is vital [40:<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. 1 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. 1 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. 1 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. 1 (See Special Populations under Pharmacokinetics.) 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. 1 Optimal duration of therapy not known. 29 32 33 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. 1 22 28 29 32 33 37 (See Complications Following Treatment Discontinuance under Cautions.) Adults Paroxysmal Nocturnal Hemoglobinuria IV Initially, 600 mg every 7 days for 4 weeks, followed by one dose of 900 mg 7 days later (week 5), then 900 mg every 14 days thereafter. 1 6 Administer drug at these recommended time points, or within 2 days of each time point, to achieve maximum benefit. 1 16 17 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). 1 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. 1 Administer drug at these recommended time points, or within 2 days of each time point, to achieve maximum benefit. 1 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. 1 (See Special Populations under Pharmacokinetics.) 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. 1 Optimal duration of therapy not known. 29 32 33 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. 1 22 28 29 32 33 37 (See Complications Following Treatment Discontinuance under Cautions.) Cautions for Eculizumab Contraindications Active, severe N. meningitidis infection. 1 Patients not currently vaccinated against N. meningitidis , unless risk of delaying treatment outweighs risk of developing a meningococcal infection. 1 Warnings/Precautions Warnings Serious Meningococcal Infections Serious, sometimes life-threatening or fatal meningococcal infections (e.g., sepsis, meningitis) reported. 1 6 Do not initiate therapy in patients with unresolved, serious N. meningitidis infections or in those not immunized against N. meningitidis unless risk of delaying therapy outweigh risks of infection. 1 (See Contraindications and also see Boxed Warning.) Unvaccinated patients must receive an appropriate polyvalent meningococcal vaccine series at least 2 weeks prior to first dose of eculizumab and receive revaccination of booster doses thereafter according to current vaccination guidelines. 1 5 6 (See Vaccinations under Dosage and Administration.) If urgent treatment with eculizumab is necessary in an unvaccinated patient, administer meningococcal vaccine as soon as possible. 1 Vaccination can reduce, but does not eliminate, risk of meningococcal infection; cases of meningococcal septicemia reported in patients treated with eculizumab despite immunization. 1 6 10 36 Prophylactic use of antibiotics (e.g., penicillin) also has been employed and is recommended by some clinicians; 1 27 29 31 35 however, benefits and risks of antibiotic prophylaxis not established. 1 Monitor closely for early manifestations of meningococcal infection during therapy. 1 (See Advice to Patients.) Evaluate immediately if infection is suspected; discontinue therapy if serious infection requiring treatment occurs. 1 Other Warning and Precautions Hypersensitivity Reactions Infusion reactions requiring discontinuance of eculizumab not observed during clinical trials, but hypersensitivity or anaphylaxis possible with all therapeutic proteins. 1 6 Monitor for infusion-related reactions; if manifestations of cardiovascular instability or respiratory compromise occur, interrupt infusion and initiate appropriate treatment. 1 Other Infections Eculizumab increases susceptibility to infections caused by encapsulated bacteria, particularly meningococcal infections. 1 5 10 27 31 35 36 (See Boxed Warning.) Also increases risk of S. pneumoniae and Hib infections in children; administer appropriate vaccinations. 1 (See Vaccinations under Dosage and Administration.) Use caution in patients with any systemic infection. 1 Complications Following Treatment Discontinuance Possible risk of serious hemolysis following discontinuance of therapy in patients with PNH. 1 6 10 Monitor patients for ≥8 weeks after discontinuing therapy for manifestations of hemolysis. 1 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). 1 22 28 32 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. 1 Consider reinitiation of drug, plasma therapy, and/or supportive measures if manifestations of thrombotic microangiopathy recur after discontinuance of therapy. 1 Thrombosis Prevention and Management High risk of venous thrombosis (potentially life-threatening or fatal) in patients with PNH. 4 8 18 20 Effects of withdrawing anticoagulant therapy in patients receiving eculizumab not established. 