhibit the edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and scar formation associated with inflammation. While glucocorticoids are known to bind to and activate the glucocorticoid receptor, the molecular mechanisms involved in glucocorticoid/glucocorticoid receptor-dependent modulation of inflammation are not clearly established. However, corticosteroids are thought to inhibit prostaglandin production.

Loteprednol etabonate is lipid soluble and can penetrate 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, PJ-91 and PJ-90.

Following bilateral topical ocular dosing of two drops of EYSUVIS four times a day for 14 days in 20 healthy adult subjects, the plasma concentrations of loteprednol etabonate were below the limit of quantitation (1 ng/mL) at all timepoints.

Long-term animal studies have not been conducted to evaluate the carcinogenic potential of loteprednol etabonate. Loteprednol etabonate was not genotoxic in vitro in the Ames test, the mouse lymphoma thymidine kinase (tk) assay, in a chromosome aberration test in human lymphocytes, or in vivo in the single dose mouse micronucleus assay. Treatment of male and female rats with 25 mg/kg/day of loteprednol etabonate (174 times the RHOD based on body surface area, assuming 100% absorption) prior to and during mating caused pre-implantation loss and decreased the number of live fetuses/live births. The NOAEL for fertility in rats was 5 mg/kg/day (34 times the RHOD).

The safety and efficacy of EYSUVIS for the treatment of dry eye disease was assessed in approximately 2900 patients with dry eye disease. Patients received either EYSUVIS or vehicle (1:1 ratio) four times a day for 2 weeks in 4 multi-centered, randomized, double-masked, placebo-controlled trials. The use of artificial tears was not allowed during the trials.

{ "type": "p", "children": [], "text": "The safety and efficacy of EYSUVIS for the treatment of dry eye disease was assessed in approximately 2900 patients with dry eye disease. Patients received either EYSUVIS or vehicle (1:1 ratio) four times a day for 2 weeks in 4 multi-centered, randomized, double-masked, placebo-controlled trials. The use of artificial tears was not allowed during the trials. " }

Effects on Symptoms of Dry Eye Disease

{ "type": "p", "children": [], "text": "\nEffects on Symptoms of Dry Eye Disease\n" }

Ocular discomfort severity (ODS) was rated by patients daily over the course of the trial using a visual analog scale (0 = very mild, 100 = very severe). A larger reduction in ocular discomfort severity favoring EYSUVIS was observed at Day 15 in the patient population (see Figure 1).

{ "type": "p", "children": [], "text": "Ocular discomfort severity (ODS) was rated by patients daily over the course of the trial using a visual analog scale (0 = very mild, 100 = very severe). A larger reduction in ocular discomfort severity favoring EYSUVIS was observed at Day 15 in the patient population (see Figure 1)." }

Figure 1: Mean Change (SD) from Baseline and Treatment Difference (EYSUVIS- Vehicle) in Ocular Discomfort Severity Score in Patients with Dry Eye Disease

{ "type": "p", "children": [], "text": "\nFigure 1: \tMean Change (SD) from Baseline and Treatment Difference (EYSUVIS- Vehicle) in Ocular Discomfort Severity Score in Patients with Dry Eye Disease\n" }

Treatment differences between the EYSUVIS and vehicle groups are displayed for each study, based on least square means and 2-sided confidence intervals for the change from baseline.

{ "type": "p", "children": [], "text": "Treatment differences between the EYSUVIS and vehicle groups are displayed for each study, based on least square means and 2-sided confidence intervals for the change from baseline." }

Effects on Signs of Dry Eye Disease

{ "type": "p", "children": [], "text": "\nEffects on Signs of Dry Eye Disease\n" }

Conjunctival hyperemia was graded using the Cornea and Contact Lens Research Unit (CCLRU) grading scale (0 = none; 1 = very slight; 2 = slight; 3 = moderate; 4 = severe). A larger reduction in hyperemia favoring EYSUVIS was observed at Day 15 in all four trials (Figure 2).

