Section 07 · Monograph

Zilucoplan

Reviewed Nov 2026FDA label

ZilbrysqComplement C5 inhibitor

Black Box Warning

Life-threatening and fatal meningococcal (Neisseria meningitidis) infections have occurred in patients treated with complement inhibitors, including zilucoplan
Complement inhibition increases susceptibility to serious meningococcal infection, including any serogroup and non-groupable strains
Patients must complete or update meningococcal vaccination (serogroups A, C, W, Y and B) at least 2 weeks before the first dose, unless the risk of delaying therapy outweighs the risk of meningococcal infection
Vaccination does not eliminate the risk of meningococcal infection; monitor patients closely
Available only through the restricted ZILBRYSQ REMS program

Generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positiveFDA-labeled

Small macrocyclic peptide (not a monoclonal antibody) that binds complement protein C5 with high affinity at two distinct sites
Sterically blocks C5 cleavage by the C5 convertase, preventing generation of C5a and C5b, and downstream formation of the C5b-9 membrane attack complex
In gMG, thought to reduce complement-mediated destruction of the postsynaptic neuromuscular junction membrane and AChR density
Low molecular weight allows subcutaneous self-administration, unlike the large monoclonal antibody C5 inhibitors that require IV infusion

Self-administered subcutaneous injection once daily, at approximately the same time each day, into the abdomen, thigh, or upper arm with site rotation
Weight-based fixed dose determined by prefilled syringe color: <56 kg → 16.6 mg; 56–77 kg → 23 mg; ≥77 kg → 32.4 mg
Reassess weight-based dose if body weight changes significantly and crosses a weight-band threshold
If a dose is missed, administer as soon as possible; do not double the dose
No dedicated IV loading dose or infusion required — self-injectable at home after training

No renal or hepatic dose adjustment data established for severe impairment; use caution

Patients with unresolved serious Neisseria meningitidis infection
Patients not currently vaccinated against meningococcus unless receiving prophylactic antibiotics until 2 weeks post-vaccination

No formal clinical drug-drug interaction studies conducted; in vitro data suggest low likelihood of CYP450 enzyme or transporter-mediated interactions
Concomitant use with other complement inhibitors is not studied and not recommended
Theoretical reduced vaccine immunogenicity during complement blockade — administer indicated vaccines before or per guidance during therapy

Injection site reactions (bruising, pain, erythema) — most common
Upper respiratory tract infection
Diarrhea
Elevated lipase (~7%) and amylase (~5%), typically asymptomatic
Headache
Urinary tract infection
Meningococcal infection (serious, boxed warning)
Worsening of myasthenia gravis symptoms/myasthenic crisis reported during trials

Verify and document meningococcal vaccination at least 2 weeks before initiation; if urgent start needed, give prophylactic antibiotics
ZILBRYSQ REMS enrollment for prescribers and pharmacies; patient must carry a Patient Safety Card for 2 months after last dose
Educate patient/caregiver on signs/symptoms of meningococcal infection and to seek immediate care
Periodic lipase/amylase monitoring if pancreatitis symptoms develop
Assess injection technique and rotate injection sites
Monitor MG-ADL/QMG clinical scores for treatment response
Immunize against S. pneumoniae and H. influenzae type b per current ACIP recommendations

No adequate data on use in pregnant women; limited human pregnancy data available
Animal reproduction studies in cynomolgus monkeys demonstrated increased embryofetal death at exposures similar to the human therapeutic dose
Zilucoplan crosses the placenta (increasing with gestational age); untreated maternal infection risk must be weighed against fetal drug exposure
No data on presence in human milk, effects on the breastfed infant, or on milk production
Consider the developmental and health benefits of breastfeeding along with the mother's clinical need and potential infant risk