eculizumab

Therapeutic Classification: hemostatic agents

Pharmacologic Classification: complement.inhibitors

REMS

Bkemv, Epysqli, and Soliris

Treatment of the following conditions:
- Paroxysmal nocturnal hemoglobinuria;
- Atypical hemolytic uremic syndrome.

Soliris and Epysqli

Generalized myasthenia gravis in patients who are antiacetylcholine receptor antibody positive.

Soliris

Neuromyelitis optica spectrum disorder in patients who are anti-aquaporin-4 antibody positive.

Eculizumab is a monoclonal antibody that binds to complement protein C5. This binding inhibits complement activation, a necessary step in the initiation of hemolysis due to paroxysmal nocturnal hemoglobinuria and the development of thrombotic microangiopathy in atypical hemolytic uremic syndrome. Its mechanism of effect in generalized myasthenia gravis and neuromyelitis optica spectrum disorder is unknown.

Therapeutic effects:

Decreased hemolysis associated with paroxysmal nocturnal hemoglobinuria.
Reduced complement-mediated thrombotic microangiopathy in atypical hemolytic uremic syndrome.
Improved ability to perform activities of daily living in generalized myasthenia gravis.
Decreased relapse rates in neuromyelitis optica spectrum disorder.

Absorption: IV administration results in complete bioavailability.

Distribution: Distributed to tissues.

Metabolism/Excretion: Unknown.

Half-Life: 272 hr.

ROUTE	ONSET	PEAK	DURATION
IV	rapid	end of infusion	1–2 wk

Contraindicated in:

Unresolved serious Neisseria meninigitidis infection;
Patients not vaccinated against Neisseria meninigitidis (unless risk of delaying treatment outweighs risks of developing a meningococcal infection) (vaccinate ≥2 wk prior to 1st dose).

Use Cautiously in:

Systemic infection;
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Lactation: Safety not established in breastfeeding;
Pedi: Safety and effectiveness not established for treatment of paroxysmal nocturnal hemoglobinuria or generalized myasthenia gravis in children.

CV: hypertension, tachycardia, peripheral edema

EENT: nasopharyngitis, sinusitis, vertigo

GI: diarrhea, nausea, vomiting, constipation

Hemat: anemia, leukopenia

MS: back pain , extremity pain, myalgia

Neuro: headache, insomnia, fatigue

Resp: cough

Misc: fever, Haemophilus influenzae infection, herpes simplex infection, influenza-like illness, MENINGOCOCCAL INFECTIONS, Neisseria gonorrhoeae infection, Streptococcus pneumoniae infection

Drug-drug:

Plasma exchange, plasmapheresis, or fresh frozen plasma may ↓ levels and effectiveness; administer supplemental dose of eculizumab.
Neonatal Fc receptor blockers may ↓ levels and effectiveness.

Paroxysmal Nocturnal Hemoglobinuria

IV (Adults ): Bkemv, Epysqli, or Soliris: 600 mg once weekly during Weeks 1–4 (total of 4 doses); then 900 mg one wk later during Week 5; then 900 mg every 2 wk.

