eculizumab


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eculizumab

(e-ku-liz-oo-mab) ,

Soliris

(trade name)

Classification

Therapeutic: hemostatic agents
Pharmacologic: complement inhibitors
Pregnancy Category: C

Indications

To reduce hemolysis in patients with paroxysmal nocturnal hemoglobinuria (PNH).To inhibit complement-mediated thrombotic microangiopathy in patients with atypical hemolytic uremic syndrome (aHUS).

Action

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 PNH and the development of thrombotic microangiopathy in aHUS.

Therapeutic effects

Decreased hemolysis associated with PNH.
Reduced complement-mediated thrombotic microangiopathy in aHUS.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.
Distribution: Crosses placenta; enters breast milk.
Metabolism and Excretion: Unknown.
Half-life: 272 hr.

Time/action profile

ROUTEONSETPEAKDURATION
IVrapid end of infusion1–2 wk

Contraindications/Precautions

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 at least 2 wk prior to first dose).
Use Cautiously in: Systemic infection; Discontinuation requires monitoring for intravascular hemolysis; Obstetric: Use only if maternal benefit outweighs fetal risk; Lactation: Lactation; Pediatric: Safety and effectiveness not established for treatment of PNH.

Adverse Reactions/Side Effects

Central nervous system

  • headache (most frequent)
  • insomnia (most frequent)
  • fatigue

Cardiovascular

  • hypertension (most frequent)
  • tachycardia (most frequent)
  • peripheral edema

Ear, Eye, Nose, Throat

  • nasopharyngitis (most frequent)
  • sinusitis
  • vertigo

Respiratory

  • cough (most frequent)

Gastrointestinal

  • diarrhea (most frequent)
  • nausea (most frequent)
  • vomiting (most frequent)
  • constipation

Musculoskeletal

  • back pain (most frequent)
  • extremity pain
  • myalgia

Hematologic

  • anemia (most frequent)
  • leukpenia (most frequent)

Miscellaneous

  • ↑ risk of meningococcal infections (life-threatening)
  • fever
  • Haemophilus influenzae infection
  • herpes simplex infection
  • influenza-like illness
  • Streptococcus pneumoniae infection

Interactions

Drug-Drug interaction

None known.

Route/Dosage

Paroxysmal Nocturnal Hemoglobinuria

Intravenous (Adults) 600 mg every 7 days for 4 doses, then 900 mg 7 days later, then 900 mg every 14 days.

Atypical Hemolytic Uremic Syndrome

Intravenous (Adults) 900 mg every 7 days for 4 doses, then 1200 mg 7 days later, then 1200 mg every 14 days.
Intravenous (Children <18 yr and ≥40 kg) 900 mg every 7 days for 4 doses, then 1200 mg 7 days later, then 1200 mg every 14 days.
Intravenous (Children <18 yr and 30–<40 kg) 600 mg every 7 days for 2 doses, then 900 mg 7 days later, then 900 mg every 14 days.
Intravenous (Children <18 yr and 20–<30 kg) 600 mg every 7 days for 2 doses, then 600 mg 7 days later, then 600 mg every 14 days.
Intravenous (Children <18 yr and 10–<20 kg) 600 mg, then 300 mg 7 days later, then 300 mg every 14 days.
Intravenous (Children <18 yr and 5–<10 kg) 300 mg, then 300 mg 7 days later, then 300 mg every 21 days.

Availability

Solution for IV administration (requires further dilution): 10 mg/mL

Nursing implications

Nursing assessment

  • Monitor for infusion reaction (anaphylaxis, infection, headache, anemia, fever) during and for at least 1 hr following infusion. If reaction occurs, solution may be slowed or stopped, if infused 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 increased risk for serious hemolysis (serum LDH levels > pretreatment level with either >25% absolute decrease in PNH clone size (in the absence of dilution due to transfer) in 1 wk or less, hemoglobin level <5 gm/dL, or decrease of >4 gm/dL in 1 wk or less; angina, change in mental status, 50% increase in serum creatinine level; or thrombosis. Monitor patients who discontinue therapy for at least 8 wks to detect serious hemolysis or other reactions. If serious reactions occur, consider blood transfusion (packed RBCs), or exchange transfusion if the PNH PBCs are >50% of total RBCs by flow cytometry, anticoagulation, corticosteriods, or reinstitution of eculizumab.
  • Lab Test Considerations: Serum LDH levels increase during hemolysis and may assist in monitoring effects of eculizumab, including response to discontinuation to therapy.

