Important Safety Information

 

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

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Indication


ADAKVEO® (crizanlizumab-tmca) is indicated to reduce the frequency of vaso-occlusive crises (VOCs) in adults and pediatric patients, aged 16 years and older, with sickle cell disease.

Dosing and Administration

Dosing Schedule

ADAKVEO is the first and only FDA-approved, once-monthly treatment to reduce the frequency of VOCs in SCD1

ADAKVEO® (crizanlizumab-tmca) 5 mg/kg is administered by IV infusion over a period of 30 minutes at Weeks 0 and 2, then every 4 weeks

ADAKVEO may be given with or without hydroxyurea. Do not mix or coadminister with other drugs through the same IV line. 

FDA, US Food and Drug Administration; SCD, sickle cell disease; VOCs, vaso-occlusive crises.
 

 

Missed Dose

If a dose is missed, administer ADAKVEO as soon as possible1

  • If ADAKVEO is administered within 2 weeks after the missed dose, continue dosing according to the patient’s original schedule
  • If ADAKVEO is administered more than 2 weeks after the missed dose, schedule the next appointment 4 weeks later

 

Before the Infusion

Calculate

Calculate the required volume and number of vials of ADAKVEO needed based on the patient’s actual body weight1

Formula
Example

Each vial of ADAKVEO is single-dose only. Discard any unused portion.

Each vial of ADAKVEO is single-dose only. Discard any unused portion.

Please refer to full Prescribing Information for additional dosage and administration instructions.

Prepare

  1. Bring vials to room temperature for up to 4 hours prior to the start of preparation (piercing the first vial)
    • For vials that have not been pierced, the cumulative time out of refrigeration cannot exceed 4 hours
  2. Visually inspect the vials
    • The solution should be clear to opalescent, colorless, or may have a slightly brownish-yellow tint
    • Do not use if particles are present in the solution

 

Important Reminder:

Before preparation, ADAKVEO vials should be stored and transported:

  • Under refrigeration at 2°C to 8°C (36°F to 46°F)
  • Protected from light by keeping them in the original carton

Do not shake or freeze the vials.

ADAKVEO® (crizalizumab-tmca) packaging
Dosing Dilute

Dilute

Dilute ADAKVEO in 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP to a total volume of 100 mL for intravenous infusion as follows:
  1. Obtain a 100-mL Infusion bag/container (containing either 0.9% Sodium Chloride or 5% Dextrose)
  2. Remove the volume of 0.9% Sodium Chloride or 5% Dextrose from the infusion bag/container that is equal to the calculated volume of ADAKVEO solution
  3. Add the 0.9% solution from the vials to the infusion bag/container
    • The volume of ADAKVEO added to the infusion bag/container should not exceed 96 mL
  4. Gently invert (don't shake) the infusion bag to mix the diluted solution

 

Important Reminder:

  • Infusion bags/containers must be made of either polyvinyl chloride (PVC), polyethylene (PE), or polypropylene (PP)
  • Each vial of ADAKVEO is single-dose only. Discard any unused portion
 

Store the Diluted Solution

Once prepared, if not administering ADAKVEO immediately, store the diluted solution (infusion bag/container) either:
  • At room temperature up to 25°C (77°F) for no more than 4.5 hours
    • From the start of preparation (piercing the first vial) to the completion of infusion
  • Under refrigeration at 2°C to 8°C (36°F to 46°F) for no more than 24 hours
    • From the start of preparation (piercing the first vial) to the completion of infusion
      This includes the storage of the diluted solution and the time to warm up to room temperature
    • Protect the diluted solution from light during storage under refrigeration
 

Infusion and Monitoring

Dosing Administer

Administer

  1. Be sure to administer ADAKVEO diluted solution by intravenous infusion as soon as possible1
  2. Infuse ADAKVEO diluted solution over a 30-minute period through an IV line
    • IV line must contain a sterile, nonpyrogenic 0.2-micron inline filter
  3. Flush the line with at least 25 mL 0.9% sodium chloride or 5% dextrose after administration of ADAKVEO

Important Reminder:

  • Dispose of any unused product or waste material in accordance with local requirements
  • Do not mix or coadminister with other drugs through the same IV line

CLINICAL TRIAL PROTOCOLS FOR ADAKVEO DID NOT RECOMMEND PROPHYLAXIS FOR IRRS. USE YOUR CLINICAL JUDGMENT.2 CAUTION IS RECOMMENDED WHEN CONSIDERING CORTICOSTEROIDS3

 
Dosing monitor

Monitor

IRRs may happen during and within 24 hours of infusion1

With monoclonal antibodies such as ADAKVEO, there is the potential for IRRs.