{ "type": "p", "children": [], "text": "Conjunctival hyperemia was graded using the Cornea and Contact Lens Research Unit (CCLRU) grading scale (0 = none; 1 = very slight; 2 = slight; 3 = moderate; 4 = severe). A larger reduction in hyperemia favoring EYSUVIS was observed at Day 15 in all four trials (Figure 2)." }

Figure 2: Mean Change (SD) from Baseline and Treatment Difference (EYSUVIS- Vehicle) in Conjunctival Hyperemia in Patients with Dry Eye Disease

{ "type": "p", "children": [], "text": "\nFigure 2: Mean Change (SD) from Baseline and Treatment Difference (EYSUVIS- Vehicle) in Conjunctival Hyperemia in Patients with Dry Eye Disease\n" }

Treatment differences between the EYSUVIS and vehicle groups are displayed for each study, based on least square means and 2-sided confidence intervals for the change from baseline.

{ "type": "p", "children": [], "text": "Treatment differences between the EYSUVIS and vehicle groups are displayed for each study, based on least square means and 2-sided confidence intervals for the change from baseline." }

EYSUVIS (loteprednol etabonate ophthalmic suspension) 0.25% is a sterile ophthalmic suspension. It is supplied in a white, low-density polyethylene dropper bottle with a linear low-density polyethylene tip, a pink high-density polyethylene cap, and a white low-density polyethylene tamper-evident overcap in the following size:

{ "type": "p", "children": [], "text": "EYSUVIS (loteprednol etabonate ophthalmic suspension) 0.25% is a sterile ophthalmic suspension. It is supplied in a white, low-density polyethylene dropper bottle with a linear low-density polyethylene tip, a pink high-density polyethylene cap, and a white low-density polyethylene tamper-evident overcap in the following size:" }

8.3 mL in a 10 mL bottle (NDC 71571-333-83)

{ "type": "p", "children": [], "text": "8.3 mL in a 10 mL bottle (NDC 71571-333-83)" }

Storage and Handling

{ "type": "p", "children": [], "text": "\nStorage and Handling\n" }

Do not use if tamper-evident overcap seal is not intact.

{ "type": "p", "children": [], "text": "Do not use if tamper-evident overcap seal is not intact." }

The white tamper-evident overcap can be thrown away. Retain the pink cap and keep the bottle tightly closed when not in use.

{ "type": "p", "children": [], "text": "The white tamper-evident overcap can be thrown away. Retain the pink cap and keep the bottle tightly closed when not in use." }

Store upright at 15°C to 25°C (59°F to 77°F). Do not freeze. After opening, EYSUVIS can be used until the expiration date on the bottle.

{ "type": "p", "children": [], "text": "Store upright at 15°C to 25°C (59°F to 77°F). Do not freeze. After opening, EYSUVIS can be used until the expiration date on the bottle." }

Advise the patient to read the FDA-approved patient labeling (Instructions for Use).

{ "type": "p", "children": [], "text": "Advise the patient to read the FDA-approved patient labeling (Instructions for Use)." }

Administration

{ "type": "p", "children": [], "text": "\nAdministration\n" }

Instruct the patient to shake the bottle for two to three seconds before using. If a dose is missed, take the missed dose when remembered.

{ "type": "p", "children": [], "text": "Instruct the patient to shake the bottle for two to three seconds before using. If a dose is missed, take the missed dose when remembered." }

Corneal Status and Intraocular Pressure Monitoring

{ "type": "p", "children": [], "text": "\nCorneal Status and Intraocular Pressure Monitoring\n" }

The initial prescription and each renewal of the medication order should be made only after evaluation of the intraocular pressure and examination of the patient with the aid of magnification, such as slit-lamp biomicroscopy.

{ "type": "p", "children": [], "text": "The initial prescription and each renewal of the medication order should be made only after evaluation of the intraocular pressure and examination of the patient with the aid of magnification, such as slit-lamp biomicroscopy." }

Risk of Contamination

{ "type": "p", "children": [], "text": "\nRisk of Contamination\n" }

Advise patients to wash their hands well before each use. Advise patients not to allow the dropper tip to touch any surface, as this may contaminate the suspension.

