Version July 2025
Eculizumab, a complement inhibitor, increases the risk of serious infections caused by Neisseria meningitidis. Life-threatening and fatal meningococcal infections have occurred in patients treated with complement inhibitors. These infections may become rapidly life-threatening or fatal if not recognized and treated early.
Complete or update vaccination for meningococcal bacteria (for serogroups A, C, W, Y, and B) at least 2 weeks prior to the first dose of eculizumab, unless the risks of delaying therapy with eculizumab outweigh the risk of developing a serious infection. Comply with the most current Advisory Committee on Immunization Practices recommendations for vaccinations against meningococcal bacteria in patients receiving a complement inhibitor.
Patients receiving eculizumab are at increased risk for invasive disease caused by N. meningitidis, even if they develop antibodies following vaccination. Monitor patients for early signs and symptoms of serious meningococcal infections and evaluate immediately if infection is suspected.
Because of the risk of serious meningococcal infections, eculizumab is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called ULTOMIRIS and SOLIRIS REMS.
Dosage guidance:
Safety: Vaccinate patients against meningococcal infection (serogroups A, C, W, Y, and B) according to current guidelines at least 2 weeks prior to treatment initiation; revaccinate according to current guidelines. If urgent eculizumab initiation is necessary in a patient that is not up to date with meningococcal vaccines according to current guidelines, provide antibacterial prophylaxis and administer vaccines as soon as possible. Administer eculizumab at the recommended time interval or within 2 days of the interval.
Clinical considerations: To reduce the risk for meningococcal disease, consider antimicrobial prophylaxis with oral antibiotics (penicillin, or macrolides if penicillin-allergic) for the duration of eculizumab therapy (Ref).
Dosage form information: In the United States, Bkemv (eculizumab-aeeb) is approved as a biosimilar to Soliris (eculizumab).
Atypical hemolytic uremic syndrome (Soliris and eculizumab biosimilars): IV: Induction: 900 mg weekly for 4 doses; Maintenance: 1.2 g at week 5, then 1.2 g every 2 weeks thereafter. Note: Monitor for recurrence for at least 12 weeks after discontinuation and which may require treatment re-initiation.
Supplemental dosing for patients receiving plasmapheresis or plasma exchange:
If most recent dose was ≥600 mg, administer 600 mg within 60 minutes after each plasmapheresis or plasma exchange.
If most recent dose was 300 mg, administer 300 mg within 60 minutes after each plasmapheresis or plasma exchange.
Supplemental dosing for patients receiving fresh frozen plasma infusion: If most recent dose was ≥300 mg, administer 300 mg within 60 minutes prior to each infusion of fresh frozen plasma.
Heart transplant, antibody-mediated rejection, treatment (off-label use): Note: Optimal regimen has not been established; refer to published and institutional protocols. Administer antibiotic prophylaxis against Neisseria meningitides for the duration of treatment (Ref).
IV: 900 mg weekly for up to 8 weeks in combination with other immunosuppression (eg rabbit antithymocyte globulin) (Ref).
Heart transplant, perioperative desensitization (off label use): Note: Optimal regimen has not been established; refer to published and institutional protocols. Vaccinate against Neisseria meningitides at least 2 weeks prior to transplant; if unable to vaccinate, administer appropriate prophylactic antibiotics for the duration of therapy (Ref).
IV: 1.2 g on the day of transplant administered immediately prior to reperfusion in combination with rabbit antithymocyte globulin and IV immune globulin; then 900 mg on postoperative days 1, 7, 14, 21 followed by 1.2 g on days 28, 42, 56 and 900 mg on day 60 (Ref).
Kidney transplant, antibody-mediated rejection, treatment (adjunctive) (off-label use): Note: Patients should receive prophylactic antibiotics against N. meningitidis while receiving therapy, and then should receive appropriate vaccination (Ref). Optimal regimen has not been established; refer to published and institutional protocols.
IV: 1.2 g within 24 hours of the rejection; then 600 mg after each plasmapheresis session followed by 900 mg weekly for 30 days or until clinical goals are met (eg, donor-specific antibody mean fluorescence intensity ≤5,000; stabilization of kidney function) (Ref).