1 Treatment with eculizumab should not affect concomitant anticoagulant management. 1 Immunogenicity As with all therapeutic proteins, there is a risk of immunogenicity with eculizumab. 1 3 6 Antibodies to eculizumab, including some that were neutralizing, have been detected; no apparent relationship between the development of antibodies and clinical response. 1 Laboratory Monitoring In patients with PNH, serum LDH concentrations may be used to monitor response to therapy (e.g., hemolysis, PNH erythrocytes). 1 10 Following withdrawal of therapy, monitor serum LDH concentrations and other parameters to detect serious hemolysis. 1 6 (See Complications Following Treatment Discontinuance under Cautions.) In patients with aHUS, platelet counts, serum LDH concentrations, and S cr may be used to monitor the effects of eculizumab therapy as well as to monitor for signs of thrombotic microangiopathy. 1 (See Complications Following Treatment Discontinuance under Cautions.) Specific Populations Pregnancy Category C. 1 Lactation Not known whether eculizumab is distributed into human milk. 1 (See Extent under Pharmacokinetics.) Caution if used in nursing women. 1 Pediatric Use Safety and efficacy for the treatment of PNH not established in children> <18 years of age. 1 Safety and efficacy for the treatment of aHUS has been established in children ≥2 months of age. 1 Response and safety in these pediatric patients were similar to those in adults. 1 Ensure that pediatric patients receive appropriate vaccinations for the prevention of N. meningitidis , S. pneumoniae , and Hib infections. 1 (See Serious Meningococcal Infections and also see Other Infections under Cautions.) Geriatric Use Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger patients. 1 Common Adverse Effects Patients with PNH: Headache, 1 3 4 21 nasopharyngitis, 1 3 4 back pain, 1 3 21 nausea, 1 3 4 21 fatigue, 1 cough, 1 1 herpes simplex infections, 1 sinusitis, 1 respiratory tract infection, 1 constipation, 1 myalgia, 1 pain in extremity, 1 influenza-like illness. 1 Patients with aHUS: Hypertension, upper respiratory tract infection, 1 diarrhea, 1 headache, 1 anemia, 1 vomiting, 1 nausea, 1 urinary tract infection, 1 leukopenia, 1 insomnia, 1 cough, 1 pharyngolaryngeal pain, 1 abdominal pain, 1 fatigue, 1 peripheral edema, 1 pyrexia, 1 vertigo, 1 extremity pain. 1 Interactions for Eculizumab No formal drug interaction studies to date. 1 Eculizumab Pharmacokinetics Absorption Plasma Concentrations Plasma concentrations ≥35 mcg/mL required to block complement. 16 17 Duration Complement activity inhibited for 2 weeks following single dose. 19 Reduction of hemolysis (as determined by reduction in LDH concentrations) maintained at least 52 weeks in open-label study. 1 17 Distribution Extent Human IgG crosses placenta and is distributed into milk. 1 Potential exists for eculizumab to cross placenta and distribute into milk. 1 Elimination Metabolism Metabolic fate of immunoglobulins not well characterized; catabolized in various tissues via diffuse cellular processes. 15 Elimination Route Minimal excretion in urine expected due to large molecular size. 1 15 Small quantities of immunoglobulin found in bile. 15 Half-life Patients with PNH: Approximately 272 hours. 1 Patients with aHUS: Approximately 291 hours. 1 Special Populations In patients with aHUS undergoing plasma exchange interventions, clearance was increased and half-life reduced (to 1.26 hours). 1 Stability Storage Parenteral Injection 2 8°C. 1 Do not freeze or shake. 1 Store in manufacturer s carton and protect from light. 1 Following dilution, stable for 24 hours at 2 8°C or at room temperature. 1 Single-use vials do not contain preservative. 1 Discard unused portions. 1 Compatibility For information on systemic interactions resulting from concomitant use, see Interactions. Parenteral Solution Compatibility 1 Compatible Dextrose 5% in water Sodium chloride 0.45 or 0.9% Ringer s injection Actions IgG 2/4 kappa immunoglobulin containing human framework (i.e., variable and constant regions) and murine complementarity-determining regions. 1 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. 1 4 8 9 10 18 20 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). 1 3 10 19 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). 1 22 31 Eculizumab blocks formation of terminal complement, thereby inhibiting complement-mediated thrombotic microangiopathy. 1 Advice to Patients Importance of patients fully understanding risks and benefits of therapy prior to initiation. 