Eculizumab

Pronunciation: (E-kue-LIZ-oo-mab)
Class: Monoclonal antibody

Trade Names

Soliris
- Injection, solution, concentrate 10 mg/mL

Pharmacology

Inhibits terminal complement–mediated intravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria.

Pharmacokinetics

Absorption

C _max and C _min by wk 26 are 194 and 97 mcg/mL, respectively.

Distribution

Vd is 7.7 L.

Elimination

Half-life is 272 h; Cl is 22 mL/h.

Special Populations

Renal Function Impairment

Studies have not been conducted.

Hepatic Function Impairment

Studies have not been conducted.

Elderly

Studies have not been conducted.

Children

Studies have not been conducted.

Gender

Studies have not been conducted.

Race

Studies have not been conducted.

Indications and Usage

Treatment of paroxysmal nocturnal hemoglobinuria to reduce hemolysis.

Contraindications

Unresolved Neisseria meningitidis infection; current vaccination against N. meningitidis .

Dosage and Administration

Adults

IV 600 mg every 7 days for the first 4 wk, then 900 mg 7 days later for the fifth dose, then 900 mg every 14 days thereafter.

General Advice

• Administer a meningococcal vaccine at least 2 wk prior to starting eculizumab therapy and revaccinate according to current medical guidelines.
• Administer by IV infusion over 35 min via gravity feed, syringe-type pump, or infusion pump.
• 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. Total infusion time should not exceed 2 h.
• Visually inspect product for particulate matter and discoloration.

Storage/Stability

Store in original container under refrigeration, between 36° and 46°F, until time of use. Protect from light. Do not freeze. Admixed solution is stable for 24 h at 36° to 46°F and at room temperature.

Drug Interactions

None well documented.

Adverse Reactions

CNS

Headache (44%); fatigue (12%).

EENT

Nasopharyngitis (23%).

GI

Nausea (16%); constipation (7%).

Musculoskeletal

Back pain (19%); myalgia (7%).

Respiratory

Cough (12%); respiratory tract infection, sinusitis (7%).

Miscellaneous

Herpes simplex infections, pain in extremities (7%); flu-like illness (5%); anemia, pyrexia, viral infection (2%); meningococcal infection.

Precautions

Warnings Eculizumab increases the risk of meningococcal infections. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. Vaccinate patients according to current medical guidelines at least 2 wk prior to administering the first dose of eculizumab. Monitor patients for early signs of meningococcal infections and evaluate immediately if infection is suspected; treat with antibiotics if necessary.

Monitor Monitor for serious hemolysis and other reactions for at least 8 wk 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.

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Discontinuation of therapy

Patients who discontinue treatment with eculizumab may be at increased risk for serious hemolysis.

Immunogenicity

As with all proteins, there is a potential for immunogenicity.

Infection

Risk of infection, especially with encapsulated bacteria, is increased. Use with caution in patients with systemic infection.

Infusion reactions

As with any protein product, anaphylaxis or other hypersensitivity reactions may occur. Interrupt treatment and administer medical therapy if a severe infusion reaction occurs.

Overdosage

Symptoms

No cases reported.

Patient Information

• Advise patient to read the Medication Guide before using product for the first time and with each refill.
• Inform patient of the need to receive meningococcal vaccination at least 2 wk 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, moderate to severe headache and fever, moderate to severe headache with nausea or vomiting, moderate to severe headache with stiff neck or stiff back, severe 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 of the risk of serious hemolysis when treatment is discontinued, and that they need to be monitored for at least 8 wk after completion of treatment.

Copyright © 2009 Wolters Kluwer Health.