Dosing & Uses
Dosage Forms & Strengths
injectable solution
- 200mg/mL (2-mL single-dose vial)
CHAPLE Disease
Indicated for CD55-deficient protein-losing enteropathy (PLE), also known as CHAPLE disease, in adults and pediatric patients aged ≥1 year
Loading dose
Maintenance dose
- Day 8 and thereafter: 10 mg/kg SC qWeek
- May be increased to 12 mg/kg qWeek (not to exceed 800 mg qWeek) if there is inadequate clinical response after at least 3 weekly doses (ie, starting from Week 4)
- Doses >400 mg require 2 injections
Dosage Modifications
Renal or hepatic impairment
- Not likely to undergo renal or hepatic excretion
Dosing Considerations
Vaccination and prophylaxis for meningococcal infection
-
Before first dose
- Vaccinate for meningococcal infection (serogroups A, C, W, and Y [MenACWY] and serogroup B [MenB]) according to current Advisory Committee on Immunization Practices (ACIP) recommendations for patients receiving a complement inhibitor at least 2 weeks before administering the first dose
- If urgent therapy is needed and patient is not up-to-date with vaccines for both MenACWY and MenB according to ACIP recommendations, administer meningococcal vaccine(s) as soon as possible and provide antibacterial drug prophylaxis
- Efficacy, duration, and drug regimens for antibacterial drug prophylaxis not studied in patients receiving complement inhibitors
Dosage Forms & Strengths
injectable solution
- 200mg/mL (2-mL single-dose vial)
CHAPLE Disease
Indicated for CD55-deficient protein-losing enteropathy (PLE), also known as CHAPLE disease, in adults and pediatric patients aged ≥1 year
<1 year: Safety and effectiveness not established
≥1 year
-
Loading dose
-
Maintenance dose
- Day 8 and thereafter: 10 mg/kg SC qWeek
- May be increased to 12 mg/kg qWeek (not to exceed 800 mg qWeek) if there is inadequate clinical response after at least 3 weekly doses (ie, starting from Week 4)
- Doses >400 mg require 2 injections
Dosage Modifications
Renal or hepatic impairment
- Not likely to undergo renal or hepatic excretion
Dosing Considerations
Vaccination and prophylaxis for meningococcal infection
-
Before first dose
- Vaccinate for meningococcal infection (serogroups A, C, W, and Y [MenACWY] and serogroup B [MenB]) according to current Advisory Committee on Immunization Practices (ACIP) recommendations for patients receiving a complement inhibitor at least 2 weeks before administering the first dose
- If urgent therapy is needed and patient is not up-to-date with vaccines for both MenACWY and MenB according to ACIP recommendations, administer meningococcal vaccine(s) as soon as possible and provide antibacterial drug prophylaxis
- Efficacy, duration, and drug regimens for antibacterial drug prophylaxis not studied in patients receiving complement inhibitors
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (4)
- efgartigimod alfa
efgartigimod alfa will decrease the level or effect of pozelimab by receptor binding competition. Avoid or Use Alternate Drug. Coadministration of Fc receptor antagonists with medications that bind to the human neonatal Fc receptor may lower systemic exposures and effectiveness of such medications. Closely monitor for reduced effectiveness of medications that bind to the human neonatal Fc receptor. If long-term use of such medications is essential, consider discontinuing efgartigimod and using alternative therapies.
- efgartigimod/hyaluronidase SC
efgartigimod/hyaluronidase SC will decrease the level or effect of pozelimab by receptor binding competition. Avoid or Use Alternate Drug. Coadministration of Fc receptor antagonists with medications that bind to the human neonatal Fc receptor may lower systemic exposures and effectiveness of such medications. Closely monitor for reduced effectiveness of medications that bind to the human neonatal Fc receptor. If long-term use of such medications is essential, consider discontinuing efgartigimod and using alternative therapies.
