crizanlizumab

General

Pronunciation:
kriz-an-liz-ue-mab


Trade Name(s)

  • Adakveo

Ther. Class.

none assigned

Pharm. Class.

monoclonal antibodies

selectin inhibitors

Indications

Vaso-occlusive crises in patients with sickle cell disease.

Action

Binds to P-selectin on the surface of the activated endothelium and platelets to prevent their interaction with endothelial cells, platelets, red blood cells, and white blood cells.

Therapeutic Effect(s):

Reduction in frequency of vaso-occlusive crises.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.

Distribution: Minimally distributed to extravascular tissues.

Metabolism and Excretion: Metabolized by catabolic pathways into smaller peptides; excretion pathway unknown.

Half-life: 7.6 days.

TIME/ACTION PROFILE (plasma concentrations)

ROUTEONSETPEAKDURATION
IVunknownunknownunknown

Contraindication/Precautions

Contraindicated in:

  • None reported.

Use Cautiously in:

  • OB:   Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
  •  Lactation:  Use while breast feeding only if potential maternal benefit justifies potential risk to infant;
  • Pedi:   Children <16 yr (safety and effectiveness not established).

Adverse Reactions/Side Effects

Derm: pruritus

GI: abdominal pain, nausea, diarrhea, vomiting

MS: arthralgia, back pain, myalgia

Local: infusion-site reaction

Misc: fever, infusion-related reactions

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

None reported.

Route/Dosage

IV (Adults and Children ≥16 yr): 5 mg/kg initially, then in 2 wk, and then every 4 wk thereafter.

Availability

Solution for injection: 10 mg/mL

Assessment

  • Monitor frequency of vaso-occlusive crises during therapy.
  • Monitor for signs and symptoms of infusion-related reactions (severe pain, fever, chills, nausea, vomiting, fatigue, dizziness, pruritus, urticaria, sweating, shortness of breath, wheezing) during and within 24 hr of infusion. For mild to moderate reactions, interrupt infusion or slow rate of infusion. Begin symptomatic therapy (acetaminophen, NSAIDs, opioids, antihistamines, intravenous fluids, and/or oxygen therapy). Consider premedication and/or reduce infusion rate of subsequent infusions. Discontinue therapy for severe reactions.

Lab Test Considerations:

May interfere with automated platelet counts (platelet clumping), in particular when blood samples are collected in tubes containing ethylenediaminetetraacetic acid (EDTA). Run blood samples within 4 hrs of blood collection or collect blood samples in tubes containing citrate. When needed, estimate platelet count via peripheral blood smear.

Implementation

  • Intermittent Infusion:  Obtain number of vials needed; one vial for every 10 mL crizanlizumab. Allow vials to reach room temperature for up to 4 hr before preparing. Solution is clear to opalescent, colorless, or may have a slightly brownish-yellow tint; do not use solutions with particulate matter. Dilution:  Dilute in 0.9% NaCl or D5W to a total volume of 100 mL in an infusion bag of either polyvinyl chloride (PVC), polyethylene (PE), or polypropylene (PP) by withdrawing the volume to be added. Gently invert to mix; do not shake. Solution is stable for up to 4.5 hr at room temperature, including infusion time and up to 24 hr if refrigerated and protected from light.
  • Rate: Infuse over 30 min through a sterile, nonpyrogenic 0.2 micron inline filter. Flush the line with at least 25 mL of 0.9% NaCl or D5W following infusion.
  • Y-Site Incompatibility: Do not mix or coadminister with other drugs through the same IV line.

Patient/Family Teaching

  • Explain the purpose of crizanlizumab to patient. Do not stop receiving crizanlizumab without consulting health care professional. If an appointment is missed, contact health care professional as soon as possible to reschedule. Advise patient to read  Medication Guide  before starting and periodically during therapy in case of changes.
  • Advise patient to notify health care professional if signs and symptoms of infusion reactions (fever, chills or shivering, nausea, vomiting, tiredness, dizziness, sweating, hives, itching, shortness of breath, wheezing) occur.
  • Instruct patient to inform health care professional of crizanlizumab therapy before blood tests due to potential interference with laboratory tests used to measure platelet counts.
  • 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.
  • Rep:  May cause fetal harm. Advise patient to notify health care professional if pregnancy is planned or suspected or if breast feeding.

Evaluation/Desired Outcomes

Decreased frequency of vaso-occlusive crises in patients with sickle cell disease.

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