Brand name: Soliris
Drug class: Complement Inhibitor Agents

Medically reviewed by Drugs.com on Feb 10, 2025. Written by ASHP.

Introduction

Terminal complement inhibitor; a recombinant humanized immunoglobulin IgG_2/4 kappa monoclonal antibody.

Uses for Eculizumab

Paroxysmal Nocturnal Hemoglobinuria

Treatment of paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis; designated an orphan drug by FDA for this use.

Improves symptoms of PNH by reducing hemolysis, stabilizing hemoglobin concentrations, and reducing transfusion requirements. Reduced fatigue and improved quality of life also reported. Only curative treatment of PNH to date is stem cell transplantation.

Atypical Hemolytic Uremic Syndrome

Treatment of atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy; designated an orphan drug by FDA for this use.

Improves outcomes related to thrombotic microangiopathy (e.g., increased platelet counts, normalization of hematologic parameters) and improves renal function.

Generalized Myasthenia Gravis

Treatment of generalized myasthenia gravis in adults who are anti-acetylcholine receptor (anti-AChR) antibody positive; designated an orphan drug by FDA for the treatment of myasthenia gravis.

Complement inhibitors (e.g., eculizumab, ravulizumab) may play a role in the treatment of AChR-positive generalized myasthenia gravis by reducing deposition of complement and membrane attack complexes at the neuromuscular junction. International experts recommend consideration of eculizumab for treatment of severe, refractory anti-AChR antibody-positive generalized myasthenia gravis

Neuromyelitis Optica Spectrum Disorder

Treatment of adults with neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody positive; designated an orphan drug by FDA for treatment of neuromyelitis optica).

Monoclonal antibody complement inhibitors (eculizumab, ravulizumab) are recommended as one of several options for long-term immunotherapy in patients with AQP4-IgG-positive NMOSD. Other monoclonal antibodies that have demonstrated efficacy include inebilizumab, rituximab, and satralizumab; choice of therapy should be based on disease severity, comorbidities, patient age, family planning, adherence, patient and physician preferences, and drug-related factors (mechanism, onset of action, adverse effects, safety, route of administration, cost, availability).

Eculizumab Dosage and Administration

General

Pretreatment Screening

• Assess immunization status prior to initiating eculizumab therapy.

Patient Monitoring

• Closely monitor patients for early signs and symptoms of meningococcal infections during treatment with eculizumab, and evaluate immediately if infection is suspected.

• Monitor for infusion-related reactions during administration and for at least 1 hour following completion of infusion.

• Monitor for signs and symptoms of hemolysis for at least 8 weeks after discontinuing eculizumab therapy in patients with PNH.

• Monitor for signs and symptoms of thrombotic microangiopathy complications for at least 12 weeks after discontinuing eculizumab in patients with aHUS.

Premedication and Prophylaxis

• Vaccinate or revaccinate patients against meningococcal infection (serogroups A, C, W, Y, and B) according to current Advisory Committee on Immunization Practices (ACIP) recommendations at least 2 weeks prior to initiating eculizumab. If eculizumab must be started urgently in a patient who is not up to date with meningococcal vaccines, provide antibacterial drug prophylaxis and administer these vaccines as soon as possible.

REMS

• Because of the risk of meningococcal infections, eculizumab can only be obtained through a restricted distribution program called the Ultomiris and Soliris REMS. The drug may be prescribed only by clinicians who are enrolled in the REMS program. In addition, clinicians must counsel patients regarding the risk of meningococcal infection, provide educational materials, and ensure that patients are compliant with meningococcal vaccine and antibacterial drug prophylaxis requirements. Healthcare settings and pharmacies that dispense eculizumab must be certified in the REMS and must verify that prescribers are certified. Patients must carry the Patient Safety Card with them at all times during and for 3 months following treatment with the drug.

• Additional information is available at 888-765-4747 or [Web].

Administration

IV Administration

Administer by IV infusion only using gravity flow or a controlled-infusion device (e.g., infusion pump or syringe pump). Do not administer by rapid IV injection such as IV push or bolus.