1 21 Risk of serious meningococcal infections and other systemic infections (e.g., S. pneumoniae , Hib infections). 1 21 Importance of immunization against meningococcal infections at least 2 weeks prior to initiation of therapy and revaccination or booster doses according to current guidelines while on therapy. 1 6 21 Advise patients that vaccination may not prevent infection; importance of informing clinician immediately if manifestations of meningococcal infection (headache with nausea, vomiting, fever, stiff neck or back; temperature ≥39.4°C; fever with rash; confusion; severe muscle aches with flu-like symptoms; light sensitivity) develop. 1 21 Advise parents/caregivers of children with aHUS that their child should be vaccinated against S. pneumoniae and Hib infections prior to initiation of therapy. 1 Importance of informing patients with PNH that discontinuance of therapy may cause sudden hemolysis; importance of monitoring for hemolysis for at least 8 weeks following treatment discontinuance. 1 21 Importance of informing patients with aHUS that discontinuance of therapy may result in a worsening of disease symptoms or problems related to thrombotic microangiopathy. 1 Importance of patients carrying a patient safety card (describing symptoms requiring immediate medical attention) at all times during treatment and for 3 months following discontinuance of therapy because the risk of meningococcal infection may persist for weeks after the last dose is given. 1 21 Importance of women informing their clinicians if they are or plan to become pregnant or plan to breast-feed. 1 21 Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses. 1 21 Importance of informing patients of other important precautionary information. 1 21 (See Cautions.) 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. 1 (See Restricted Distribution Program under Dosage and Administration.) Eculizumab Routes Dosage Forms Strengths Brand Names Manufacturer Parenteral For injection, concentrate, for IV infusion only 10 mg/mL (300 mg) Soliris Alexion AHFS DI Essentials. Copyright 2017, Selected Revisions January 2, 2014. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814. References 1. Alexion Pharmaceuticals, Inc. Soliris (eculizumab) concentrated solution for intravenous infusion prescribing information. Chesire, CT; 2012 Dec. 2. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97 414). Rockville, MD. From FDA web site (). Accessed 2013 Sept 25. 3. Hillmen P, Young NS, Schubert J et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med . 2006; 355:1233-43. [PubMed 16990386] 4. Young NS, Antonioli E, Rotoli B et al. Safety and efficacy of the terminal complement inhibitor eculizumab in patients with paroxysmal nocturnal hemoglobinuria: SHEPHERD phase III clincial study results. Paper presented at American Society of Hematology Annual Meeting. Orlando, FL: 2006 Dec 9. 5. Centers for Disease Control and Prevention. Prevention and control of meningococcal disease recommendations of the advisory committee on immunization practices (ACIP). MMWR . 2013; 62 (No. RR02):1-22. [PubMed 23302815] 6. Alexion Pharmaceuticals, Cheshire, CT: Personal communication. 7. The Soliris (eculizumab) OneSource Program for Healthcare Professionals and Patients. Soliris website. Available at: . Accessed 2007 July 25. 8. Hillmen P, Lewis SM, Bessler M et al. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med . 1995; 333:1253-8. [PubMed 7566002] 9. Parker C, Omine M, Richards S et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood . 2005; 106:3699-709. [PubMed 16051736] 10. Hill A, Richards SJ, Hillmen P. Recent developments in the understanding and management of paroxysmal nocturnal hemoglobinuria. Br J Haematol . 2007; 137:181-92. [PubMed 17408457] 11. US Food and Drug Administration. FDA approves first-of-its-kind drug to treat rare blood disorder. FDA News. P07-47. 2007 Mar 16. Available at: . Accessed 2007 Jul 5. 12. Pazdur R. Approval letter for eculizumab (application number 125166). Rockville, MD: US Food and Drug Administration; 2007 Mar 16. From FDA website (). 13. Alexion Pharmaceuticals. FDA approves Alexion s Soliris for all patients with PNH: first therapy approved for this rare and life-threatening blood disease. Cheshire, CT; 2007 Mar 16. Press release from website (). 14. PNH Source. PNHSource website. Available at: . Accessed 2007 Aug 15. 15. Lobo ED, Hansen RJ, Balthasar JP. Antibody pharmacokinetics and pharmacodynamics. J Pharm Sci . 2004; 93:2645-68. [PubMed 15389672] 16. Hillmen P, Hall C, Marsh JCW et al. Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria. N Engl J Med . 