Loteprednol Etabonate

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.

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.

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.

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.

• •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. (
  5.1
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• •Cataracts – Use of corticosteroids may result in posterior subcapsular cataract formation. (
  5.2 Cataracts

  Use of corticosteroids may result in posterior subcapsular cataract formation.
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• •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 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. (
  5.3 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 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.
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• •Bacterial infections – Prolonged use of corticosteroids may suppress the host response and thus increase the hazard of secondary ocular infection. In acute purulent conditions, steroids may mask infection or enhance existing infection. (
  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 of the eye, steroids may mask infection or enhance existing infection.
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• •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 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).
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• •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 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 cultures should be taken when appropriate.
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