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.

Safety

Infusion-Related Reactions (IRRs)

IRRs may happen during and 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) within 24 hours of infusion1
  • Monitor for signs and symptoms such as1:
  • 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
  • Advise your patients to contact their health care provider immediately if they experience any possible signs and symptoms of IRRs during and within 24 hours of the infusion1
  • Discontinue the ADAKVEO infusion for severe reactions and institute appropriate medical care

 

Adverse Reactions (ARs)

Majority of ARs with ADAKVEO were mild to moderate (grade 1 or 2)1

Adverse Drug Reactions Reported ≥10% of ADAKVEO® (crizanlizumab-tmca) Patients With a Difference Between Arms of >3% Compared With Placebo in SUSTAIN

 

 

 

ADAKVEO (5 mg/kg)
N=66; n (%)

Placebo
N=62; n (%)

Adverse
Drug Reactions

All Grades

Grades ≥3

All Grades

Grades ≥3

Gastrointestinal disorders

       

Nausea

12 (18)

0

7 (11)

1 (2)

Musculoskeletal disorders and connective tissue disorders

 

 

 

 

Arthralgia
Back pain

12 (18)
10 (15)

1 (2)
0

5 (8)
7 (11)

1 (2)
0

General disorders and administration site conditions

 

 

 

 

Pyrexia

7 (11)

1 (2)

4 (7)

0

  • Clinically relevant ARs (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 IRRs
  • Two deaths (3%) occurred in the ADAKVEO 5 mg/kg treatment group. None of the deaths were considered to be related to ADAKVEO
  • Serious ARs were reported in 2 patients (3%) treated with ADAKVEO 5 mg/kg; both reactions were pyrexia

Management considerations for IRRs and the Most Common ARs*

Guidance to consider along with your institution's protocols

IRRs

IRRs

 
Most Common ARs

Follow up with your patients who have experienced an IRR OR AR to assess whether symptoms resolved

* These considerations are based on the clinical study protocols for ADAKVEO (including SUSTAIN), current medical literature, and guidelines from the American Society of Hematology. These considerations are not meant to replace your clinical judgment, as well as your institution's protocols. Each patient should be considered individually when decisions are made to manage potential IRRs. Decisions should be made by considering the signs and symptoms with which the patient is presenting.

Safety Profile and Management Considerations

Watch Nirmish R. Shah, MD, outline the safety profile of ADAKVEO and share considerations for managing infusion-related reactions and the most common adverse reactions

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Other Safety Measures

Rates of infection, blood count results, and blood chemistry findings were similar to those with placebo11

Infection rates
  • Similar infection rates were observed with ADAKVEO and placebo (overall, 51.5% vs 53.2%; serious, 12.1% vs 16.1%)
    • Infections were observed with ADAKVEO and placebo, and included urinary tract infection (13.6% vs 11.3%), upper respiratory tract infection (10.6% vs 9.7%), pneumonia (6.1% vs 4.8%), and influenza (1.5% vs 0%)
Blood count results
  • The incidence of neutropenia was 3.0% for ADAKVEO vs 6.5% for placebo
  • No significant clinical differences between ADAKVEO vs placebo in hemoglobin (LSM: 1.5; 0.8 vs -0.7); reticulocyte count (LSM: -9.79; -7.12 vs 2.68); or haptoglobin (LSM: 0.03; 0.04 vs 0.01)
Blood chemistry findings
  • No significant clinical differences between ADAKVEO vs placebo in LDH (LSM: 8.2; -25.4 vs -33.5) or indirect bilirubin (LSM: -3.0; -2.3 vs 0.7)

Laboratory Test Interference: Platelet Counts

Lab interference with automated platelet counts (platelet clumping) has been observed following administration of ADAKVEO when blood samples were collected in tubes containing ethylenediaminetetraacetic acid (EDTA). Run test as soon as possible or use citrate tubes.

AR, adverse reaction; IRR, infusion-related reaction; LSM, least squares mean; LDH, lactate dehydrogenase; NSAID, nonsteroidal anti-inflammatory drug; SCD, sickle cell disease.

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. 4. Picard M, Galvão VR. Current knowledge and management of hypersensitivity reactions to monoclonal antibodies. J Allergy Clin Immunol Pract. 2017;5(3):600-609. 5. Vogel WH. Infusion reactions: diagnosis, assessment, and management. Clin J Oncol Nurs. 2010;14(2):E10-E21. 6. Nausea & vomiting. Cleveland Clinic. https://my.clevelandclinic.org/health/symptoms/8106-nausea—vomiting. Accessed September 1, 2020. 7. Flake ZA, Linn BS, Hornecker JR. Practical selection of antiemetics in the ambulatory setting. Am Fam Physician. 2015;91(5):293-296. 8. Joint pain. Mayo Clinic. https://www.mayoclinic.org/symptoms/joint-pain/basics/definition/sym-20050668. Accessed September 1, 2020. 9. Back pain. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/back-pain/symptoms-causes/syc-20369906. Accessed September 1, 2020. 10. Yawn BP, John-Sowah J. Management of sickle cell disease: recommendations from the 2014 expert panel report. Am Fam Physician. 2015;92(12):1069-1076A. 11. Data on file. Study NCT01895361. Novartis Pharmaceuticals Corp; 2016.

Next: Dosing and Administration

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.