Action and Spectrum

Actions and Spectrum: 

• The mechanism of action of pegcetacoplan involves binding to C3 protein, which blocks the activation of the complement system and prevents the formation of membrane attack complexes (MACs). MACs are complexes of proteins that form on the surface of cells and can cause cell destruction. By inhibiting the formation of MACs, pegcetacoplan helps prevent the destruction of red blood cells in patients with PNH 
• The spectrum of activity of pegcetacoplan is limited to PNH, a rare disease characterized by the destruction of red blood cells, which can lead to symptoms such as fatigue, abdominal pain, shortness of breath, and blood in the urine. pegcetacoplan has been shown to reduce the destruction of red blood cells and improve symptoms in patients with PNH. However, it is inadequate for treating other blood disorders or conditions unrelated to the complement system 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Infection (29%) 

Fatigue (12%) 

Abdominal pain (20%) 

Diarrhea (22%) 

Viral infection(12%) 

Infusion-site reactions (39%) 

Respiratory tract infection (15%) 

1-10% 

Headache (7%) 

Biliary sepsis (<5%) 

Intestinal ischemia(7%) 

Systemic hypertension (7%) 

Back pain (7%) 

Chest pain (7%) 

Hypersensitivity pneumonitis (<5%) 

Black Box Warning

Black box warning: 

Meningococcal infections and septicemia 

• Meningococcal infections/sepsis may occur. 
• Use may predispose people to serious infections, especially those caused by encapsulated bacteria like Streptococcus pneumoniae, Neisseria meningitidis types A, C, W, Y, and B, and Haemophilus influenzae type B. 
• In complement-deficient patients, follow the latest ACIP meningococcal vaccination guidelines. 
• Unless delaying pegcetacoplan outweighs the risk of meningococcal infection, vaccinate against encapsulated bacteria at least two weeks before the first dose. 
• Meningococcal vaccination reduces but does not eliminate risk. 
• Assess early meningococcal infection symptoms. 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

• Hypersensitivity to pegcetacoplan or any of the excipients is contraindicated 
• Patients who are not immunised against particular encapsulated bacteria, unless the risks of delaying pegcetacoplan treatment outweigh the risks of developing a bacterial infection with an encapsulated organism 
• Patients with unresolved infections caused by encapsulated bacteria, such as S pneumoniae, N meningitidis, and H influenzae. 

Caution: 

• Risk of serious infections: pegcetacoplan works by inhibiting the complement system, which can increase the risk of serious infections caused by encapsulated bacteria such as Streptococcus pneumoniae, Neisseria meningitides types A, C, W, Y, and B, and Haemophilus influenzae type B 
• Hypersensitivity reactions: As with any medication, there is a risk of hypersensitivity reactions with pegcetacoplan. Patients should be monitored closely for signs of allergic reactions, and treatment should be discontinued if a reaction occurs. 
• Thrombotic events: In clinical trials, some patients receiving pegcetacoplan experienced thrombotic events, such as deep vein thrombosis and pulmonary embolism 

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.   

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

It works by inhibiting the complement system, part of the immune system that can cause damage to red blood cells in patients with PNH 

Specifically, pegcetacoplan is a synthetic peptide conjugated with polyethylene glycol (PEG). It binds to complement protein C3, an essential protein in the complement system, preventing its activation and subsequent destruction of red blood cells 

Pharmacodynamics: 

The pharmacodynamics of pegcetacoplan involves its ability to inhibit the complement system, reduce hemolysis in patients with PNH, and its potential anti-inflammatory effects 

Pharmacokinetics: 

Absorption 

It is administered subcutaneously and is slowly absorbed into the bloodstream. The peak plasma time for pegcetacoplan is approximately 108-144 hours (4.5-6 days) after administration.  

Distribution 

The volume of distribution (Vd) of pegcetacoplan is approximately 3.9 L.  

Metabolism 

pegcetacoplan is expected to be metabolized into small peptides and amino acids by catabolic pathways.  

Elimination and Excretion 

The half-life of pegcetacoplan is approximately eight days, and its clearance is approximately 0.37 L/day. Steady-state concentrations of pegcetacoplan are achieved after approximately 4-6 weeks of dosing 

Adminstartion

Administration: 

Sub cutaneous administration: 

• pegcetacoplan is administered subcutaneously (under the skin) by a healthcare professional or trained caregiver.  
• The recommended dose of pegcetacoplan for paroxysmal nocturnal hemoglobinuria (PNH) is 1080 mg (four 270 mg injections) once weekly for the first four weeks, followed by a maintenance dose of 1620 mg (six 270 mg injections) once weekly. 
• Before administration, the injection site should be cleaned with an alcohol swab. 
• The medication should be allowed to enter room temperature for approximately 30 minutes before administration.  
• The injection should be given into the abdomen, thigh, or upper arm, rotating the injection site with each dose. The medication should not be injected into areas where the skin is red, bruised, or tender. 
• After injection, the site should be covered with a sterile adhesive bandage. The used needle and syringe should be appropriately disposed of in an appropriate sharps container 

Storage: 

The medication should be stored in the refrigerator between 2-8°C (36-46°F) until ready for use 

Patient Information Leaflet

Patient information leaflet 

Generic Name: pegcetacoplan 

Pronounced: [ peg-SET-a-KOE-plan ] 

Why do we use pegcetacoplan? 

pegcetacoplan is a medication that is used to treat certain rare blood disorders. Specifically, it is approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS) 

• paroxysmal nocturnal hemoglobinuria (PNH): It is a rare blood disorder that destroys red blood cells, leading to symptoms such as anemia, fatigue, and shortness of breath 
• atypical hemolytic uremic syndrome (aHUS): It is another rare blood disorder that can cause kidney failure and other serious health problems