crizanlizumab (Rx)

Brand and Other Names:Adakveo, crizanlizumab-tmca
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injectable solution

  • 10 mg/mL (10 mL)

Sickle Cell Disease

Indicated to reduce the frequency of vasoocclusive crises in adults with sickle cell disease

5 mg/kg IV on Week 0, Week 2, and q4Weeks thereafter

Dosage Modifications

Renal and hepatic impairment: Effect of renal or hepatic impairment on the pharmacokinetics of crizanlizumab-tmca is unknown

Dosage Forms & Strengths

injectable solution

  • 10 mg/mL (10 mL)

Sickle Cell Disease

Indicated to reduce the frequency of vasoocclusive crises in adults and pediatric patients aged ≥16 years with sickle cell disease

<16 years: Safety and efficacy not established

≥16 years

  • 5 mg/kg IV on Week 0, Week 2, and q4Weeks thereafter

Dosage Modifications

Renal and hepatic impairment: Effect of renal or hepatic impairment on the pharmacokinetics of crizanlizumab-tmca is unknown

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Adverse Effects

>10%

Nausea (18%)

Arthralgia (18%)

Back pain (15%)

Pyrexia (11%)

<10%

Oropharyngeal pain

Abdominal pain (abdominal pain, upper abdominal pain, lower abdominal pain, abdominal discomfort, and abdominal tenderness)

Diarrhea

Vomiting

Pruritus (pruritus and vulvovaginal pruritus)

Musculoskeletal chest pain

Myalgia

Infusion-site reaction (infusion-site extravasation, infusion-site pain, and infusion-site swelling)

Infusion-related reaction

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Warnings

Contraindications

None

Cautions

In a clinical trial, infusion-related reactions (defined as occurring within 24 hours of infusion) were observed; monitor patients for signs and symptoms of infusion-related reactions, which may include fever, chills, nausea, vomiting, fatigue, dizziness, pruritus, urticaria, sweating, shortness of breath, or wheezing; discontinue infusion for severe reactions and institute appropriate medical care

Drug interaction overview

  • Interference with automated platelet counts (platelet clumping) has been observed following administration, in particular when blood samples were collected in tubes containing ethylenediaminetetraacetic acid (EDTA); mitigation strategies are recommended
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Pregnancy & Lactation

Pregnancy

Based on data from animal studies, fetal harm may occur when administered to a pregnant woman

There are insufficient human data on use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

Advise pregnant women of the potential risk to a fetus

Only use during pregnancy if expected benefit justifies the potential risk to the fetus

Animal data

  • In an animal reproduction study, IV administration of crizanlizumab-tmca to pregnant cynomolgus monkeys from onset of organogenesis through delivery resulted in a non-dose-related increased fetal loss (abortions/stillbirths) at doses ~2.8 times the exposure at the recommended clinical dose at 5 mg/kg/dose once q4Weeks

Disease-associated maternal and/or embryofetal risk

  • Women with sickle cell disease have an increased risk of adverse pregnancy outcomes for the mother and the fetus
  • Pregnant women are at greater risk for vasoocclusive crises, preeclampsia, eclampsia, and maternal mortality
  • For the fetus, there is an increased risk for intrauterine growth restriction, preterm delivery, low birth weight, and perinatal mortality

Lactation

There are no data on the presence of crizanlizumab-tmca in human or animal milk, the effects on the breastfed child, or the effects on milk production

Maternal IgG is known to be present in human milk

Effects of local gastrointestinal exposure and

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

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Pharmacology

Mechanism of Action

A humanized IgG2 kappa monoclonal antibody binds to P-selectin and blocks interactions with its ligands, including P-selectin glycoprotein ligand 1

Binding P-selectin on the surface of the activated endothelium and platelets blocks interactions between endothelial cells, platelets, red blood cells, and leukocytes

Absorption

Peak plasma concentration: 0.16 mg/mL

AUC(inf): 34.6 mg⋅hr/mL

Distribution

Vd: 4.26 L (single 5-mg/kg dose)

Metabolism

Metabolized into small peptides by catabolic pathways

Elimination

Half-life: 10.6 days

Clearance: 11.7 mL/hr

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Administration

IV Incompatibilities

Do not mix or coadminister with other drugs through the same IV line

IV Compatibilities

0.9% NaCl

Dextrose 5%

IV Preparation

Bring vials to room temperature

Visually inspect the vials and parenteral drug products for particulate matter and discoloration prior to administration

Crizanlizumab is clear to opalescent, colorless, or may have a slightly brownish-yellow tint; do not use if particles are present in the solution

Obtain a 100-mL 0.9% NaCl or dextrose 5% infusion bag/container

Infusion bags/containers must be made of either polyvinyl chloride (PVC), polyethylene (PE), or polypropylene (PP)

Remove a volume from the infusion bag/container that is equal to the required drug

Withdraw required drug solution and dilute by adding to the infusion bag/container

Drug volume added to the infusion bag/container should not exceed 96 mL

Gently invert the infusion bag to mix the diluted solution; do not shake

Discard any unused portion

Dilute drug in 0.9% NaCl or dextrose 5% to a total volume of 100 mL

IV Administration

Infuse IV over 30 minutes through a line that must contain a sterile, nonpyrogenic 0.2-micron inline filter

No incompatibilities have been observed with infusion sets composed of PVC, polyethylene (PE-lined PVC), polyurethane (PU), and inline filter membranes composed of polyethersulfone (PES, neutral and positively charged), positively charged polyamide (PA), and polysulphone (PSU)

After administration, flush line with at least 25 mL of 0.9% NaCl or dextrose 5%

Dispose of any unused product or waste material in accordance with local requirements

May be given with or without hydroxyurea

Missed dose

  • If missed dose, administer as soon as possible
  • If dose is administered within 2 weeks after missed dose, continue dosing according to the patient's original schedule
  • If dose is administered >2 weeks after missed dose, continue dosing q4Weeks thereafter

Storage

Unused vials: Refrigerate at 2-8ºC (36-46ºF) in the original carton to protect from light; do not shake; do not freeze

Diluted solutions

  • Administer diluted solution as soon as possible
  • If not administered immediately
    • Store at room temperature up to 25ºC (77ºF) for no more than 4.5 hr from start of preparation (piercing the first vial) to the completion of infusion OR
    • Refrigerate at 2-8ºC (36-46ºF) for no more than 24 hr, from the start of the time of the preparation (piercing the first vial) to the completion of infusion; this includes storage of the diluted solution and the time to warm up to room temperature
    • Protect from light during storage under refrigeration
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Images

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Formulary

FormularyPatient Discounts

Adding plans allows you to compare formulary status to other drugs in the same class.

To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

Adding plans allows you to:

  • View the formulary and any restrictions for each plan.
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  • Compare formulary status to other drugs in the same class.
  • Access your plan list on any device – mobile or desktop.

The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

Tier Description
1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC NOT COVERED – Drugs that are not covered by the plan.
Code Definition
PA Prior Authorization
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
QL Quantity Limits
Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
ST Step Therapy
Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
OR Other Restrictions
Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.