Class: Monoclonal antibody
- Injection, solution, concentrate 10 mg/mL
Inhibits terminal complement–mediated intravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria and complement-mediated thrombotic microangiopathy in patients with atypical hemolytic uremic syndrome by binding to complement protein C5.
C max and C min by week 26 are 194 and 97 mcg/mL, respectively, for patients with paroxysmal nocturnal hemoglobinuria.
Vd is 7.7 (paroxysmal nocturnal hemoglobinuria) and 6.14 L (atypical hemolytic uremic syndrome).
Half-life is 272 (paroxysmal nocturnal hemoglobinuria) and 291 h (atypical hemolytic uremic syndrome); Cl is 22 (paroxysmal nocturnal hemoglobinuria) and 14.6 mL/h (atypical hemolytic uremic syndrome).
Special PopulationsRenal Function Impairment
Pharmacokinetics are not influenced by renal impairment.Hepatic Function Impairment
Dedicated studies have not been conducted.Elderly
Dedicated studies have not been conducted.Children
Pharmacokinetics are not influenced by age.Gender
Pharmacokinetics are not influenced by gender.Race
Pharmacokinetics are not influenced by race.
Indications and Usage
Treatment of patients with paroxysmal nocturnal hemoglobinuria to reduce hemolysis; treatment of patients with atypical hemolytic uremic syndrome to inhibit complement-mediated thrombotic microangiopathy.
Unresolved Neisseria meningitidis infection; patients not currently vaccinated against N. meningitidis .
Dosage and AdministrationAtypical hemolytic uremic syndrome
IV 900 mg every 7 days for the first 4 weeks, then 1,200 mg 7 days later for the fifth dose, then 1,200 mg every 14 days thereafter.Children (younger than 18 y) IV Children 5 kg to less than 10 kg Induction
300 mg weekly for 1 dose.Maintenance
300 mg at week 2, then 300 mg every 3 weeks.Children 10 kg to less than 20 kg Induction
600 mg weekly for 1 dose.Maintenance
300 mg at week 2, then 300 mg every 2 weeks.Children 20 kg to less than 30 kg Induction
600 mg weekly for 2 doses.Maintenance
600 mg at week 3, then 600 mg every 2 weeks.Children 30 kg to less than 40 kg Induction
600 mg weekly for 2 doses.Maintenance
900 mg at week 3, then 900 mg every 2 weeks.Children at least 40 kg Induction
900 mg weekly for 4 doses.Maintenance
1,200 mg at week 5, then 1,200 mg every 2 weeks.Supplemental dosing Patients receiving plasmapheresis or plasma exchange
If most recent dose was 300 mg, administer 300 mg within 60 min after each plasmapheresis or plasma exchange session. If most recent dose was 600 mg or more, administer 600 mg within 60 min after each plasmapheresis or plasma exchange session.Patients receiving fresh frozen plasma infusion
If most recent dose was 300 mg or more, administer 300 mg within 60 min prior to each unit of fresh frozen plasma infusion.Paroxysmal nocturnal hemoglobinuria
IV 600 mg every 7 days for the first 4 weeks, then 900 mg 7 days later for the fifth dose, then 900 mg every 14 days thereafter.
- Administer a meningococcal vaccine at least 2 weeks prior to starting eculizumab therapy and revaccinate according to current medical guidelines.
- Administer eculizumab at the recommended dosage time points, or within 2 days of these time points.
- Administer by IV infusion over 35 min via gravity feed, syringe-type pump, or infusion pump. Do not administer as an IV push or bolus injection.
- Dilute to a final administration concentration of 5 mg/mL by adding the appropriate amount of sodium chloride 0.9% or 0.45%, dextrose 5% in water, or Ringer's lactate injection.
- Ensure thorough mixing by gently inverting the infusion bag. Do not shake.
- Prior to administration, allow admixture to adjust to room temperature. Do not microwave or use heat source other than ambient air temperature.
