Due to challenges with completion of required laboratory testing or imaging studies for REMS drugs because of self-isolation or quarantine during the COVID-19 public health emergency, the FDA is recommending health care providers prescribing and/or dispensing REMS drugs consider whether there are compelling reasons or not to complete these requirements during this public health emergency and weigh with the patient the benefits and risks of continuing treatment in the absence of the laboratory testing and imaging studies. The FDA will not take action against sponsors and others during the public health emergency for failing to adhere to REMS requirements.
Further information may be found at https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-provides-update-patient-access-certain-rems-drugs-during-covid-19.
Life-threatening and fatal meningococcal infections have occurred in patients treated with eculizumab. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early.
Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients with complement deficiencies.
Immunize patients with meningococcal vaccines at least 2 weeks prior to administering the first dose of eculizumab, unless the risks of delaying eculizumab therapy outweigh the risk of developing a meningococcal infection.
Vaccination reduces, but does not eliminate, the risk of meningococcal infections. Monitor patients for early signs of meningococcal infections and evaluate immediately if infection is suspected.
Eculizumab is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Under the Soliris REMS, health care providers must enroll in the program. Enrollment in the Soliris REMS program and additional information are available from the manufacturer (1-888-765-4747) or solirisrems.com.
Note: Patients must receive meningococcal vaccine at least 2 weeks prior to treatment initiation; revaccinate according to current guidelines. If urgent eculizumab initiation is necessary and <2 weeks after vaccination, provide 2 weeks of antibacterial prophylaxis; in unvaccinated patients, administer meningococcal vaccine as soon as possible and provide 2 weeks of antibacterial prophylaxis. 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 (McNamara 2017). Administer eculizumab at the recommended time interval or within 2 days of the interval.
Atypical hemolytic uremic syndrome: IV: Induction: 900 mg weekly for 4 doses; Maintenance: 1,200 mg at week 5, then 1,200 mg 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.
Myasthenia gravis, generalized refractory, chronic immunosuppressive therapy:
Note: For use in patients with anti-acetylcholine receptor antibody positive (AChR+) myasthenia gravis.
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 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.
Neuromyelitis optica spectrum disorder: IV: Induction: 900 mg weekly for 4 doses; Maintenance: 1,200 mg at week 5, then 1,200 mg 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: IV: Induction: 600 mg weekly for 4 doses; Maintenance: 900 mg at week 5; then 900 mg every 2 weeks thereafter.
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).
(For additional information see "Eculizumab: Pediatric drug information")
Note: 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 (penicillin, or macrolides if penicillin-allergic) for the duration of eculizumab therapy (McNamara 2017). 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:
Patient weight:
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.
Supplemental dosing for patients receiving plasmapheresis or plasma exchange:
If most recent dose was 300 mg, administer 300 mg within 60 minutes after each plasmapheresis or plasma exchange.
If most recent dose was ≥600 mg, administer 600 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.
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).
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Soliris: 300 mg/30 mL (30 mL) [contains polysorbate 80]
No
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]
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/125166s431lbl.pdf#page=40, must be dispensed with this medication.
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 eculizumab must be initiated urgently and less than 2 weeks after vaccination, provide 2 weeks of antibacterial prophylaxis; in unvaccinated patients, administer meningococcal vaccine as soon as possible and provide 2 weeks of antibacterial prophylaxis.
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. 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).
Atypical hemolytic uremic syndrome: 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 refractory, chronic immunosuppressive therapy: Treatment of refractory generalized myasthenia gravis in adults who are antiacetylcholine receptor antibody positive (AChR+) (AAN [Narayanaswami 2021]; manufacturer's labeling).
Neuromyelitis optica spectrum disorder: Treatment of neuromyelitis optica spectrum disorder in adults who are aquaporin-4-antibody positive.
Paroxysmal nocturnal hemoglobinuria: Treatment of paroxysmal nocturnal hemoglobinuria to reduce hemolysis.
Eculizumab may be confused with elotuzumab, emicizumab-kxwh, evolocumab
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Hypertension (adolescents and adults: 17% to 59%; infants and children: 22%), tachycardia (infants and children: 40%; children: 20%), peripheral edema (adolescents and adults: 20% to 29%; adults: 8%), hypotension (adolescents and adults: 12% to 20%)
Central nervous system: Headache (adolescents and adults: 37% to 50%; infants and children: 17%), insomnia (adolescents and adults: 10% to 24%), fatigue (adolescents and adults: 7% to 20%), dizziness (adults: 15%)
Dermatologic: Skin rash (12% to 22%), pruritus (adolescents and adults: 6% to 15%)
Endocrine & metabolic: Hypokalemia (adolescents and adults: 10% to 18%)
Gastrointestinal: Diarrhea (16% to 47%), vomiting (10% to 47%), nausea (adolescents and adults: 12% to 40%), abdominal pain (8% to 33%), gastroenteritis (adolescents and adults: 5% to 20%)
Genitourinary: Urinary tract infection (adolescents and adults: 15% to 35%; infants and children: 17%), urinary tract symptoms (infants and children: 17%), proteinuria (adolescents and adults: 5% to 12%)
Hematologic & oncologic: Anemia (adolescents and adults: 17% to 35%), neoplasm (adolescents and adults: 6% to 30%), leukopenia (adolescents and adults: 5% to 24%)
Infection: Infection (adolescents and adults: 24%), influenza (adults: 11%)
Local: Catheter infection (infants and children: 17%)
Neuromuscular & skeletal: Asthenia (adolescents and adults: 5% to 20%), back pain (adolescents and adults: 5% to 19%), arthralgia (adolescents and adults: 6% to 17%), musculoskeletal pain (adults: 6% to 15%), muscle spasm (5% to 11%)
Ophthalmic: Eye disease (adolescents and adults: 10% to 29%; infants and children: 17%)
Renal: Renal insufficiency (adolescents and adults: 15% to 29%)
