Version July 2025
Pegcetacoplan, a complement inhibitor, increases the risk of serious infections, especially those caused by encapsulated bacteria, such as Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type B. Life-threatening and fatal infections with encapsulated bacteria have occurred in patients treated with complement inhibitors. These infections may become rapidly life-threatening or fatal if not recognized and treated early.
Complete or update vaccination for encapsulated bacteria at least 2 weeks prior to the first dose of pegcetacoplan, unless the risks of delaying therapy with pegcetacoplan outweigh the risk of developing a serious infection. Comply with the most current Advisory Committee on Immunization Practices recommendations for vaccinations against encapsulated bacteria in patients receiving a complement inhibitor.
Patients receiving pegcetacoplan are at increased risk for invasive disease caused by encapsulated bacteria, even if they develop antibodies following vaccination. Monitor patients for early signs and symptoms of serious infections and evaluate immediately if infection is suspected.
Because of the risk of serious infections caused by encapsulated bacteria, pegcetacoplan is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the EMPAVELI REMS.
Dosage guidance:
Safety: Vaccinate against S. pneumoniae and N. meningitidis (serogroups A, C, W, Y and B), according to current guidelines, at least 2 weeks prior to pegcetacoplan initiation; revaccinate according to current guidelines. If immediate pegcetacoplan administration is necessary in a patient not up to date with vaccines for S. pneumoniae and N. meningitidis according to current guidelines, provide antibacterial prophylaxis and administer vaccines as soon as possible.
Paroxysmal nocturnal hemoglobinuria: SUBQ: 1,080 mg twice weekly (Ref).
Dosage adjustment: For lactate dehydrogenase (LDH) >2 times ULN, adjust pegcetacoplan dosing regimen to 1,080 mg every 3 days. Monitor LDH twice weekly for at least 4 weeks after a dose increase.
Conversion from C5 inhibitors:
Conversion from eculizumab: When converting from eculizumab to pegcetacoplan, initiate pegcetacoplan while continuing eculizumab at its current dose. After 4 weeks, discontinue eculizumab and continue pegcetacoplan monotherapy.
Conversion from ravulizumab: Initiate pegcetacoplan no more than 4 weeks after the last ravulizumab dose.
Missed dose: Administer pegcetacoplan as soon as possible after a missed dose; resume the regular dosing schedule following administration of the missed dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; however, there were no clinically significant differences in pegcetacoplan pharmacokinetics based on renal impairment.
There are no dosage adjustments provided in the manufacturer's labeling; however, there were no clinically significant differences in pegcetacoplan pharmacokinetics based on hepatic function (total bilirubin 0.3 to 4.3 mg/dL, albumin 3.6 to 4.9 g/dL, AST 13 to 116 units/L, or ALT 9 to 61 units/L).
Hemolysis (after pegcetacoplan discontinuation): Consider restarting pegcetacoplan therapy.
Infection: Evaluate immediately for suspected infection; promptly treat known infection. Consider interruption of pegcetacoplan therapy if undergoing treatment for serious infection.
Infusion-related reaction: If a severe hypersensitivity reaction occurs (including anaphylaxis), discontinue pegcetacoplan immediately; administer appropriate treatment per standard of care.
Refer to adult dosing.
Pegcetacoplan commonly causes infection (eg, respiratory tract infection, viral infection) and may cause serious infection caused by encapsulated bacteria (eg, Streptococcus pneumoniae; Neisseria meningitidis types A, C, W, Y, and B; Haemophilus influenzae type B). Meningococcal infection may occur and become rapidly life-threatening. Meningococcal infections, including life-threatening and fatal infections, have been reported with another complement inhibitor (ie, eculizumab [C5 inhibitor]) (Ref). Therapy interruption may be warranted in patients who are undergoing treatment for serious infections.
