Important Safety Information

 

Infusion-Related Reactions (IRRs)

In the SUSTAIN clinical trial, IRRs (occurring during/within 24 hours of infusion) were observed in 2 (3%) patients treated with ADAKVEO

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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.
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Communicate that ADAKVEO is a long-term treatment and stress the importance of making it to each infusion1

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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
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USE ASEPTIC TECHNIQUE TO PREPARE THE SOLUTION FOR INFUSION.
ADAKVEO SHOULD BE PREPARED AND ADMINISTERED BY A HEALTH CARE PROFESSIONAL

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Dilute

  1. Obtain a 100-mL Infusion bag/container injection, USP (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 required volume of ADAKVEO 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
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REMEMBER, THE DILUTED ADAKVEO SOLUTION SHOULD BE ADMINISTERED AS SOON AS POSSIBLE

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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
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Prophylaxis is not required. Exercise caution with corticosteroids in patients with SCD unless clinically indicated (eg, treatment of anaphylaxis)1

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Dosing monitor

Monitor

IRRs may happen during/within 24 hours of infusion1

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

  • In the SUSTAIN study, IRRs were observed in 2 (3%) patients treated with ADAKVEO® (crizanlizumab-tmca) 5 mg/kg (N=66) during/within 24 hours of infusion1
  • Postmarketing cases of IRRs, including severe pain events requiring hospitalizations, have been reported. The majority of these IRRs occurred during the first and second infusions. The management of pain events included acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, antihistamines, intravenous fluids, and/or oxygen therapy. Some patients have also experienced subsequent complications, such as acute chest syndrome and fat embolism, particularly those treated with steroids1
  1. Monitor for signs and symptoms of IRRs such as:

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

2. If an IRR occurs, manage medically:

  • For mild or moderate infusion-related reactions, temporarily interrupt or slow the rate of infusion and initiate symptomatic treatment. For subsequent infusions, consider premedication and/or reduce the infusion rate
  • For severe IRRs, discontinue infusion, institute appropriate medical care, and consider permanent discontinuation of ADAKVEO
  • Exercise caution with corticosteroids in patients with SCD unless clinically indicated (eg, treatment of anaphylaxis)

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

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

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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

Watch Now

A Nurse’s Guide to the ADAKVEO Infusion Experience

A pocket guide of the need-to-know information to help infusion nurses initiate treatment, answer questions, and engage their patients.

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

Reference: 1. Adakveo [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2021.

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 (IRRs)

In the SUSTAIN clinical trial, IRRs (occurring during/within 24 hours of infusion) were observed in 2 (3%) patients treated with ADAKVEO 5 mg/kg. Postmarketing cases of IRRs, including severe pain events requiring hospitalizations, have been reported. The majority of these IRRs occurred during the first and second infusions. The management of pain events included acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, antihistamines, intravenous fluids, and/or oxygen therapy. Some patients have also experienced subsequent complications such as acute chest syndrome and fat embolism, particularly those treated with steroids.

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

For severe IRRs, discontinue infusion, institute appropriate medical care, and consider permanent discontinuation of ADAKVEO. For mild or moderate IRRs, temporarily interrupt or slow the rate of infusion and initiate symptomatic treatment. For subsequent infusions, consider premedication and/or reduce the infusion rate.

Exercise caution with corticosteroids in patients with sickle cell disease unless clinically indicated (eg, treatment of anaphylaxis).

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%), abdominal pain (12%), 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, 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 accompanying full Prescribing Information.