Eculizumab (Soliris)

Ashley N. Lewis, PharmD, BCPS
Published Online: Monday, May 20, 2013

Background
Eculizumab (Soliris) is FDA-approved for the treatment of atypical hemolytic uremic syndrome (aHUS) in adult and pediatric patients to inhibit complement-mediated thrombotic microangiopathy (TMA) and also for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis. Eculizumab is not indicated for the treatment of patients with Shiga toxin E coli–related hemolytic uremic syndrome (STEC-HUS).1,2

Pharmacology/Pharmacokinetics
Eculizumab is a monoclonal antibody that binds with high affinity to complement protein C5 and prevents the generation of the terminal complement complex C5b-9. In patients with PNH, eculizumab inhibits terminal complement–mediated intravascular hemolysis and in patients with aHUS, eculizumab inhibits complement-mediated TMA.1,2 Minimal eculizumab is excreted in urine with small quantities of immunoglobulin found in bile. The elimination half-life for PNH patients is 8 to 15 days and for aHUS patients, the elimination half-life is approximately 12 days.1,2

Dosing and Administration
Eculizumab dosing for adults with PNH is 600 mg IV every 7 days for the first 4 weeks, then 900 mg IV for the fifth dose 7 days later, then 900 mg every 14 days thereafter. Eculizumab dosing for adults with aHUS is 900 mg IV every 7 days for the first 4 weeks, then 1200 mg IV for the fifth dose 7 days later, then 1200 mg IV every 14 days thereafter. Pediatric dosing is based on body weight, with doses ranging from 300 mg to 900 mg.1,2 Eculizumab should be administered by IV infusion over 35 minutes via an infusion pump; it should not be administered as an IV push or bolus injection. Eculizumab should be diluted to a final concentration of 5 mg/mL by adding appropriate amounts of 0.9% sodium chloride (NaCl), 0.45% NaCl, 5% dextrose in water (D5W), or Ringer’s injection. The final infusion volume is 60 mL for 300-mg doses, 120 mL for 600-mg doses, 180 mL for 900-mg doses, and 240 mL for 1200-mg doses.1,2

Clinical Efficacy
In clinical trials of eculizumab in PNH patients, significant reductions in lactate dehydrogenase (LDH) levels were achieved within the first week of treatment, with near-normal levels achieved at week 2 and maintained up to 36 months in certain patients. Eculizumab achieved rapid and sustained efficacy, regardless of baseline LDH levels or platelet counts.1 In adults with PNH, eculizumab treatment for 26 weeks achieved stabilization of hemoglobin levels in significantly more patients than placebo treatment, and reduced the need for packed red cell transfusions to a significantly greater extent than placebo. Eculizumab was also associated with significant improvements in fatigue and health-related quality-of-life scores in several trials.3

There are limited published studies available on eculizumab in aHUS patients; however, reduction in terminal complement activity has been observed in patients receiving eculizumab. Additionally, eculizumab reduced signs of complement-mediated TMA activity, as shown by an increase in mean platelet counts from baseline to 26 weeks.1,2

Medication Safety
Eculizumab therapy increases the risk of serious meningococcal infections, which can be fatal if not treated early. Patients must have received a meningococcal vaccine at least 2 weeks before the first dose of eculizumab unless already immunized; however, a booster dose may be required. Common adverse effects occurring in ≥30% of adult patients include hypertension, upper respiratory tract infection, headache, and diarrhea.1,2

Product Availability and Cost Considerations
Eculizumab is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) and is supplied as 300-mg single-use vials containing 30 mL of 10 mg/ mL sterile, preservative-free solution per vial. Vials must be stored in the original carton until time of use under refrigerated conditions at 2° to 8° C (36o to 46° F) and protected from light. The vials should not be frozen, shaken or used beyond the expiration date stamped on the carton. The acquisition cost of Soliris is $6830 per 300-mg vial; the cost per dose would range between $6830 and $27,320, depending on dose and indication. Complete prescribing information is available at www.soliris.com.1,2


Ashley N. Lewis, PharmD, BCPS, is a drug information specialist at University of North Carolina Hospitals (UNCH). She is currently the pharmacy and therapeutics secretary at UNCH and manages the day-to-day operations of the Drug Information Center and serves as a clinical assistant professor at the UNC Eshelman School of Pharmacy.
References
  1. Soliris [package insert]. Cheshire, CT: Alexion Pharmaceuticals, Inc; December 2012.
  2. Eculizumab. In: DRUGDEX System [Internet database]. Greenwood Village, CO: Thomson Reuters (Healthcare) Inc. Updated periodically.
  3. McKeage K. Eculizumab: a review of its use in paroxysmal nocturnal haemoglobinuria. Drugs. 2011;71(17):2327-2345.


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