Allow solution to warm to room temperature before administering to patient. Do not heat (e.g., in a microwave).

Monitor patients for infusion-related reactions during and for >1 hour following each infusion. Slow infusion rate or discontinue therapy if adverse reaction occurs.

Dilution

Must dilute commercially available 10-mg/mL eculizumab concentrate for IV infusion prior to administration.

Withdraw appropriate dose of eculizumab from vial, add to infusion bag, and dilute with 5% dextrose, 0.9% sodium chloride, 0.45% sodium chloride, or Ringer’s injection to provide a final concentration of 5 mg/mL. (See Table 1.)

Gently invert diluted solution to mix completely.

Vials are for single use only. Discard any unused portion after preparing dose.

Rate of Administration

Administer by IV infusion over 35 minutes in adults and 1—4 hours in pediatric patients; if infusion must be slowed due to adverse effects, do not exceed 2 hours total infusion time in adults.

Dosage

Pediatric Patients

Atypical Hemolytic Uremic Syndrome

IV

Adhere to recommended time points of administration, or within 2 days of each time point, to achieve maximum benefit.

Pediatric patients ≥2 months of age weighing ≥40 kg: 900 mg once a week for 4 weeks, followed by a dose of 1200 mg at week 5, then 1200 mg every 2 weeks thereafter.

Pediatric patients ≥2 months of age weighing 30 to <40 kg: 600 mg once a week for 2 weeks, followed by a dose of 900 mg at week 3, then 900 mg every 2 weeks thereafter.

Pediatric patients ≥2 months of age weighing 20 to <30 kg: 600 mg once a week for 2 weeks, followed by a dose of 600 mg at week 3, then 600 mg every 2 weeks thereafter.

Pediatric patients ≥2 months of age weighing 10 to <20 kg: Initial dose of 600 mg, followed by a dose of 300 mg at week 2, then 300 mg every 2 weeks thereafter.

Pediatric patients ≥2 months of age weighing 5 to <10 kg: Initial dose of 300 mg, followed by a dose of 300 mg at week 2, then 300 mg every 3 weeks thereafter.

In patients receiving plasmapheresis or plasma exchange, administer supplemental dose of 300 mg (if most recent dose was 300 mg) or 600 mg (if most recent dose was ≥600 mg) within 60 minutes after each plasmapheresis or plasma exchange.

In patients receiving fresh frozen plasma infusion in whom most recent eculizumab dose was ≥300 mg, administer supplemental dose of 300 mg 60 minutes prior to each unit of fresh frozen plasma infused.

Optimal duration of therapy not known. Because of chronic nature of aHUS and some evidence suggesting that treatment discontinuance may result in a return of disease manifestations, long-term (e.g., at least 1 year) therapy may be beneficial; some experts recommend lifelong therapy.

Adults

Paroxysmal Nocturnal Hemoglobinuria

IV

600 mg once a week for 4 weeks, followed by one dose of 900 mg 1 week later (week 5), then 900 mg every 2 weeks thereafter.

Administer drug at these recommended time points, or within 2 days of each time point, to achieve maximum benefit. A few patients have required a decrease in the recommended dosage interval (i.e., from 14 to 12 days) to achieve optimal reduction in hemolysis (as determined by reduction in LDH levels).

Atypical Hemolytic Uremic Syndrome

IV

900 mg once a week for 4 weeks, followed by a dose of 1200 mg 1 week later (at week 5), then 1200 mg every 2 weeks thereafter. Administer drug at these recommended time points, or within 2 days of each time point, to achieve maximum benefit.

In patients receiving plasmapheresis or plasma exchange, administer supplemental dose of 300 mg (if most recent dose was 300 mg) or 600 mg (if most recent dose was ≥600 mg) within 60 minutes after each plasmapheresis or plasma exchange.

In patients receiving fresh frozen plasma infusion in whom most recent eculizumab dose was ≥300 mg, administer supplemental dose of 300 mg 60 minutes prior to each unit of fresh frozen plasma infused.