Kidney transplant, perioperative desensitization (adjunctive) (off label): Note: Vaccinate against N. meningitidis 14 days prior to receiving therapy or administer appropriate antibiotic prophylaxis if vaccination is not possible (Ref). Optimal regimen has not been established; refer to published and institutional protocols.
Fixed duration: IV: 1.2 g administered 1 hour prior to reperfusion on day 0, then 900 mg on day(s) 1, 7, 14, 21, and 28, then 1.2 g once weekly during weeks 5, 7, and 9 (Ref).
Unspecified duration: IV: 1.2 g administered 1 hour prior to reperfusion on day 0, then 600 mg on day 1 and weekly thereafter for 4 weeks; may continue 1.2 g during week 5 and then every 2 weeks until clinical goals are met (eg, reduction in donor-specific antibody levels) based on institutional protocol (Ref).
Myasthenia gravis, generalized refractory (Soliris and eculizumab biosimilars):
Note: For use as chronic immunosuppressive therapy in refractory anti-acetylcholine receptor antibody positive (AChR+) myasthenia gravis in selected patients (eg, severe disease, dependence on maintenance IVIG or plasma exchange, lack of response to at least one other immunotherapeutic agent administered with glucocorticoids, and/or intolerance of other immunotherapies) (Ref). Consider administration of prophylactic antibiotics regardless of vaccination status (Ref).
IV: Induction: 900 mg once weekly for 4 doses; Maintenance: 1.2 g at week 5, then 1.2 g every 2 weeks thereafter.
Supplemental dosing for patients receiving concomitant plasmapheresis or plasma exchange:
If most recent dose was ≥600 mg, administer 600 mg within 60 minutes after each plasmapheresis or plasma exchange.
If most recent dose was 300 mg, administer 300 mg within 60 minutes after each plasmapheresis or plasma exchange.
Supplemental dosing for patients receiving concomitant fresh frozen plasma infusion: If most recent dose was ≥300 mg, administer 300 mg within 60 minutes prior to each infusion of fresh frozen plasma.
Supplemental dosing for patients receiving concomitant IVIG:
Note: Supplemental eculizumab doses are not required for IVIG acute rescue therapy.
IVIG administered every 4 weeks or more frequently than every 4 weeks:
Most recent eculizumab dose ≥900 mg: Administer an additional eculizumab 600 mg dose at the same time as the regularly scheduled eculizumab dose.
Most recent eculizumab dose ≤600 mg: Administer an additional eculizumab 300 mg dose at the same time as the regularly scheduled eculizumab dose.
IVIG administered less frequently than every 4 weeks:
Most recent eculizumab dose ≥900 mg: Administer an additional eculizumab 600 mg dose with the next scheduled eculizumab dose following the last IVIG cycle.
Most recent eculizumab dose ≤600 mg: Administer an additional eculizumab 300 mg dose with the next scheduled eculizumab dose following the last IVIG cycle.
Neuromyelitis optica spectrum disorder (Soliris only): IV: Induction: 900 mg weekly for 4 doses; Maintenance: 1.2 g at week 5, then 1.2 g every 2 weeks thereafter.
Supplemental dosing for patients receiving plasmapheresis or plasma exchange:
If most recent dose was ≥600 mg, administer 600 mg within 60 minutes after each plasmapheresis or plasma exchange.
If most recent dose was 300 mg, administer 300 mg within 60 minutes after each plasmapheresis or plasma exchange.
Supplemental dosing for patients receiving fresh frozen plasma infusion: If most recent dose was ≥300 mg, administer 300 mg within 60 minutes prior to each infusion of fresh frozen plasma.
Paroxysmal nocturnal hemoglobinuria (Soliris and eculizumab biosimilars): IV: Induction: 600 mg weekly for 4 doses; Maintenance: 900 mg at week 5; then 900 mg every 2 weeks thereafter. Note: Monitor for recurrence for at least 8 weeks after discontinuation.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Meningococcal infection: Immediately treat infection and consider interrupting eculizumab therapy in patients being treated for serious infections.
Refer to adult dosing.