Mechanism: Dose-related; related to the pharmacologic action of pegcetacoplan (a pegylated C3 inhibitor) (Ref)
Risk factors:
• Unresolved serious infection caused by encapsulated bacteria
• Unvaccinated against encapsulated bacteria
• Nonadherence with antibacterial drug prophylaxis (potential risk factor)
Injection site reactions were common with pegcetacoplan self-administered SUBQ infusion. The majority of reactions were described as mild in severity and resolved quickly, with some reported as moderate in severity. Injection-site reactions typically manifest as injection-site erythema, swelling, or induration, although pain and pruritus have also been reported (Ref). Systemic hypersensitivity reactions (eg, rash, urticaria, facial swelling) may also occur, including the potential for severe reactions, such as anaphylaxis.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Gastrointestinal: Abdominal pain (20%), diarrhea (22%)
Infection: Infection (29%; serious infection: 5%) (table 1), viral infection (12%) (table 2)
|
Drug (Pegcetacoplan) |
Comparator (Eculizumab) |
Number of Patients (Pegcetacoplan) |
Number of Patients (Eculizumab) |
|---|---|---|---|
|
29% |
26% |
41 |
39 |
|
Drug (Pegcetacoplan) |
Comparator (Eculizumab) |
Number of Patients (Pegcetacoplan) |
Number of Patients (Eculizumab) |
|---|---|---|---|
|
12% |
8% |
41 |
39 |
Local: Injection site reaction (39%) (table 3)
|
Drug (Pegcetacoplan) |
Comparator (Eculizumab) |
Number of Patients (Pegcetacoplan) |
Number of Patients (Eculizumab) |
|---|---|---|---|
|
39% |
5% |
41 |
39 |
Nervous system: Fatigue (12%)
Respiratory: Respiratory tract infection (15%) (table 4)
|
Drug (Pegcetacoplan) |
Comparator (Eculizumab) |
Number of Patients (Pegcetacoplan) |
Number of Patients (Eculizumab) |
|---|---|---|---|
|
15% |
13% |
41 |
39 |
1% to 10%:
Cardiovascular: Chest pain (7%), hypertension (7%)
Gastrointestinal: Mesenteric ischemia (<5%)
Infection: Sepsis (biliary: <5%)
Nervous system: Headache (7%)
Neuromuscular & skeletal: Back pain (7%)
Respiratory: Hypersensitivity pneumonitis (<5%)
<1%: Hypersensitivity: Severe hypersensitivity reaction
Frequency not defined: Infection: Meningococcal infection
Hypersensitivity to pegcetacoplan or any component of the formulation; initiation in patients with unresolved serious infection caused by encapsulated bacteria including S. pneumoniae, N. meningitidis, and H. influenzae type B.
Other warnings/precautions:
• Discontinuation in paroxysmal nocturnal hemoglobinuria: If hemolysis signs/symptoms (including elevated lactate dehydrogenase) occur after discontinuation, consider restarting pegcetacoplan treatment.
• REMS program: Pegcetacoplan is available only through a restricted program under a REMS. Under the EMPAVELI REMS, prescribers must enroll in the program. Enrollment in the EMPAVELI REMS program and additional information are available at https://www.empavelirems.com or 1-888-343-7073.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Subcutaneous [preservative free]:
Empaveli: 1080 mg/20 mL (20 mL)
No
Solution (Empaveli Subcutaneous)
1080 mg/20 mL (per mL): $291.54
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Subcutaneous:
Empaveli: 1080 mg/20 mL (20 mL)
SUBQ: Do not administer in sites where the skin is tender, bruised, red, or hard; avoid infusion into tattoos, scars, or stretch marks. Allow pegcetacoplan to reach room temperature for ~30 minutes prior to use. Pegcetacoplan may be self-administered or administered by a caregiver after proper training.
Infusion pump: Administer SUBQ over ~30 minutes (if using 2 infusion sites) or ~60 minutes (if using 1 infusion site) via an infusion pump with a reservoir of at least 20 mL. Infusion sites may 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, infuse into sites that are at least 3 inches apart. Also refer to manufacturer's infusion pump instructions for use.
