Introduction
Empaveli (pegcetacoplan) is a complement inhibitor approved by the FDA in May 2021 for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). It represents a novel therapeutic approach targeting the complement system, specifically designed to address both intravascular and extravascular hemolysis in PNH patients.
Mechanism of Action
Empaveli is a targeted C3 inhibitor that works by binding to complement protein C3 and its activation fragment C3b. This mechanism regulates the cleavage of C3 and the generation of downstream effectors of complement activation. By inhibiting C3, Empaveli controls both proximal and terminal complement activity, thereby reducing both intravascular hemolysis (mediated by membrane attack complex) and extravascular hemolysis (mediated by C3 opsonization).
Indications
- Treatment of paroxysmal nocturnal hemoglobinuria (PNH) in adults
- Approved for both treatment-naïve patients and those switching from other complement inhibitors (C5 inhibitors)
Dosage and Administration
Standard dosing: 1080 mg administered subcutaneously twice weekly via infusion pump Initial dose: Administer under healthcare supervision Preparation: Requires reconstitution with provided diluent Administration: Subcutaneous infusion over approximately 30-60 minutes Special populations:- Renal impairment: No dosage adjustment required
- Hepatic impairment: Use with caution (limited data)
- Elderly: No specific dosage adjustment recommended
Pharmacokinetics
Absorption: Bioavailability approximately 90% following subcutaneous administration Distribution: Volume of distribution approximately 7-8 L Metabolism: Underges proteolytic degradation to small peptides and amino acids Elimination: Half-life approximately 8 days Excretion: Primarily renal elimination of metabolitesContraindications
- Hypersensitivity to pegcetacoplan or any component of the formulation
- Patients with unresolved serious Neisseria meningitidis infection
- Patients not currently vaccinated against Neisseria meningitidis
Warnings and Precautions
Boxed Warning: Serious infections caused by encapsulated bacteria- Meningococcal infections may occur despite vaccination
- Must be vaccinated against Neisseria meningitidis at least 2 weeks prior to initiation
- Monitor for early signs of meningococcal infection
- Consider additional antibacterial prophylaxis if necessary
- Infusion-related reactions
- Monitoring for hemolysis upon discontinuation
- Pregnancy and lactation considerations
- Immunosuppressed patients
Drug Interactions
Significant interactions:- Other complement inhibitors: Avoid concomitant use
- Immunosuppressive therapies: Increased infection risk
- Live vaccines: Avoid concurrent administration
Adverse Effects
Most common adverse reactions (≥10%):- Injection site reactions (35%)
- Infections (19%)
- Diarrhea (12%)
- Abdominal pain (11%)
- Fatigue (11%)
- Viral infection (11%)
- Meningococcal infections
- Other serious infections
- Hemolysis upon discontinuation
- Hypersensitivity reactions
Monitoring Parameters
Baseline monitoring:- Meningococcal vaccination status
- Complete blood count with reticulocytes
- Lactate dehydrogenase (LDH) levels
- Renal and hepatic function
- Signs/symptoms of infection (especially meningococcal)
- LDH levels monthly
- Hemoglobin and reticulocyte count
- Injection site reactions
- Hemolytic parameters
- Monitor for hemolysis for at least 8 weeks after discontinuation
Patient Education
Key points for patients:- Complete all recommended vaccinations before starting treatment
- Recognize signs of meningococcal infection (fever, headache, stiff neck, nausea)
- Carry patient safety card at all times
- Report any signs of infection immediately
- Understand proper administration technique if self-administering
- Do not stop medication without medical supervision
- Report any injection site reactions
- Inform all healthcare providers about Empaveli therapy
References
1. FDA Prescribing Information: Empaveli (pegcetacoplan). May 2021. 2. Hillmen P, Szer J, Weitz I, et al. Pegcetacoplan versus Eculizumab in Paroxysmal Nocturnal Hemoglobinuria. N Engl J Med. 2021;384(11):1028-1037. 3. Brodsky RA. Paroxysmal nocturnal hemoglobinuria. Blood. 2014;124(18):2804-2811. 4. Schrezenmeier H, Röth A, Araten DJ, et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2006;355(12):1233-1243. 5. ClinicalTrials.gov: PEGASUS Study (NCT03500549) 6. Hill A, Kelly RJ, Hillmen P. Thrombosis in paroxysmal nocturnal hemoglobinuria. Blood. 2013;121(25):4985-4996.