(For additional information see "Eculizumab (including biosimilars): Pediatric drug information")
Dosage guidance:
Safety: Patients must receive meningococcal vaccine at least 2 weeks prior to treatment initiation; if the risk of treatment delay outweighs the risk of developing meningococcal infection, then administer vaccine as soon as possible. Revaccinate according to current guidelines with consideration of eculizumab therapy duration. To reduce the risk for meningococcal disease, consider antimicrobial prophylaxis with oral antibiotics for the duration of eculizumab therapy (Ref).
Dosing: Treatment should be administered at the recommended time interval although administration may be varied by ± 2 days. Dosing interval is weight dependent.
Atypical hemolytic uremic syndrome (aHUS):
Infants, Children, and Adolescents:
5 kg to <10 kg: IV: Induction: 300 mg weekly for 1 dose; Maintenance: 300 mg at week 2, then 300 mg every 3 weeks.
10 kg to <20 kg: IV: Induction: 600 mg weekly for 1 dose; Maintenance: 300 mg at week 2, then 300 mg every 2 weeks.
20 kg to <30 kg: IV: Induction: 600 mg weekly for 2 doses; Maintenance: 600 mg at week 3, then 600 mg every 2 weeks.
30 kg to <40 kg: IV: Induction: 600 mg weekly for 2 doses; Maintenance: 900 mg at week 3, then 900 mg every 2 weeks.
≥40 kg: Induction: IV: 900 mg weekly for 4 doses; Maintenance: 1,200 mg at week 5, then 1,200 mg every 2 weeks.
Myasthenia gravis, generalized refractory: Note: For use as chronic immunosuppressive therapy in refractory anti-acetylcholine receptor antibody positive (AChR+) myasthenia gravis in select patients (eg, dependence on maintenance IVIG or plasma exchange or lack of response to at least one other immunosuppressant) (Ref). In clinical trials, if patient's meningococcal vaccine was administered <2 weeks before the start of eculizumab, prophylactic antibiotics were administered for at least 2 weeks (Ref).
Children ≥6 years and Adolescents:
10 kg to <20 kg: IV: Induction: 600 mg weekly for 1 dose; Maintenance: 300 mg at week 2, then 300 mg every 2 weeks.
20 kg to <30 kg: IV: Induction: 600 mg weekly for 2 doses; Maintenance: 600 mg at week 3, then 600 mg every 2 weeks.
30 kg to <40 kg: IV: Induction: 600 mg weekly for 2 doses; Maintenance: 900 mg at week 3, then 900 mg every 2 weeks.
≥40 kg: Induction: IV: 900 mg weekly for 4 doses; Maintenance: 1,200 mg at week 5, then 1,200 mg every 2 weeks.
Supplemental dosing for concomitant plasma exchange (PE), plasmapheresis (PP), or fresh frozen plasma (FFP):
Infants, Children and Adolescents: IV:
|
Concomitant therapy |
Current eculizumab dose |
Supplemental eculizumab dose |
Timing of supplemental dose |
|---|---|---|---|
|
PP or PE |
300 mg |
300 mg |
Within 60 minutes after each PP or PE |
|
≥600 mg |
600 mg | ||
|
FFP |
≥300 mg |
300 mg |
Within 60 minutes prior to each FFP |
Supplemental dosing for concomitant IVIG:
Children ≥6 years and Adolescents: IV: Note: Dosing dependent on frequency of IVIG therapy.
|
IVIG frequency |
Current eculizumab dose |
Supplemental eculizumab dose |
Timing of supplemental dose |
|---|---|---|---|
|
Acute exacerbation, rescue therapy |
No supplemental eculizumab dose needed. | ||
|
< every 4 weeks |
≤600 mg |
300 mg |
At next scheduled eculizumab dose after last IVIG cycle |
|
≥900 mg |
600 mg | ||
|
≥ every 4 weeks |
≤600 mg |
300 mg |
At the same time as scheduled eculizumab dose |
|
≥900 mg |
600 mg | ||
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in infants, children, adolescents, and adults unless otherwise indicated.
