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Crizanlizumab

Medically reviewed by Drugs.com. Last updated on Jul 22, 2020.

Pronunciation

(KRIZ an LIZ ue mab)

Index Terms

  • Adakveo
  • Crizanlizumab-tmca
  • SEG101
  • SelG1

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous [preservative free]:

Adakveo: crizanlizumab-tmca 100 mg/10 mL (10 mL) [contains polysorbate 80]

Brand Names: U.S.

  • Adakveo

Pharmacologic Category

  • Monoclonal Antibody
  • Monoclonal Antibody, Anti-P-Selectin

Pharmacology

Crizanlizumab is a humanized IgG2 kappa monoclonal antibody which binds to P-selectin and blocks interaction with ligands, including P-selectin glycoprotein ligand 1. Translocation of P-selectin to the activated endothelial cell surface results in adhesion of sickle erythrocytes to vessels and the development of vascular occlusion (Ataga 2017). By binding to P-selectin, crizanlizumab inhibits interactions between endothelial cells, platelets, red blood cells, and leukocytes, which may result in decreased platelet aggregation, maintenance of blood flow, and minimized sickle cell-related pain crises.

Distribution

Vd: 4.26 L.

Metabolism

Expected to be metabolized into small peptides by catabolic pathways.

Excretion

Clearance: 11.7 mL/hour in healthy volunteers.

Half-Life Elimination

7.6 days in patients with sickle cell disease; 10.6 days in healthy volunteers.

Use: Labeled Indications

Sickle cell disease: To reduce the frequency of vaso-occlusive crises in adults and pediatric patients ≥16 years of age with sickle cell disease.

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Dosing: Adult

Sickle cell disease (to reduce frequency of vaso-occlusive crises):

IV: Initial: 5 mg/kg once every 2 weeks for 2 doses (at week 0 and week 2), followed by 5 mg/kg once every 4 weeks thereafter; crizanlizumab may be administered with or without hydroxyurea (Ataga 2017).

Missed dose: If a dose is missed, administer crizanlizumab as soon as possible; if administered within 2 weeks after the missed dose, continue dosing according to the original schedule. If administered >2 weeks after the missed dose, continue dosing every 4 weeks thereafter.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Sickle cell disease, to reduce frequency of vaso-occlusive crises: Note: May be given with or without hydroxyurea.

Adolescents ≥16 years: IV: 5 mg/kg on week 0, week 2, then every 4 weeks.

Missed dose: Administer missed dose as soon possible.

If dose administered within 2 weeks of missed dose, continue original schedule.

If dose administered more than 2 weeks after missed dose, administer dose every 4 weeks thereafter.

Dosing: Adjustment for Toxicity

Infusion-related reactions, severe: Discontinue crizanlizumab for severe reactions and manage as clinically necessary.

Reconstitution

Determine appropriate dose volume; bring vials to room temperature for a maximum of 4 hours prior to piercing the first vial. Remove the volume equal to the dose volume from a 100 mL bag of NS or D5W (infusion bags/containers must be made of either polyvinyl chloride, polyethylene, or polypropylene). Add the appropriate crizanlizumab dose volume to the infusion bag; crizanlizumab volume added to infusion bag should not exceed 96 mL. Gently invert infusion bag to mix; do not shake. The total volume of solution diluted for infusion should be 100 mL. Do not mix with other medications.

Administration

IV: Infuse over 30 minutes through a sterile, nonpyrogenic 0.2-micron inline filter. After infusion is complete, flush the line with ≥25 mL of NS or D5W. Do not mix or administer with other medications. Infusion must be completed within 4.5 hours of preparation (if stored at room temperature) or 24 hours (if refrigerated). Discontinue crizanlizumab for severe infusion-related reactions and manage as clinically necessary.

Incompatibilities have not been observed between crizanlizumab and infusion sets made of polyvinyl chloride, polyethylene, or polyurethane, or with inline membrane filters composed of polyethersulfone (neutral and positively charged), positively charged polyamide, and polysulphone.