{ "type": "p", "children": [], "text": "Advise patients to wash their hands well before each use. Advise patients not to allow the dropper tip to touch any surface, as this may contaminate the suspension." }

Risk of Secondary Infection

{ "type": "p", "children": [], "text": "\nRisk of Secondary Infection\n" }

Advise the patient to consult a physician, if pain develops, redness, itching, or inflammation becomes aggravated.

{ "type": "p", "children": [], "text": "Advise the patient to consult a physician, if pain develops, redness, itching, or inflammation becomes aggravated." }

Contact Lens Wear

{ "type": "p", "children": [], "text": "\nContact Lens Wear\n" }

Advise patients that the preservative in EYSUVIS may be absorbed by soft contact lenses. Contact lenses should be removed prior to instillation of EYSUVIS and may be reinserted 15 minutes following administration.

{ "type": "p", "children": [], "text": "Advise patients that the preservative in EYSUVIS may be absorbed by soft contact lenses. Contact lenses should be removed prior to instillation of EYSUVIS and may be reinserted 15 minutes following administration." }

Manufactured for: Alcon Laboratories, Inc. Fort Worth, Texas 76134 USA Part # 70016481-00 U.S. Pat.: www.alconpatents.com © 2023 Alcon Inc. Alcon

{ "type": "p", "children": [], "text": "Manufactured for: Alcon Laboratories, Inc. Fort Worth, Texas 76134 USA\nPart # 70016481-00\nU.S. Pat.: www.alconpatents.com\n\n© 2023 Alcon Inc.\n\nAlcon\n" }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <tbody class="Headless"> <tr> <td align="center"> <p class="First"> <span class="Bold">INSTRUCTIONS FOR USE</span> </p> <br/> <br/> <p> <span class="Bold">EYSUVIS [eye-SU-vis] <br/> <br/>(loteprednol etabonate ophthalmic suspension) 0.25%<br/> <br/>for topical ophthalmic use</span> </p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<tbody class=\"Headless\">\n<tr>\n<td align=\"center\">\n<p class=\"First\">\n<span class=\"Bold\">INSTRUCTIONS FOR USE</span>\n</p>\n<br/>\n<br/>\n<p>\n<span class=\"Bold\">EYSUVIS [eye-SU-vis] <br/>\n<br/>(loteprednol etabonate ophthalmic suspension) 0.25%<br/>\n<br/>for topical ophthalmic use</span>\n</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

This Instructions for Use contains information on how to properly administer EYSUVIS.

{ "type": "p", "children": [], "text": "This Instructions for Use contains information on how to properly administer EYSUVIS." }

Important Information You Need to Know Before Using EYSUVIS

{ "type": "p", "children": [], "text": "\nImportant Information You Need to Know Before Using EYSUVIS\n" }

{ "type": "ul", "children": [ "EYSUVIS is for use in the eye.", "Wash your hands before using EYSUVIS.", "\nDo not use if the tamper-evident seal is not intact.", "\nDo not let the EYSUVIS dropper tip touch your eye, fingers, or any other surfaces to avoid contamination or injury to your eye.", "Use EYSUVIS exactly as your doctor tells you to.", "If you are using EYSUVIS with other eye (ophthalmic) medicines, you should wait at least 5 minutes between using EYSUVIS and the other medicine.", "If you wear contact lenses, remove them before using EYSUVIS.", "Put the pink cap back on EYSUVIS after each use." ], "text": "" }

Before you use EYSUVIS for the first time:

{ "type": "p", "children": [], "text": "\nBefore you use EYSUVIS for the first time:\n" }

There are two caps on your bottle of EYSUVIS. Hold the bottle firmly by its neck. Remove the white cap by twisting it clockwise (See Figure A). Throw away the white cap. EYSUVIS is now ready to use.