>10%:
Cardiovascular: Hypertension (infants, children: 22%; adolescents, adults: 17% to 59%; severe hypertension: 5% to 9%), hypotension (adolescents, adults: 12% to 20%), peripheral edema (adolescents, adults: 8% to 29%), tachycardia (infants, children: 40%; children: 20%)
Dermatologic: Pruritus (adolescents, adults: 6% to 15%), skin rash (12% to 22%)
Endocrine & metabolic: Hypokalemia (adolescents, adults: 10% to 18%)
Gastrointestinal: Abdominal pain (8% to 33%), diarrhea (16% to 47%), gastroenteritis (adolescents, adults: 5% to 20%), nausea (adolescents, adults: 12% to 40%), vomiting (10% to 47%)
Genitourinary: Proteinuria (adolescents, adults: 5% to 12%), urinary tract infection (infants, children: 17%; adolescents, adults: 15% to 35%), urinary tract symptoms (infants, children: 17%)
Hematologic & oncologic: Anemia (adolescents, adults: 17% to 35%), leukopenia (adolescents, adults: 5% to 24%), neoplasm (adolescents, adults: 6% to 30%)
Infection: Infection (adolescents, adults: 24%), influenza (adults: 11%)
Nervous system: Asthenia (adolescents, adults: 5% to 20%), dizziness (adults: 15%), fatigue (adolescents, adults: 7% to 20%), headache (infants, children: 17%; adolescents, adults: 37% to 50%), insomnia (adolescents, adults: 10% to 24%)
Neuromuscular & skeletal: Arthralgia (adolescents, adults: 6% to 17%), back pain (adolescents, adults: 5% to 19%), muscle spasm (5% to 11%), musculoskeletal pain (adults: 6% to 15%)
Ophthalmic: Eye disease (infants, children: 17%; adolescents, adults: 10% to 29%)
Renal: Kidney impairment (adolescents, adults: 15% to 29%)
Respiratory: Bronchitis (adolescents, adults: 9% to 18%), cough (infants, children: 20% to 60%; adolescents, adults: 12% to 30%), nasal congestion (infants, children: 40%; children: 20%), nasopharyngitis (infants, children: 17%; adolescents, adults: 17% to 55%), rhinitis (infants, children: 22%), upper respiratory tract infection (5% to 40%)
Miscellaneous: Fever (infants, children: 40% to 80%; adolescents, adults: 7% to 25%)
1% to 10%:
Dermatologic: Alopecia (adults: 5%), cellulitis (adults: 5%)
Gastrointestinal: Constipation (adults: 7% to 9%), decreased appetite (adults: 5%), viral gastroenteritis (infants, children: 9%)
Genitourinary: Cystitis (adults: 8%)
Hematologic & oncologic: Bruise (adults: 8% to 10%), lymphocytopenia (adults: 5%)
Immunologic: Antibody development (≤3%; neutralizing: 1%)
Infection: Herpes simplex infection (adults: 7% to 8%), meningococcal infection (1%)
Nervous system: Paresthesia (adults: 8%)
Neuromuscular & skeletal: Limb pain (adults: 7%), myalgia (adults: 7%)
Ophthalmic: Cataract (adults: 6%), conjunctivitis (adults: 9%), hordeolum (adults: 7%)
Renal: Chronic renal failure (adolescents, adults: 5%)
Respiratory: Flu-like symptoms (adults: 5%), oropharyngeal pain (6% to 7%), pharyngitis (adults: 10%), respiratory tract infection (adults: 7%), sinusitis (adults: 6% to 7%)
Frequency not defined (any population):
Infection: Septic meningitis
Nervous system: Agitation
Neuromuscular & skeletal: Systemic lupus erythematosus
Postmarketing (any population):
Genitourinary: Genitourinary infection
Hepatic: Hepatic injury (cholestatic or mixed pattern), increased liver enzymes, increased serum bilirubin
Infection: Aspergillosis
US labeling: Initiation in patients with unresolved serious N. meningitidis infection.
Canadian labeling: Hypersensitivity to eculizumab, murine proteins, or any component of the formulation; unresolved N. meningitidis infection; patients not currently vaccinated against N. meningitidis (unless receiving appropriate prophylactic antibiotic treatment until 2 weeks after vaccination).
