Pegcetacoplan (Monograph)

Drug class: Complement Inhibitor Agents

Medically reviewed by Drugs.com on May 10, 2024. Written by ASHP.

Introduction

Complement inhibitor.

Uses for Pegcetacoplan

Paroxysmal Nocturnal Hemoglobinuria

Treatment of paroxysmal nocturnal hemoglobinuria (PNH) in adults.

Designated an orphan drug by FDA for this use.

Options for PNH management include supportive care (e.g., iron supplementation, RBC transfusion, antibiotics for bacterial infection, corticosteroids), allogeneic bone marrow transplantation, and/or terminal complement inhibitors (e.g., ravulizumab, eculizumab); choice of therapy is based on the patient’s PNH classification and symptom severity.

Pegcetacoplan Dosage and Administration

General

Pretreatment Screening

• Assess immunization status prior to initiation of pegcetacoplan therapy.

• Perform pregnancy testing in females of reproductive potential prior to initiation of pegcetacoplan therapy.

Patient Monitoring

• Closely monitor patients for early signs and symptoms of serious infections during treatment with pegcetacoplan, and evaluate immediately if infection is suspected.

• Monitor patients for infusion-related reactions during treatment with pegcetacoplan.

• Closely monitor for signs and symptoms of hemolysis for at least 8 weeks after discontinuation of pegcetacoplan therapy.

• Monitor lactate dehydrogenase (LDH) levels during treatment; if the dosage of pegcetacoplan is increased, monitor LDH twice weekly for at least 4 weeks.

Premedication and Prophylaxis

• Vaccinate patients against encapsulated bacteria, including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type B at least 2 weeks prior to initiation of pegcetacoplan therapy according to Advisory Committee on Immunization Practices (ACIP) guidelines. If immediate pegcetacoplan administration is necessary and vaccines are administered <2 weeks prior to starting therapy, provide 2 weeks of antibacterial drug prophylaxis.

REMS

• Due to the risk of serious infections, the distribution of pegcetacoplan is restricted under a Risk Evaluation and Mitigation Strategy (REMS). Healthcare professionals who prescribe pegcetacoplan must enroll in the REMS program, counsel patients on the risk of serious infection, provide patients with educational materials, and ensure that patients are vaccinated against encapsulated bacteria. Prescribers can enroll in the program by calling 1-888-343-7073 or visiting [Web].

Administration

Sub-Q Administration

Administered sub-Q using an infusion pump or disposable on-body injector. Available in single-dose vials containing pegcetacoplan 1080 mg/20 mL (54 mg/mL).

Intended for use under the guidance of a healthcare professional. May be self-administered or administered by a caregiver after proper training, if determined appropriate by a healthcare provider.

Allow vial to reach room temperature for approximately 30 minutes prior to preparation. Do not use if the liquid is cloudy or dark yellow or contains particles.

Use a needleless transfer device (e.g., a vial adapter) or a transfer needle (if administering via infusion pump) to transfer pegcetacoplan from the vial. Refer to the manufacturer's instructions for use for full preparation and administration information.

Do not administer into sites where the skin is tender, bruised, red, or hard; avoid administration into tattoos, scars, or stretch marks.

On-body injector is for abdominal sub-Q use only; rotate the site of each sub-Q administration.

If using an infusion pump, appropriate infusion sites include the abdomen, thighs, hips, and upper arms. Rotate infusion sites from one infusion to the next. If multi-infusion sets are required for a single administration, infusion sites should be ≥3 inches apart.

If a dose is missed, administer as soon as possible; resume the regular dosing schedule following administration of the missed dose.

Administration Rate

If using an infusion pump, administer over approximately 30 minutes (if using 2 infusion sites) or approximately 60 minutes (if using 1 infusion site).

If administering via on-body injector, injection time is approximately 30–60 minutes.

Dosage

Adults

Paroxysmal nocturnal hemoglobinuria

Sub-Q

1080 mg twice weekly.

If switching from eculizumab to pegcetacoplan: initiate pegcetacoplan while continuing eculizumab at its current dose; after 4 weeks, discontinue eculizumab and continue pegcetacoplan monotherapy.