Storage

Store and transport intact vials at 2°C to 8°C (36°F to 46°F); do not freeze. Do not shake. Store in original carton to protect from light. If not used immediately, solution diluted for infusion may be stored at up to 25°C (77°F) for ≤4.5 hours (from piercing the first vial) to infusion completion. Diluted solution may also be stored at 2°C to 8°C (36°F to 46°F) for ≤24 hours (from piercing the first vial) to infusion completion, including storage and the time to arrive at room temperature (the manufacturer recommends infusing diluted solutions as soon as possible). Do not shake diluted solutions.

Drug Interactions

There are no known significant interactions.

Test Interactions

Crizanlizumab may interfere with automated platelet counts (platelet clumping), particularly when blood samples are collected in tubes containing ethylenediaminetetraacetic acid (EDTA); platelet count may be unevaluable or falsely decreased. Management: Collect blood samples in citrate-containing tubes, and run blood samples within 4 hours of sample collection. If necessary, estimate platelet count through peripheral blood smear.

Adverse Reactions

>10%:

Gastrointestinal: Nausea (18%)

Neuromuscular & skeletal: Arthralgia (18%), back pain (15%)

Miscellaneous: Fever (11%)

1% to 10%:

Dermatologic: Pruritus (<10%)

Gastrointestinal: Abdominal distress (<10%), abdominal pain (<10%), diarrhea (<10%), vomiting (<10%)

Genitourinary: Vulvovaginal pruritus (<10%)

Immunologic: Antibody development (2%)

Local: Infusion site pain (<10%), infusion site reaction (<10%), injection site extravasation (<10%), swelling at injection site (<10%)

Neuromuscular & skeletal: Musculoskeletal chest pain (<10%), myalgia (<10%)

Respiratory: Oropharyngeal pain (<10%)

Miscellaneous: Infusion related reaction (3% to 10%)

Frequency not defined: Hematologic & oncologic: Abnormal platelet aggregation

Warnings/Precautions

Concerns related to adverse effects:

• Infusion-related reactions: Infusion-related reactions (occurring within 24 hours of infusion) have been reported. Symptoms may include fever, chills, nausea, vomiting, fatigue, dizziness, pruritus, urticaria, sweating, dyspnea, or wheezing. Monitor for signs/symptoms of infusion-related reactions; discontinue crizanlizumab for severe reactions and manage as clinically necessary.

Dosage form specific issues:

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

Other warnings/precautions:

• Laboratory test interference: Crizanlizumab may interfere with automated platelet counts (platelet clumping), particularly when blood samples are collected in tubes containing ethylenediaminetetraacetic acid (EDTA); platelet count may be unevaluable or falsely decreased. Collect blood samples in citrate-containing tubes, and run samples within 4 hours of sample collection.

Monitoring Parameters

Monitor for signs/symptoms of infusion-related reactions.

Pregnancy Considerations

Based on data from animal reproduction studies, in utero exposure to crizanlizumab may cause fetal harm.

Crizanlizumab is a humanized monoclonal antibody (IgG2). Placental transfer of human IgG is dependent upon the IgG subclass, maternal serum concentrations, birth weight, and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009).

Sickle cell disease increases the risk of adverse maternal and fetal outcomes, including an increased risk for vaso-occlusive crises, preeclampsia, eclampsia, intrauterine growth restriction, preterm delivery, low birth weight, and maternal and perinatal mortality.

Patient Education

What is this drug used for?

• It is used in people with sickle cell disease to lower the number of certain symptoms (crises).

Frequently reported side effects of this drug

• Nausea

• Joint pain

• Back pain

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Infusion reaction

• Chills

• Severe nausea

• Vomiting

• Dizziness

• Fatigue

• Loss of strength and energy

• Sweating a lot

• Shortness of breath

• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Further information

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