Epioxa HD and Epioxa

Description for Epioxa HD and Epioxa

EPIOXA HD (riboflavin 5’-phosphate ophthalmic solution) 0.239% and EPIOXA (riboflavin 5’- phosphate ophthalmic solution) 0.177% contain riboflavin 5’-phosphate, a photoenhancer, for topical ophthalmic use.

EPIOXA HD 0.239% is a clear, yellow, sterile buffered solution containing 2.39 mg/mL riboflavin 5’-phosphate. The pH of the solution is 6.7 to 7.7 and the osmolality is 200 mOsm/kg to 260 mOsm/kg. Each mL of solution contains 2.50 mg of riboflavin 5’-phosphate sodium (equivalent to 1.97 mg/mL riboflavin). Riboflavin 5’-phosphate sodium is a mixture of the sodium salts of riboflavin, riboflavin monophosphates, and riboflavin diphosphates. The inactive ingredients are hydroxypropyl methylcellulose, sodium chloride, dibasic sodium phosphate dihydrate, edetate disodium dihydrate, tromethamine, monobasic sodium phosphate dihydrate, benzalkonium chloride, and water for injection. Sodium hydroxide and/or hydrochloric acid may be added to adjust pH.

EPIOXA 0.177% is a clear, yellow, sterile buffered solution containing 1.77 mg/mL riboflavin 5’-phosphate. The pH of the solution is 6.5 to 7.5 and the osmolality is 330 mOsm/kg to 400 mOsm/kg. Each mL of solution contains 1.85 mg of riboflavin 5’-phosphate sodium (equivalent to 1.46 mg/mL riboflavin). Riboflavin 5’-phosphate sodium is a mixture of the sodium salts of riboflavin, riboflavin monophosphates, and riboflavin diphosphates. The inactive ingredients are sodium chloride, dibasic sodium phosphate dihydrate, tromethamine, monobasic sodium phosphate dihydrate, and water for injection. Sodium hydroxide and/or hydrochloric acid may be added to adjust pH.

The molecular formula for riboflavin 5’-phosphate sodium (Vitamin B2) is C₁₇H₂₀N₄NaO₉P with a molecular weight of 478.33 g/mol.

ADVERSE REACTIONS

The following clinically significant adverse reactions are described elsewhere in the labeling: Herpetic keratitis [see Warnings and Precautions (5.1)]

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 safety of EPIOXA HD and EPIOXA in the epithelium-on corneal collagen cross-linking procedure with UV-A irradiation and supplemental oxygen was evaluated in two randomized, parallel-group, sham procedure/vehicle-controlled trials. Study eyes were randomized in a 2:1 treatment allocation to receive corneal collagen cross-linking (CXL) or sham procedure/vehicle control at the baseline visit. In both trials, CXL-treated eyes were followed for 12 months.

Safety data were obtained from a total of 389 CXL-treated eyes.

The most commonly reported adverse reaction in CXL-treated eyes was conjunctival hyperaemia (31%). Other adverse reactions occurring in 5% to 25% of CXL-treated eyes included: corneal opacity (haze), photophobia, punctate keratitis, eye pain, eye irritation, lacrimation increased, corneal epithelium defect, eyelid oedema, corneal striae, visual acuity reduced, dry eye, and anterior chamber flare.

Drug Interactions for Epioxa HD and Epioxa

No information provided.

Warnings for Epioxa HD and Epioxa

Included as part of the PRECAUTIONS section.

Precautions for Epioxa HD and Epioxa

Herpetic Keratitis

Corneal collagen cross-linking should be used with caution in patients with a history of herpetic keratitis due to the potential for reactivation of herpes keratitis.

NONCLINICAL TOXICOLOGY

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Animal studies have not been conducted to determine the carcinogenic potential of photoexcited riboflavin.

Mutagenesis

Photoexcited riboflavin has been shown to be genotoxic in the Ames Salmonella reverse mutation assay and in the SOS/umu test system.

The genotoxicity of riboflavin, in the absence of photoexcitation has been examined in vitro in bacterial reverse mutation assays, sister chromatid exchange assay, chromosomal aberration assays and in vivo in a mouse micronucleus study. The overall weight of evidence indicates that riboflavin, in the absence of photoexcitation, is not genotoxic.

Impairment of Fertility

Animal studies to determine the effects of the EPIOXA HD and EPIOXA epithelium-on corneal collagen cross-linking procedure on fertility were not conducted.

OVERDOSES

No information provided.

Contraindications for Epioxa HD and Epioxa

Hypersensitivity

EPIOXA HD and EPIOXA are contraindicated in patients with known hypersensitivity to benzalkonium chloride or any ingredients in EPIOXA HD and EPIOXA.

Aphakic and Pseudophakic Patients

Epithelium-on corneal collagen cross-linking is contraindicated in aphakic patients and pseudophakic patients without a UV-blocking intraocular lens.

Clinical Pharmacology for Epioxa HD and Epioxa

Mechanism Of Action

Riboflavin 5’-phosphate sodium (Vitamin B2) is the precursor of two coenzymes, flavin adenine dinucleotide and flavin mononucleotide, which catalyze oxidation/reduction reactions involved in a number of metabolic pathways.

Under the conditions used for corneal collagen cross-linking, riboflavin 5’-phosphate functions as a photoenhancer and generates singlet oxygen which is responsible for the cross-linking.

Pharmacodynamics

The pharmacodynamics of EPIOXA HD and EPIOXA have not been characterized.

Pharmacokinetics

The pharmacokinetics of EPIOXA HD and EPIOXA have not been characterized.

Patient Information for Epioxa HD and Epioxa

• Advise patients that there may be discomfort in the treated eye and that sunglasses may help with light sensitivity.
• Instruct patients that they should contact their physician immediately if they experience severe pain in the treated eye or any sudden decrease in their vision.

EPIOXA HD, EPIOXA, the O₂n System, and Boost Goggles are marketed by:
Avedro, a Glaukos company
30 North Avenue
Burlington, MA 01803 USA
Issued MM/YYYY ML-000159