Introduction
Zilbrysq (zilucoplan) is a complement inhibitor indicated for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive. It represents a novel therapeutic approach in the management of this autoimmune neuromuscular disorder.
Mechanism of Action
Zilucoplan is a macrocyclic peptide that inhibits the complement component 5 (C5) protein, preventing the formation of the membrane attack complex (MAC), which is implicated in the destruction of the neuromuscular junction in myasthenia gravis. By blocking C5 cleavage into C5a and C5b, it prevents the terminal complement cascade activation that contributes to the pathophysiology of gMG.
Indications
Zilbrysq is approved for the treatment of generalized myasthenia gravis in adult patients who are anti-acetylcholine receptor (AChR) antibody positive.
Dosage and Administration
- Recommended dosage: 0.3 mg/kg once daily
- Route of administration: Subcutaneous injection
- Special populations: No dosage adjustment required for renal or hepatic impairment
- Administration instructions: Administer subcutaneously in the abdomen, thigh, or upper arm. Rotate injection sites.
Pharmacokinetics
- Absorption: Peak plasma concentrations achieved approximately 2 hours after subcutaneous administration
- Distribution: Volume of distribution: 0.1 L/kg
- Metabolism: Not metabolized by cytochrome P450 enzymes
- Elimination: Primarily excreted unchanged in urine with a half-life of approximately 8 hours
Contraindications
- Known hypersensitivity to zilucoplan or any component of the formulation
- Patients with unresolved Neisseria meningitidis infection
Warnings and Precautions
- Meningococcal infections: Zilbrysq increases the risk of serious infections caused by Neisseria meningitidis. Vaccinate or revaccinate according to current guidelines at least 2 weeks prior to initiating Zilbrysq unless the risks of delaying therapy outweigh the risks of developing a meningococcal infection.
- Monitor for signs and symptoms of meningococcal infection and treat immediately if infection is suspected.
Drug Interactions
- No formal drug interaction studies have been conducted.
- Based on its pharmacokinetic profile, no clinically significant interactions are expected with drugs metabolized by CYP enzymes.
Adverse Effects
- Most common adverse reactions (≥10%): Injection site reactions, upper respiratory tract infection, headache, oropharyngeal pain
- Serious adverse reactions: Meningococcal infection
Monitoring Parameters
- Monitor for signs and symptoms of meningococcal infection
- Monitor for injection site reactions
- Monitor for signs of myasthenia gravis exacerbation
- Monitor for signs of hypersensitivity reactions
Patient Education
- Educate patients about the risk of meningococcal infection and the need for vaccination
- Instruct patients to seek immediate medical attention for signs of meningococcal infection
- Instruct patients on proper injection technique and rotation of injection sites
- Inform patients about the importance of reporting any signs of infection or injection site reactions
