Version May 2024
Life-threatening and fatal meningococcal infections have occurred in patients treated with complement inhibitors. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. Complete or update meningococcal vaccination (for serogroups A, C, W and Y, and serogroup B) at least 2 weeks prior to administering the first dose of pozelimab, unless the risks of delaying therapy outweigh the risk of developing a meningococcal infection. Follow the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients receiving a complement inhibitor. Patients receiving pozelimab are at increased risk for invasive disease caused by Neisseria meningitidis, even if they develop antibodies following vaccination. Monitor patients for early signs of meningococcal infections and evaluate immediately if infection is suspected.
Dosage guidance:
Safety: Vaccinate patient against meningococcal infection at least 2 weeks prior to treatment initiation, according to current recommendations. If urgent therapy is needed in a patient who is not up to date, administer meningococcal vaccines as soon as possible and use antibacterial drug prophylaxis.
CD55-deficient protein-losing enteropathy:
Children and Adolescents:
Loading dose: IV: 30 mg/kg once on day 1.
Maintenance dose: SUBQ: 10 mg/kg/dose once weekly beginning 7 days after loading dose. If inadequate response after 3 maintenance doses, may increase to 12 mg/kg/dose once weekly. Maximum dose: 800 mg/dose.
Dosage adjustment for toxicity: Interrupt therapy in patients undergoing treatment for a serious encapsulated bacterial infection (eg, Neisseria meningitidis, Streptococcus pneumoniae) until the infection resolves.
There are no dosage adjustments provided in the manufacturer's labeling; however, pozelimab is not likely to undergo renal excretion.
There are no dosage adjustments provided in the manufacturer's labeling; however, pozelimab is not likely to undergo hepatic excretion.
(For additional information see "Pozelimab: Drug information")
CD55-deficient protein-losing enteropathy : Note: Patients must receive meningococcal vaccine at least 2 weeks prior to treatment initiation; revaccinate according to current guidelines. If urgent pozelimab initiation is necessary and vaccination is not up to date with MenACWY and MenB vaccines according to Advisory Committee on Immunization Practices recommendations, vaccinate and provide antibacterial prophylaxis.
Loading dose: IV: 30 mg/kg as a single dose on day 1.
Maintenance dose: SUBQ: 10 mg/kg once weekly starting on day 8; at week 4, dose may be increased to 12 mg/kg once weekly if inadequate clinical response after 3 weekly doses; maximum dose: 800 mg once weekly. Note: Doses >400 mg require 2 SUBQ injections.
Missed maintenance dose:
≤3 days from the assigned day: Administer the missed dose as soon as possible, then administer the next weekly dose on the regular schedule.
>3 days from the assigned day: Omit the missed dose, then administer the next weekly dose on the regular schedule.
The day the weekly dose is administered can be revised at any time as long as 96 hours elapse between doses.
There are no dosage adjustments provided in the manufacturer's labeling; however, pozelimab is not likely to undergo renal excretion.
There are no dosage adjustments provided in the manufacturer's labeling; however, pozelimab is not likely to undergo hepatic excretion.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in children, adolescents, and adults.
>10%:
Cardiovascular: Increased blood pressure
Dermatologic: Alopecia, urticaria
Neuromuscular & skeletal: Bone fracture
Respiratory: Upper respiratory tract infection
1% to 10%:
Endocrine & metabolic: Increased uric acid, metabolic acidosis
Gastrointestinal: Gingival hemorrhage
Genitourinary: Hematuria, proteinuria
Hepatic: Increased liver enzymes
Local: Injection-site reaction (including dermatitis and erythema at injection site)
Frequency not defined: Infection: Meningococcal infection
Patients with unresolved N. meningitidis infection.
Concerns related to adverse effects:
• Infections: Pozelimab blocks terminal complement activation and therefore may increase the risk for susceptibility to bacterial infections, especially encapsulated bacteria, such as infections caused by Neisseria meningitidis but also Streptococcus pneumoniae, Haemophilus influenzae, and, to a lesser extent, Neisseria gonorrhoeae. Patients receiving pozelimab may be at increased risk for serious S. pneumoniae and H. influenzae type b (Hib) infections; vaccinate for S. pneumoniae and Hib according to the Advisory Committee on Immunization Practices (ACIP) recommendations. Therapy should be interrupted in patients undergoing treatment for a serious encapsulated bacterial infection until the infection resolves. Educate patients on the risks and prevention strategies for gonorrhea.
• Infusion reactions: Administration of pozelimab may result in infusion reactions, including anaphylaxis and hypersensitivity. If signs of cardiovascular instability or respiratory compromise occur, interrupt therapy and manage supportively.