Atypical Hemolytic Uremic Syndrome

IV (Adults ): Bkemv, Epysqli, or Soliris: 900 mg once weekly during Weeks 1–4 (total of 4 doses); then 1200 mg one wk later during Week 5; then 1200 mg every 2 wk; Supplemental dose if patient receiving plasmapheresis or plasma exchange: Bkemv, Epysqli, or Soliris: 600 mg per each plasmapheresis or plasma exchange session; Supplemental dose if patient receiving fresh frozen plasma infusion: Bkemv, Epysqli, or Soliris: 300 mg per infusion of fresh frozen plasma.
IV (Children <18 yr and ≥40 kg): Bkemv, Epysqli, or Soliris: 900 mg once weekly during Weeks 1–4 (for a total of 4 doses); then 1200 mg one wk later during Week 5; then 1200 mg every 2 wk; Supplemental dose if patient receiving plasmapheresis or plasma exchange: Bkemv, Epysqli, or Soliris: 600 mg per each plasmapheresis or plasma exchange session; Supplemental dose if patient receiving fresh frozen plasma infusion: Bkemv, Epysqli, or Soliris: 300 mg per infusion of fresh frozen plasma.
IV (Children <18 yr and 30–<40 kg): Bkemv, Epysqli, or Soliris: 600 mg once weekly during Weeks 1 and 2 (total of 2 doses); then 900 mg one wk later during Week 3; then 900 mg every 2 wk; Supplemental dose if patient receiving plasmapheresis or plasma exchange: Bkemv, Epysqli, or Soliris: 600 mg per each plasmapheresis or plasma exchange session; Supplemental dose if patient receiving fresh frozen plasma infusion: Bkemv, Epysqli, or Soliris: 300 mg per infusion of fresh frozen plasma.
IV (Children <18 yr and 20–<30 kg): Bkemv, Epysqli, or Soliris: 600 mg once weekly during Weeks 1 and 2 (total of 2 doses); then 600 mg one wk later during Week 3; then 600 mg every 2 wk; Supplemental dose if patient receiving plasmapheresis or plasma exchange: Bkemv, Epysqli, or Soliris: 600 mg per each plasmapheresis or plasma exchange session; Supplemental dose if patient receiving fresh frozen plasma infusion: Bkemv, Epysqli, or Soliris: 300 mg per infusion of fresh frozen plasma.
IV (Children <18 yr and 10–<20 kg): Bkemv, Epysqli, or Soliris: 600 mg initially during Week 1; then 300 mg one wk later during Week 2; then 300 mg every 2 wk; Supplemental dose if patient receiving plasmapheresis or plasma exchange: Bkemv, Epysqli, or Soliris: 300 mg per each plasmapheresis or plasma exchange session; Supplemental dose if patient receiving fresh frozen plasma infusion: Bkemv, Epysqli, or Soliris: 300 mg per infusion of fresh frozen plasma.
IV (Children <18 yr and 5–<10 kg): Bkemv, Epysqli, or Soliris: 300 mg initially during Week 1; then 300 mg one wk later during Week 2; then 300 mg every 3 wk; Supplemental dose if patient receiving plasmapheresis or plasma exchange: Bkemv, Epysqli, or Soliris: 300 mg per each plasmapheresis or plasma exchange session; Supplemental dose if patient receiving fresh frozen plasma infusion: Bkemv, Epysqli, or Soliris: 300 mg per infusion of fresh frozen plasma.

Generalized Myasthenia Gravis

IV (Adults ): Epysqli or Soliris: 900 mg once weekly during Weeks 1–4 (total of 4 doses); then 1200 mg one wk later during Week 5; then 1200 mg every 2 wk; Supplemental dose if patient receiving plasmapheresis or plasma exchange: Epysqli or Soliris: 600 mg per each plasmapheresis or plasma exchange session; Supplemental dose if patient receiving fresh frozen plasma infusion: Epysqli or Soliris: 300 mg per infusion of fresh frozen plasma.

Neuromyelitis Optica Spectrum Disorder

IV (Adults ): Soliris: Soliris: 900 mg once weekly during Weeks 1–4 (total of 4 doses); then 1200 mg one wk later during Week 5; then 1200 mg every 2 wk.

Solution for injection: 10 mg/mL

Monitor for hypersensitivity reactions, including anaphylaxis and infusion-related reactions, during infusion and for ≥1 hr following. If reactions occur, infusion may be slowed or stopped, if infusion completed within 2 hr.
Monitor for early signs and symptoms of meningococcal infections. Evaluate immediately if infection is suspected. Consider discontinuation of therapy during treatment of serious meningococcal infections.
Patients who discontinue eculizumab are at ↑ risk for serious hemolysis (serum LDH levels > pretreatment level with either >25% absolute ↓ in paroxysmal nocturnal hemoglobinuria clone size [in the absence of dilution due to transfer] in ≤1 wk, hemoglobin <5 g/dL, or ↓ in hemoglobin of >4 g/dL in ≤1 wk), angina, change in mental status, 50% ↑ in serum creatinine level, or thrombosis. Monitor patients who discontinue therapy for ≥8 wk to detect serious hemolysis or other reactions. If serious reactions occur, consider blood transfusion (packed RBCs) or exchange transfusion if the paroxysmal nocturnal hemoglobinuria RBCs are >50% of total RBCs by flow cytometry, anticoagulation, corticosteroids, or reinstitution of eculizumab.

