Zylet®

Tobramycin 0.3% / Loteprednol 0.5% · ophthalmic suspension

Antibiotic/Steroid

Approved uses

Steroid-responsive ocular inflammation with superficial bacterial infection or a risk of it

One or two drops into the conjunctival sac of the affected eye every 4 to 6 hours, increased to every 1 to 2 hours during the initial 24 to 48 hours, then tapered; not more than 20 mL initially

Matches dexamethasone/tobramycin on signs and symptoms at 2 weeks without its 1 mmHg IOP rise.

Chronic anterior uveitis, or corneal injury from chemical, radiation or thermal burns or foreign body penetration, where superficial bacterial ocular infection or a risk of it exists

One or two drops into the conjunctival sac of the affected eye every 4 to 6 hours, increased to every 1 to 2 hours during the initial 24 to 48 hours, then tapered; not more than 20 mL initially

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.

Available Forms

Ophthalmic suspension, loteprednol etabonate 0.5% (5 mg/mL) with tobramycin 0.3% (3 mg/mL), 5 mL fill in a 7.5 mL bottle, 10 mL fill in a 10 mL bottle

Mechanism of Action

Loteprednol etabonate is a 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, capillary dilation, leukocyte migration, fibroblast proliferation, and collagen deposition while probably delaying healing; it lacks the position 20 ketone group of other corticosteroids. Tobramycin, the anti-infective component, binds the bacterial 30S ribosomal subunit to block protein synthesis, covering staphylococci including penicillin-resistant strains, some streptococci, Pseudomonas aeruginosa, Haemophilus influenzae, Moraxella lacunata, and several Enterobacteriaceae.

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: Corticosteroid use may result in it.
Delayed healing after cataract surgery: Steroids may delay healing and increase the incidence of bleb formation; in diseases causing thinning of the cornea or sclera, perforations have occurred with topical steroids.
Magnified examination before prescribing: Initial prescription and renewal only after examination with magnification such as slit lamp biomicroscopy and, where appropriate, fluorescein staining.
Secondary or masked infection: Prolonged corticosteroid use may suppress host response and increase the hazard of secondary ocular infection; in acute purulent conditions steroids may mask infection or enhance existing infection; re-evaluate if signs and symptoms fail to improve after 2 days.
Viral infection exacerbation: Ocular steroids may prolong the course and worsen the severity of many viral eye 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 application; consider fungal invasion in any persistent corneal ulceration where a steroid has been used or is in use, and culture when appropriate.
Aminoglycoside hypersensitivity: Sensitivity to topically applied aminoglycosides may occur; discontinue and institute appropriate therapy if it develops.
Dropper tip contamination: Do not allow the tip to touch any surface.

Common Side Effects

Ocular, 42-day safety study: Injection approximately 20%, superficial punctate keratitis approximately 15%, burning and stinging on instillation 9%.
IOP elevation, 42-day study: Reported in 10% of treated subjects versus 4% of placebo subjects.
Ocular, under 4%: Vision disorders, discharge, itching, lacrimation disorder, photophobia, corneal deposits, ocular discomfort, eyelid disorder.
Non-ocular: Headache in approximately 14%; all other non-ocular reactions under 5%.
Tobramycin component, under 4%: Hypersensitivity and localized ocular toxicity, including lid itching, lid swelling, and conjunctival erythema, which the label attributes to tobramycin ophthalmic solution 0.3% rather than to the combination.
Loteprednol pooled IOP data: In controlled randomized studies of 28 days or longer, a rise of 10 mmHg or more occurred in 2% (15/901) on loteprednol etabonate, 7% (11/164) on prednisolone acetate 1%, and 0.5% (3/583) on placebo.
Corticosteroid class effects: Elevated IOP with infrequent optic nerve damage and visual acuity and field defects, posterior subcapsular cataract formation, delayed wound healing, and perforation of the globe where the cornea or sclera is thinned.
Secondary infection: Fungal corneal infection is particularly prone to develop coincidentally with long-term steroid application, secondary bacterial infection follows suppression of host responses, and ophthalmic steroids are associated with secondary infection from pathogens including herpes simplex.

Pregnancy & Lactation

Soft contact lens wear: Lenses should not be worn during treatment; the suspension is preserved with benzalkonium chloride 0.01%.

Pregnancy: No adequate and well-controlled studies in pregnant women. Oral loteprednol etabonate was teratogenic at clinically relevant doses: malformations in rabbits at 0.54 times the recommended human ophthalmic dose (RHOD) and above (spina bifida including meningocele, with exencephaly and craniofacial malformations at 2.1 times RHOD), malformations in rats at 13 times RHOD and above, and reduced offspring survival in rats dosed from late gestation through lactation at 1.3 times RHOD and above. Subcutaneous tobramycin produced abortions in rabbits at 180 times RHOD and did not affect fetal development in rats at 450 times RHOD.

Lactation: No data on presence in human milk, effects on the breastfed infant, or effects on milk production.

Pediatric Use

Efficacy not demonstrated in children age 0 to 6 years.