dostarlimab

Action and Spectrum

Actions and Spectrum 

Action: The drug exerts its action by binding to PD-1, a protein expressed on the surface of T cells, B cells, and natural killer (NK) cells. PD-1 acts as a checkpoint to regulate the immune response and prevent excessive activation.   

By binding to PD-1, drug blocks the interaction between PD-1 and its ligands PD-L1 and PD-L2. This prevents the cancer cells from inhibiting the immune response and allows the immune system to recognize and attack cancer cells more effectively.  

Spectrum: drug is primarily indicated for the treatment of certain types of cancer characterized by microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) status. These conditions result in abnormalities in the DNA repair mechanism within the cancer cells, making them more vulnerable to immune attack. 

Drug Interaction

Adverse Reaction

Frequency defined  

>10% 

All grades 

Hyponatremia (26%) 

Increased creatinine (27%) 

Nausea (30%) 

Lymphopenia (37%) 

Hypoalbuminemia (30%) 

Increased alkaline phosphatase (25%) 

Leukopenia (21%) 

Fatigue (48%) 

Anemia (24%) 

Vomiting (18%) 

Constipation (20%) 

Diarrhea (26%) 

Anemia (24%) 

Grade 3 or 4 

1-10% 

All grades 

Pyrexia (2.9%) 

Urinary tract infection (2.9%) 

Acute kidney injury (2.9%) 

Sepsis (2.9%) 

Abdominal pain (2.9%) 

Grade 3 or 4 

Fatigue (1%) 

Increased ALT (2.9%) 

Hypoalbuminemia (2.9%) 

Increased creatinine (2.9%) 

Leukopenia (2.9%) 

Hyponatremia (4.8%) 

Hypercalcemia (1.9%) 

Urinary tract infection (1.9%) 

Diarrhea (1.9%) 

Increased alkaline phosphatase (2.9%) 

Hypercalcemia (1.9%) 

Lymphopenia (9%) 

Increased AST (1.9%) 

Pruritus (1%) 

<1% 

Constipation (0.9%) 

Black Box Warning

Black Box Warning:  

None  

Contraindication / Caution

Contraindication/Caution:  

Hypersensitivity: dostarlimab should not be used in individuals with a known hypersensitivity or severe allergic reaction to the medication or any of its components. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: N/A 

Lactation: Excreted into human milk is unknown 

Pregnancy Categories:         

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester. 

Category B: There were a lack of studies on pregnant women and no evidence of risk to the fetus in animal experiments.   

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.   

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology:  

The drug is a monoclonal antibody that specifically binds to the programmed death receptor 1 (PD-1). PD-1 is a protein found on the outer membrane of immune cells, specifically T cells. 

Pharmacodynamics:  

The drug works by binding to PD-1 and blocking its interaction with PD-L1 and PD-L2. This prevents the inhibitory signals from PD-1 and allows T cells to remain active and attack cancer cells. By blocking the PD-1 pathway, dostarlimab helps to restore the immune response against cancer cells, leading to their destruction.   

Pharmacokinetics: 

Absorption 

The drug is administered intravenously, meaning it is directly infused into the bloodstream. As a result, the drug is rapidly and completely absorbed into the systemic circulation. 

Distribution 

The drug is distributed throughout the body to reach its target sites, which are typically tumors expressing PD-1. The exact distribution pattern may vary depending on the specific tumor type and patient characteristics. 

Metabolism 

As a monoclonal antibody, The drug undergoes minimal metabolism in the body. Monoclonal antibodies are primarily cleared from the body through proteolytic degradation, with the help of proteolytic enzymes.  

Excretion and elimination 

The primary route of excretion for dostarlimab is via the reticuloendothelial system (RES) and renal elimination. The drug is metabolized and broken down into smaller peptides, which are then eliminated through the kidneys. 

Adminstartion

Administration:  

The dosage and administration of this drug may vary depending on the specific indication and patient’s condition.  

The infusion of dostarlimab is usually given over a period of 30 minutes.

Patient Information Leaflet

Patient information leaflet 

Generic Name: dostarlimab 

Why do we use dostarlimab?   

Advanced or recurrent endometrial cancer: The drug is used for the treatment of advanced or recurrent endometrial cancer that is microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR). These molecular characteristics indicate a specific subset of endometrial cancers that may respond well to immune checkpoint inhibitors like dostarlimab.  

Advanced or recurrent cervical cancer: The drug is also approved for the treatment of advanced or recurrent cervical cancer that has progressed on or after chemotherapy. It offers a treatment option for patients who have limited therapeutic alternatives.