If switching from ravulizumab to pegcetacoplan: initiate pegcetacoplan no more than 4 weeks after the last ravulizumab dose.

<C> Dosage Modifications

If LDH >2 times ULN, adjust pegcetacoplan dosage regimen to 1080 mg every 3 days. Monitor LDH twice weekly for at least 4 weeks after a dosage increase.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Use

No specific dosage recommendations.

Cautions for Pegcetacoplan

Contraindications

• Hypersensitivity to pegcetacoplan or any component in the formulation.

• Patient not currently vaccinated against certain encapsulated bacteria, unless the risks of delaying pegcetacoplan treatment outweigh those of developing an infection with encapsulated bacteria.

• Unresolved serious infection caused by encapsulated bacteria including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae.

Warnings/Precautions

Warnings

Serious Infections Caused by Encapsulated Bacteria

Risk of serious infections caused by encapsulated bacteria. (See Boxed Warning.)

Vaccinate all patients in accordance with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for patients with altered immunocompetence associated with complement deficiencies. Revaccinate patients according to ACIP recommendations with consideration of therapy duration.

For patients without known vaccination history, administer required vaccines at least 2 weeks prior to administering the first dose of pegcetacoplan, unless the risks of delaying therapy outweigh those of developing a serious infection. If immediate pegcetacoplan therapy is indicated, administer required vaccines as soon as possible and provide patients with 2 weeks of antibacterial drug prophylaxis.

Closely monitor patients for early signs and symptoms of serious infections. Evaluate patients quickly if infection is suspected; treat known infections immediately. Consider drug discontinuation in patients being treated for serious infections.

Pegcetacoplan available only through a REMS program due to risk of serious infections. Prescribers must enroll in the REMS program prior to prescribing. Prescribers must counsel patients about risk of serious infections, provide patients with REMS educational materials, and ensure that patients are vaccinated against encapsulated bacteria. For enrollment and additional information, visit [Web] or call 1-888-343-7073.

Other Warnings and Precautions

Infusion-related Reactions

Systemic hypersensitivity reactions (e.g., rash, facial swelling, urticaria) reported.

If a severe hypersensitivity reaction (including anaphylaxis) occurs, immediately discontinue pegcetacoplan infusion, initiate appropriate treatment, and monitor until signs and symptoms are resolved.

Monitoring Paroxysmal Nocturnal Hemoglobinuria (PNH) Manifestations after Discontinuation

Closely monitor patients for signs and symptoms of hemolysis after treatment discontinuation. Hemolysis may be identified by elevated LDH levels in combination with sudden decrease in PNH clone size or hemoglobin, or by reappearance of symptoms such as fatigue, abdominal pain, dyspnea, major adverse vascular events (including thrombosis), dysphagia, hemoglobinuria, or erectile dysfunction.

Monitor patients for ≥8 weeks after pegcetacoplan discontinuation to detect hemolysis and other reactions. Consider restarting pegcetacoplan if signs and symptoms of hemolysis (including elevated LDH) occur after discontinuation.

Interference with Laboratory Tests

Artificially prolonged aPTT may occur due to interference between pegcetacoplan and silica reagents in coagulation panels.

Avoid use of silica reagents in coagulation panels.

Specific Populations

Pregnancy

Data insufficient to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

Untreated PNH in pregnancy is associated with adverse maternal outcomes (e.g., worsening cytopenia, thrombosis, infections, bleeding, miscarriage, maternal mortality) and adverse fetal outcomes (e.g., fetal death, premature delivery).

Evaluate pregnancy status prior to treatment initiation. Consider use during pregnancy following assessment of risks and benefits.

Lactation

Unknown whether pegcetacoplan distributes into human milk or affects milk production. Potential for drug absorption and harm to the infant also unknown. Detected in milk of lactating monkeys.

Breast-feeding not recommended during treatment and for 40 days after the last dose.

Females and Males of Reproductive Potential

Use during pregnancy may cause embryo-fetal harm.

