avacincaptad pegol intravitreal (Rx)

>10%

Conjunctival hemorrhage (13%)

1-10%

Increased intraocular pressure (IOP) (9%)

Blurred vision (8%)

Choroidal neovascularization (7%)

Eye pain (4%)

Vitreous floaters (2%)

Blepharitis (2%)

Contraindications

Ocular or periocular infections

Active intraocular inflammation

Cautions

Use may be associated with increased rates of neovascular (wet) AMD or choroidal neovascularization; monitor for signs of neovascular AMD

Transient increases in IOP observed after administration; monitor perfusion of optic nerve head following injection and manage accordingly

Endophthalmitis and retinal detachments

• Intravitreal injection may be associated with endophthalmitis and retinal detachments
• Use proper aseptic technique during administration to minimize risk of endophthalmitis
• Instruct patients to promptly report any symptoms suggestive of endophthalmitis or retinal detachment and manage appropriately

Pregnancy

There are no adequate and well-controlled studies of use in pregnant females

Animal data

• Administration to pregnant rats and rabbits during organogenesis resulted in no evidence of adverse effects to fetus or pregnant female at IV doses 5.1x and 3.2x the human exposure (based on AUC) at the maximum recommended human dose of 2 mg once monthly, respectively
• At all doses evaluated, an increased incidence of a non-adverse skeletal variation, described as short thoracolumbar (ossification site without distal cartilage) supernumerary ribs, was observed

Lactation

There is no information regarding the presence of avacincaptad pegol in human milk or its effects on breastfed infants or on milk production

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Pegylated oligonucleotide that binds to and inhibits complement protein C5

Inhibiting C5 may prevent its cleavage to C5a and C5b thus decreasing membrane attack complex (MAC) formation

Absorption

Peak plasma concentration: 68.4 ng/mL (single dose)

Peak plasma time: 7 days (single dose)

Metabolism

Expected to be catabolized by endonucleases and exonucleases to oligonucleotides of shorter lengths

Elimination

May be excreted renally in a similar manner to the elimination of endogenous RNA

Half-life (estimated): ~12 days

Intravitreal Preparation

Vial contains 20 mg/1 mL solution

Prepare using the following

• Use provided 5-micron filter needle (19-gauge x 1.5-inch)
• 1-mL sterile Luer lock syringe with a 0.1-mL dose mark
• Sterile injection needle (30-gauge x 0.5-inch)

Preparation

• Allow vial to reach room temperature, 20-25⁰C (68-77⁰F) for up to 24 hours; keep vial in original carton to protect from light
• Visually inspect vial; solution should appear as a clear to slightly opalescent, colorless to slightly yellow liquid solution; discard if particulates, cloudiness, or discoloration are visible
• Do not use if packaging, vial, filter needle, injection needle, and/or empty syringe are expired or damaged or have been tampered with

• Using filter needle, prepare syringe

  • Place vial upright on a flat surface for about 1 minute after removal from packaging to make sure all liquid settles at the bottom of vial; gently tap vial with your finger to remove any liquid remaining on the top of vial
  • Remove 19-gauge x 1.5-inch, 5-micron filter needle and 1-mL syringe from packaging; attach filter needle to syringe by twisting it clockwise onto Luer lock syringe tip
  • Withdraw all contents of vial (tilt vial slightly so needle touches bottom edge of vial; ensure bevel of filter needle is submerged in liquid to avoid air bubbles)
  • Remove and discard filter needle

• Attaching new injection needle, prepare syringe for administration

  • Replace needle with 30-gauge x 0.5-inch needle (provided in kit), attaching it to Luer lock syringe tip
  • Gently tap syringe to remove bubbles; expel air and set dose (0.1 mL)
  • Each vial should only be used for a single eye

Intravitreal Administration

Intravitreal administration only by qualified physician

Provide adequate anesthesia and a broad-spectrum topical microbicide

Use aseptic conditions for the intravitreal injection procedure

Inject slowly until rubber stopper reaches the end of the syringe to deliver 0.1 mL

Confirm delivery of full dose by checking that rubber stopper has reached the end of syringe barrel

If contralateral eye requires treatment, use a new vial and syringe and change sterile field, gloves, drapes, eyelid speculum, filter needle, and injection needle before administering to the other eye

Repeat the same procedure steps as above

Discard any unused product or waste material in accordance with local regulations

Monitoring parameters

• Before administering, monitor for elevated IOP using tonometry
• If necessary, administer ocular hypotensive medication to lower the IOP
• Immediately following the intravitreal injection, monitor for elevation in IOP
• Appropriate monitoring may consist of a check for perfusion of optic nerve head or tonometry
• Following intravitreal injection, instruct patient to report any symptoms suggestive of endophthalmitis (eg, eye pain, redness of the eye, photophobia, blurring of vision) without delay

Storage

Unopened vial

• Refrigerate at 2-8ºC (36-46ºF)
• Do not freeze
• Do not shake
• Once removed from refrigerator, may keep at room temperature, 20-25⁰C (68-77⁰F) for up to 24 hours; keep vial in original carton to protect from light