  1. Monitor your patient for infusion-related reactions according to your facility’s infusion protocol. Discontinue the ADAKVEO infusion for severe reactions and institute appropriate medical care.
  2. Watch for signs and symptoms of infusion-related reactions, such as:
  • Fever
  • Chills
  • Nausea
  • Vomiting
  • Fatigue
  • Dizziness
  • Pruritus
  • Urticaria
  • Sweating
  • Shortness of breath or wheezing
  • Pain (generalized, arthralgia, back pain)

These are not all the potential signs and symptoms of IRRs.

For additional safety information, including most common adverse reactions (ARs) and management considerations, see Safety.

ADVISE YOUR PATIENTS TO CONTACT THEIR HEALTH CARE PROVIDER IMMEDIATELY IF THEY EXPERIENCE ANY OF THE ABOVE SIGNS OR SYMPTOMS OF IRRs DURING AND WITHIN 24 HOURS OF THE INFUSION

Resources

 

Dosing and Administration Guide

Download this resource designed to guide you through dosing and administering ADAKVEO

Download

Dosing and Administration Video

Watch this video for more information about the ADAKVEO dosing schedule, dosing calculation, and administration process

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Helpful Information for ADAKVEO Infusion Appointments

Brochure that provides suggested strategies for engaging with patients at their ADAKVEO infusion appointments and details safety considerations, including management considerations for infusion-related reactions and the most common adverse reactions.

Download

Logistics for ADAKVEO Infusion Appointments

Watch this video for firsthand tips from nurse practitioner, Dr. Artangela Henry, on managing and explaining the logistics of ADAKVEO infusion appointments.

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3 Things to Remind Your Patients About Their Treatment Journey

Watch this video for a short overview of 3 important things to remind your patients receiving treatment with ADAKVEO. Featuring nurse practitioner, Dr. Artangela Henry.

Watch Now

For additional ADAKVEO Safety Information, click here

IRR, infusion-related reaction.

References: 1. Adakveo [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2019. 2. Data on file. CSEG101A2202 Clinical Trial Protocol. Novartis Pharmaceuticals Corp; 2017. 3. Brandow AM, Carroll CP, Creary S, et al. American Society of Hematology 2020 guidelines for sickle cell disease: management of acute and chronic pain. Blood Adv. 2020;4(12):2656-2701.

Next: Mechanism of Action

Indication

ADAKVEO® (crizanlizumab-tmca) is indicated to reduce the frequency of vaso-occlusive crises (VOCs) in adults and pediatric patients, aged 16 years and older, with sickle cell disease.

Important Safety Information

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 ADAKVEO 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, or shortness of breath or wheezing. Discontinue ADAKVEO infusion for severe reactions and institute appropriate medical care.

Laboratory Test Interference: Platelet Counts

Interference with automated platelet counts (platelet clumping) has been observed following administration of ADAKVEO, in particular, when blood samples were collected in tubes containing EDTA.

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.

Pregnancy

Based on animal data, ADAKVEO has the potential to cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. ADAKVEO should only be used during pregnancy if the expected benefit to the patient justifies the potential risk to the fetus.

Most Common Adverse Reactions

The most frequently reported adverse reactions (≥10%) in patients treated with ADAKVEO were nausea (18%), arthralgia (18%), back pain (15%), and pyrexia (11%).

Other Clinically Important Adverse Reactions

Clinically relevant adverse reactions (all grades) that were reported in <10% of patients treated with ADAKVEO included: 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), and infusion-related reaction.

Please see full Prescribing Information.