pegcetacoplan (Rx)

Brand and Other Names:Empaveli
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injection, solution

  • 1,080mg/20mL (54mg/mL) single-dose vial

Paroxysmal Nocturnal Hemoglobinuria

Indicated for paroxysmal nocturnal hemoglobinuria (PNH)

1,080 mg SC infusion twice weekly

Switching to pegcetacoplan from C5 inhibitors

  • Switching from eculizumab: Initiate pegcetacoplan while continuing eculizumab at its current dose; after 4 weeks, discontinue eculizumab before continuing on monotherapy with pegcetacoplan
  • Switching from ravulizumab: Initiate pegcetacoplan no more than 4 weeks after last ravulizumab dose

Dosage Modifications

Lactate dehydrogenase (LDH) levels

  • LDH >2x ULN: Adjust dose to 1,080 mg SC q3 days
  • Monitor LDH twice weekly for at least 4 weeks following dosage increase

Renal or hepatic impairment

  • No clinically significant differences in the pharmacokinetics based on renal impairment or hepatic function

Dosing Considerations

Vaccination and antibiotic prophylaxis

Vaccinate for meningococcal disease according to current Advisory Committee on Immunization Practices (ACIP) guidelines to reduce the risk of serious infection

Provide antibacterial drug prophylaxis for 2 weeks if pegcetacoplan must be initiated immediately and vaccines are administered <2 weeks before initiating pegcetacoplan

Safety and efficacy not established

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Adverse Effects

>10%

Infusion-site reactions (39%)

Infection (29%)

Diarrhea (22%)

Abdominal pain (20%)

Respiratory tract infection (15%)

Viral infection (12%)

Fatigue (12%)

1-10%

Chest pain (7%)

Back pain (7%)

Headache (7%)

Systemic hypertension (7%)

Intestinal ischemia (<5%)

Biliary sepsis (<5%)

Hypersensitivity pneumonitis (<5%)

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Warnings

Black Box Warnings

Meningococcal infections/sepsis

  • Meningococcal infections/sepsis may occur
  • Meningococcal infections may become rapidly lifethreatening or fatal if not recognized and treated early
  • Use may predispose individuals to serious infections, especially those caused by encapsulated bacteria, such as Streptococcus pneumoniae, Neisseria meningitidis types A, C, W, Y, and B, and Haemophilus influenzae type B
  • Comply with the most current ACIP recommendations for meningococcal vaccination in patients with complement deficiencies
  • Vaccinate against encapsulated bacteria at least 2 weeks before administering the first pegcetacoplan dose, unless the risks of delaying pegcetacoplan outweigh the risk of developing a meningococcal infection
  • Vaccination reduces, but does not eliminate, meningococcal infection risk
  • Monitor for early signs of meningococcal infections and evaluate immediately if infection is suspected

Risk evaluation and mitigation strategy (REMS)

  • Available only through REMS program
  • Prescribers must enroll in the program
  • 1-888-343-7073 or at www.empavelirems.com

Contraindications

Hypersensitivity to pegcetacoplan or to any of the excipients

Patients not vaccinated against certain encapsulated bacteria, unless the risks of delaying pegcetacoplan treatment outweigh risks of developing a bacterial infection with an encapsulated organism

Patients with unresolved serious infection caused by encapsulated bacteria, including S pneumoniae, N meningitidis, and H influenzae

Cautions

Available only through restricted access program

Infusion-related reactions reported, including systemic hypersensitivity reactions (eg, facial swelling, rash, urticaria); discontinue infusion immediately and provide appropriate treatment, per standard of care, if severe hypersensitivity reaction, including anaphylaxis, occurs; monitor until signs and symptoms resolve

Serious infections caused by encapsulated bacteria

  • May increase risk for serious infections caused by encapsulated bacteria
  • All patients must be vaccinated against these bacteria according to the most current ACIP recommendations for patients with altered immunocompetence associated with complement deficiencies
  • Revaccinate patients in accordance with ACIP recommendations considering the duration of therapy
  • If vaccination history unknown, administer required vaccines at least 2 weeks before first pegcetacoplan dose
  • If immediate therapy with pegcetacoplan indicated, administer required vaccine as soon as possible and provide patients with 2 weeks of antibacterial drug prophylaxis
  • Closely monitor for infection

