Pegcetacoplan (Monograph)

Brand name: Syfovre
Drug class: EENT Drugs, Miscellaneous

Introduction

Pegcetacoplan is a complement inhibitor.

Uses for Pegcetacoplan

Pegcetacoplan has the following uses:

Pegcetacoplan is indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

Pegcetacoplan Dosage and Administration

General

Pegcetacoplan is available in the following dosage form(s) and strength(s):

150 mg/mL in a single-dose vial for intravitreal injection.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

Pegcetacoplan must be administered by a qualified physician.

Prior to the intravitreal injection, patients should be monitored for elevated intraocular pressure (IOP) using tonometry. If necessary, ocular hypotensive medication can be given to lower the IOP.

The intravitreal injection procedure should be carried out under aseptic conditions, which includes the use of surgical hand disinfection, sterile gloves, a sterile drape, and a sterile eyelid speculum (or equivalent). Adequate anesthesia and a broad-spectrum topical microbicide to disinfect the periocular skin, eyelid, and ocular surface should be administered prior to the injection.

The recommended dose for pegcetacoplan is 15 mg (0.1 mL of the 150 mg/mL solution) administered by intravitreal injection to each affected eye once every 25 to 60 days.

Each vial should only be used for the treatment of a single eye. If the other eye requires treatment, a new sterile vial should be used and the sterile field, syringe, gloves, drapes, eyelid speculum, filter, and injection needles should be changed before administration.

See Full Prescribing Information for additional details on preparation and administration of the intravitreal injection.

Related/similar drugs

Vabysmo, Eylea, Izervay, ranibizumab ophthalmic, Lucentis, aflibercept ophthalmic, Syfovre

Cautions for Pegcetacoplan

Contraindications

• Ocular or periocular infections.

• Active intraocular inflammation.

Warnings/Precautions

Endophthalmitis and Retinal Detachments

Intravitreal injections, including those with pegcetacoplan, may be associated with endophthalmitis and retinal detachments. Proper aseptic injection technique must always be used when administering pegcetacoplan in order to minimize the risk of endophthalmitis. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately.

Neovascular Age-related Macular Degeneration (AMD)

In clinical trials, use of pegcetacoplan 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. Patients receiving pegcetacoplan should be monitored for signs of neovascular AMD. In case anti-vascular endothelial growth factor (anti-VEGF) is required, it should be given separately from pegcetacoplan administration.

Intraocular Inflammation

In clinical trials, use of pegcetacoplan was associated with episodes of intraocular inflammation including vitritis, vitreal cells, iridocyclitis, uveitis, anterior chamber cells, iritis, and anterior chamber flare. After inflammation resolves, patients may resume treatment with pegcetacoplan.

Increased Intraocular Pressure (IOP)

Acute increase in IOP may occur within minutes of any intravitreal injection, including with pegcetacoplan. Perfusion of the optic nerve head should be monitored following the injection and managed as needed.

Specific Populations

Pregnancy

There are no adequate and well-controlled studies of pegcetacoplan administration in pregnant women to inform a drug-associated risk. The use of pegcetacoplan may be considered following an assessment of the risks and benefits.

Systemic exposure of pegcetacoplan following ocular administration is low. 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) of pegcetacoplan (based on the area under the curve (AUC) systemically measured levels). No adverse maternal or fetal effects were observed in monkeys at systemic exposures approximately 470-fold higher than that observed in humans at the MRHOD.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

In embryofetal development studies, subcutaneous administration of pegcetacoplan to pregnant cynomolgus monkeys from the mid gestation period through birth produced increased incidences of abortions and stillbirths at doses of 28 mg/kg/day [approximately 1040-fold higher than the MRHOD based on exposure (AUC)]. Pegcetacoplan was not maternally toxic and did not produce adverse embryofetal effects in the monkey at subcutaneous doses of 7 mg/kg/day (approximately 470-fold higher than the MRHOD). No developmental effects were observed in infants up to 6 months postpartum. Minimal systemic exposure to pegcetacoplan (less than 1%, not pharmacologically significant) was detected in fetuses from monkeys treated subcutaneously with 28 mg/kg/day from the period of organogenesis through the second trimester.

Lactation

It is not known whether intravitreal 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. Because many drugs are excreted in human milk, and because the potential for absorption and harm to infant growth and development exists, caution should be exercised when pegcetacoplan is administered to a nursing woman.

Pegcetacoplan was detectable in milk of lactating monkeys after subcutaneous administration at less than 1% concentration of serum levels but was not detectable in the serum of nursing infants.

Females and Males of Reproductive Potential

It is recommended that women of childbearing potential use effective contraception methods to prevent pregnancy during treatment with intravitreal pegcetacoplan. Advise female patients of reproductive potential to use effective contraception during treatment with pegcetacoplan and for 40 days after the last dose. For women planning to become pregnant, the use of pegcetacoplan may be considered following an assessment of the risks and benefits.

Pediatric Use

The safety and effectiveness of pegcetacoplan in pediatric patients have not been established.

Geriatric Use

In clinical studies, approximately 97% (813/839) of patients randomized to treatment with pegcetacoplan were ≥ 65 years of age and approximately 72% (607/839) were ≥ 75 years of age. No significant differences in efficacy or safety were seen with increasing age in these studies. No dosage regimen adjustment is recommended based on age.

Common Adverse Effects

Most common adverse reactions (incidence ≥5%) are ocular discomfort, neovascular age-related macular degeneration, vitreous floaters, and conjunctival hemorrhage.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

Mechanism of Action

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

Advice to Patients

• Advise patients that following pegcetacoplan administration, patients are at risk of developing neovascular AMD, endophthalmitis, and retinal detachments. If the eye becomes red, sensitive to light, painful, or if a patient develops any change in vision such as flashing lights, blurred vision or metamorphopsia, instruct the patient to seek immediate care from an ophthalmologist.

• Patients may experience temporary visual disturbances associated either with the intravitreal injection with pegcetacoplan or the eye examination. Advise patients not to drive or use machinery until visual function has recovered sufficiently.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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