{ "type": "p", "children": [], "text": "There are two caps on your bottle of EYSUVIS. Hold the bottle firmly by its neck. Remove the white cap by twisting it clockwise (See Figure A). Throw away the white cap. EYSUVIS is now ready to use." }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <tbody class="Headless"> <tr> <td align="center"> <p class="First"> <a name="figurea"></a><img alt="Figure A" src="/dailymed/image.cfm?name=eysuvis-04.jpg&amp;setid=a2169d82-4275-4ab6-a1c3-c274080b815c"/></p> <p> <span class="Bold">Figure A</span> </p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<tbody class=\"Headless\">\n<tr>\n<td align=\"center\">\n<p class=\"First\">\n<a name=\"figurea\"></a><img alt=\"Figure A\" src=\"/dailymed/image.cfm?name=eysuvis-04.jpg&amp;setid=a2169d82-4275-4ab6-a1c3-c274080b815c\"/></p>\n<p>\n<span class=\"Bold\">Figure A</span>\n</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

Follow Steps 1 to 6 each time you use EYSUVIS.

{ "type": "p", "children": [], "text": "\nFollow Steps 1 to 6 each time you use EYSUVIS.\n" }

{ "type": "", "children": [], "text": "" }

If you use contact lenses, wait for 15 minutes before placing them back in.

{ "type": "p", "children": [], "text": "If you use contact lenses, wait for 15 minutes before placing them back in." }

How should I store EYSUVIS?

{ "type": "p", "children": [], "text": "\nHow should I store EYSUVIS?\n" }

{ "type": "ul", "children": [ "Store EYSUVIS upright between 59ºF to 77ºF (15ºC to 25ºC).", "\nDo not freeze.", "After opening, EYSUVIS can be used until the expiration date (EXP) on the bottle. The expiration date can be found on the lower right side of the label on the bottle." ], "text": "" }

Keep EYSUVIS and all medicines out of the reach of children.

{ "type": "p", "children": [], "text": "\nKeep EYSUVIS and all medicines out of the reach of children.\n" }

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

{ "type": "p", "children": [], "text": "This Instructions for Use has been approved by the U.S. Food and Drug Administration." }

Manufactured for:Alcon Laboratories, Inc.Fort Worth, Texas 76134 USA Approved 11/2023

{ "type": "p", "children": [], "text": "Manufactured for:Alcon Laboratories, Inc.Fort Worth, Texas 76134 USA\nApproved 11/2023\n\n" }

NDC 71571-333-83    Rx Only EYsuVIS® (loteprednol etabonateophthalmic suspension) 0.25% Sterile 8.3 mL FOR TOPICAL APPLICATIONIN THE EYE. Dosage: See Prescribing Information. Manufactured for: Alcon Laboratories, Inc.Fort Worth, TX 76134 USA

{ "type": "p", "children": [], "text": "NDC 71571-333-83    Rx Only\n\n\nEYsuVIS®\n(loteprednol etabonateophthalmic suspension) 0.25%\nSterile\n\n8.3 mL\n\n\nFOR TOPICAL APPLICATIONIN THE EYE.\n\n\nDosage: See Prescribing Information.\nManufactured for: Alcon Laboratories, Inc.Fort Worth, TX 76134 USA\n\n" }

NDC 71571-333-83    Rx Only EYsuVIS® (loteprednol etabonateophthalmic suspension) 0.25% FOR TOPICAL APPLICATIONIN THE EYE. Sterile 8.3 mL Alcon Dosage: See Prescribing Information. SHAKE FOR 2 TO 3 SECONDS Storage: Store upright at15°C to 25°C (59°F to 77°F). Do not freeze. DO NOT USE IFTAMPER-EVIDENTOVERCAP IS NOT INTACT 300064649-1123 Store Upright Manufactured for: Alcon Laboratories, Inc.Fort Worth, TX 76134 USA