Monitoring after discontinuation

  • Closely monitor for signs and symptoms of hemolysis, identified by elevated LDH levels along with sudden decrease in PNH clone size or hemoglobin, or reappearance of symptoms (eg, fatigue, hemoglobinuria, abdominal pain, dyspnea, major adverse vascular events [including thrombosis], dysphagia, erectile dysfunction)
  • Monitor for at least 8 weeks to detect hemolysis and other reactions
  • If hemolysis, including elevated LDH, occurs, consider restarting treatment

Interference with laboratory tests

  • Drug may interfere with silica reagents in coagulation panels that results in artificially prolonged activated partial thromboplastin time; avoid silica reagents in coagulation panels
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Pregnancy & Lactation

Pregnancy

Insufficient data regarding use in pregnant females to inform of drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

There are risks to the mother and fetus associated with untreated PNH during pregnancy

Animal studies

  • Treatment of pregnant cynomolgus monkeys (28 mg/kg/day SC) (2.9 times human exposure based on AUC) from gestation through parturition resulted in a statistically significant increase in abortions or stillbirths compared with controls

Clinical considerations

  • PNH in pregnancy associated with adverse maternal outcomes, including worsening cytopenias, thrombotic events, infections, bleeding, miscarriages, and increased maternal mortality, and adverse fetal outcomes, including fetal death and premature delivery

Contraception

  • May cause embryofetal harm when administered to pregnant females
  • Pregnancy testing recommended for females of reproductive potential before treatment
  • Advise female patients of reproductive potential to use effective contraception during treatment and for 40 days after last dose

Lactation

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

There are no data on effects on milk production

Pegcetacoplan is present in milk of lactating monkeys; since many medicinal products are secreted into human milk, and the potential exists for serious adverse reaction in a breastfeeding child, breastfeeding should be discontinued during treatment and for 40 days after the last dose

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.

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Pharmacology

Mechanism of Action

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

In PNH, extravascular hemolysis (EVH) is facilitated by C3b opsonization while intravascular hemolysis (IVH) is mediated by the downstream membrane attack complex

Pegcetacoplan acts proximally in the complement cascade controlling both C3b-mediated EVH and terminal complement-mediated IVH

Absorption

Peak plasma time: 108-144 hr (4.5-6 days)

Trough serum concentration (steady-state): 655-706 mcg/mL (at 16 weeks)

Steady-state achieved ~4-6 weeks

Distribution

Vd: ~3.9 L

Metabolism

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

Elimination

Half-life: 8 days

Clearance: 0.37 L/day

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Administration

SC Preparation

Allow pegcetacoplan to reach room temperature for ~30 minutes; keep vial in carton until ready for use to protect from light

Visually inspect for particulate matter and discoloration prior to use; solution should appear clear, colorless to slightly yellowish; discard if cloudy, contains particles, or is dark yellow

Use needleless transfer device (eg, vial adapter) or transfer needle to fill syringe

Refer to prescribing information and infusion pump instructions for full details

SC Administration

Infuse via commercially available infusion pump with a reservoir of at least 20 mL

Rotate infusion sites (ie, abdomen, thighs, hips, upper arms) from 1 infusion to the next

Do not infuse where skin is tender, bruised, red, or hard; avoid infusing into tattoos, scars, or stretch marks

Typical infusion time ~30 minutes (if using 2 infusion sites) or ~60 minutes (if using 1 infusion site)

Discard any unused portion

Self-administration

  • After proper training in SC infusion, patient/caregiver may administer, if the healthcare provider deems appropriate

Missed dose

  • Administer as soon as possible after missed dose
  • Resume regular dosing schedule following administration of missed dose

Discontinuation

  • Inform patients that they may develop hemolysis due to PNH when pegcetacoplan discontinued and that they need to be monitored by their healthcare professional for at least 8 weeks
  • Instruct patients who discontinue pegcetacoplan to keep the Patient Safety Card with them for 2 months after the last dose, owing to increased risk of serious infection that persists for several weeks

Storage

Refrigerate at 2-8ºC (36-46ºF) in original carton to protect from light

Keep out of reach of children

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Images

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Patient Handout

A Patient Handout is not currently available for this monograph.
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Formulary

FormularyPatient Discounts

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The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

Tier Description
1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC NOT COVERED – Drugs that are not covered by the plan.
Code Definition
PA Prior Authorization
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
QL Quantity Limits
Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
ST Step Therapy
Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
OR Other Restrictions
Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.