Leos

Uses

Loteprednol etabonate is used for the treatment of steroid responsive inflammatory conditions of the palpebral and bulbar conjunctiva, cornea and anterior segment of the globe such as:

• Allergic conjunctivitis
• Acne rosacea
• Superficial punctate keratitis
• Herpes zoster keratitis
• Iritis
• Cyclitis

It is also used for the treatment of post-operative inflammation following ocular surgery.

Leos is also used to associated treatment for these conditions: Dry Eye Syndrome (DES), Eye Pain, Ocular Inflammation

How Leos works

Corticosteroids like loteprednol etabonate inhibit the inflammatory response to a variety of inciting agents and likely delay or slow healing . They inhibit the edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and scar formation that are commonly 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 . Moreover, corticosteroids are thought to inhibit prostaglandin production through several independent mechanisms . In particular, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins . It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid . Arachidonic acid is released from membrane phospholipids by phospholipase A2 .

The use of LE subsequently treats post-operative inflammation and pain following ocular surgery by managing the prostaglandin release, recruitment and travel of neutrophils and macrophages, and production of other inflammatory mediators that are intrinsically associated with the physical trauma of surgery .

Dosage

Leos dosage

Shake the bottle vigorously before using

Steroid responsive disease treatment: Apply 1 to 2 drops of Loteprednolinto the conjunctival sac of the affected eye(s) four times daily. During the initial treatment within the first week, the dosing may be increased, up to 1 drop every hour, if necessary. Care should be taken not to discontinue therapy prematurely.

Post-Operative Inflammation: Apply 1 to 2 drops of Loteprednolinto the conjunctival sac of the operated eye(s) four times daily beginning 24 hours after surgery and continuing throughout the first 2 weeks of the post-operative period.

Side Effects

Local reactions (e.g. blurred vision, burning, itching, dry eye), photophobia, headache, rhinitis, pharyngitis. Prolonged use may increase IOP, which may be associated with possible development of glaucoma and infrequent optic nerve damage; posterior sub-capsular cataract formation and perforation of the globe where there is thinning of the cornea or sclera.

Toxicity

The most common adverse drug reactions reported during clinical trials for the medication were eye pain and posterior capsular opacification, both of which may also be the consequence of the very surgical procedures performed on the eye(s) .

The agent is not absorbed systemically following topical ophthalmic administration and maternal use is not expected to result in fetal exposure to the drug .

The medication is not absorbed systemically by the mother following topical ophthalmic administration, and breastfeeding is not expected to result in exposure of the child to the agent .

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 .

Overdose is not expected to be likely to occur after ocular administration .

Precaution

• Shake the bottle well before use
• Patients should be advised not to allow the dropper tip to touch the eye, eyelid, fingers, or any other surface to prevent contamination
• Patients should be advised not to wear soft contact lenses when using this drug
• If this product is used for 10 days or longer, intraocular pressure should be monitored.
• The possibility of fungal infections of the cornea should be considered after long-term steroid dosing
• The use of steroids may delay wound healing.

Interaction

Since Leos is not detected in plasma following the topical administration, it is not expected to affect the pharmacokinetics of systemically administered medicinal products.

Food Interaction

Volume of Distribution

The only data available regarding the volume of distribution of loteprednol etabonate (LE) is the volume of distribution the agent demonstrated when administered to dogs - a value of 3.7 L/kg . It has been shown, however, that the topical ocular administration of LE distributes preferentially into the cellular components of blood .

Elimination Route

Loteprednol etabonate (LE) demonstrates good ocular permeation properties as it is lipid soluble, allowing the agent to penetrate into cells with relative ease .

Results from the ocular administration of loteprednol in normal, healthy volunteers have shown that there are low or undetectable concentrations of either unchanged material or its metabolite . Following twice-daily unilateral topical ocular dosing of LE for 14 days in healthy subjects, the plasma concentrations of loteprednol etabonate were below the limit of quantitation (1 ng/mL) at all time points . These finds suggest that limited, if any, systemic absorption of LE occurs .

Half Life

The terminal half-life of loteprednol etabonate as determined when administered intravenously at a dose of 5 mg/kg in the dog animal model is 2.8 hours .

Clearance

Loteprednol etabonate was slowly hydrolyzed in liver at clearance rates of 0.21 +/- 0.04 and 2.41 +/- 0.13 ml/h/kg in the liver and plasma, respectively .

Elimination Route

Following systemic administration to rats, loteprednol etabonate is eliminated primarily via the biliary/faecal route, with most of the dose eliminated in the form of the metabolite, PJ-90 .

Pregnancy & Breastfeeding use

It is Pregnancy Category C. It is not known whether topical ophthalmic administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human milk.

Contraindication

Loteprednol, 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.

Loteprednol is also contraindicated in individuals with known or suspected hypersensitivity to any of the ingredients of Leos and to other corticosteroids.

Storage Condition

Protect from light. Store in cool & dry place. Keep out of the reach of children. Do not use more than 4 weeks after opening. Shake well before using.

Innovators Monograph

You find simplified version here Leos