Concerns related to adverse effects:
• Infections: Serious infections with Neisseria species (other than N. meningitides), including disseminated gonococcal infections, have been reported. In addition to meningitis, the risk of other infections, especially with encapsulated bacteria (eg, Streptococcus pneumoniae, H. influenzae) is increased with eculizumab treatment (because eculizumab blocks terminal complement activation). Aspergillus infections have occurred in immunocompromised and neutropenic patients. Children should receive vaccination for prevention of S. pneumoniae, H. influenzae according to current Advisory Committee on Immunization Practices (ACIP) guidelines. Use with caution when administering to patients with any systemic infection.
• Infusion reactions: Infusion reactions, including anaphylaxis or hypersensitivity, may occur.
• Meningococcal infection: Serious, life-threatening, or fatal meningococcal infections developed in some patients despite vaccination. ACIP vaccination recommendations differ from the administration schedule in the vaccine prescribing information. Prophylactic antibiotics were administered in clinical studies until at least 2 weeks after vaccination. Discontinue eculizumab during the treatment of serious meningococcal infections.
Concurrent drug therapy issues:
• Anticoagulation: In clinical trials, anticoagulant therapy was continued in patients who were receiving these agents (due to history of or risk for thromboembolism) prior to initiation of eculizumab. The effect of anticoagulant therapy withdrawal is unknown. Treatment with eculizumab should not alter anticoagulation management.
Dosage form specific issues:
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
Other warnings/precautions:
• Discontinuation in aHUS: Monitor patients for at least 12 weeks after treatment discontinuation for signs/symptoms of thrombotic microangiopathy (TMA) complications. Signs/symptoms of TMA include angina, dyspnea, mental status changes, seizure, or thrombosis; occurrence of two or repeated measurement of any one of the following: Serum creatinine elevation (≥25% from baseline or nadir), serum LDH elevation (≥25% from baseline or nadir), thrombocytopenia (platelet decrease by ≥25% compared to baseline or peak). If TMA complications occur after stopping eculizumab, consider reinitiation of treatment, plasmapheresis, plasma exchange, fresh frozen plasma infusion, and/or appropriate organ-specific measures.
• Discontinuation in generalized myasthenia gravis: In patients with generalized myasthenia gravis, relapse and/or myasthenic crisis have been reported with abrupt discontinuation of eculizumab; symptoms have been reported 2 months after discontinuation of therapy (Quasthoff 2024; Uzawa 2020); monitor closely after treatment discontinuation.
• Discontinuation in PNH: Patients with PNH who discontinue eculizumab treatment may be at increased risk for serious hemolysis; monitor closely for at least 8 weeks after treatment discontinuation.
• Immunizations: Patients should be up to date with all immunizations before initiating therapy.
• REMS program: Prescribers must be enrolled in the program; enrollment and additional information is available at 1-888-765-4747 or https://www.UltSolREMS.com. Counsel patients on the risk of meningococcal infection; ensure patients are vaccinated and provide educational materials.
Epysqli (eculizumab-aagh): FDA approved July 2024; anticipated availability currently unknown. Epysqli is approved as a biosimilar to Soliris.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Bkemv: Eculizumab-aeeb 300 mg/30 mL (30 mL) [contains edetate (edta) disodium, polysorbate 80]
Epysqli: Eculizumab-aagh 300 mg/30 mL (30 mL) [contains polysorbate 80]
Soliris: 300 mg/30 mL (30 mL) [contains polysorbate 80]
No
Solution (Bkemv Intravenous)
300 mg/30 mL (per mL): $234.83
Solution (Epysqli Intravenous)
300 mg/30 mL (per mL): $182.64
Solution (Soliris Intravenous)
300 mg/30 mL (per mL): $260.92
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Soliris: 300 mg/30 mL (30 mL) [contains polysorbate 80]
IV: Allow to reach room temperature prior to administration. Infuse over 35 minutes in adults and over 1 to 4 hours in pediatric patients; do not administer as an IV push or bolus. Decrease infusion rate or discontinue for infusion reactions; do not exceed a maximum 2-hour duration of infusion in adults. Monitor for at least 1 hour following completion of infusion (for signs/symptoms of infusion reaction).
Assess vaccination status prior to initiation; patients must receive meningococcal vaccine at least 2 weeks prior to treatment initiation. If urgent eculizumab initiation is necessary in a patient that is not up to date with meningococcal vaccines according to current guidelines, provide antibacterial prophylaxis and administer vaccines as soon as possible.
