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 SCD1,2

ADAKVEO® (crizanlizumab-tmca) 5 mg/kg is administered by IV infusion over 30 minutes at Weeks 0 and 2, then every 4 weeks1

ADAKVEO may be given with or without hydroxyurea.

Guidance for missed doses of ADAKVEO1
  • If a dose is missed, administer ADAKVEO as soon as possible
  • 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, continue dosing every 4 weeks thereafter
ADAKVEO®(crizanlizumab-tmca) packaging

Dosing and Administration

Preparation and administration1

ADAKVEO should be prepared and administered by a health care professional.

Preparation1
  • Use aseptic technique to prepare the solution for infusion
  • Calculate the dose (mg) and the total volume (mL) of ADAKVEO solution required, and the number of ADAKVEO vials needed based on the patient’s actual body weight
    • Prepare 5 mg of ADAKVEO per kg of actual body weight
  • Calculate the volume of ADAKVEO to be used according to the following equation:

ADAKVEO preparation

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

Dilute ADAKVEO in 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP to a total volume of 100 mL for IV infusion as follows:

  1. Obtain the number of vials required. One vial is needed for every 10 mL of ADAKVEO.
  2. Bring vials to room temperature for a maximum of 4 hours prior to the start of preparation (piercing the first vial).
  3. Visually inspect the vials.
    • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit
    • ADAKVEO is clear to opalescent, colorless or may have a slightly brownish-yellow tint
    • Do not use if particles are present in the solution
  1. Obtain a 100 mL 0.9% Sodium Chloride Injection or 5% Dextrose Injection infusion bag/container.
    • Infusion bags/containers must be made of either polyvinyl chloride (PVC), polyethylene (PE), or polypropylene (PP)
  1. Remove a volume of 0.9% Sodium Chloride Injection or 5% Dextrose Injection from the infusion bag/container that is equal to the required volume of ADAKVEO solution.
  2. Withdraw the necessary amount of ADAKVEO solution and dilute by adding to the infusion bag/container containing 0.9% Sodium Chloride Injection or 5% Dextrose Injection.
    • The volume of ADAKVEO added to the infusion bag/container should not exceed 96 mL
  1. Gently invert the infusion bag to mix the diluted solution. DO NOT SHAKE.
  2. Single-dose vials. Discard unused portion.

Administer ADAKVEO diluted solution as soon as possible. If not administered immediately, store the prepared solution either:

  • At room temperature up to 25°C (77°F) for no more than 4.5 hours from the start of the 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 the time of the 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
  • Administer ADAKVEO diluted solution by IV infusion over a period of 30 minutes through an IV line, which must contain a sterile, nonpyrogenic 0.2 micron inline filter
  • No incompatibilities have been observed between ADAKVEO and infusion sets composed of PVC, polyethylene (PE-lined PVC), polyurethane (PU), and in-line filter membranes composed of polyethersulfone (PES, neutral and positively charged), positively charged polyamide (PA), and polysulphone (PSU)
  • Do not mix or coadminister with other drugs through the same IV line
  • After administration of ADAKVEO, flush the line with at least 25 mL 0.9% Sodium Chloride Injection or 5% Dextrose Injection
  • Dispose of any unused product or waste material in accordance with local requirements

IV, intravenous.

Resources

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Dosing and Administration Video

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

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Dosing and Administration Guide

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

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For additional ADAKVEO Safety Information, click here

References: 1. Adakveo [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2019. 2. National Heart, Lung, and Blood Institute. SBIR Success Stories. NHLBI funding leads to promising drug candidate to prevent sickle cell pain. http://www.nhlbi.nih.gov/grants-and-training/funding-opportunities-and-contacts/small-business-program/sbir-success-stories/nhlbi-funding-leads-promising-drug-candidate-prevent-sickle-cell-pain. Accessed June 5, 2019.
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.