Respiratory: Cough (infants and children: 20% to 60%; adolescents and adults: 12% to 30%), nasopharyngitis (adolescents and adults: 17% to 55%; infants and children: 17%), nasal congestion (infants and children: 40%; children: 20%), upper respiratory tract infection (5% to 40%), rhinitis (infants and children: 22%), bronchitis (adolescents and adults: 9% to 18%)
Miscellaneous: Fever (infants and children: 40% to 80%; adolescents and adults: 17% to 25%; adults: 7%)
1% to 10%:
Cardiovascular: Severe hypertension (5% to 9%)
Central nervous system: High fever (infants and children: 9%), paresthesia (adults: 8%)
Dermatologic: Alopecia (adults: 5%), cellulitis (adults: 5%)
Gastrointestinal: Viral gastroenteritis (infants and children: 9%), constipation (adults: 7% to 9%), decreased appetite (adults: 5%)
Genitourinary: Cystitis (adults: 8%), chronic renal failure (adolescents and adults: 5%)
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% to 2%)
Neuromuscular & skeletal: Limb pain (adults: 7%), myalgia (adults: 7%)
Ophthalmic: Conjunctivitis (adults: 9%), hordeolum (adults: 7%), cataract (adults: 6%)
Respiratory: Pharyngitis (adults: 10%), respiratory tract infection (adults: 7%), oropharyngeal pain (6% to 7%), sinusitis (adults: 6% to 7%), flu-like symptoms (adults: 5%)
<1%, postmarketing, and/or case reports: Aspergillosis, genitourinary infection, septic meningitis, systemic lupus erythematosus
US labeling: Unresolved serious Neisseria meningitidis infection; patients not currently vaccinated against Neisseria meningitidis (unless risks of treatment delay outweigh risk of developing a meningococcal infection)
Canadian labeling: Hypersensitivity to eculizumab, murine proteins, or any component of the formulation; unresolved Neisseria meningitidis infection; patients not currently vaccinated against Neisseria 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 ACIP guidelines. Use with caution when administering to patients with any systemic infection.
• Infusion reactions: Infusion reactions, including anaphylaxis or hypersensitivity, may occur; interrupt infusion for severe reaction (eg, cardiovascular instability, respiratory compromise). Continue monitoring for 1 hour after completion of infusion.
• Meningococcal infection: [US Boxed Warning]: Meningococcal (Neisseria meningitidis) infections have occurred in patients receiving eculizumab; may be fatal or life-threatening if not detected and treated promptly. Monitor closely for early signs of meningococcal infection; evaluate and treat promptly if suspected. Follow current meningococcal immunization recommendations for patients with complement deficiencies. Vaccination reduces, but does not eliminate, the risk of meningococcal infections. Vaccinate with meningococcal vaccines at least 2 weeks prior to initiation of treatment (unless the risks of delaying eculizumab outweigh the risk of developing meningococcal infection); revaccinate according to current guidelines, considering the eculizumab duration of therapy. If eculizumab must be initiated urgently and less than 2 weeks after vaccination, provide 2 weeks of antibacterial prophylaxis. If urgent treatment is necessary in an unvaccinated patient, administer meningococcal vaccine(s) as soon as possible and provide patients with 2 weeks of antibacterial prophylaxis. Meningococcal infections developed in some patients despite vaccination. Prophylactic antibiotics were administered in clinical studies until at least 2 weeks after vaccination. 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 (McNamara 2017). Discontinue eculizumab during the treatment of serious meningococcal infections. Eculizumab is associated with a ~2,000-fold increased risk of meningococcal disease (compared to the general population risk).
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 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: [US Boxed Warning]: Access is restricted through a REMS program. Prescribers must be enrolled in the program; enrollment and additional information is available at 1-888-765-4747 or solirisrems.com. Counsel patients on the risk of meningococcal infection; ensure patients are vaccinated and provide educational materials.
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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Androgens: Hypertension-Associated Agents may enhance the hypertensive effect of Androgens. Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Cladribine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
Coccidioides immitis Skin Test: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. 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
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
Denosumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect 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 enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Leflunomide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect 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
Meningococcal Group B Vaccine: May diminish the therapeutic effect of Eculizumab. The meningococcal vaccine may result in increased complement activation, possibly worsening the symptoms of any underlying complement-mediated diseases, such as hemolysis and anemia. Eculizumab may diminish the therapeutic effect of Meningococcal Group B Vaccine. Management: Administer meningococcal vaccine at least 2 weeks prior to initiation of eculizumab in unvaccinated patients. If eculizumab is indicated urgently, administer meningococcal vaccine as soon as possible and administer 2 weeks of antibiotic prophylaxis. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Pidotimod: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Pimecrolimus. Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the potential for allergic or hypersensitivity reactions to 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
Ruxolitinib (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect 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 enhance the hypertensive effect of Hypertension-Associated Agents. Risk C: Monitor therapy
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect 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 combination
Tertomotide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect 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 combination
Upadacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
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; 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 MAC. Terminal complement-mediated intravascular hemolysis is a key clinical feature of paroxysmal nocturnal hemoglobinuria (PNH); blocking the formation of membrane attack complex (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).
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)
Solution (Soliris Intravenous)
300 mg/30 mL (per mL): $260.92
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