Potential Nursing Diagnoses

Fatigue (Indications)
Risk for infection (Adverse Reactions)

Implementation

  • Available through a restricted program only to enrolled prescribers. Call 1-888-SOLIRIS (1-888-765-4747) to enroll.
  • Vaccinate patient with meningococcal vaccine at least 2 wks prior to first dose; revaccinate according to current medical guidelines for vaccine use Children should also be vaccinated for Streptococcus pneumoniae and Haemophilus influenza type b (Hib).
  • Intravenous 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 diluent of 0.9% NaCl, 0.45% NaCl, D5W, or LR. Final admixture is 60 mL for 300 mg, 120 mL for 600 mg dose, 180 mL for 900 mg dose, or 240 mL for 1200 mg dose. Concentration: 5 mg/mL. Gently invert bag to ensure thorough mixing; discard unused portion in vial. Prior to administration, allow admixture to adjust to room temperature; do not use microwave or water bath. Discard solutions that are discolored or contain particulate matter. Solution is stable for 24 hr at room temperature or if refrigerated.
  • Rate: Administer over 35 min via gravity feed, syringe pump, or infusion pump; total infusion time should not exceed 2 hr.

Patient/Family Teaching

  • 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 at least 2 wks prior to therapy and revaccination 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 stiff back; fever of 103°F or 39.4°C or higher; fever and a rash; confusion; or severe muscle aches with flu-like symptoms; and eyes sensitive to light).
  • Advise patient to notify health care professional if pregnancy is planned or suspected.
  • Inform patient to carry Soliris Patient Safety Card describing symptoms which, if experienced, patient should seek medical evaluation, at all times.
  • Advise patient of potential for serious hemolysis if eculizumab is discontinued and of need for monitoring by health care professional for at least 8 wks following discontinuation. Caution patient to notify health care professional immediately if a large drop in red blood cell count causing anemia, confusion, chest pain, kidney problems, and blood clots occur.

Evaluation/Desired Outcomes

  • Reduced hemolysis resulting in improvements in anemia (increased hemoglobin stabilization, reduced need for RBC transfusions), less fatigue, and improved health-related quality of life.
  • Inhibition of complement-mediated thrombotic microangiopathy in patients with atypical hemolytic uremic syndrome.

eculizumab

a monoclonal antibody.
indications This drug is used to treat proximal nocturnal hemoglobinuria, a rare, genetic form of hemolytic anemia.
contraindications Known hypersensitivity to this drug prohibits its use. Rapid discontinuation may result in serious hemolysis.
adverse effects Adverse effects of this drug include rash, dyspnea, calf or leg pain, chest pain, confusion, coughing up blood, sensitivity to light, fever, chills, persistent sore throat, mental changes, headache, nausea, vomiting, fever, stiff neck or back, mouth sores, fever blisters, and severe muscle aches. A life-threatening side effect is meningococcal infection. Common side effects are headache, nasopharyngitis, back pain, nausea, fatigue, and cough.

eculizumab

A humanized monoclonal antibody drug against the terminal complement protein C5. The drug has been found useful in paroxysmal nocturnal haemoglobinuria. It is well tolerated and safe and reduces haemolysis, haemoglobinuria and the need for transfusion.
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However, Nice has reviewed the clinical evidence and has concluded that there is no evidence that the use of Eculizumab is effective and safe for patients with Abi's particular condition.
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The trust said it believed in Damien's case eculizumab would not be of significant benefit.
A poster titled "Modification of the Eculizumab Dose to Successfully Manage Intravascular Breakthrough Hemolysis in Patients with Paroxysmal Nocturnal Hemoglobinuria" was presented yesterday at the ASH annual meeting by Richard Kelly, M.
I really hope that Damien will be able to continue getting eculizumab.
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001), indicating sustained inhibition of complement-mediated TMA with ongoing eculizumab treatment.
Alexion's two lead product candidates, pexelizumab and eculizumab, are currently undergoing evaluation in several clinical development programs, including two Phase III trials of eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria (PNH), a Phase III trial of pexelizumab in coronary artery bypass graft (CABG) surgery patients undergoing cardiopulmonary bypass (CPB), and a Phase III trial of pexelizumab in acute myocardial infarction (AMI) patients.
THANKS to a review sparked by the Sunday People, Abi may get her drug Eculizumab provided - quite rightly - on the NHS.
On 11th December the National Institute for Health and Care Excellence's (NICE) First Appraisal meeting is taking place to judge whether eculizumab should be recommended in England as a treatment for the ultra-rare disease atypical Haemolytic Uraemic Syndrome (aHUS).
An application was submitted to the Advisory Group for National Specialised Services, which provides advice to ministers on which services should be nationally commissioned, to make eculizumab available to all clinically appropriate patients in England.
Results from clinical trials including patients in the North East have shown that the drug eculizumab is the best first-line of treatment for patients as it prevents kidney damage by blocking an immune protein called 'complement'.

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