{ "type": "p", "children": [], "text": "NDC 71571-333-83    Rx Only\n\n\nEYsuVIS®\n(loteprednol etabonateophthalmic suspension) 0.25%\n\nFOR TOPICAL APPLICATIONIN THE EYE.\n\nSterile\n8.3 mL\n\n\nAlcon\n\n\nDosage: See Prescribing Information.\n\nSHAKE FOR 2 TO 3 SECONDS\n\n\nStorage: Store upright at15°C to 25°C (59°F to 77°F).\n\nDo not freeze.\n\n\nDO NOT USE IFTAMPER-EVIDENTOVERCAP IS NOT INTACT\n\n300064649-1123\n\nStore Upright\n\nManufactured for: Alcon Laboratories, Inc.Fort Worth, TX 76134 USA\n\n" }

LOTEMAX® (loteprednol etabonate ophthalmic ointment) 0.5% ointment is a corticosteroid indicated for the treatment of post-operative inflammation and pain following ocular surgery.

{ "type": "p", "children": [], "text": "LOTEMAX® (loteprednol etabonate ophthalmic ointment) 0.5% ointment is a corticosteroid indicated for the treatment of post-operative inflammation and pain following ocular surgery. " }

Wash hands prior to using LOTEMAX ointment.

{ "type": "p", "children": [], "text": "Wash hands prior to using LOTEMAX ointment." }

Apply a small amount (approximately ½ inch ribbon) into the conjunctival sac(s) four times daily beginning 24 hours after surgery and continuing throughout the first 2 weeks of the post-operative period.

{ "type": "p", "children": [], "text": "Apply a small amount (approximately ½ inch ribbon) into the conjunctival sac(s) four times daily beginning 24 hours after surgery and continuing throughout the first 2 weeks of the post-operative period." }

Ophthalmic ointment containing loteprednol etabonate 0.5%.

{ "type": "p", "children": [], "text": "Ophthalmic ointment containing loteprednol etabonate 0.5%." }

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.

{ "type": "p", "children": [], "text": "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. " }

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.

Use of corticosteroids may result in posterior subcapsular cataract formation.

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.

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.

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).

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.

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.

Patients should not wear contact lenses during their course of therapy with LOTEMAX ointment.

LOTEMAX is not indicated for intraocular administration.

Adverse 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.

{ "type": "p", "children": [], "text": "Adverse 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." }

The most common ocular adverse event reported at approximately 25% in subjects in clinical studies with LOTEMAX ointment was anterior chamber inflammation. Other common adverse events, with an incidence of 4-5%, were conjunctival hyperemia, corneal edema, and eye pain. Many of these events may have been the consequence of the surgical procedure. The only non-ocular adverse event occurring at ≥ 1% was headache (1.5%).

{ "type": "p", "children": [], "text": "The most common ocular adverse event reported at approximately 25% in subjects in clinical studies with LOTEMAX ointment was anterior chamber inflammation. Other common adverse events, with an incidence of 4-5%, were conjunctival hyperemia, corneal edema, and eye pain. Many of these events may have been the consequence of the surgical procedure. The only non-ocular adverse event occurring at ≥ 1% was headache (1.5%). " }

Risk Summary

There are no adequate and well-controlled studies with loteprednol etabonate in pregnant women.

Loteprednol etabonate produced teratogenicity at clinically relevant doses in the rabbit and rat when administered orally during pregnancy. Loteprednol etabonate produced malformations when administered orally to pregnant rabbits at doses ≥ 1.6 times the recommended human ophthalmic dose (RHOD) and to pregnant rats at doses ≥ 41 times the RHOD. In pregnant rats receiving oral doses of loteprednol etabonate during the period equivalent to the last trimester of pregnancy through lactation in humans, survival of offspring was reduced at doses ≥ 4 times the RHOD. Maternal toxicity was observed in rats at doses ≥ 405 times the RHOD, and a maternal no observed adverse effect level (NOAEL) was established at 41 times the RHOD.

The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk in the U.S. general population of major birth defects is 2 to 4%, and of miscarriage is 15 to 20%, of clinically recognized pregnancies.