- immune globulin IV (IGIV)
immune globulin IV (IGIV) will decrease the level or effect of pozelimab by receptor binding competition. Avoid or Use Alternate Drug. IV immunoglobulin may interfere with the endosomal neonatal Fc receptor (FcRn) recycling mechanism of monoclonal antibodies such as pozelimab, and thereby decrease serum pozelimab concentrations. If use is avoidable, monitor for worsening of clinical signs and symptoms of CHAPLE disease.
- rozanolixizumab
rozanolixizumab will decrease the level or effect of pozelimab by receptor binding competition. Avoid or Use Alternate Drug. Coadministration of Fc receptor antagonists with medications that bind to the human neonatal Fc receptor may lower systemic exposures and effectiveness of such medications. Closely monitor for reduced effectiveness of medications that bind to the human neonatal Fc receptor. If long-term use of such medications is essential, consider discontinuing efgartigimod and using alternative therapies.
Monitor Closely (0)
Minor (0)
Adverse Effects
>10%
Upper respiratory tract infection (30%)
Fracture (30%)
Urticaria (20%)
Alopecia (20%)
Frequency Not Defined
Injection site reactions (including dermatitis and erythema)
Metabolic acidosis
Gingival bleeding
Increased blood uric acid
Increased liver enzymes
Hematuria
Proteinuria
Warnings
Black Box Warnings
Serious meningococcal infections
- Life-threatening and fatal meningococcal infections have occurred in patients treated with complement inhibitors
- Meningococcal infection may rapidly develop into life-threatening or fatal infection if not recognized and treated early
- Complete or update meningococcal vaccination (for serogroups A, C, W, and Y [MenACWY], and serogroup B [MenB]) at least 2 weeks before administering first dose, unless risks of delaying therapy outweigh risks of developing meningococcal infection
- Follow current ACIP recommendations for meningococcal vaccination in patients receiving a complement inhibitor
- Treated patients may be at increased risk for invasive disease caused by N. meningitidis, even if antibodies develop following vaccination
- Monitor for early signs of meningococcal infections and evaluate immediately if infection is suspected
Contraindications
Unresolved Neisseria meningitidis infection
Cautions
and unvaccinated patients treated with complement inhibitors; use increases susceptibility to serious and life-threatening meningococcal infections (septicemia and/or meningitis) caused by any serogroup, including non-groupable strains (see Black Box Warnings)
Hypersensitivity reactions, including anaphylaxis, reported; interrupt and institute appropriate supportive measures if signs of cardiovascular instability or respiratory compromise occur
Immune complex formation reported during transition between complement inhibitors, resulting in transient decreased drug concentrations and possible hypersensitivity reactions; consider this potential if switching complement inhibitors
Other bacterial infections
- Pozelimab blocks terminal complement activation
- May increase susceptibility to encapsulated bacterial infections, especially caused by Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria gonorrhoeae (lesser extent)
- Vaccinate against Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) according to ACIP guidelines
- Therapy may cause an increased risk for infections due to these organisms, even if antibodies were developed following vaccination
- Interrupt treatment in patients who are undergoing treatment for a serious encapsulated bacterial infection until infection is resolved
- Counsel patients about gonorrhea prevention and advise regular testing for patients at risk
Drug interaction overview
-
IV immunoglobulin
- Avoid coadministration; if unavoidable, monitor for worsening of clinical signs and symptoms of disease
- IV immunoglobulins may decrease pozelimab concentrations; avoid concomitant use
Pregnancy & Lactation
Pregnancy
There are no data on pozelimab use in pregnant females to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes
However, monoclonal antibodies can be actively transported across the placenta
Animal data
- No adverse effects were observed on maintenance of pregnancy, pregnancy outcome, or on the developing offspring through postnatal day 90 at doses up to 3.3-3.8x the predicted clinical exposures
