pegcetacoplan ophthalmic
Pegcetacoplan ophthalmic
Generic Name
Pegcetacoplan ophthalmic
Mechanism
- Pegcetacoplan binds with high affinity to the surface of C3, occluding its active sites and thereby blocking the formation of both the classical and alternative pathway C3 convertases (C4b2a and C3bBb).
- Inhibition of C3 convertase prevents the downstream cascade that generates the potent pro‑inflammatory C3a/C5a anaphylatoxins and the membrane attack complex (MAC).
- By limiting complement‑mediated opsonization and inflammation of retinal pigment epithelial (RPE) cells, pegcetacoplan slows the progression of GA lesions.
Pharmacokinetics
| Parameter | Detail | Notes |
| Route | Intravitreal injection | Local delivery ensures high ocular concentrations and minimal systemic exposure |
| Dose | 2 mg in 0.066 mL vitreous | Standard therapeutic dose (per FDA‑approved formulation) |
| Distribution | Primarily within vitreous and retina; limited diffusion to aqueous humor | PEGylation prolongs ocular residence time (~10–12 days) |
| Metabolism | Proteolytic degradation by retinal peptidases | Clearance mainly intravitreal; negligible systemic absorption |
| Half‑life | ~6–8 days in the vitreous | Supports once‑monthly dosing schedule |
| Systemic exposure | <1 % of intravitreal dose | Low risk of systemic complement inhibition |
Indications
- Geographic atrophy secondary to age‑related macular degeneration (GA‑AMD)
- Used to slow GA expansion velocity in patients with at least one active GA lesion ≥2 mm in diameter.
- Not indicated for neovascular AMD or ocular inflammation unrelated to complement over‑activation.
Contraindications
- Absolute contraindications
- Active intra‑ocular infection (e.g., endophthalmitis)
- Known hypersensitivity to pegcetacoplan, polyethylene glycol (PEG), or any excipient
- Relative contraindications
- Angle‑closure glaucoma / uncontrolled intra‑ocular pressure (IOP)
- Severe ocular surface disease (e.g., severe dry eye, blepharitis)
- Warnings
- Possible increase in IOP; monitor closely post‑injection
- Risk of conjunctival hemorrhage or postoperative inflammation
- Local complement inhibition may predispose to opportunistic infections of the eye; apply standard sterile technique and consider prophylactic antibiotics
Dosing
- Loading phase
- 4–6 intravitreal injections, 2 weeks apart (alternatively 4 weeks for some regimens).
- Maintenance phase
- 1 injection every 4 weeks thereafter.
- Technique
- Use sterile phaconic 23‑gauge needle; inject posterior to the limbus, 3.5–4 mm posterior to the corneal edge (standard for intravitreal drug).
- Apply topical antibiotics and steroids prophylactically as per institutional protocol.
- Retreatment
- Resume monthly dosing if lesion progression observed on OCT or visual acuity decline >2 lines.
Adverse Effects
| Adverse Effect | Frequency | Management |
| Subconjunctival hemorrhage | ≤5 % | Usually self‑resolving |
| Injection‑site pain/herniation | ~4 % | Use lidocaine, mild antiseptics |
| Increased IOP | ~2 % | Topical β‑blockers, α‑agonists; consider discontinuation if >35 mmHg |
| Posterior capsule opacification | Rare | Ophthalmic evaluation |
| Endophthalmitis | Very rare | Immediate vitrectomy and antibiotics |
| CME (cystoid macular edema) | <1 % | Oral/topical steroids |
Monitoring
| Parameter | Frequency | Rationale |
| Best‑corrected visual acuity (BCVA) | Baseline, 1 wk post‑dose, then monthly | Detect functional changes |
| Intra‑ocular pressure | Pre‑dose, 1 wk post‑dose, then monthly | Identify pressure spikes |
| Spectral‑domain OCT | Baseline, 1 wk post‑dose, then monthly | Track GA lesion size & central subfield thickness |
| Fundus photography | Baseline, 3 mo, then as needed | Document morphological changes |
| Systemic complement activity (optional) | At baseline & every 6 mo | Ensure systemic complement is not unduly suppressed |
| Adverse event review | Per‑visit | Early detection of ocular complications |
Clinical Pearls
- PEGylation is key – The polyethylene glycol moiety extends ocular half‑life, permitting a monthly dosing schedule rather than weekly exposure.
- Anti‑VEGF synergy – In patients with concurrent exudative AMD, pegcetacoplan may be combined with anti‑VEGF therapy; watch for cumulative ocular toxicity.
- IOP monitoring is critical – Even mild pressure elevations can precipitate glaucomatous damage; consider routine baseline IOP screening for patients with a history of ocular hypertension.
- Patient education – Counsel patients on red‑flag symptoms (pain, vision loss, floaters) that warrant immediate ophthalmologic evaluation.
- Compliance and adherence – Monthly clinic visits can be burdensome; teleophthalmology check‑in with OCT imaging may improve compliance for stable patients.
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