Data

Animal Data

Embryofetal studies were conducted in pregnant rabbits administered loteprednol etabonate by oral gavage on gestation Days 6 to 18, to target the period of organogenesis. Loteprednol etabonate produced fetal malformations at doses ≥ 0.1 mg/kg (1.6 times the recommended human ophthalmic dose (RHOD) based on body surface area, assuming 100% absorption). Spina bifida (including meningocele) was observed at doses ≥ 0.1 mg/kg, and exencephaly and craniofacial malformations were observed at doses ≥ 0.4 mg/kg (6.5 times the RHOD). At 3 mg/kg (49 times the RHOD), loteprednol etabonate was associated with increased incidences of abnormal left common carotid artery, limb flexures, umbilical hernia, scoliosis, and delayed ossification. Abortion and embryofetal lethality (resorption) occurred at doses ≥ 6 mg/kg (97 times the RHOD). A NOAEL for developmental toxicity was not established in this study. The NOAEL for maternal toxicity in rabbits was 3 mg/kg/day.

Embryofetal studies were conducted in pregnant rats administered loteprednol etabonate by oral gavage on gestation Days 6 to 15, to target the period of organogenesis. Loteprednol etabonate produced fetal malformations, including absent innominate artery at doses ≥ 5 mg/kg (41 times the RHOD); and cleft palate, agnathia, cardiovascular defects, umbilical hernia, decreased fetal body weight and decreased skeletal ossification at doses ≥ 50 mg/kg (410 times the RHOD). Embryofetal lethality (resorption) was observed at 100 mg/kg (811 times the RHOD). The NOAEL for developmental toxicity in rats was 0.5 mg/kg (4 times the RHOD). Loteprednol etabonate was maternally toxic (reduced body weight gain) at doses of ≥ 50 mg/kg/day. The NOAEL for maternal toxicity was 5 mg/kg.

A peri-/postnatal study was conducted in rats administered loteprednol etabonate by oral gavage from gestation Day 15 (start of fetal period) to postnatal Day 21 (the end of lactation period). At doses ≥ 0.5 mg/kg (4 times the clinical dose), reduced survival was observed in live-born offspring. Doses ≥ 5 mg/kg (41 times the RHOD) caused umbilical hernia/incomplete gastrointestinal tract. Doses ≥ 50 mg/kg (410 times the RHOD) produced maternal toxicity (reduced body weight gain, death), decreased number of live-born offspring, decreased birth weight, and delays in postnatal development. A developmental NOAEL was not established in this study. The NOAEL for maternal toxicity was 5 mg/kg.

There are no data on the presence of loteprednol etabonate in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered, along with the mother’s clinical need for LOTEMAX (loteprednol etabonate ophthalmic ointment) 0.5% and any potential adverse effects on the breastfed infant from LOTEMAX.

Safety and effectiveness in pediatric patients have not been established.

No overall differences in safety and effectiveness have been observed between elderly and younger adult patients.

LOTEMAX® (loteprednol etabonate ophthalmic ointment) 0.5% is a sterile, topical corticosteroid for ophthalmic use. Loteprednol etabonate is a white to off-white powder.

{ "type": "p", "children": [], "text": "LOTEMAX® (loteprednol etabonate ophthalmic ointment) 0.5% is a sterile, topical corticosteroid for ophthalmic use. Loteprednol etabonate is a white to off-white powder." }

Loteprednol etabonate is represented by the following structural formula:

{ "type": "p", "children": [], "text": "Loteprednol etabonate is represented by the following structural formula:" }

Chemical name:

{ "type": "p", "children": [], "text": "Chemical name:" }

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

{ "type": "p", "children": [], "text": "chloromethyl 17α-[(ethoxycarbonyl)oxy]-11β-hydroxy-3-oxoandrosta-1,4-diene-17β-carboxylate" }

Each gram contains:

{ "type": "p", "children": [], "text": "\nEach gram contains:\n" }

Active: Loteprednol etabonate 5 mg (0.5%);

{ "type": "p", "children": [], "text": "\nActive: Loteprednol etabonate 5 mg (0.5%);" }

Inactives: Mineral Oil and White Petrolatum.

