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

See More
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.

Mechanism of Action

Selectin Blocker

P-selectin plays a key role in multicellular interactions that can lead to vaso-occlusion in SCD1

Multicellular interaction leading to vaso-occlusion in sickle cell disease
  • In the proinflammatory state associated with SCD, P-selectin is overexpressed on activated endothelial cells and platelets2,3
  • This environment can promote the recruitment of white and red blood cells, as well as platelets. As these cells interact via adhesion mediators, such as P-selectin, multicellular clusters are formed in the bloodstream1-3
  • These events can result in vaso-occlusion, which reduces or blocks blood flow to organs1-3

ADAKVEO is a first-in-class targeted monoclonal antibody that binds to P-selectin4,5

ADAKVEO binds to P-selectin
  • ADAKVEO® (crizanlizumab-tmca) is a targeted monoclonal antibody that binds to P-selectin on the surface of activated endothelial cells and platelets4
  • The binding of ADAKVEO to P-selectin blocks interactions among endothelial cells, platelets, red blood cells, and white blood cells4

Based on in vivo and in vitro studies. Preclinical activity does not necessarily correlate with clinical outcomes.

Video

 

Mechanism of Action

Watch this video for a better understanding of how ADAKVEO plays a key role in multicellular interactions that can lead to vaso-occlusion

Watch Now

References: 1. Gutsaeva DR, Parkerson JB, Yerigenahally SD, et al. Inhibition of cell adhesion by anti-P-selectin aptamer: a new potential therapeutic agent for sickle cell disease. Blood. 2011;117(2):727-735. 2. Zhang D, Xu C, Manwani D, Frenette PS. Neutrophils, platelets, and inflammatory pathways at the nexus of sickle cell disease pathophysiology. Blood. 2016;127(7):801-809. 3. Conran N, Franco-Penteado CF, Costa FF. Newer aspects of the pathophysiology of sickle cell disease vaso-occlusion. Hemoglobin. 2009;33(1):1-16. 4. Adakveo [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2019. 5. 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.