lusutrombopag

Action and Spectrum

Actions and Spectrum: 

Action:  

lusutrombopag is a thrombopoietin receptor agonist. Thrombopoietin is a hormone responsible for stimulating the production of platelets in the bone marrow. lusutrombopag mimics the action of thrombopoietin and activates its receptors on the surface of platelet-producing cells, known as megakaryocytes. This enhances the production and release of platelets into the bloodstream, thereby raising the platelet count. 

Spectrum:  

lusutrombopag is specifically used in patients with chronic liver disease (e.g., cirrhosis) who have thrombocytopenia and are scheduled to undergo an invasive process. Chronic liver disease can lead to a reduced platelet count due to portal hypertension, splenic sequestration, and decreased production in the bone marrow. A lower platelet count can increase the risk of bleeding during invasive procedures. lusutrombopag helps to temporarily raise the platelet count and diminish the risk of bleeding associated with the procedure. 

Drug Interaction

Adverse Reaction

Frequency defined 

1-10% 

Portal vein thrombosis (1%) 

Headache (5%) 

Black Box Warning

Black Box Warning: 

None 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

• Hypersensitivity: lusutrombopag should not be used in individuals with known hypersensitivity or allergic reactions to the drug or its components. 
• Thrombosis Risk: lusutrombopag can increase the risk of thrombosis (formation of blood clots). It is contraindicated in patients at an increased risk of thrombosis, such as those with a history of blood clotting disorders or a predisposition to clot formation. 
• Hematologic Disorders: Patients with certain hematologic disorders, such as myelodysplastic syndromes (MDS) or aplastic anemia, should avoid using lusutrombopag due to the potential risk of exacerbating these conditions. 
• Severe Liver Disease: lusutrombopag is primarily used in patients with chronic liver disease.  
• Pregnancy and Breastfeeding: lusutrombopag should not be used during pregnancy condition or breastfeeding unless the potential benefits outweigh the risks. There may be limited data on its use in pregnant and breastfeeding women. 
• Pediatric Use: lusutrombopag’s safety and effectiveness have not been established in pediatric patients, so it is generally not recommended for use in children. 

Caution 

• Risk of Thrombosis: lusutrombopag can increase the risk of blood clot formation (thrombosis). Patients with a history of thrombotic events or those at an increased risk of thrombosis, such as individuals with cardiovascular diseases, should be closely monitored during treatment. 
• Hepatic Impairment: lusutrombopag is mainly used in patients with chronic liver disease. However, patients with moderate liver impairment (Child-Pugh class B) should use the drug cautiously, as its safety and efficacy in this population may be reduced. 
• Monitoring Platelet Counts: During treatment with lusutrombopag, healthcare providers will regularly monitor the patient’s platelet counts to avoid excessive increases that may lead to complications like thrombosis. The dose may need to be adjusted or discontinued if platelet counts rise excessively. 
• Bleeding Risk: While lusutrombopag aims to raise platelet counts and reduce bleeding risk, it may not eliminate the possibility of bleeding during invasive procedures. Patients should be carefully assessed for bleeding risks before the procedure and during treatment. 
• Drug Interactions: lusutrombopag metabolism may be affected by other medications. To avoid potential interactions, you must inform your healthcare provider about all the drugs, supplements, and herbal products you are taking. 
• Use in Specific Populations: lusutrombopag’s safety and efficacy have not been established in specific populations, such as pregnant or breastfeeding women and pediatric patients. It should be used with caution or avoided in these groups. 
• Immune Thrombocytopenia (ITP): lusutrombopag is not indicated for treating immune thrombocytopenia. Caution should be exercised to avoid its use in patients with ITP, as it may be ineffective and could lead to potential risks. 

Pregnancy / Lactation

Pregnancy consideration:  

US FDA pregnancy category: Not assigned. 

Lactation:   

Excreted into human milk: Not known. 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• 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: 

lusutrombopag is a thrombopoietin receptor agonist with pharmacological properties that stimulate platelet production in patients with thrombocytopenia. By binding to and also activating the thrombopoietin receptor on megakaryocytes in the bone marrow, lusutrombopag promotes their proliferation and differentiation, increasing the production and release of platelets into the bloodstream.