{ "type": "p", "children": [], "text": "\nInactives: Mineral Oil and White Petrolatum." }

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. While glucocorticoids are known to bind to and activate the glucocorticoid receptor, the molecular mechanisms involved in glucocorticoid/glucocorticoid receptor‑dependent modulation of inflammation are not clearly established. However, corticosteroids are thought to inhibit prostaglandin production through several independent mechanisms.

The systemic exposure to loteprednol etabonate following ocular administration of LOTEMAX ointment has not been studied in humans. However, results from a bioavailability study with LOTEMAX suspension in normal volunteers established that plasma concentrations 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 suspension, 8 times daily for 2 days or 4 times daily for 42 days. The maximum systemic exposure to loteprednol following administration of the ointment product dosed 4 times daily is not expected to exceed exposures attained with LOTEMAX suspension dosed up to two drops 4 times daily.

Long-term animal studies have not been conducted to evaluate the carcinogenic potential of loteprednol etabonate. Loteprednol etabonate was not genotoxic in vitro in the Ames test, the mouse lymphoma tk assay, or in a chromosome aberration test in human lymphocytes, or in vivo in the single-dose mouse micronucleus assay.

Treatment of female and male rats with doses ≥ 25 mg/kg/day of loteprednol etabonate (203 times the RHOD based on body surface area, assuming 100% absorption) prior to and during mating caused preimplantation loss and decreased the number of live fetuses/live births. The NOAEL for fertility in rats was 5 mg/kg/day (41 times the RHOD).

In two independent, randomized, multicenter, double-masked, parallel-group, vehicle-controlled studies in 805 subjects meeting a protocol-specified threshold amount of anterior chamber inflammation, LOTEMAX ointment was more effective compared to its vehicle for complete resolution of post-operative anterior chamber cell, flare, and pain following cataract surgery. Primary endpoint was complete resolution of anterior chamber cells and flare (cell count of 0 and no flare) and no pain at post-operative Day 8. The individual clinical trial results are provided below.

{ "type": "p", "children": [], "text": "In two independent, randomized, multicenter, double-masked, parallel-group, vehicle-controlled studies in 805 subjects meeting a protocol-specified threshold amount of anterior chamber inflammation, LOTEMAX ointment was more effective compared to its vehicle for complete resolution of post-operative anterior chamber cell, flare, and pain following cataract surgery. Primary endpoint was complete resolution of anterior chamber cells and flare (cell count of 0 and no flare) and no pain at post-operative Day 8. The individual clinical trial results are provided below." }

In the two studies, LOTEMAX had statistically significant higher incidence of complete clearing of anterior chamber cells and flare at post-operative Day 8 (24-32% vs. 11-14%) and also had a statistically significant higher incidence of subjects that were pain free at post-operative Day 8 (73-78% vs. 41-45%).

{ "type": "p", "children": [], "text": "In the two studies, LOTEMAX had statistically significant higher incidence of complete clearing of anterior chamber cells and flare at post-operative Day 8 (24-32% vs. 11-14%) and also had a statistically significant higher incidence of subjects that were pain free at post-operative Day 8 (73-78% vs. 41-45%)." }

LOTEMAX® (loteprednol etabonate ophthalmic ointment) 0.5% is a sterile ointment supplied in a tin tube with a pink polypropylene cap in the following size:

{ "type": "p", "children": [], "text": "LOTEMAX® (loteprednol etabonate ophthalmic ointment) 0.5% is a sterile ointment supplied in a tin tube with a pink polypropylene cap in the following size:" }

NDC 24208-443-35 3.5 g tube

{ "type": "p", "children": [], "text": "NDC 24208-443-35 3.5 g tube " }

DO NOT USE IF TAMPER-EVIDENT SKIRT IS VISIBLE ON BOTTOM OF CAP.