IV infusion: Allow to reach room temperature prior to administration. In pediatric patients, infuse over 1 to 4 hours; in adults, infuse over 35 minutes. Do not administer as an IV push or bolus.
Rate adjustment for infusion-related reactions: Decrease infusion rate or discontinue for infusion reactions; for slowed infusion rates, do not exceed a maximum 2-hour duration of infusion in adults. Monitor for at least 1 hour following completion of infusion.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Soliris: https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/125166s448,761108s038lbl.pdf#page=37
Atypical hemolytic uremic syndrome (Soliris and eculizumab biosimilars): Treatment of atypical hemolytic uremic syndrome to inhibit complement-mediated thrombotic microangiopathy.
Limitation of use: Eculizumab is not indicated for the treatment of patients with Shiga toxin Escherichia coli-related hemolytic uremic syndrome.
Myasthenia gravis, generalized: Treatment of generalized myasthenia gravis in adults (Soliris and biosimilars) and pediatric patients ≥6 years of age (Soliris only) who are antiacetylcholine-receptor antibody positive (AChR+).
Neuromyelitis optica spectrum disorder (Soliris only): Treatment of neuromyelitis optica spectrum disorder in adults who are aquaporin-4-antibody positive.
Paroxysmal nocturnal hemoglobinuria (Soliris and eculizumab biosimilars): Treatment of paroxysmal nocturnal hemoglobinuria to reduce hemolysis.
Heart transplant, antibody-mediated rejection, treatment; Heart transplant, perioperative desensitization; Kidney transplant, antibody-mediated rejection, treatment; Kidney transplant, perioperative desensitization
Eculizumab may be confused with elotuzumab, emicizumab-kxwh, evolocumab
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Androgens: Hypertension-Associated Agents may increase hypertensive effects of Androgens. Risk C: Monitor
Antithymocyte Globulin (Equine): Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Baricitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
Brincidofovir: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Cladribine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Therapeutic Immunosuppressant Agents) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing therapeutic immunosuppressants several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification
Crovalimab: May increase adverse/toxic effects of Eculizumab. Specifically, the risk of type III hypersensitivity reactions is increased. Eculizumab may decrease serum concentration of Crovalimab. Risk C: Monitor
Denosumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Denosumab. Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor for signs/symptoms of serious infections. Risk D: Consider Therapy Modification
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Efgartigimod Alfa: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Immune Globulin: May decrease serum concentration of Eculizumab. Management: Supplemental doses of eculizumab are recommended in patients with generalized myasthenia gravis who receive routine infusions of IVIg. See full monograph for details. Risk D: Consider Therapy Modification
Inebilizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Leflunomide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider Therapy Modification
Nadofaragene Firadenovec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
Nipocalimab: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor
Ocrelizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
Pidotimod: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Pimecrolimus. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification
Ritlecitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Rozanolixizumab: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor
Ruxolitinib (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Sipuleucel-T: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification
Solriamfetol: May increase hypertensive effects of Hypertension-Associated Agents. Risk C: Monitor
Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk C: Monitor
Tacrolimus (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid
Tertomotide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Tofacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Tofacitinib. Management: Coadministration of tofacitinib with potent immunosuppressants is not recommended. Use with non-biologic disease-modifying antirheumatic drugs (DMARDs) was permitted in psoriatic arthritis clinical trials. Risk X: Avoid
Ublituximab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Upadacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Eculizumab crosses the placenta (Duineveld 2019; Eliesen 2021; Gustavsen 2017; Hallstensen 2015; Kelly 2015; Miyasaka 2016).
The Alexion pharmacovigilance database has collected data on 434 pregnancies following in utero exposure to eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria (PNH, 335 patients) or atypical hemolytic uremic syndrome (aHUS, 99 patients), 70% of which resulted in a live birth. Among the 260 pregnancies with known outcomes, rates of congenital malformations in liveborn infants and the rates of miscarriage following in utero exposure to eculizumab were similar to those observed in the general population (Socié 2019).
Due to pregnancy-induced physiologic changes, dose adjustments of eculizumab may be required during pregnancy (Miyasaka 2016; Sarno 2019).