2004; 350:552-59. [PubMed 14762182] 17. Hill A, Hillmen P, Richards SJ et al. Sustained response and long-term safety of eculizumab in paroxysmal nocturnal hemoglobinuria. Blood . 2005; 106:2559-65. [PubMed 15985537] 18. In: Lee RG, Bithell TC, Foerster J et al, eds. Winthrobe s clinical hematology. 9th ed. Malver, PA: Lea and Febiger; 1993:1232-44. 19. Anon. Eculizumab: 5G1.1, h5G1.1, long-acting anti-C5 monoclonal antibody 5G1-1, long-acting anti-C5 monoclonal antibody 5G1.1. Drugs R D . 2007; 8:61-8. 20. Socie G, Jean-Yves M, de Gramont A et al. Paroxysmal nocturnal haemoglobinuria: long term follow-up and prognostic factors. Lancet . 1996; 348:573-77. [PubMed 8774569] 21. Alexion Pharmaceuticals, Inc. Soliris (eculizumab) medication guide. Chesire, CT; 2011 Sept. 22. Legendre CM, Licht C, Muus P et al. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med . 2013; 368:2169-81. [PubMed 23738544] 23. Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med . 2009; 361:1676-87. [PubMed 19846853] 24. US Food and Drug Administration. Soliris (eculizumab) BLA #125166: Risk evaluation mitigation strategy. From FDA website. 25. Nürnberger J, Philipp T, Witzke O et al. Eculizumab for atypical hemolytic-uremic syndrome. N Engl J Med . 2009; 360:542-4. [PubMed 19179328] 26. Gruppo RA, Rother RP. Eculizumab for congenital atypical hemolytic-uremic syndrome. N Engl J Med . 2009; 360:544-6. [PubMed 19179329] 27. Tschumi S, Gugger M, Bucher BS et al. Eculizumab in atypical hemolytic uremic syndrome: long-term clinical course and histological findings. Pediatr Nephrol . 2011; 26:2085-8. [PubMed 21877169] 28. Vilalta R, Lara E, Madrid A et al. Long-term eculizumab improves clinical outcomes in atypical hemolytic uremic syndrome. Pediatr Nephrol . 2012; 27:2323-6. [PubMed 22890512] 29. Fakhouri F, Delmas Y, Provot F et al. Insights From the Use in Clinical Practice of Eculizumab in Adult Patients With Atypical Hemolytic Uremic Syndrome Affecting the Native Kidneys: An Analysis of 19 Cases. Am J Kidney Dis . 2013; :. [PubMed 24021908] 30. Ariceta G, Arrizabalaga B, Aguirre M et al. Eculizumab in the treatment of atypical hemolytic uremic syndrome in infants. Am J Kidney Dis . 2012; 59:707-10. [PubMed 22196848] 31. Schmidtko J, Peine S, El-Housseini Y et al. Treatment of atypical hemolytic uremic syndrome and thrombotic microangiopathies: a focus on eculizumab. Am J Kidney Dis . 2013; 61:289-99. [PubMed 23141475] 32. Köse O, Zimmerhackl LB, Jungraithmayr T et al. New treatment options for atypical hemolytic uremic syndrome with the complement inhibitor eculizumab. Semin Thromb Hemost . 2010; 36:669-72. [PubMed 20865644] 33. Rees L. Atypical HUS: time to take stock of current guidelines and outcome measures?. Pediatr Nephrol . 2013; 28:675-7. [PubMed 23389238] 34. Lapeyraque AL, Malina M, Fremeaux-Bacchi V et al. Eculizumab in severe Shiga-toxin-associated HUS. N Engl J Med . 2011; 364:2561-3. [PubMed 21612462] 35. Bouts A, Monnens L, Davin JC et al. Insufficient protection by Neisseria meningitidis vaccination alone during eculizumab therapy. Pediatr Nephrol . 2011; 26:1919-20. [PubMed 21643943] 36. Struijk GH, Bouts AH, Rijkers GT et al. Meningococcal sepsis complicating eculizumab treatment despite prior vaccination. Am J Transplant . 2013; 13:819-20. [PubMed 23289494] 37. Alexion Europe SAS. Soliris 300 mg concentrate solution for injection summary of product characteristics. Paris, France; 2013 Apr 29. Next Interactions Print this page Add to My Med List More about eculizumab Side Effects During Pregnancy or Breastfeeding Dosage Information Drug Interactions Compare Alternatives Support Group En Español 0 Reviews Add your own review/rating Drug class: selective immunosuppressants Consumer resources Eculizumab Eculizumab Intravenous (Advanced Reading) Professional resources Eculizumab (Wolters Kluwer) Other brands: Soliris Related treatment guides Hemolytic Uremic Syndrome Myasthenia Gravis Paroxysmal Nocturnal Hemoglobinuria> ]} FEATURED: CAR-T Cell Therapy Overview Mechanism of Action KTE-C19 Studies KTE-C19 Cancer Targets Adverse Events Manufacturing Drug Status Rx Availability Prescription only C Pregnancy Category Risk cannot be ruled out N/A CSA Schedule Not a controlled drug Approval History Drug history at FDA Drug Class Selective immunosuppressants Related Drugs Myasthenia Gravis pyridostigmine , Mestinon , ephedrine , neostigmine , Soliris , huperzine a , Prostigmin , Prostigmin Bromide , More... Hemolytic Uremic Syndrome Soliris , More... Paroxysmal Nocturnal Hemoglobinuria Soliris , More... Eculizumab Rating No Reviews - Be the first! No Reviews - Be the first! Not Rated - Be the first!} } putting forward
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