Optimal duration of therapy not known. Because of chronic nature of aHUS and some evidence suggesting that treatment discontinuance may result in a return of disease manifestations, long-term (e.g., at least 1 year) therapy may be beneficial; some experts recommend lifelong therapy.

Myasthenia Gravis

900 mg once a week for 4 weeks, followed by a dose of 1200 mg 1 week later (at week 5), then 1200 mg every 2 weeks thereafter. Administer drug at these recommended time points, or within 2 days of each time point, to achieve maximum benefit.

In patients receiving plasmapheresis or plasma exchange, administer supplemental dose of 300 mg (if most recent dose was 300 mg) or 600 mg (if most recent dose was ≥600 mg) within 60 minutes after each plasmapheresis or plasma exchange.

In patients receiving fresh frozen plasma infusion in whom most recent eculizumab dose was ≥300 mg, administer supplemental dose of 300 mg 60 minutes prior to each unit of fresh frozen plasma infused.

NMOSD

900 mg once a week for 4 weeks, followed by a dose of 1200 mg 1 week later (at week 5), then 1200 mg every 2 weeks thereafter. Administer drug at these recommended time points, or within 2 days of each time point, to achieve maximum benefit.

In patients receiving plasmapheresis or plasma exchange, administer supplemental dose of 300 mg (if most recent dose was 300 mg) or 600 mg (if most recent dose was ≥600 mg) within 60 minutes after each plasmapheresis or plasma exchange.

In patients receiving fresh frozen plasma infusion in whom most recent eculizumab dose was ≥300 mg, administer supplemental dose of 300 mg 60 minutes prior to each unit of fresh frozen plasma infused.

Cautions for Eculizumab

Contraindications

• Patients with unresolved serious Neisseria meningitidis infection.

Warnings/Precautions

Warnings

Serious Meningococcal Infections

Serious, life-threatening, or fatal meningococcal infections (e.g., sepsis, meningitis) reported (see Boxed Warning).

Complete or update meningococcal vaccination (for serogroups A, C, W, Y, and B) at least 2 weeks prior to first dose of eculizumab according to ACIP recommendations for patients receiving a complement inhibitor. Revaccinate patients according to ACIP recommendations considering duration of eculizumab therapy.

If urgent eculizumab therapy indicated in a patient not up to date with meningococcal vaccines, provide antibacterial drug prophylaxis and administer these vaccines as soon as possible. Because optimal duration and drug regimen for prophylaxis has not been studied in unvaccinated or vaccinated patients, weigh benefits and risks of eculizumab treatment and antibacterial drug prophylaxis against risks for serious infections caused by Neisseria meningitidis.

Vaccination does not eliminate risk of serious encapsulated bacterial infections.

Monitor closely for early manifestations of meningococcal infection during therapy. Evaluate immediately if infection is suspecteds.

Inform patients of signs and symptoms of infection; instruct patients to seek immediate medical care if these occur. Treat known infections promptly.

Consider interruption of therapy in patients undergoing treatment for serious meningococcal infection.

Due to risk of meningococcal infections, eculizumab is available only through a REMS program. (See REMS under Dosage and Administration.)

Other Warning and Precautions

Other Infections

Blocks terminal complement activation and may increase susceptibility to infections, especially those caused by encapsulated bacteria such as Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae, and, to a lesser extent, Neisseria gonorrhoeae.

Also increases risk of S. pneumoniae and H. influenzae type b (Hib) infections in children.

Vaccinate patients for the prevention of Streptococcus pneumoniae and Hib infections in accordance with current ACIP guidelines. Patients receiving eculizumab are at increased risk of infections due to these organisms even if they develop antibodies following vaccination.

Complications Following Treatment Discontinuance

Possible risk of serious hemolysis following discontinuance of therapy in patients with PNH. Monitor patients for ≥8 weeks after discontinuing therapy for manifestations of hemolysis.