Pregnant patients with PNH and their fetuses have high rates of morbidity and mortality during pregnancy and the postpartum period. Adverse maternal outcomes include bleeding, infections, miscarriages, worsening cytopenias, and thrombotic events; increased fetal death and premature delivery is also reported. Treatment of PNH with eculizumab may increase fetal survival and decrease maternal complications; however, additional study may be needed (Al-Dosari 2021; Kelly 2015; Manning 2022; Miyasaka 2016).
Adverse maternal outcomes observed with aHUS include preeclampsia and preterm delivery; intrauterine growth restriction, low birth weight, and fetal death are also observed. Pregnancy-associated aHUS is rare, and outcome data following maternal use of eculizumab for the treatment of aHUS in pregnant patients are limited. Treatment may improve pregnancy outcomes (Fakhouri 2021; Gupta 2020; Huerta 2018; Rondeau 2022; Servais 2016).
Case reports describing the use of eculizumab in pregnant patients for myasthenia gravis (Vu 2021) and other diseases characterized by complement activation are limited (Burwick 2022; Sarno 2019; Stefanovic 2019).
Health care providers are encouraged to enroll patients exposed to eculizumab during pregnancy by contacting the disease specific registry websites (www.pnhregistry.com or www.ahusregistry.com for PNH or aHUS) or by calling 215-616-3558 (for PNH, aHUS, or gMG).
Eculizumab may be present in breast milk.
Eculizumab was not detected in breast milk samples in a study of 10 women treated for paroxysmal nocturnal hemoglobinuria (PNH) (Kelly 2015) or a report which included information from three women also treated for PNH when milk was sampled immediately following the infusion (Miyasaka 2016). In a separate case report, eculizumab was detected in the initial breast milk sample of a woman, but not subsequent samples (Kelly 2015).
The Alexion pharmacovigilance database has collected data on 31 patients who breastfed while treated with eculizumab for PNH (20 patients) or atypical hemolytic uremic syndrome (aHUS, 11 patients). One patient reported adverse events (painful breast lump, mastitis, sepsis, and fever). Adverse events were not observed in the other 30 patients or any neonates (Socié 2019).
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
CBC with differential, lactic dehydrogenase (LDH), serum creatinine, AST, urinalysis; early signs/symptoms of meningococcal infection, other encapsulated bacteria (eg, S. pneumoniae, H. influenzae, N. gonorrhoeae); signs and symptoms of infusion reaction (during infusion and for 1 hour after infusion complete). Assess meningococcal vaccination status prior to initiation.
After discontinuation:
aHUS: Signs/symptoms of thrombotic microangiopathy (TMA) complications (monitor for at least 12 weeks after treatment discontinuation), including angina, dyspnea, mental status changes, seizure, or thrombosis; occurrence of two or repeated measurement of any one of the following: Serum creatinine elevation (≥25% from baseline or nadir), serum LDH elevation (≥25% from baseline or nadir), thrombocytopenia (platelet decrease by ≥25% compared to baseline or peak).
PNH: Signs and symptoms of intravascular hemolysis (monitor for at least 8 weeks after discontinuation), including anemia, fatigue, pain, dark urine, dyspnea, or thrombosis.
Eculizumab is a humanized monoclonal IgG antibody that binds to complement protein C5, preventing cleavage into C5a and C5b. Blocking the formation of C5b inhibits the subsequent formation of terminal complex C5b-9 or membrane attack complex (MAC). Terminal complement-mediated intravascular hemolysis is a key clinical feature of paroxysmal nocturnal hemoglobinuria (PNH); blocking the formation of MAC results in stabilization of hemoglobin and a reduction in the need for RBC transfusions. Impairment of complement activity regulation leads to uncontrolled complement activation in atypical hemolytic uremic syndrome (aHUS). In generalized myasthenia gravis (gMG), the exact mechanism of action is not fully defined; it is theorized that the formation and deposition of the MAC C5b-9 and destruction of the neuromuscular junction are reduced (Dhillon 2018).
Onset of action: PNH: Reduced hemolysis: ≤1 week
Distribution: 5 to 8 L
Half-life elimination: ~270 to 414 hours (during plasma exchange the half-life is reduced to 1.26 hours)