Lactation
There are no data on the presence of pozelimab in either human or animal milk, the effects on breastfed infants, or effects on milk production
Endogenous maternal IgG and monoclonal antibodies are transferred into human milk
Effects of local gastrointestinal exposure and the extent of systemic exposure in breastfed infants to pozelimab are unknown
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.Pharmacology
Mechanism of Action
Monoclonal immunoglobulin G4P (IgG4P) antibody directed against terminal complement protein C5
C5 inhibits terminal complement activation by blocking cleavage of C5 into C5a (anaphylatoxin) and C5b, thereby blocking formation of the membrane-attack complex (C5b-C9, a structure mediating cell lysis)
Absorption
Bioavailability: 51%
Trough concentration: 180 mg/L (Week 1)
Peak plasma time: 7 days (post 300-mg or 600-mg SC dose)
Steady-state reached at ~20 weeks following SC injection qWeek in CD55-deficient PLE patients
Distribution
Vd
- IV: 3.3 L
- SC: 6-8.6 L
Metabolism
Expected to degrade into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG
Elimination
Half-life
- IV: 13.5 days
- SC: 14.1 days
Administration
IV Compatibilities for Loading Dose
0.9% NaCl
Dextrose 5% (D5W)
Preparation
Remove vial(s) from refrigerator and recalibrate to room temperature 20-25ºC (68-77ºF) for at least 45 minutes before use
Visually inspect vial(s) for particulate matter and discoloration before administering; solution is clear to slightly opalescent, colorless to pale yellow solution; discard vial if solution is cloudy, discolored, or contains particulate matter
Gently swirl vial(s) in an upright position; do not shake vial(s) to avoid foaming
Use a 21-gauge stainless steel needle with Luer-Lok to withdraw the calculated volume from vial(s); discard any unused product remaining in the vial(s)
-
IV preparation for loading dose
- Dilute in an IV infusion bag of 25-250 mL of either 0.9% NaCl or D5W to a final concentration of 6.7-20 mg/mL
- Mix diluted solution by gentle inversion; do not shake
-
SC preparation for maintenance dose
- For dose >400 mg, prepare 2 separate injections for SC administration of total dose volume
- Change needle on syringe to an injection needle fulfilling the following criteria: 25- to 27-gauge and ½ or 5/8-inch stainless steel needle with Luer-Lok
IV Administration for Loading Dose
Infuse through an IV line containing a sterile, in-line or add on 0.2-micron to 5-micron filter
Infusion rate: Infuse over minimum of 1 hr; do not exceed 1000 mg/hr
Do not coadminister other medications through same IV line
Observe patient for 30 min once infusion completed
SC Administration for Maintenance Dose
Inject into abdomen, thigh, or upper arm
Rotate sites; do not inject into moles, scars, or areas where the skin is tender, bruised, red, hard, or not intact
When administering >1 injection, administer consecutively, each at different injection sites
Observe patient for 30 mins after completing the first SC injection
Missed SC dose
- Missed dose 3 days: Administer as soon as possible; do not double dose on the same day to make up for missed dose
- Missed dose >3 days: Skip missed dose and administer next dose on the regularly scheduled day
- In each case, patients may resume once-weekly dosing schedule
- Day of weekly administration can be changed, if necessary, as long as the time between 2 doses is at least 4 days (96 hours)
Storage
Unopened vials
- Refrigerate at 2-8ºC (36-46ºF) in the original carton to protect from light
- Do not freeze; do not shake
- Discard unused portion
Diluted IV solution for loading dose
- If not used immediately, store at room temperature up to 25ºC (77ºF) for 8 hr or refrigerate at 2-8Cº (36-46ºF) for 24 hr from time of preparation to end of infusion
- If refrigerated, allow diluted solution to come to room temperature before administering
- Discard unused diluted solution after 8 hr if stored at room temperature or after 24 hr if refrigerated
- Do not freeze diluted solution
Prepared SC injection
- Use within 4 hr of preparation
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Formulary
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