{ "type": "p", "children": [], "text": "\nDO NOT USE IF TAMPER-EVIDENT SKIRT IS VISIBLE ON BOTTOM OF CAP.\n" }

Storage: Store between 15°C to 25°C (59°F to 77°F). After opening, LOTEMAX can be used until the expiration date on the tube.

{ "type": "p", "children": [], "text": "\nStorage: Store between 15°C to 25°C (59°F to 77°F). After opening, LOTEMAX can be used until the expiration date on the tube. " }

Risk of Contamination

{ "type": "p", "children": [], "text": "\nRisk of Contamination\n" }

Advise patients to wash hands prior to using LOTEMAX ointment.

{ "type": "p", "children": [], "text": "Advise patients to wash hands prior to using LOTEMAX ointment. " }

Advise patients not to touch the eyelid or surrounding areas with the tip of the tube. The cap should remain on the tube when not in use.

{ "type": "p", "children": [], "text": "Advise patients not to touch the eyelid or surrounding areas with the tip of the tube. The cap should remain on the tube when not in use. " }

Contact Lens Wear

{ "type": "p", "children": [], "text": "\nContact Lens Wear\n" }

Advise patients not to wear contact lenses during their course of therapy.

{ "type": "p", "children": [], "text": "Advise patients not to wear contact lenses during their course of therapy. " }

Risk of Secondary Infection

{ "type": "p", "children": [], "text": "\nRisk of Secondary Infection\n" }

Advise patients to consult a physician if pain, redness, itching or inflammation becomes aggravated [see Warnings and Precautions (5.4)].

{ "type": "p", "children": [], "text": "Advise patients to consult a physician if pain, redness, itching or inflammation becomes aggravated [see Warnings and Precautions (5.4)]. " }

Distributed by:

{ "type": "p", "children": [], "text": "\nDistributed by:\n" }

Bausch & Lomb Americas Inc.

{ "type": "p", "children": [], "text": "Bausch & Lomb Americas Inc." }

Bridgewater, NJ 08807 USA

{ "type": "p", "children": [], "text": "Bridgewater, NJ 08807 USA" }

Manufactured by:

{ "type": "p", "children": [], "text": "\nManufactured by:\n" }

Bausch & Lomb Incorporated

{ "type": "p", "children": [], "text": "Bausch & Lomb Incorporated" }

Tampa, FL 33637 USA

{ "type": "p", "children": [], "text": "Tampa, FL 33637 USA\n" }

LOTEMAX is a trademark of Bausch & Lomb Incorporated or its affiliates.

{ "type": "p", "children": [], "text": "LOTEMAX is a trademark of Bausch & Lomb Incorporated or its affiliates." }

© 2022 Bausch & Lomb Incorporated or its affiliates

{ "type": "p", "children": [], "text": "© 2022 Bausch & Lomb Incorporated or its affiliates" }

9234905 (Folded)

{ "type": "p", "children": [], "text": "9234905 (Folded)" }

9234805 (Flat)

{ "type": "p", "children": [], "text": "9234805 (Flat)" }

NDC 24208-443-35

{ "type": "p", "children": [], "text": "\nNDC 24208-443-35" }

BAUSCH + LOMB

{ "type": "p", "children": [], "text": "\nBAUSCH + LOMB\n" }

Lotemax® loteprednol etabonateophthalmic ointment 0.5%

{ "type": "p", "children": [], "text": "\nLotemax®\nloteprednol etabonateophthalmic ointment 0.5%" }

FOR TOPICAL OPHTHALMIC USE

{ "type": "p", "children": [], "text": "\nFOR TOPICAL OPHTHALMIC USE\n" }

Rx only

{ "type": "p", "children": [], "text": "\nRx only\n" }

Sterile

{ "type": "p", "children": [], "text": "Sterile\n" }

Net. Wt. (3.5 g) 1/8oz.

{ "type": "p", "children": [], "text": "\nNet. Wt. (3.5 g) 1/8oz. \n" }