Possible return of thrombotic microangiopathic symptoms following discontinuance of therapy in patients with aHUS; monitor patients for ≥12 weeks after discontinuing therapy for manifestations of thrombotic microangiopathy (e.g., mental status changes, seizures, angina, dyspnea, thrombosis). In addition, the occurrence of 2 of the following laboratory changes or a repeat occurrence of any one of the changes may indicate the development of thrombotic microangiopathy: a decrease in platelet count by ≥25% compared with baseline or the peak platelet count during eculizumab treatment; an increase in S_cr by ≥25% compared with baseline or the nadir value during eculizumab treatment; or an increase in serum LDH concentration by ≥25% from baseline or the nadir value during eculizumab treatment. Consider reinitiation of drug, plasma therapy, and/or supportive measures if manifestations of thrombotic microangiopathy recur after discontinuance of therapy.

Thrombosis Prevention and Management

High risk of venous thrombosis (potentially life-threatening or fatal) in patients with PNH. Effects of withdrawing anticoagulant therapy in patients receiving eculizumab not established. Treatment with eculizumab should not affect concomitant anticoagulant management.

Infusion-related Reactions

Infusion reactions requiring discontinuance of eculizumab were not observed during clinical trials, but hypersensitivity reactions, including anaphylaxis, are possible with all therapeutic proteins. Patients should be monitored for infusion-related reactions during treatment; if manifestations of cardiovascular instability or respiratory compromise occur, the infusion should be interrupted and appropriate treatment instituted.

Immunogenicity

Antibodies to eculizumab, including some that were neutralizing, have been detected in patients with PNH or aHUS. Anti-drug antibodies also detected in patients with NMOSD; however, none were neutralizing.

No apparent relationship between the development of antibodies and clinical response observed.

Specific Populations

Pregnancy

Limited data in pregnant women receiving eculizumab have not identified any concerns of adverse developmental outcomes.

Untreated PNH and aHUS in pregnancy associated with adverse maternal and fetal outcomes.

Increased rates of developmental abnormalities and increased rate of dead and moribund offspring observed in animal reproduction studies.

Lactation

Does not appear to distribute into human milk; however, maternal IgG is known to be present in human milk.

Insufficient information to inform the effect of eculizumab on the breast-fed infant. No data on effects of eculizumab on milk production.

Consider developmental and health benefits of breastfeeding along with the mother's clinical need for eculizumab and any potential adverse effects on the breastfed child from the drug or underlying maternal condition.

Pediatric Use

Safety and efficacy for the treatment of PNH, myasthenia gravis, or NMOSD not established in pediatric patients.

Safety and efficacy for the treatment of aHUS has been established in children ≥2 months of age. Response and safety in these pediatric patients were similar to those in adults.

Ensure that pediatric patients receive appropriate vaccinations for the prevention of N. meningitidis, S. pneumoniae, and Hib infections according to ACIP guidelines.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger patients.

Renal Impairment

Renal impairment not likely to affect pharmacokinetics.

Common Adverse Effects

Patients with PNH (≥10%): headache, nasopharyngitis, back pain, nausea.

Patients with aHUS (≥20%): headache, diarrhea, hypertension, upper respiratory infection, abdominal pain, vomiting, nasopharyngitis, anemia, cough, peripheral edema, nausea, urinary tract infections, pyrexia.

Patients with generalized myasthenia gravis (≥10%): musculoskeletal pain.

Patients with NMOSD (≥10%): upper respiratory infection, nasopharyngitis, diarrhea, back pain, dizziness, influenza, arthralgia, pharyngitis, contusion.

Drug Interactions

No formal drug interaction studies to date.

Plasma Exchange, Plasmapheresis, or Fresh Frozen Plasma

Concomitant use of eculizumab with plasma exchange, plasmapheresis, or fresh frozen plasma can reduce serum eculizumab concentrations. Administer a supplemental dose of eculizumab.

Neonatal Fc Receptor Blockers

Concomitant use of eculizumab with neonatal Fc receptor blockers may lower systemic exposure and reduce effectiveness of eculizumab. Closely monitor for reduced effectiveness of eculizumab.

Eculizumab Pharmacokinetics

Absorption

Plasma Concentrations

Plasma concentrations ≥35 mcg/mL required to block complement.

Duration

Complement activity inhibited for ≤2 weeks following single dose.

