Lotemax®

Loteprednol 0.5% · ophthalmic suspension

Steroid

Approved uses

Steroid-responsive inflammation of the anterior segment

1 to 2 drops into the conjunctival sac of the affected eye QID; may be increased up to 1 drop every hour during the first week

Post-operative inflammation following ocular surgery

1 to 2 drops into the conjunctival sac of the operated eye QID beginning 24 hours after surgery, continuing through the first 2 post-operative weeks

Contact lens associated giant papillary conjunctivitis

1 drop QID for 6 weeks was the pivotal trial regimen; the labeled steroid-responsive regimen is 1 to 2 drops QID

Signs and symptoms improve after 1 week and continue improving through 6 weeks of use.

Acute anterior uveitis (iritis, cyclitis)

1 to 2 drops into the conjunctival sac of the affected eye QID; may be increased up to 1 drop every hour during the first week

Anterior chamber cells resolve by day 28 in 72% of eyes versus 87% on prednisolone acetate 1%.

OFF-LABELNot in the FDA label for this product

Keratoconjunctivitis sicca with ocular surface inflammation

QID for 4 weeks was the trial regimen; the report states frequency and duration but not drops per instillation

RCT · n=64 · pilot

Randomized, double-masked, placebo-controlled multicenter trial in 64 patients with keratoconjunctivitis sicca and delayed tear clearance, tagged by PubMed as a pilot project. In subsets with at least moderate clinical inflammation the difference from vehicle was significant at 2 weeks but did not reach statistical significance at 4 weeks, although the improvement was retained. The authors concluded only that QID use may be beneficial in patients whose keratoconjunctivitis sicca has at least a moderate inflammatory component. Tolerability was similar between arms.

Pflugfelder SC, Maskin SL, Anderson B, Chodosh J, Holland EJ, De Paiva CS, Bartels SP, Micuda T, Proskin HM, Vogel R. A randomized, double-masked, placebo-controlled, multicenter comparison of loteprednol etabonate ophthalmic suspension, 0.5%, and placebo for treatment of keratoconjunctivitis sicca in patients with delayed tear clearance. Am J Ophthalmol. 2004;138(3):444-457.

Contraindications

Most viral diseases of the cornea and conjunctiva, including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella.
Mycobacterial infection of the eye.
Fungal diseases of ocular structures.
Known or suspected hypersensitivity to any ingredient of the preparation or to other corticosteroids.

Available Forms

0.5% suspension (loteprednol etabonate 5 mg/mL), 5 mL, 10 mL, 15 mL bottles

Mechanism of Action

Corticosteroid: thought to act by inducing lipocortins that inhibit phospholipase A2, cutting release of arachidonic acid and the prostaglandins and leukotrienes downstream of it, and suppressing edema, fibrin deposition, capillary dilation, leukocyte migration, fibroblast proliferation, and collagen deposition, while probably delaying healing. Highly lipid soluble and lacking the position-20 ketone group of other corticosteroids, it is built for predictable conversion to inactive carboxylic acid metabolites; after 1 drop OU 8 times daily for 2 days or QID for 42 days, plasma levels of drug and primary metabolite stayed below the 1 ng/mL limit of quantitation.

Warnings & Precautions

IOP elevation and glaucoma: Prolonged corticosteroid use may result in glaucoma with optic nerve damage and defects in visual acuity and visual fields; use with caution in the presence of glaucoma, and monitor IOP if this product is used 10 days or longer.
Posterior subcapsular cataract: Prolonged corticosteroid use may produce it.
Secondary ocular infection: Prolonged use may suppress host response and increase the hazard of secondary ocular infection; in acute purulent conditions of the eye steroids may mask infection or enhance existing infection.
Viral infection exacerbation: Ocular steroids may prolong the course and worsen the severity of many ocular viral infections including herpes simplex; a history of herpes simplex requires great caution.
Fungal keratitis: Fungal corneal infection is particularly prone to develop coincidentally with long-term local steroid use; consider fungal invasion and culture in any persistent corneal ulceration where a steroid has been used or is in use.
Corneal or scleral perforation: In diseases causing thinning of the cornea or sclera, perforations have occurred with topical steroids.
Delayed healing after cataract surgery: Steroids used after cataract surgery may delay healing and increase the incidence of bleb formation.
Renewal beyond 14 days: Initial prescription and renewal past 14 days only after examination with magnification such as slit lamp biomicroscopy and, where appropriate, fluorescein staining.
Soft contact lenses: Lenses should not be worn during therapy with this suspension, which is preserved with benzalkonium chloride 0.01%.

Common Side Effects

Ocular, 5% to 15%: Abnormal vision or blurring, burning on instillation, chemosis, discharge, dry eye, epiphora, foreign body sensation, itching, injection, photophobia.
Ocular, under 5%: Conjunctivitis, corneal abnormalities, eyelid erythema, keratoconjunctivitis, ocular irritation, pain or discomfort, papillae, uveitis. Some of these events were similar to the underlying ocular disease being studied.
Systemic, under 15%: Headache, rhinitis, pharyngitis.
Intraocular pressure, pooled studies: In controlled randomized studies of 28 days or longer, a rise of 10 mmHg or more occurred in 2% (15/901) on drug versus 7% (11/164) on prednisolone acetate 1% and 0.5% (3/583) on placebo.
Corticosteroid class effects: Elevated IOP with optic nerve damage and visual acuity and field defects, posterior subcapsular cataract formation, secondary ocular infection from pathogens including herpes simplex, and perforation of the globe where the cornea or sclera is thinned.

Pregnancy & Lactation

Pregnancy: Oral dosing of rabbits during organogenesis at 3 mg/kg/day (35 times the maximum daily clinical dose) was embryotoxic (delayed ossification) and teratogenic (increased meningocele, abnormal left common carotid artery, limb flexures) at a dose causing no maternal toxicity; the no-observed-effect level was 0.5 mg/kg/day (6 times the maximum daily clinical dose). Oral dosing of rats during organogenesis produced teratogenicity from 5 mg/kg/day and embryotoxicity at higher doses, with no reproductive toxicity at 0.5 mg/kg/day (6 times the maximum clinical dose).

Lactation: Whether topical ophthalmic corticosteroid dosing yields detectable quantities in human milk is unknown. Systemic steroids appear in human milk and could suppress growth or interfere with endogenous corticosteroid production; use with caution in a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.