Lab Test Considerations:

Serum LDH levels ↑ during hemolysis and may assist in monitoring effects of eculizumab, including response to discontinuation of therapy. Monitor patients after discontinuing for ≥8 wk to detect hemolysis.

REMS: Only available through enrollment in restricted programs. Bkemv REMS: 1-866-718-6927 or www.bkemvrems.com. Epysqli REMS:1-866-318-8144 or www.epysqlirems.comUltomiris and Soliris REMS: 1-888-SOLIRIS 1-888-765-4747 or www.ultsolrems.com.
Vaccinate patient with meningococcal vaccine ≥2 wk prior to 1st dose; revaccinate according to current medical guidelines. If eculizumab must be started immediately and patient is not up to date with vaccine, provide antibacterial drug prophylaxis and administer meningococcal vaccine as soon as possible. Children should also be vaccinated for Streptococcus pneumoniae and Haemophilus influenza type b prior to treatment with eculizumab.

IV Administration:

Intermittent Infusion: Withdraw required amount of eculizumab from vial into sterile syringe and transfer to an infusion bag. Diluent: Dilute with equal amount of drug volume to 0.9% NaCl, 0.45% NaCl, D5W, or LR. Final admixture is 60 mL for 300-mg dose, 120 mL for 600-mg dose, 180 mL for 900-mg dose, or 240 mL for 1200-mg dose. Gently invert bag to ensure thorough mixing; discard unused portion in vial. Prior to administration, allow admixture to adjust to room temperature. Solution is clear to opalescent and colorless to slightly yellow; do not use solutions that are discolored or contain particulates. Solution is stable for 24 hr at room temperature or if refrigerated. Concentration: 5 mg/mL.
Rate: Administer over 35 min (not to exceed 2 hr) for adults and 1–4 hr for children.
Y-Site Incompatibility: Do not administer other drugs through same IV line.

Explain the risks and benefits of eculizumab to patient. Instruct patient to read the Medication Guide before starting therapy and with each dose in case of changes.
Instruct patient to obtain required meningococcal vaccination ≥2 wk prior to therapy and revaccinate according to guidelines. Caution patient to report symptoms of meningococcal infection (moderate to severe headache with nausea or vomiting, headache, fever, or stiff neck or back; fever ≥103°F; rash; confusion; severe muscle aches with flu-like symptoms; eyes sensitive to light). Inform patient or caregiver that vaccination does not eliminate risk of serious meningococcal infections, despite development of antibodies.
Inform patients that eculizumab may ↑ risk of other infections. Encourage patient and caregiver to notify health care professional of signs and symptoms of infection and maintain current vaccinations.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Inform patient to carry the Patient Safety Card at all times during and for 3 mo following therapy due to ↑ risk of meningococcal infection.
Advise patient with paroxysmal nocturnal hemoglobinuria of potential for serious hemolysis when eculizumab is discontinued and of need for monitoring by health care professional for ≥8 wk following discontinuation. Caution patient to notify health care professional immediately if a large ↓ in RBC count causing anemia, confusion, chest pain, kidney problems, and blood clots occurs.
Advise patient with atypical hemolytic uremic syndrome of potential for serious thrombotic microangiopathy when eculizumab is discontinued and of need for monitoring by health care professional for ≥12 wk following discontinuation. Caution patient to notify health care professional immediately if changes in mental status, seizures, angina, dyspnea, or thrombosis occur.
Rep: Advise women of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

Reduced hemolysis resulting in improvements in anemia (↑ hemoglobin stabilization, ↓ need for RBC transfusions), ↓ fatigue, and improved health-related quality of life.
Inhibition of complement-mediated thrombotic microangiopathy in patients with atypical hemolytic uremic syndrome.
Improved ability to perform activities of daily living in generalized myasthenia gravis.
Decreased relapse rates in neuromyelitis optica spectrum disorder.

Bkemv, Epysqli, Soliris

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