Evaluate pregnancy status prior to treatment initiation. Use effective contraception during therapy and for 40 days after the last dose.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

Clinical studies did not include sufficient numbers of geriatric patients (≥65 years of age) to determine if they respond differently from younger patients. Differences in responses between geriatric and younger patients not identified in other reported clinical experience.

No clinically important differences in pegcetacoplan pharmacokinetics based on age (19–81 years old).

Hepatic Impairment

No clinically important differences in pegcetacoplan pharmacokinetics based on hepatic impairment as assessed by total bilirubin (0.06–8.8 mg/dL), albumin (3–5.5 g/dL), AST (6–302 IU/L), or ALT (4–209 IU/L).

Renal Impairment

No clinically important differences in pegcetacoplan pharmacokinetics based on renal impairment.

Common Adverse Effects

Most common adverse effects (≥10%): injection-site reactions, infections (including respiratory tract infections and viral infections), cough, abdominal pain, diarrhea, pain in the extremities, hypokalemia, fatigue, arthralgia, dizziness, headache, rash.

Drug Interactions

No drug-drug interactions noted by manufacturer.

Pegcetacoplan Pharmacokinetics

Absorption

Bioavailability

Median time to peak plasma drug concentration: 108–144 hours (4.5–6 days).

Steady-state concentrations achieved 4–6 weeks after first dose.

Distribution

Extent

Not known whether distrubuted into human milk.

Elimination

Metabolism

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

Half-life

8.6 days.

Stability

Storage

Parenteral

Injection, for sub-Q use

2–8ºC in original carton to protect from light.

Actions

• Pegylated complement inhibitor targeting complement C3.

• Binds to complement protein C3 (and its activation fragment C3b) and regulates the cleavage of C3 and the generation of downstream effectors of complement activation.

• Acts proximally in the complement cascade that controls both C3b-mediated extravascular hemolysis and terminal complement-mediated intravascular hemolysis.

• Works higher in the complement system than the complement C5 inhibitors, eculizumab and ravulizumab, which are also used in management of paroxysmal nocturnal hemoglobinuria.

Advice to Patients

• Advise patients to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

• Advise patients of the risk of serious infection with pegcetacoplan. Inform patients that they must be vaccinated against encapsulated bacteria ≥2 weeks prior to receiving the first dose of pegcetacoplan if they have not been previously vaccinated. Inform patients that revaccination according to current medical guidelines for encapsulated bacteria is required during pegcetacoplan therapy.

• Advise patients to seek immediate medical attention if signs or symptoms of an infection occur (e.g., fever with or without chills, rash accompanied by fever, shortness of breath, extreme pain, headache accompanied by nausea, vomiting, stiff neck, stiff back, and/or fever, high heart rate, confusion, muscle aches, clammy skin, sensitivity to light).

• Instruct patients to always carry their provided Patient Safety Card for pegcetacoplan, which describes symptoms that should prompt them to seek immediate medical evaluation. Inform patients who discontinue pegcetacoplan to keep the Patient Safety Card with them for 2 months after the last dose, since the risk of serious infections persists for several weeks following treatment discontinuation.

• Advise patients of the risk of anaphylaxis and infusion-related reactions. Advise patients to seek immediate medical attention if signs or symptoms of anaphylaxis occur (e.g., difficulty breathing, swollen tongue/throat, dizziness or fainting, rapid heart rate, hives/itching, nausea/vomiting, confusion, anxiety).

• Inform patients that they will be monitored by their clinician for ≥8 weeks following discontinuation of pegcetacoplan since they are at risk for developing hemolysis due to paroxysmal nocturnal hemoglobinuria.

• 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 women to inform their clinician if they are or plan to become pregnant. Advise women that pegcetacoplan may cause embryo-fetal harm when administered during pregnancy, and that pregnancy testing is recommended for females of reproductive potential prior to treatment initiation. Advise females of reproductive potential to use effective contraception during pegcetacoplan therapy and for 40 days after the last dose.

• Advise women to inform their clinician if they plan to breast-feed. Advise patients to not breast-feed during pegcetacoplan therapy and for 40 days after the last dose.

• 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.

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