• Meningococcal infections: Life-threatening and fatal meningococcal infections have been reported in vaccinated and unvaccinated patients treated with complement inhibitors. The use of pozelimab increases susceptibility to serious meningococcal infections (septicemia and/or meningitis). Meningococcal disease due to any serogroup may occur. Complete or update meningococcal vaccination (serogroups A, C, W, Y and B) at least 2 weeks prior to the first dose of pozelimab. If urgent pozelimab therapy is indicated in an unvaccinated patient, administer meningococcal vaccine(s) as soon as possible and provide antibacterial prophylaxis. Infection can be caused by nongroupable strains of N. meningitidis; therefore, vaccination does not eliminate the risk of infection despite presence of antibodies following vaccination. Educate patients on signs/symptoms of meningitis and steps necessary to seek immediate medical care. Consider pozelimab discontinuation in patients who are undergoing treatment for serious meningococcal infection. Revaccinate for meningococcal disease according to ACIP recommendations, taking the duration of pozelimab therapy into consideration.
Concurrent drug therapy issues:
• Immune complex formation: Transition between complement inhibitors has resulted in immune complex formation leading to a decrease in drug concentration and symptoms consistent with hypersensitivity reactions. Immune complex formation has not been observed with switching to pozelimab.
Veopoz: FDA approved August 2023; availability anticipated in 2023.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection [preservative free]:
Veopoz: Pozelimab-bbfg 400 mg/2 mL (2 mL) [contains polysorbate 80]
No
Solution (Veopoz Injection)
400 mg/2 mL (per mL): $20,769.23
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.
Parenteral:
IV infusion (loading dose only): Infuse IV through a 0.2- to 5-micron filter over at least 1 hour; maximum rate: 1,000 mg/hour. If stored in refrigerator, allow to reach room temperature prior to administration. Infusion should be completed within 8 hours of preparation if not refrigerated or 24 hours if refrigerated after preparation. Observe patient for 30 minutes following infusion completion.
Subcutaneous injection (maintenance doses): Administer SUBQ into abdomen, thigh, or upper arm. Rotate injection sites and avoid injecting into moles, scars, or areas that are tender, bruised, red, scaly, hard, or not intact. If multiple injections are required for a single dose (ie, doses >400 mg), administer each injection at a different injection site. Observe patient for 30 minutes after completion of first SUBQ injection.
Missed maintenance dose: If it has been ≤3 days since dose was missed, administer as soon as possible, then resume regular once-weekly schedule. If >3 days since missed dose, skip dose and administer next dose on regularly scheduled day. Do not administer 2 doses on the same day. The day of weekly dose can change as long as there are ≥4 days (96 hours) between doses.
IV: Prior to infusion, allow the diluted solution to warm to room temperature if refrigerated. Infuse through IV line that contains a 0.2- to 5-micron filter over a minimum of 1 hour; infusion rate should not exceed 1 g/hour. Do not administer other medications through the same IV line.
SUBQ: Administer dose into the abdomen, thigh, or upper arm. Rotate injection sites; do not administer into moles, scars, or areas where the skin is tender, bruised, red, hard, or not intact. Doses >400 mg should be separated into 2 injections administered at different sites.
Store intact vial at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze.
IV: Store diluted solution at room temperature up to 25°C (77°F) for no more than 8 hours (including infusion time) or between 2°C to 8°C (36°F to 46°F) for no more than 24 hours (including infusion time). Do not freeze.
SUBQ: Administer within 4 hours of preparation.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Veopoz: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761339s000lbl.pdf#page=16
Treatment of CD55-deficient protein-losing enteropathy, also known as CHAPLE disease (FDA approved in ages ≥1 year and adults).
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
Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
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
Immune Globulin: May diminish the therapeutic effect of Pozelimab. Management: Avoid concurrent use of intravenous immunoglobulin with pozelimab. If the combination cannot be avoided, monitor for evidence of a diminished effect of pozelimab and worsening underlying disease. Risk D: Consider therapy modification
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
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
Rozanolixizumab: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
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
Adverse events were not observed in animal reproduction studies.
Pozelimab is a humanized monoclonal antibody (IgG4). Human IgG crosses the placenta. Fetal exposure is dependent upon the IgG subclass, maternal serum concentrations, placental integrity, newborn birth weight, and GA, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis and the highest during the third trimester (Clements 2020; Palmeira 2012; Pentsuk 2009).
Monitor for signs/symptoms of meningococcal disease; regular gonorrhea testing (for sexually active patients). Monitor for hypersensitivity reactions; observe for 30 minutes after end of IV loading dose and after the first SUBQ injection.
Pozelimab-bbfg is a human, monoclonal immunoglobulin G4P (IgG4P ) antibody directed against the terminal complement protein C5 that inhibits terminal complement activation by blocking cleavage of C5 into C5a (anaphylatoxin) and C5b, thereby blocking the formation of the membrane-attack complex (C5b-C9, a structure mediating cell lysis).
Distribution: Vd: 3.3 L (following 30 mg/kg IV); 8.6 L (following 600 mg SUBQ).
Metabolism: Degraded into small particles and amino acids through catabolic pathways similar to endogenous IgG.
Bioavailability: 51% (following 600 mg SUBQ).
Half-life elimination: 13.5 days (following 30 mg/kg IV); 14.1 days (following 600 mg SUBQ).
Time to peak: 7 days.
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