Reduction of hemolysis (as determined by reduction in LDH concentrations) maintained at least 52 weeks in open-label study.

Distribution

Extent

Human IgG crosses placenta and is distributed into human milk. Potential exists for eculizumab to cross placenta and distribute into milk.

Elimination

Metabolism

Metabolic fate of immunoglobulins not well characterized; catabolized in various tissues via diffuse cellular processes.

Elimination Route

Minimal excretion in urine expected due to large molecular size. Small quantities of immunoglobulin found in bile.

Half-life

Approximately 270 to 414 hours.

Special Populations

In patients undergoing plasma exchange interventions, clearance was increased and half-life reduced (to 1.26 hours).

Stability

Storage

Parenteral

Injection

2–8°C. Do not freeze or shake. Store in manufacturer’s carton and protect from light.

Following dilution, stable for 24 hours at 2–8°C or at room temperature.

Single-use vials do not contain preservative. Discard unused portions.

Actions

• IgG_2/4 kappa immunoglobulin containing human framework (i.e., variable and constant regions) and murine complementarity-determining regions.

• Hemolysis in PNH results from a genetic deficiency of glycosylphosphatidylinositol (GPI)-linked complement inhibitor CD-59 on the surface of RBCs (PNH erythrocytes), which renders such erythrocytes sensitive to persistent terminal complement-mediated destruction.

• In patients with PNH, eculizumab prevents destruction of PNH erythrocytes that lack complement protection with CD-59 by binding specifically and with high affinity to complement protein C5, preventing activation of terminal complement components (cleavage to C5a and C5b and subsequent formation of C5b–C9 terminal complement complex).

• In patients with aHUS, an acquired or inherited defect in regulation of the alternative complement pathway results in uncontrolled terminal complement activation; this leads to platelet activation, endothelial cell damage, thrombotic microangiopathy, and damage to multiple organ systems (e.g., CNS, kidneys, heart, GI tract). Eculizumab blocks formation of terminal complement, thereby inhibiting complement-mediated thrombotic microangiopathy.

Advice to Patients

• Advise patients and/or caregivers to read the FDA-approved patient labeling (Medication Guide).

• Advise patients of the risk of serious meningococcal infection. Inform patients of the need to complete or update their meningococcal vaccinations at least 2 weeks prior to receiving the first dose of eculizumab or receive antibacterial drug prophylaxis if eculizumab treatment must be initiated immediately and they have not been previously vaccinated. Inform patients that vaccination may not prevent meningococcal infection. Inform patients about the signs and symptoms of serious meningococcal infection (e.g., headache with nausea or vomiting, fever with high heart rate, headache with fever, headache with a stiff neck or stiff back, fever with or without rash, confusion, muscle aches with flu-like symptoms, eyes sensitive to light). Advise patients to seek immediate medical attention if these signs or symptoms occur.

• Inform patients with PNH that discontinuance of therapy may cause sudden hemolysis; importance of monitoring for hemolysis for at least 8 weeks following treatment discontinuance. Inform patients with aHUS that discontinuance of therapy may result in a worsening of disease symptoms or problems related to thrombotic microangiopathy.

• Inform patients of the importance of carrying a patient safety card at all times during treatment and for 3 months following discontinuance of therapy.

• Inform patients that eculizumab is available only through a restricted program called Ultomiris and Soliris REMS, and that this program requires patients to receive counseling (including written educational materials) about the risk of serious meningococcal infections, as well as comply with the most current recommendations for meningococcal vaccination.

• Advise patients of the increased risk of other infections, particularly those due to encapsulated bacteria such as Neisseria species. Inform patients about gonorrhea prevention and advise regular testing for patients at risk. Advise patients to report any new signs and symptoms of infection.

• Inform patients of the risk of infusion-related reactions.

• Advise patients to inform their clinicians if they are or plan to become pregnant or plan to breast-feed.

• Advise patients to inform their clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.

• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Distribution of eculizumab is restricted. (See REMS under Dosage and Administration.)

Reload page with references included

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Find detailed information on biosimilars for this medication.

Frequently asked questions

• How does Empaveli compare to Soliris?

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