This mechanism of action helps elevate platelet counts in adult individuals with chronic liver disease who are undergoing invasive medical or dental procedures, reducing the risk of bleeding associated with thrombocytopenia in this population. lusutrombopag is primarily administered orally, and its effects are typically observed within a few days of treatment initiation, making it an essential pharmacological option for managing thrombocytopenia before invasive procedures in patients with chronic liver disease. 

Pharmacodynamics: 

Mechanism of action: lusutrombopag is a thrombopoietin receptor agonist, and its mechanism of action is to stimulate the production and release of platelets in the bone marrow. Platelets are crucial for blood clotting and hemostasis, and their deficiency can lead to a condition called thrombocytopenia, characterized by low platelet counts in the blood. 

The primary target of lusutrombopag’s action is the thrombopoietin receptor (also known as a c-Mpl receptor) located on the surface of megakaryocytes, the cells responsible for platelet production. Thrombopoietin is a hormone that binds to these receptors and signals the bone marrow to produce more platelets. 

lusutrombopag mimics the action of thrombopoietin by binding to and activating the thrombopoietin receptors on megakaryocytes. This activation leads to a series of intracellular signaling events that stimulate platelet proliferation, maturation, and release from the megakaryocytes into the bloodstream. 

By increasing platelet production, lusutrombopag effectively raises the platelet count in individuals with thrombocytopenia, particularly in individuals with chronic liver disease who are scheduled to undergo invasive medical or dental procedures. The temporary increase in platelet count helps reduce the risk of bleeding during these procedures, providing a critical benefit for patients with thrombocytopenia and chronic liver disease. 

Pharmacokinetics: 

Absorption 

lusutrombopag is orally administered in the form of tablets. After ingestion, it is absorbed from the gastrointestinal tract into the bloodstream. Food intake may influence absorption, but specific details on its bioavailability and absorption characteristics were not widely reported. 

Distribution 

Once absorbed, lusutrombopag is distributed throughout the body via the bloodstream. 

Metabolism 

lusutrombopag undergoes metabolism in the liver, where various enzymes likely metabolize it. 

Elimination and Excretion 

The elimination of lusutrombopag from the body primarily occurs through the hepatic (liver) route. It is likely excreted in the bile and feces. 

Adminstartion

Administration: 

Oral administration 

lusutrombopag is typically available in the form of oral tablets.  

• Dosage: A healthcare professional prescribes The dosage of lusutrombopag based on the patient’s needs and medical condition.  
• Timing: lusutrombopag is usually administered for seven consecutive days before the scheduled invasive medical or dental procedure. It is essential to follow the prescribed dosing schedule strictly. 
• Administration: lusutrombopag tablets are taken orally with or without food.  
• Platelet Count Monitoring: During the treatment period, the patient’s platelet count will be monitored closely by the healthcare provider to assess the response to the medication and to avoid excessive increases in platelet counts, which could lead to thrombotic events. 
• Procedure Timing: The invasive medical or dental procedure is typically scheduled 2 to 8 days after completing the 7-day course of lusutrombopag. This allows enough time for the platelet count to increase and helps reduce the risk of bleeding during the procedure. 
• Discontinuation: lusutrombopag is a short-term treatment intended to raise platelet counts before the procedure. After the procedure is completed, the use of lusutrombopag is discontinued. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: lusutrombopag 

Pronounced: [ LOO-soo-TROM-boe-pag ] 

Why do we use lusutrombopag? 

lusutrombopag is a drug used to treat Thrombocytopenia in Chronic Liver Disease Patients Before Invasive Procedures. 

lusutrombopag is primarily used to treat thrombocytopenia in adult individuals with chronic liver disease who are scheduled to undergo an invasive medical or dental procedure. Thrombocytopenia is a condition characterized by lower platelet counts in the blood, which can increase the risk of bleeding during surgical/invasive procedures. Chronic liver disease may lead to a reduction in platelet production and an increased risk of bleeding. 

lusutrombopag, a thrombopoietin receptor agonist, works by stimulating the production and release of platelets from the bone marrow, thereby increasing the platelet count in the blood. Raising the platelet levels helps reduce the risk of bleeding during invasive process in patients with chronic liver disease.