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.

5.1 Intraocular Pressure (IOP) Increase

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. 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.

5.2 Cataracts

Use of corticosteroids may result in posterior subcapsular cataract formation.

5.3 Delayed Healing

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.

5.4 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.

5.5 Viral Infections

Use of 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 cultures should be taken when appropriate.

5.7 Risk of Contamination

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

5.8 Contact Lens Wear

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

6.1 Clinical Trials Experience

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 drug reactions in the clinical trials with INVELTYS were eye pain and posterior capsular opacification, both reported in 1% of patients. These reactions may have been the consequence of the surgical procedure.

8.1 Pregnancy

8.2 Lactation

8.3 Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

8.4 Geriatric Use

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

12.1 Mechanism of Action

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.

12.3 Pharmacokinetics

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 twice-daily unilateral topical ocular dosing of INVELTYS for 14 days in healthy subjects, the plasma concentrations of loteprednol etabonate were below the limit of quantitation (1 ng/mL) at all timepoints.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

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, or in a chromosome aberration test in human lymphocytes, or in vivo in the single dose mouse micronucleus assay.

Storage and Handling

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.

Store upright at 15°C to 25°C (59°F to 77°F). Do not freeze.

Administration

Instruct the patient to shake the bottle 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.

Risk of Contamination

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

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

Contact Lens Wear

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