Version May 2024
Meningococcal infections may occur in patients treated with pegcetacoplan and may become rapidly life-threatening or fatal if not recognized and treated early. Use of pegcetacoplan 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 Advisory Committee on Immunization Practices (ACIP) recommendations for vaccinations against encapsulated bacteria in patients with altered immunocompetence associated with complement deficiencies.
Vaccinate patients against encapsulated bacteria as recommended at least 2 weeks prior to administering the first dose of pegcetacoplan unless the risks of delaying therapy with pegcetacoplan outweigh the risk of developing a serious infection.
Vaccination reduces, but does not eliminate, the risk of serious infections. Monitor patients for early signs of serious infections and evaluate immediately if infection is suspected.
Pegcetacoplan is available only through a restricted program under a REMS. Under the pegcetacoplan REMS, prescribers must enroll in the program. Enrollment in the pegcetacoplan REMS program and additional information are available by telephone: 1-888-343-7073 or at https://www.empavelirems.com.
Dosage guidance:
Safety: Vaccinate against S. pneumoniae, N. meningitidis, and H. influenzae type B at least 2 weeks prior to pegcetacoplan initiation; revaccinate according to current guidelines. If immediate pegcetacoplan administration is necessary and less than 2 weeks after vaccination, provide 2 weeks of antibacterial prophylaxis. In patients without a known vaccination history, administer appropriate vaccines at least 2 weeks prior to the first pegcetacoplan dose; if immediate pegcetacoplan treatment is necessary, administer the required vaccines as soon as possible and provide 2 weeks of antibacterial prophylaxis.
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 pegcetacoplan discontinuation 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; patients who are not currently vaccinated against certain encapsulated bacteria, unless the risks of delaying pegcetacoplan treatment outweigh the risks of developing a bacterial infection with an encapsulated organism; unresolved serious infection caused by encapsulated bacteria including S. pneumoniae, N. meningitidis, and H. influenzae.
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): $281.68
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 at https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/215014s003lbl.pdf#page=18, must be dispensed with this medication.
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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Antithymocyte Globulin (Equine): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Cladribine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
Coccidioides immitis Skin Test: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. 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 enhance the immunosuppressive effect 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 enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Leflunomide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect 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 enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Natalizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Pegloticase: May diminish the therapeutic effect of PEGylated Drug Products. Risk C: Monitor therapy
Pegvaliase: PEGylated Drug Products may enhance the adverse/toxic effect of Pegvaliase. Specifically, the risk of anaphylaxis or hypersensitivity reactions may be increased. Risk C: Monitor therapy
Pidotimod: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Pimecrolimus. Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the potential for allergic or hypersensitivity reactions to 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 enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Ruxolitinib (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect 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 Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect 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 combination
Tertomotide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect 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 combination
Ublituximab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Upadacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
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.
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