On-body injector: Administer SUBQ over ~30 to 60 minutes via on-body injector. Infuse into abdomen only; rotate site within the abdomen with each administration. Also refer to manufacturer's on-body injector instructions for use.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Empaveli: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/215014s003lbl.pdf
Paroxysmal nocturnal hemoglobinuria: Treatment of paroxysmal nocturnal hemoglobinuria (PNH) in adults.
Pegcetacoplan may be confused with eculizumab, pegaspargase, pegfilgrastim, pegloticase, peginterferon, ravulizumab.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Antithymocyte Globulin (Equine): Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Baricitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
Brincidofovir: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Cladribine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Therapeutic Immunosuppressant Agents) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing therapeutic immunosuppressants several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification
Denosumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Denosumab. Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor for signs/symptoms of serious infections. Risk D: Consider Therapy Modification
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Inebilizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Leflunomide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider Therapy Modification
Nadofaragene Firadenovec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
Ocrelizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
Pegloticase: May decrease therapeutic effects of PEGylated Drug Products. Risk C: Monitor
Pegvaliase: PEGylated Drug Products may increase adverse/toxic effects of Pegvaliase. Specifically, the risk of anaphylaxis or hypersensitivity reactions may be increased. Risk C: Monitor
Pidotimod: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Pimecrolimus. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification
Ritlecitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Ruxolitinib (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Sipuleucel-T: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification
Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk C: Monitor
Tacrolimus (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid
Tertomotide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Tofacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Tofacitinib. Management: Coadministration of tofacitinib with potent immunosuppressants is not recommended. Use with non-biologic disease-modifying antirheumatic drugs (DMARDs) was permitted in psoriatic arthritis clinical trials. Risk X: Avoid
Ublituximab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Upadacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Evaluate pregnancy status prior to use in patients who could become pregnant.
Patients who could become pregnant should use effective contraception during therapy and for 40 days after the last pegcetacoplan dose.
Based on data from animal reproduction studies, in utero exposure to pegcetacoplan may cause fetal harm.
Adverse pregnancy outcomes are associated with untreated paroxysmal nocturnal hemoglobinuria. Adverse maternal outcomes include bleeding, infections, miscarriages, worsening cytopenias, and thrombotic events; increased fetal death and premature delivery is also reported.
It is not known if pegcetacoplan is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during treatment and for 40 days after the last pegcetacoplan dose.
Assess immunization status prior to treatment. Lactate dehydrogenase (LDH) at baseline, periodically, and twice weekly for at least 4 weeks after a dose increase. Evaluate pregnancy status prior to use in patients who may become pregnant. Monitor for signs/symptoms of serious infection and for serious hypersensitivity reactions (eg, anaphylaxis, facial swelling, rash, urticaria). Monitor for signs/symptoms of hemolysis for at least 8 weeks after pegcetacoplan discontinuation; hemolysis may be identified by elevated LDH levels in combination with sudden decrease in paroxysmal nocturnal hemoglobinuria clone size or hemoglobin, or by reappearance of symptoms such as fatigue, hemoglobinuria, abdominal pain, dyspnea, major adverse vascular events (including thrombosis), dysphagia, or erectile dysfunction.
Pegcetacoplan is a pegylated pentadecapeptide that targets complement C3 (Hillmen 2021). In binding to complement protein C3 (and its activation fragment C3b), pegcetacoplan regulates the cleavage of C3 and the generation of downstream effectors of complement activation. Pegcetacoplan acts in the complement cascade that controls both C3b-mediated extravascular hemolysis and terminal complement-mediated intravascular hemolysis.
Distribution: Vd: ~3.98 L.
Metabolism: Expected to be metabolized via catabolic pathways into small peptides and amino acids.
Half-life elimination: 8 days.
Time to peak: Median: 4.5 to 6 days.
Excretion: Clearance: 0.36 L/day.
