Introduction

Sickle cell disease agent; a selectin blocker.

Uses for Crizanlizumab-tmca (Systemic)

Sickle Cell Disease

Used to reduce the frequency of vasoocclusive crises in adults and pediatric patients ≥16 years of age with sickle cell disease.

Designated an orphan drug by the FDA for this condition.

Hydroxyurea is first-line treatment for most patients with sickle cell disease. Although place of therapy for crizanlizumab-tmca remains to be determined, the drug may be considered in patients taking hydroxyurea with >2 pain crises per year, or in patients who are unable to take or tolerate hydroxyurea therapy.

Crizanlizumab-tmca (Systemic) Dosage and Administration

General

Patient Monitoring

• Monitor patients for signs and symptoms of infusion-related reactions, which may include pain in various locations, headache, fever, chills, nausea, vomiting, diarrhea, fatigue, dizziness, pruritus, urticaria, sweating, shortness of breath, or wheezing.

Premedication and Prophylaxis

• In patients who have previously experienced mild to moderate infusion reactions with crizanlizumab-tmca, consider premedication and/or a reduced infusion rate for subsequent infusions.

Other General Considerations

• Crizanlizumab-tmca may be given with or without hydroxyurea.

Administration

IV Administration

Available as a 100 mg/10 mL (10 mg/mL) clear to opalescent solution in a single-dose vial.

If a dose is missed, administer as soon as possible.

If crizanlizumab-tmca is administered within 2 weeks after the missed dose, continue dosing according to the patient's original schedule.

If crizanlizumab-tmca is administered >2 weeks after the missed dose, continue dosing every 4 weeks thereafter.

Administer as an IV infusion. Visually inspect for particulate matter or discoloration. Do not use if particles are present in solution.

Calculate the dose (mg), total volume (mL), and number of vials needed based on patient's actual body weight. Calculate volume of drug to be used using the following equation:

Dilution

Dilute in 0.9% sodium chloride injection or 5% dextrose injection to a total volume of 100 mL prior to administration. Bring the appropriate number of vials to room temperature for a maximum of 4 hours prior to piercing the first vial. Use a 100 mL 0.9% sodium chloride injection or 5% dextrose injection infusion bag or container made of either polyvinyl chloride (PVC), polyethylene (PE), or polypropylene (PP). Remove a volume of 0.9% sodium chloride injection or 5% dextrose injection from the infusion bag or container that is equal to the required volume of crizanlizumab-tmca solution. Add the calculated volume (not to exceed 96 mL) of crizanlizumab-tmca solution to the infusion bag or container. Gently invert the infusion bag or container to mix. Do not shake. Discard any unused portion.

Rate of Administration

Administer over 30 minutes as an IV infusion using a sterile, nonpyrogenic 0.2–micron inline filter. Do not mix or coadminister with other drugs through the same IV line. After administration, flush line with at least 25 mL of 0.9% sodium chloride or 5% dextrose injection.

Dosage

Pediatric Patients

Sickle Cell Disease

IV

Adolescents ≥16 years of age: 5 mg/kg over 30 minutes at Week 0, Week 2, and every 4 weeks thereafter.

Adults

Sickle Cell Disease

IV

5 mg/kg over 30 minutes at Week 0, Week 2, and every 4 weeks thereafter.

Dosage Modification for Toxicity

For mild to moderate infusion-related reactions, temporarily interrupt or slow the infusion rate. Initiate symptomatic treatment as appropriate; exercise caution in use of corticosteroids unless clinically indicated (e.g., treatment of anaphylaxis). For subsequent infusions, consider premedication and/or reduce the infusion rate.

For severe infusion-related reactions, discontinue infusion. Institute appropriate medical care and exercise caution in use of corticosteroids in patients with sickle cell disease unless clinically indicated (e.g., treatment of anaphylaxis). Consider permanent discontinuation of therapy.

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.

Renal Impairment

No specific dosage recommendations at this time.

Geriatric Use

No specific dosage recommendations at this time.

Contraindications

None.

Warnings/Precautions

Infusion-related Reactions

Infusion-related reactions, including severe pain events, reported. Most occurred during the first and second infusions. Management of pain events has included acetaminophen, nonsteroidal anti-inflammatory agents (NSAIAs), opioids, antihistamines, IV fluids, and/or oxygen therapy. Complications such as acute chest syndrome and fat embolism (particularly in those treated with steroids) also reported.

Monitor patients for pain in various locations, headache, fever, chills, nausea, vomiting, diarrhea, fatigue, dizziness, pruritus, urticaria, sweating, shortness of breath, or wheezing.

For severe infusion-related reactions, discontinue crizanlizumab-tmca and institute appropriate medical care. Exercise caution with corticosteroids in patients with sickle cell disease unless clinically indicated (e.g., treatment of anaphylaxis). Consider permanent discontinuation.

For mild to moderate infusion reactions, temporarily interrupt or slow infusion rate. Initiate symptomatic treatment (e.g., acetaminophen, NSAIAs, opioids, antihistamines, IV fluids, and/or oxygen therapy); for subsequent infusions, consider premedication and/or reducing the infusion rate.

