Vexaol (Rimexolone)

VEXOL™

Alcon

Rimexolone

Corticosteroid

Action And Clinical Pharmacology: Rimexolone is an anti-inflammatory corticosteroid. Corticosteroids suppress the inflammatory response to a variety of inciting agents of a mechanical, chemical, or immunological nature. They inhibit edema, cellular infiltration, capillary dilatation, fibroblastic proliferation, deposition of collagen and late cicatrization. Corticosteroids are capable of producing a rise in intraocular pressure in susceptible individuals.

Placebo-controlled clinical studies demonstrated that rimexolone ophthalmic suspension is efficacious for the treatment of anterior chamber inflammation following cataract surgery.

In 2 controlled clinical trials, rimexolone 1% ophthalmic suspension demonstrated clinical equivalence to 1% prednisolone acetate in reducing uveitic inflammation.

In a controlled 6-week study of steroid responsive subjects, the time to raise intraocular pressure was similar for rimexolone 1% ophthalmic suspension and 0.1% fluorometholone given 4 times daily.

Pharmacokinetics: As with other topically administered ophthalmic drugs, rimexolone 1% ophthalmic suspension is absorbed systemically. Studies in normal volunteers dosed bilaterally once every hour during waking hours for 1 week have demonstrated serum concentrations ranging from less than 80 pg/mL to 470 pg/mL. The mean serum concentrations were approximately 130 pg/mL. Serum concentrations were at or near steady state after 5 to 7 hourly doses.

After decreasing the dosing frequency to once every 2 hours while awake during the second week of administration, mean serum concentrations were approximately 100 pg/mL. The serum half-life of rimexolone could not be reliably estimated due to the large number of samples below the quantitation limit of the assay (80 pg/mL). However, based on the time required to reach steady state, the half-life appears to be short (1 to 2 hours).

Based upon in vivo and in vitro preclinical metabolism studies, and on in vitro results with human liver preparations, rimexolone undergoes extensive metabolism.

Following i.v. administration of radio-labeled rimexolone to rats, greater than 80% of the dose is excreted via the feces as rimexolone and metabolites. Metabolites have been shown to be less active than parent drug, or inactive in human glucocorticoid receptor binding assays.

Indications And Clinical Uses: For the treatment of postoperative inflammation following cli and for the treatment of anterior uveitis.

Contra-Indications: Epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, and most other viral diseases of cornea and conjunctiva; mycobacterial infection of the eye; fungal diseases of the eye; acute purulent untreated infections which, like other diseases caused by microorganisms, may be masked or enhanced by the presence of the steroid; and those persons with hypersensitivity to any component of the formulation.

Manufacturers’ Warnings In Clinical States: Not for injection. Use in the treatment of herpes simplex infection requires great caution and frequent slit-lamp examinations. Prolonged use may result in ocular hypertension/glaucoma, damage to the optic nerve, defects in visual acuity and visual fields, and posterior subcapsular cataract formation. Prolonged use may also result in secondary ocular infections due to suppression of host response. Acute purulent infections of the eye may be masked or exacerbated by the presence of corticosteroid medication. In those diseases causing thinning of the cornea or sclera, perforation has been known to occur with topical steroids. It is advisable that the intraocular pressure be checked frequently.

Precautions: General: 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 or is in use.

Information for the Patient: Do not touch dropper tip to any surface, as this may contaminate the suspension.

Carcinogenesis, Mutagenesis, Impairment of Fertility: Rimexolone has been shown to be nonmutagenic in a battery of in vitro and in vivo mutagenicity assays. Fertility and reproductive capability were not impaired in a study in rats with plasma levels (42 ng/mL) approximately 200 times those obtained in clinical studies after topical administration (
Pregnancy: Rimexolone has been shown to be teratogenic and embryotoxic in rabbits following s.c. administration at the lowest dose tested (0.5 mg/kg/day, approximately 2 times the recommended human ophthalmic dose). Corticosteroids are recognized to cause fetal resorptions and malformations in animals.

There are no adequate and well-controlled studies in pregnant women. Rimexolone ophthalmic suspension should be used in pregnant women only if the potential benefits to the mother justifies the potential risk to the fetus.

Lactation: It is not known whether topical ophthalmic administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human breast milk. Nevertheless, caution should be exercised when topical corticosteroids are administered to a nursing woman; a decision should be made whether to discontinue nursing or discontinue therapy, taking into consideration the importance of the drug to the mother.

Children: Safety and effectiveness in children have not been established.

Drug Interactions: No drug interactions or incompatibilities were identified during the clinical development program.

Adverse Reactions: Reactions associated with ophthalmic steroids include elevated intraocular pressure which may be associated with optic nerve damage, visual acuity and field defects, posterior subcapsular cataract formation, secondary ocular infection from pathogens including herpes simplex, and perforation of the globe where there is thinning of the cornea or sclera.

Ocular adverse reactions occurring in 1 to 5% of patients in clinical studies of rimexolone ophthalmic suspension included blurred vision (2.9%), discharge (2.4%), discomfort (1.8%), ocular pain (1.4%), increased intraocular pressure (1.1%) and foreign body sensation (1.1%). Other ocular related adverse reactions occurring in less than 1% of patients included hyperemia, ocular pruritus, sticky sensation, increased fibrin, dry eye, conjunctival edema, corneal staining, keratitis, tearing, photophobia, edema, irritation, corneal ulcer, browache, lid margin crusting, corneal edema, infiltrate and corneal erosion.

Nonocular adverse reactions were rare and occurred in less than 2% of patients. These included headache, hypotension, rhinitis, pharyngitis and taste perversion.

Symptoms And Treatment Of Overdose: Symptoms and Treatment: Discontinue medication when heavy or protracted use is suspected. A topical overdosage may be flushed from the eye(s) with warm tap water.

Dosage And Administration: Postoperative Inflammation: Apply 1 to 2 drops of ophthalmic suspension into the conjunctival sac of the affected eye 4 times daily beginning 24 hours after surgery and continuing throughout the first 2 weeks of the postoperative period.

Uveitis: Apply 1 to 2 drops of ophthalmic suspension into the conjunctival sac of the affected eye every hour during waking hours for the first week, 1 drop every 2 hours during waking hours of the second week, 4 times per day during the third week, then 3 times per day during the first 4 days of week 4 and then twice per day during the last 3 days of week 4.

Availability And Storage: Each mL of sterile, multidose topical ophthalmic suspension, contains: rimexolone 1%. Preservative: benzalkonium chloride 0.01%. Nonmedicinal ingredients: carbomer 934P, edetate disodium, mannitol, polysorbate 80, purified water, sodium chloride, sodium hydroxide and/or hydrochloric acid to adjust pH. Plastic Drop-Tainer dispensers of 5 and 10 mL. Store upright between 2 and 30°C.

VEXOL™ Alcon Rimexolone Corticosteroid

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Clinical Medicine

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