Riboflavin 5 Phosphate Ophthalmic

Riboflavin 5'-phosphate ophthalmic is a photoenhancer used in epithelium-on corneal collagen cross-linking for the treatment of keratoconus in conjunction with O2n system and Boost Goggles in patients aged 13 years and older (Epioxa, Epioxa HD). 

It is also used for the treatment of corneal collagen cross-linking in combination with the corneal cross-linking (KXL) system for progressive keratoconus or for corneal ectasia following refractive surgery in patients aged 14 years and older (Photrexa, Photrexa Viscous).

Riboflavin 5’-phosphate ophthalmic is available under the following different brand names: Photrexa, Photrexa Viscous, Epioxa, Epioxa HD

Common side effects of Riboflavin 5’-phosphate ophthalmic include:

• corneal opacity (haze)
• punctate keratitis
• corneal striae
• corneal epithelium defect 
• eye pain 
• reduced visual acuity
• blurred vision 
• photophobia (reported primarily in corneal ectasia patients)
• eye irritation
• increased lacrimation 
• eyelid edema
• dry eye
• anterior chamber flare
• conjunctival hyperemia

Serious side effects of Riboflavin 5’-phosphate ophthalmic include:

• ulcerative keratitis 
• herpetic keratitis

Rare side effects of Riboflavin 5’-phosphate ophthalmic include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and Pediatric dosage

Ophthalmic solution, topical (Epioxa, Epioxa HD)

• 0.177% (1.77 mg/mL; Epioxa)
• 0.239% (2.39 mg/mL; Epioxa HD)

Solution provided in single-dose glass syringe

Ophthalmic solution, topical (Photrexa, Photrexa Viscous)

• 0.146%
• Kit contains 2 single-use foil pouches, each containing one 3 mL glass syringe of Photrexa Viscous in 20% dextran or Photrexa
• For use with the KXL System

Keratoconus with O2n System and Boost Goggles (Epioxa or Epioxa HD)

Adult and pediatric dosage

• Dose and administration instructions
• Apply topical anesthetic and insert a lid speculum
• Using a cellulose spear sponge soaked with riboflavin 5’-phosphate ophthalmic 0.239% solution (Epioxa HD), remove mucin layer from corneal surface without debriding the corneal epithelium (epithelium-on) by swiping sponge 4-10 times horizontally and vertically
• Step 1: Apply 2 drops of Epioxa HD topically to the eye every 60 seconds for 4 minutes, followed by
• Step 2: Apply 2 drops of 0.177% solution (Epioxa) topically to eye every 30 seconds for 6 minutes
• Gently rinse corneal surface with ~5 mL of balanced salt solution (BSS)
• Perform ultrasound pachymetry
• If corneal thickness is less than 325 microns, irradiation should not be performed
• Apply Boost Goggles and turn on oxygen flow as per instructions in Boost Goggles User Guide
• Center optical head of O2n System over cornea and irradiate the eye as per instructions in the O2n System Operator’s Manual
• O2n System automatically delivers irradiation to the eye for 11 minutes 6 seconds at 30 mW/cm2 with an on/off cycle of 1 second UV-A on/1 second UV-A off at a wavelength of 365 nm
• Instill BSS on the cornea every 2 minutes, or more frequently as needed, to maintain corneal hydration during UV-A irradiation
• When UV-A irradiation has stopped, shut off oxygen flow, and remove the Boost Goggles and lid speculum
• Apply a bandage contact lens

Keratoconus and Corneal Ectasia Following Refractive Surgery (Photrexa or Photrexa Viscous)

Adult and pediatric dosage

• Dose and administration instructions:
  • Using topical anesthesia, debride epithelium to a diameter of ~9 mm using standard aseptic technique
  • NOTE: Both Photrexa and Photrexa Viscous are used topically during the procedure
  • Post epithelial debridement, instill 1 drop of Photrexa Viscous topically on the eye every 2minutes for 30 minutes
  • At the end of 30-minute soaking period, examine the eye under the slit lamp for the presence of a yellow flare in anterior chamber; if yellow flare is not detected, instill 1 drop of Photrexa Viscous every 2minutes for an additional 2-3 drops and recheck for the presence of a yellow flare; this process can be repeated as necessary
  • Once yellow flare observed, perform ultrasound pachymetry
  • If corneal thickness is less than 400 micrometers, instill 2 drops of Photrexa every 5-10 seconds until corneal thickness increases to at least 400 micrometers
  • Irradiation should not be performed unless this 400-micrometer threshold is met and yellow flare is seen
  • Irradiate the eye for 30 continuous minutes at 3mW/cm² at a wavelength of 365 nm, centered over cornea, using KXL System as per instructions in manual
  • During irradiation, continue topical instillation of Photrexa Viscous onto eye every 2 minutes for 30-minute irradiation period

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Visit the RxList Drug Interaction Checker for any drug interactions. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Epioxa, Epioxa HD
  • Known hypersensitivity to benzalkonium chloride or any ingredients in Epioxa HD and Epioxa
  • Epithelium-on corneal collagen cross-linking is contraindicated in aphakic patients and pseudophakic patients without a UV-blocking intraocular lens
• Photrexa, Photrexa Viscous
  • None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Riboflavin 5’-phosphate ophthalmic?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Riboflavin 5’-phosphate ophthalmic?”

Cautions

• Epioxa, Epioxa HD
  • Corneal collagen cross-linking should be used with caution in patients with a history of herpetic keratitis owing to the potential for reactivation of herpes keratitis
• Photrexa, Photrexa Viscous
  • Ulcerative keratitis can occur; monitor for resolution of epithelial defects

Pregnancy and Lactation

Pregnancy

• Animal development and reproduction studies have not been conducted
• Since it is not known whether the corneal collagen cross-linking procedure can cause fetal harm or affect reproductive capacity, it should not be performed on pregnant women

Lactation

• Unknown if distributed in human breast milk; weigh benefits against risks