Crizanlizumab
Crizanlizumab Uses, Dosage, Side Effects, Food Interaction and all others data.
Crizanlizumab is a humanized IgG2 monoclonal antibody used to reduce the frequency of vaso-occlusive crises in patients with sickle cell disease. Sickle cell disease is a genetically inherited condition prevalent in the Middle East, Africa, and certain parts of India. The genetic mutation associated with this disease leads to the formation of abnormal, sickle shaped red blood cells that aggregate and block blood vessels throughout the body, causing vaso-occlusive crises. Sickle cell disease can lead to excruciating pain, stroke, infection, and various other complications arising from the blockage of blood vessels.
Currently, patients are prescribed hydroxyurea to raise levels of fetal hemoglobin as a method of reducing morbidity and mortality. Though hydroxyurea has been shown to reduce the frequency of vaso-occlusive crises, adherence to this therapy is difficult due to adverse effects and the high variability of response to the drug between patients. Crizanlizumab, or SEG101, is given once every 4 weeks and may improve patient adherence. It was developed by Novartis and was granted FDA approval on November 15, 2019.
Crizanlizumab is a P-selectin inhibitor that prevents interactions between endothelial cells, platelets, red blood cells, and leukocytes. It has a long duration of action as it is given every 4 weeks. Patients should be counselled regarding the risk of infusion reactions as well as crizanlizumab's interference with platelet counts using EDTA tubes.
| Trade Name | Crizanlizumab |
| Availability | Prescription only |
| Generic | Crizanlizumab |
| Crizanlizumab Other Names | Crizanlizumab, crizanlizumab-tmca |
| Related Drugs | hydroxyurea, vitamin e, Hydrea, Endari, glutamine, Adakveo |
| Weight | 10mg/ml |
| Type | Intravenous solution |
| Weight | 146000.0 Da (Theoretical) |
| Protein binding | Monoclonal antibodies are generally not protein bound. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Crizanlizumab is a monoclonal antibody that targets selectin to reduce the frequency of vasooclusive crises in patients with sickle cell disease.
Crizanlizumab is indicated to reduce the frequency of vaso-occlusive crisis in patients with sickle cell diseases who are ≥16 years old.
Crizanlizumab is also used to associated treatment for these conditions: Vaso-occlusive Crisis
How Crizanlizumab works
Crizanlizumab binds to P-selectin on endothelial cells and platelets, preventing their interaction with P-selectin glycoprotein ligand 1 on endothelial cells, platelets, red blood cells, and leukocytes. By preventing this interaction, components of the blood are less likely to come together, causing a vaso-occlusive crisis in patients with sickle cell diseases. The median per year incidence of vaso-occlusive crises was 1.04 in the high-dose crizanlizumab group, 2.00 in the low-dose crizanlizumab group, and 2.08 in the placebo group.
Toxicity
Data regarding the toxicity of crizanlizumab is not readily available.
Food Interaction
No interactions found.Crizanlizumab Disease Interaction
Volume of Distribution
The volume of distribution of crizanlizumab is 4.26L.
Elimination Route
Crizanlizumab reaches a Cmax of 0.16mg/mL with an AUC of 34.6mg*hr/mL.
Half Life
Given a 5mg/kg dose of crizanlizumab, the mean terminal elimination half life of crizanlizumab is 10.6 days in healthy subjects and 7.6 days in patients with sickle cell disease.
Clearance
Given a 5mg/kg dose of crizanlizumab, the clearance rate is 11.7ml/hr in healthy subjects.
Elimination Route
Monoclonal antibodies are eventually phagocytosed and broken down to smaller peptides and amino acids which are eliminated in a similar fashion to other proteins. Monoclonal antibodies are generally not eliminated in the urine, and only a small amount is excreted in bile.
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