Usual Adult Dose for Paroxysmal Nocturnal Hemoglobinuria

Subcutaneous: 1,080 mg twice weekly infused via a commercially available infusion pump with a reservoir of at least 20 mL

To reduce the risk of hemolysis with abrupt treatment discontinuation when switching from C5 inhibitors:

• For patients switching from eculizumab, initiate this drug while continuing eculizumab at its current dose. After 4 weeks, discontinue eculizumab before continuing on monotherapy with this drug
• For patients switching from ravulizumab, initiate this drug no more than 4 weeks after the last dose of ravulizumab

• Vaccinate against encapsulated bacteria, including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type B at least 2 weeks prior to initiating therapy according to current ACIP guidelines.
• It is recommended to provide 2 weeks of antibacterial drug prophylaxis if this drug must be initiated immediately and vaccines are administered less than 2 weeks before starting therapy.

Renal Dose Adjustments

No adjustment recommended.

Liver Dose Adjustments

No adjustment recommended.

Dose Adjustments

Dose Modifications for Lactate Dehydrogenase (LDH):

• LDH levels grater than 2 times the upper limit of normal: 1,080 mg every three days
• Monitor LDH levels twice a week for at least 4 weeks in the event of dose increase

Precautions

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for pegcetacoplan. It includes a medication guide, elements to assure safe use, and an implementation system. For additional information: https://www.accessdata.fda.gov/scripts/cder/rems/index.cfm

US BOXED WARNINGS:
SERIOUS INFECTIONS CAUSED BY ENCAPSULATED BACTERIA:

• Meningococcal infections may occur in patients treated with pegcetacoplan and may become rapidly life-threatening or fatal if not recognized and treated early. Its 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.
• In patients with altered immunocompetence associated with complement deficiencies, it is recommended to comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for vaccinations against encapsulated bacteria.
• To reduce the risk of serious infections, it is recommended to vaccinate patients against encapsulated bacteria as recommended at least 2 weeks prior to administering the first dose unless the risks of delaying therapy outweigh the risk of developing a serious infection.
• Monitor for early signs of serious infections and evaluate immediately if infection is suspected.
• Pegcetacoplan is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Prescribers must enroll in the program.

• Hypersensitivity to the active component or any of the ingredients
• Not currently vaccinated against certain encapsulated bacteria, unless the risks of delaying treatment outweigh the risks of developing a bacterial infection with an encapsulated organism
• Unresolved serious infection caused by encapsulated bacteria including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae

Dialysis

Data not available

Other Comments

Administration advice:

• Refer to the product Instructions for Use and the infusion pump manufacturer's instructions for full preparation and administration information.
• Administer this drug via subcutaneous infusion using an infusion pump.
• Before the subcutaneous infusion, allow this drug to reach room temperature for approximately 30 minutes.
• Do not use if the liquid looks cloudy, contains particles, or is dark yellow.
• Rotate infusion sites (i.e., abdomen, thighs, hips, upper arms) from one infusion to the next.
• Do not infuse where the skin is tender, bruised, red, or hard, and avoid infusing into tattoos, scars, or stretch marks.
• Ensure the infusion sites are at least 3 inches apart if multi-infusion sets are needed.
• Infusion time is approximately 30 minutes (if using two infusion sites) or approximately 60 minutes (if using one infusion site).
• Discard any unused portion.
• If a dose is missed, administer the missed dose as soon as possible and resume at the regular schedule dose thereafter.

• Store refrigerated at 2C to 8C (36F to 46F) and in the original carton to protect from light.

• Hematologic: Monitor lactate dehydrogenase (LDH) twice a week for at least 4 weeks in the event of a dose increase in patients with elevated LDH.
• Infections and infestations: Monitor for early signs and symptoms of serious infection.
• Blood and lymphatic system disorders: Monitor any patient who discontinues treatment for at least 8 weeks to detect hemolysis and other reactions.
• Hypersensitivity: Monitor closely for infusion-related reactions.

• Advise the patient to read the FDA-approved patient labeling (Patient Information).
• Counsel patients about the risk of serious infection, provide the patients with the REMS educational materials.
• Advise patients that they are required to receive vaccinations against encapsulated bacteria at least 2 weeks prior to receiving the first dose if they have not been previously vaccinated.
• Advise patients of the risk of anaphylaxis and infusion-related reactions.
• Advise females of reproductive potential of the potential risk to a fetus and to inform their healthcare provider of a known or suspected pregnancy.
• Advice females of reproductive potential of the need of a pregnancy test prior to starting treatment.
• Advise female patients of reproductive potential to use effective contraception during treatment and for at least 40 days after the last dose.
• Advise lactating women not to breastfeed during therapy and for at least 40 days after the last dose.

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