Avacincaptad Pegol (Local) (Monograph)

Brand name: Izervay
Drug class: EENT Drugs, Miscellaneous

Introduction

Complement C5 inhibitor; RNA aptamer covalently bound to polyethylene glycol (PEG).

Uses for Avacincaptad Pegol (Local)

Age-related Macular Degeneration

Treatment of geographic atrophy (GA) secondary to age-related macular degeneration.

The American Academy of Ophthalmology has published guidelines on the treatment of age-related macular degeneration. Antioxidant vitamins and mineral supplementation are generally recommended to slow disease progression. At the time of guideline publication, no treatments for geographic atrophy were available; however, current treatment options now include intravitreal pegcetacoplan and intravitreal avacincaptad pegol.

Avacincaptad Pegol (Local) Dosage and Administration

General

Pretreatment Screening

Prior to injection, monitor intraocular pressure (IOP) using tonometry; If necessary, ocular hypotensive medication can be given to lower IOP.

Patient Monitoring

Monitor IOP and perfusion of optic nerve head following administration of avacincaptad pegol; provide appropriate monitoring and treatment.
Monitor for signs and symptoms of endophthalmitis (e.g., eye pain, eye redness, photophobia, blurred vision).
Monitor for symptoms of retinal detachment; provide appropriate management if needed.
Monitor for signs of neovascular age-related macular degeneration.

Premedication and Prophylaxis

Administer adequate anesthesia and broad-spectrum topical microbicide prior to injection.

Administration

Intravitreal Administration

Administer as an intravitreal injection by a qualified physician.

Supplied in a single-dose vial as a 20 mg/mL solution. Only 0.1 mL (2 mg) should be used to deliver a single dose; discard any excess volume.

Administer under controlled aseptic conditions, which includes the use of surgical hand disinfection, sterile gloves, a sterile drape, and a sterile eyelid speculum (or equivalent)

Prior to administration, allow vial to warm to room temperature (20-25°C) without using external heat sources.

Inspect liquid in vial; it should be a clear to slightly opalescent, colorless to slightly yellow solution.

Do not shake vial.

Using aseptic technique and a filter needle, withdraw all liquid from vial. Attach an injection needle to prepare dose of 0.1 mL.

Administer injection immediately after preparation and inject dose volume slowly.

Each vial and syringe should only be used for treatment of a single eye; if contralateral eye requires treatment, use a new vial and syringe.

Dosage

Adults

Age-related Macular Degeneration

Intravitreal

2 mg (0.1 mL of 20 mg/mL solution) administered to each affected eye once monthly (approximately 28 ± 7 days) for up to 12 months.

Special Populations

Hepatic Impairment

Dosage adjustments not needed. The effects of hepatic impairment on pharmacokinetics of avacincaptad pegol are unknown; however, significant increases in plasma exposures not expected with intravitreal route of administration.

Renal Impairment

Dosage adjustments not needed. The effects of renal impairment on pharmacokinetics of avacincaptad pegol are unknown; however, significant increases in plasma exposures not expected with intravitreal route of administration.

Geriatric Patients

Dosage adjustments not needed in geriatric patients.

Cautions for Avacincaptad Pegol (Local)

Contraindications

Ocular or periocular infections.
Active intraocular inflammation.

Warnings/Precautions

Endophthalmitis and Retinal Detachments

Intravitreal injections may be associated with endophthalmitis and retinal detachment. No cases of endophthalmitis reported; 1 case of retinal detachment reported in a patient receiving 4 mg of avacincaptad pegol.

Use proper aseptic injection technique during administration.

If symptoms of endophthalmitis or retinal detachment develop, provide appropriate management.

Neovascular Age-related Macular Degeneration

Increased rates of neovascular age-related macular degeneration or choroidal neovascularization reported.

Monitor for signs of neovascular age-related macular degeneration.

Increase in Intraocular Pressure (IOP)

Transient increases in IOP observed.

Monitor perfusion of optic nerve head following injection; manage as needed.

Specific Populations

Pregnancy

No adequate data on use of avacincaptad pegol in pregnant women. No maternal or embryofetal adverse effects observed in animal studies.

Use of avacincaptad pegol in pregnancy may be considered following an assessment of risks and benefits.

Lactation

Not known whether avacincaptad pegol is distributed into human milk, or if the drug has any effects on the breastfed infant or milk production. Consider benefits of breastfeeding along with mother's clinical need for avacincaptad pegol and any potential adverse effects on the breastfed infant from the drug.

Females and Males of Reproductive Potential

Female and male reproductive effects not known.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

Majority of patients (90%) in clinical studies were ≥65 years of age. No differences in efficacy or safety observed with increasing age.

Hepatic Impairment

Safety and efficacy not studied in hepatic impairment.

Renal Impairment

Safety and efficacy not studied in renal impairment.

Common Adverse Effects

Most common adverse reactions: conjunctival hemorrhage (13%), increased IOP (9%), blurred vision (8%), neovascular age-related macular degeneration (7%).

Drug Interactions

No clinical drug interaction studies performed.

Avacincaptad Pegol (Local) Pharmacokinetics

Absorption

Bioavailability

Following a single intravitreal injection, peak plasma concentrations achieved in approximately 7 days.

Elimination

Metabolism and elimination not fully characterized. Expected to be catabolized by endonucleases and exonucleases to oligonucleotides of shorter lengths; may be excreted renally.

Half-life

Approximately 12 days.

Stability

Storage

Intravitreal

Injection Solution

Store at 2-8°C in original container to protect from light. Unopened vial may be kept at 20-25ºC for up to 24 hours prior to use.

Actions

Complement C5 inhibitor; an RNA aptamer covalently bound to a branched PEG molecule.
The complement system is thought to play a role in pathophysiology of geographic atrophy. Complement C5 is a central component of the complement system that is involved in promoting inflammation and cell death.
Avacincaptad pegol inhibits complement C5, preventing its cleavage to key terminal components C5a and C5b, thus decreasing membrane attack complex formation and potentially slowing progression of retinal cell degeneration.

Advice to Patients

Advise patients that following avacincaptad pegol administration, patients are at risk of developing neovascular age-related macular degeneration, endophthalmitis, elevated intraocular pressure, and retinal detachments. If the eye becomes red, sensitive to light, painful, or if a patient develops a change in vision, instruct the patient to seek immediate care from an ophthalmologist.
Patients may experience temporary visual disturbances and blurring after an intravitreal injection with avacincaptad pegol and the associated eye examinations. Advise patients not to drive or use machinery until visual function has recovered sufficiently.
Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
Advise patients to inform their clinician if they are or plan to become pregnant or plan to breast-feed.
Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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.

Avacincaptad pegol for intravitreal injection is obtained through designated specialty distributors and specialty pharmacies. Contact the manufacturer or consult the Izervay website ([Web]) for more information.