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Adakveo

Generic Name: Crizanlizumab-tmca
Class: Blood Formation, Coagulation, and Thrombosis Agents; Miscellaneous

Medically reviewed by Drugs.com. Last updated on Dec 2, 2019.

Introduction

Crizanlizumab-tmca, a humanized monoclonal antibody, is a selectin blocker.1

Uses for Adakveo

Crizanlizumab-tmca has the following uses:

Crizanlizumab-tmca is a selectin blocker indicated to reduce the frequency of vasoocclusive crises in adults and pediatric patients aged 16 years and older with sickle cell disease.1

Adakveo Dosage and Administration

General

Crizanlizumab-tmca is available in the following dosage form(s) and strength(s):

Injection: 100 mg/10 mL (10 mg/mL) solution in a single-dose vial.1

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Pediatric Patients

Dosage and Administration in Adolescents ≥16 Years of Age

Administer crizanlizumab-tmca 5 mg/kg by intravenous infusion over a period of 30 minutes at Week 0, Week 2, and every 4 weeks thereafter.1

If a dose is missed, administer crizanlizumab-tmca as soon as possible.1

If crizanlizumab-tmca is administered within 2 weeks after the missed dose, continue dosing according to the patient's original schedule.1

If crizanlizumab-tmca is administered more than 2 weeks after the missed dose, continue dosing every 4 weeks thereafter.1

Crizanlizumab-tmca may be given with or without hydroxyurea.1

Adults

Dosage and Administration in Adults

Administer crizanlizumab-tmca 5 mg/kg by intravenous infusion over a period of 30 minutes at Week 0, Week 2, and every 4 weeks thereafter.1

If a dose is missed, administer crizanlizumab-tmca as soon as possible.1

If crizanlizumab-tmca is administered within 2 weeks after the missed dose, continue dosing according to the patient's original schedule.1

If crizanlizumab-tmca is administered more than 2 weeks after the missed dose, continue dosing every 4 weeks thereafter.1

Crizanlizumab-tmca may be given with or without hydroxyurea.1

Cautions for Adakveo

Contraindications

None.1

Warnings/Precautions

Infusion-related Reactions

In the SUSTAIN clinical trial, infusion-related reactions (defined as occurring within 24 hours of infusion) were observed in 2 (3%) patients treated with crizanlizumab-tmca 5 mg/kg. 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 crizanlizumab-tmca infusion for severe reactions and institute appropriate medical care.1

Laboratory Test Interference

Interference with automated platelet counts (platelet clumping) has been observed following administration of crizanlizumab-tmca, in particular, when blood samples were collected in tubes containing ethylenediaminetetraacetic acid (EDTA). Mitigation strategies are recommended.1

Specific Populations

Pregnancy

Risk Summary: Based on data from animal studies, crizanlizumab-tmca has the potential to cause fetal harm when administered to a pregnant woman. In an animal reproduction study, intravenous administration of crizanlizumab-tmca to pregnant cynomolgus monkeys from the onset of organogenesis through delivery resulted in a non-dose related increased fetal loss (abortions/stillbirths) at doses approximately 2.8 times the exposure at the recommended clinical dose at 5 mg/kg/dose once every 4 weeks.1

There are insufficient human data on crizanlizumab-tmca 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. Crizanlizumab-tmca should only be used during pregnancy if the expected benefit to the patient justifies the potential risk to the fetus.1

The estimated background risk of major birth defects and miscarriage for the indicated population is approximately 14% and up to 43%, respectively. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.1

Clinical Considerations: 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.1

Animal Data: In an enhanced pre- and postnatal development study in cynomolgus monkeys, pregnant animals received intravenous doses of crizanlizumab-tmca at 10 and 50 mg/kg once every 2 weeks during the period of onset of organogenesis through delivery. No maternal toxicity was observed. Maternal exposures at doses of 10 and 50 mg/kg were between 2.8 and 16 times, respectively, the human clinical exposure based on area under the curve (AUC) in patients with sickle cell disease at 5 mg/kg/dose once every 4 weeks. There was an increase in fetal loss (abortions or still births) at both crizanlizumab-tmca doses which was higher in the third trimester.1

There were no effects on infant growth and development through 6-months postpartum that were attributable to crizanlizumab-tmca.1

Measurable crizanlizumab-tmca serum concentrations were observed in the infant monkeys at postnatal Day 28, confirming that crizanlizumab crosses the placental barrier.1

Lactation

Risk Summary: There is 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. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed child to crizanlizumab-tmca are unknown.1

The developmental and health benefits of breast-feeding should be considered along with the mother’s clinical need for crizanlizumab-tmca and any potential adverse effects on the breastfed child from crizanlizumab-tmca or from the underlying maternal condition.1

Pediatric Use

The safety and effectiveness of crizanlizumab-tmca for sickle cell disease have been established in pediatric patients aged 16 years and older. Use of crizanlizumab-tmca for sickle cell disease is supported by evidence from adequate and well-controlled studies in adults and pediatric patients (SUSTAIN Trial). The SUSTAIN trial enrolled one pediatric patient treated with crizanlizumab-tmca 5 mg/kg aged 16 years old.1

The safety and efficacy of crizanlizumab-tmca in pediatric patients below the age of 16 years have not been established.1

Geriatric Use

Clinical studies of crizanlizumab-tmca did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.1

Common Adverse Effects

Most common adverse reactions (incidence > 10%) are nausea, arthralgia, back pain, and pyrexia.1

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

Mechanism of Action

Crizanlizumab-tmca is a humanized IgG2 kappa monoclonal antibody that binds to P-selectin and blocks interactions with its ligands including P-selectin glycoprotein ligand 1.1

Binding P-selectin on the surface of the activated endothelium and platelets blocks interactions between endothelial cells, platelets, red blood cells, and leukocytes.1

Advice to Patients

Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Patient Information).1

Advise patients to contact their healthcare provider immediately for signs or symptoms of infusion-related reactions.1

Advise patients to inform their healthcare provider that they are receiving crizanlizumab-tmca prior to any blood tests due to the potential interference with laboratory tests used to measure platelet counts.1

Additional Information

AHFSfirstRelease. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Crizanlizumab-tmca

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection

10 mg/1 mL

Adakveo

Novartis Pharmaceuticals Corporation

AHFS Drug Information. © Copyright 2020, Selected Revisions December 2, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. Novartis Pharmaceuticals Corporation. ADAKVEO (crizanlizumab) INTRAVENOUS prescribing information. 2019 Nov. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b2b7f8b4-fe9a-4a86-8129-9e43f99a20c6