- If an adverse reaction occurs during administration, slow or stop the infusion as needed. If the infusion is slowed, total infusion time should not exceed 2 h.
Store vials under refrigeration, between 36° and 46°F, until time of use. Protect from light. Do not freeze. Admixed solution is stable for 24 h between 36° and 46°F and at room temperature. Discard unused portion.
None well documented.
Hypertension (47%); tachycardia (40%).
Headache (44%); insomnia (24%); fatigue (18%); vertigo (15%).
Nasal congestion (40%); nasopharyngitis (23%); pharyngolaryngeal pain (20%).
Diarrhea, vomiting (40%); nausea (24%); abdominal pain (20%); constipation (7%).
Anemia (35%); leukopenia (24%).
Back pain (19%); pain in extremity (15%); myalgia (7%).
Cough (60%); upper respiratory tract infection (40%); respiratory tract infection, sinusitis (7%).
Pyrexia (80%); peripheral edema (18%); infections (14%); herpes simplex infections (7%); flu-like illness (5%); serious and/or fatal meningococcal infection (postmarketing).
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. Immunize patients with a meningococcal vaccine according to current medical guidelines for patients with complement deficiencies at least 2 weeks prior to administering the first dose of eculizumab. 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).
Monitor patients with paroxysmal nocturnal hemoglobinuria for serious hemolysis and other reactions for at least 8 weeks after discontinuing treatment. Monitor patients with atypical hemolytic uremic syndrome for thrombotic microangiopathy for at least 12 weeks after discontinuing treatment. Monitor for early signs and symptoms of meningococcal infections and evaluate immediately if an infection is suspected. Monitor patient for at least 1 h following completion of the infusion for signs and symptoms of infusion reaction.
Category C .
Undetermined. Immunoglobulin G is excreted in human milk; therefore, it is expected that eculizumab will be present in human milk.
Safety and efficacy not established for the treatment of paroxysmal nocturnal hemoglobinuria. Safety and efficacy for the treatment of atypical hemolytic uremic syndrome appear similar in pediatric and adult patients.
Discontinuation of therapy
Patients with paroxysmal nocturnal hemoglobinuria who discontinue treatment with eculizumab may be at increased risk for serious hemolysis, while patients with atypical hemolytic uremic syndrome may be at increased risk for thrombotic microangiopathy. If thrombotic microangiopathy complications occur, consider reinitiation of treatment, plasmapheresis, plasma exchange, fresh frozen plasma infusion, and/or appropriate organ-specific measures.
As with all proteins, there is a potential for immunogenicity.
Risk of infection, especially with encapsulated bacteria, is increased. Use with caution in patients with systemic infection.
As with any protein product, anaphylaxis or other hypersensitivity reactions may occur. Interrupt treatment and administer medical therapy if a severe infusion reaction occurs.
No cases reported.
- Advise patient to read the Medication Guide before using product for the first time and with each treatment.
- Inform patient of the need to receive meningococcal vaccination at least 2 weeks prior to starting therapy.
- Educate patients about signs and symptoms of meningococcal infection and advise them to seek immediate medical attention if they experience the following: confusion, fever and rash, fever of 103°F or higher, headache and fever, headache with nausea or vomiting, headache with stiff neck or stiff back, muscle aches with flu-like symptoms, or eyes sensitive to light.
- Instruct patient to carry the provided patient safety card at all times.
- Inform patients with paroxysmal nocturnal hemoglobinuria of the risk of serious hemolysis when treatment is discontinued, and that they need to be monitored for at least 8 weeks after completion of treatment.
- Inform patients with atypical hemolytic uremic syndrome that there is a potential for thrombotic microangiopathy complications when treatment is discontinued, and that they need to be monitored for 3 months after completion of treatment.
- Inform patients that there may be an increased risk of other types of infections, particularly those due to encapsulated bacteria. Inform patients or caregivers of children receiving treatment for atypical hemolytic uremic syndrome that their child should be vaccinated against Streptococcus pneumoniae and Haemophilus influenzae type b.
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