Laboratory Test Interference

Interference with automated platelet counts (platelet clumping) when blood samples are collected in tubes containing ethylenediaminetetraacetic acid (EDTA). Mitigation strategies recommended.

Specific Populations

Pregnancy

Insufficient human data to evaluate the drug-associated risks in pregnant women. Animal studies indicate a potential for fetal harm.

Advise pregnant women of the potential risk to a fetus. Use only if expected benefit to the patient justifies the potential risk to the fetus.

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, pre-eclampsia, 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

No data available on the presence of drug in human or animal milk, effects on the breastfed child, or effects on milk production.

Consider developmental and health benefits of breast-feeding along with the mother’s clinical need for crizanlizumab-tmca and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition.

Pediatric Use

Safety and effectiveness for sickle cell disease established in pediatric patients ≥16 years of age based on adequate and well-controlled studies in adults and pediatric patients.

Safety and efficacy in pediatric patients <16 years of age not established.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.

Hepatic Impairment

Effects of hepatic impairment on pharmacokinetics of crizanlizumab-tmca unknown.

Renal Impairment

Effects of renal impairment on pharmacokinetics of crizanlizumab-tmca unknown.

Common Adverse Effects

Most common adverse reactions (incidence >10%): nausea, arthralgia, back pain, abdominal pain, pyrexia.

General

Patient Monitoring

• Monitor patients for signs and symptoms of infusion-related reactions, which may include pain in various locations, headache, fever, chills, nausea, vomiting, diarrhea, fatigue, dizziness, pruritus, urticaria, sweating, shortness of breath, or wheezing.

Premedication and Prophylaxis

• In patients who have previously experienced mild to moderate infusion reactions with crizanlizumab-tmca, consider premedication and/or a reduced infusion rate for subsequent infusions.

Other General Considerations

• Crizanlizumab-tmca may be given with or without hydroxyurea.

Administration

IV Administration

Available as a 100 mg/10 mL (10 mg/mL) clear to opalescent solution in a single-dose vial.

If a dose is missed, administer as soon as possible.

If crizanlizumab-tmca is administered within 2 weeks after the missed dose, continue dosing according to the patient's original schedule.

If crizanlizumab-tmca is administered >2 weeks after the missed dose, continue dosing every 4 weeks thereafter.

Administer as an IV infusion. Visually inspect for particulate matter or discoloration. Do not use if particles are present in solution.

Calculate the dose (mg), total volume (mL), and number of vials needed based on patient's actual body weight. Calculate volume of drug to be used using the following equation:

Dilution

Dilute in 0.9% sodium chloride injection or 5% dextrose injection to a total volume of 100 mL prior to administration. Bring the appropriate number of vials to room temperature for a maximum of 4 hours prior to piercing the first vial. Use a 100 mL 0.9% sodium chloride injection or 5% dextrose injection infusion bag or container made of either polyvinyl chloride (PVC), polyethylene (PE), or polypropylene (PP). Remove a volume of 0.9% sodium chloride injection or 5% dextrose injection from the infusion bag or container that is equal to the required volume of crizanlizumab-tmca solution. Add the calculated volume (not to exceed 96 mL) of crizanlizumab-tmca solution to the infusion bag or container. Gently invert the infusion bag or container to mix. Do not shake. Discard any unused portion.

Rate of Administration

Administer over 30 minutes as an IV infusion using a sterile, nonpyrogenic 0.2–micron inline filter. Do not mix or coadminister with other drugs through the same IV line. After administration, flush line with at least 25 mL of 0.9% sodium chloride or 5% dextrose injection.

Dosage

Pediatric Patients

Sickle Cell Disease

IV

Adolescents ≥16 years of age: 5 mg/kg over 30 minutes at Week 0, Week 2, and every 4 weeks thereafter.

Adults

Sickle Cell Disease

IV

5 mg/kg over 30 minutes at Week 0, Week 2, and every 4 weeks thereafter.

Dosage Modification for Toxicity

For mild to moderate infusion-related reactions, temporarily interrupt or slow the infusion rate. Initiate symptomatic treatment as appropriate; exercise caution in use of corticosteroids unless clinically indicated (e.g., treatment of anaphylaxis). For subsequent infusions, consider premedication and/or reduce the infusion rate.

For severe infusion-related reactions, discontinue infusion. Institute appropriate medical care and exercise caution in use of corticosteroids in patients with sickle cell disease unless clinically indicated (e.g., treatment of anaphylaxis). Consider permanent discontinuation of therapy.

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.

Renal Impairment

No specific dosage recommendations at this time.

Geriatric Use

No specific dosage recommendations at this time.

Platelet Tests - Ethylenediaminetetraacetic Acid

Interferes with automated platelet counts (platelet clumping) when blood samples are collected in tubes containing ethylenediaminetetraacetic acid (EDTA); may lead to unevaluable or falsely decreased platelet counts.

Run blood samples within 4 hours of blood collection or collect blood samples in tubes containing citrate. When needed, estimate platelet count via peripheral blood smear.