pegcetacoplan intravitreal (Rx)

>10%

Ocular discomfort (13%)

Neovascular AMD (12%)

1-10%

Vitreous floaters (10%)

Conjunctival hemorrhage (8%)

Punctate keratitis (5%)

Vitreous detachment (4%)

Retinal hemorrhage (4%)

Posterior capsule opacification (4%)

Intraocular inflammation (4%)

Increased IOP (2%)

Optic ischemic neuropathy (1.7%)

<1%

Endophthalmitis

Retinal detachment

Hyphema

Retinal tears

Contraindications

Ocular or periocular infections

Active intraocular inflammation

Cautions

Endophthalmitis and retinal detachments

• Intravitreal injections may be associated with endophthalmitis and retinal detachments
• Proper aseptic injection technique must always be used during administration to minimize endophthalmitis risk
• Instruct patients to immediately report any symptoms suggestive of endophthalmitis or retinal detachment in order to enable appropriate management

Neovascular AMD

• In clinical trials, use was associated with increased rates of neovascular (wet) AMD or choroidal neovascularization (12% when administered monthly, 7% when administered every other month and 3% in the control group) by Month 24
• Monitored for signs of neovascular AMD
• If anti–vascular endothelial growth factor (anti-VEGF) is required, administer separately from pegcetacoplan intravitreal

Intraocular inflammation

• Episodes of intraocular inflammation reported, including vitritis, vitreal cells, iridocyclitis, uveitis, anterior chamber cells, iritis, and anterior chamber flare
• After inflammation resolves, patients may resume pegcetacoplan intravitreal injections

Increased intraocular pressure

• Acute increase in IOP may occur within minutes of any intravitreal injection
• Monitor perfusion of the optic nerve head following the injection and manage as needed

Pregnancy

There are no adequate and well-controlled studies of administration in pregnant women to inform a drug-associated risk

Animal studies

• Subcutaneous administration of pegcetacoplan to pregnant monkeys from the mid gestation period through birth resulted in increased incidences of abortions and stillbirths at systemic exposures 1040-fold higher than that observed in humans at the maximum recommended human ophthalmic dose (MRHOD)

Contraception

• Females of reproductive potential: Use effective contraception methods to prevent pregnancy during treatment and for 40 days after last dose
• For females planning to become pregnant: Use may be considered following an assessment of the risks and benefits

Lactation

Unknown whether intravitreally administered pegcetacoplan is secreted in human milk or whether there is potential for absorption and harm to the infant

Animal data suggest that the risk of clinically relevant exposure to the infant following maternal intravitreal treatment is minimal

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

Targeted complement-3 (C3) therapy designed to regulate excessive activation of the complement cascade

Binds to complement protein C3 and its activation fragment C3b with high affinity, thereby regulating cleavage of C3 and the generation of downstream effectors of complement activation

Absorption

Peak plasma time: 7-14 days

Peak plasma concentrations

• Monthly injections: 2.2 mcg/mL
• Every-other-month injections: 1.5 mcg/mL

Trough concentrations

• Monthly injections: 1 mcg/mL
• Every-other-month injections: 0.2 mcg/mL

Distribution

Vd: 1.85 L

Metabolism

Expected to be metabolized into small peptides and amino acids by catabolic pathways

Elimination

Half-life: 4.5 days

Clearance: 0.284 L/day

Intravitreal Preparation

Remove carton from refrigerator; keep vial in original carton at room temperature (20-25ºC [68-77ºF]) for at least 15 minutes before injection, but no longer than 8 hr

Fill syringe immediately before injection

Do not shake vial

Each vial is for use in a single eye

Inspect solution; it is a clear, colorless to light yellow aqueous solution

Discard if particulates, cloudiness, or discoloration are visible, if vial shows signs of damage or tampering, or if expiration date has passed

See prescribing information for full instructions

Intravitreal Administration

Must be administered by qualified physician

Only 0.1 mL (15 mg) should be administered to deliver a single dose; confirm delivery of full dose by checking that the rubber stopper has reached the end of the syringe barrel; dispose of any excess volume

Administer dose immediately after preparation

Monitor IOP before intravitreal injection using tonometry; if necessary, administer ocular hypotensive medication to lower IOP

Monitor perfusion of the optic nerve head following the injection, and manage as needed

Storage

Unopened single-use vials

Refrigerate at 2-8ºC (36-46ºF)

Keep vial in original carton to protect from light