What are the considerations for using pazopanib (tyrosine kinase inhibitor) in patients with a high risk of bleeding?

From the Guidelines

Pazopanib should be used with extreme caution in patients with a high risk of bleeding due to its potential to impair vascular integrity and platelet function, as evidenced by its mechanism of action as a tyrosine kinase inhibitor targeting VEGFR-1, -2, and -3, PDGFR-α and -β, and c-KIT 1. When considering the use of pazopanib in patients with a high risk of bleeding, several key factors must be taken into account to minimize the risk of adverse events.

• A thorough bleeding risk assessment should be performed before initiating therapy, including evaluation of coagulation parameters, platelet count, and screening for varices in patients with liver disease.
• The standard starting dose is 800 mg once daily, but dose reduction to 400-600 mg daily may be considered in high-risk patients.
• Concurrent use of anticoagulants, antiplatelet agents, and NSAIDs should be avoided when possible or used with careful monitoring, as these can further increase the risk of bleeding.
• Regular monitoring should include complete blood counts, coagulation studies, blood pressure checks, and prompt evaluation of any bleeding symptoms, as pazopanib has been associated with hepatotoxicity and heart rhythm irregularities 1.
• Patients should be educated to immediately report any signs of bleeding, including black stools, hemoptysis, unusual bruising, or severe headaches.
• Treatment should be temporarily interrupted for any significant bleeding event and permanently discontinued for severe hemorrhage. It is crucial to weigh the potential benefits of pazopanib against the risks, particularly in patients with a history of bleeding events or those at high risk of bleeding, and to closely monitor these patients for any signs of bleeding or other adverse effects 1.

From the FDA Drug Label

Hemorrhagic Events: Fatal hemorrhagic events have occurred. Pazopanib has not been studied in patients who have a history of hemoptysis, cerebral hemorrhage, or clinically significant gastrointestinal hemorrhage in the past 6 months. Withhold pazopanib and resume at reduced dose or permanently discontinue based on severity of hemorrhagic events. ( 2.2,5. 4)

When using pazopanib in patients with a high risk of bleeding, the main considerations are:

• Fatal hemorrhagic events have occurred in patients taking pazopanib.
• Pazopanib has not been studied in patients with a history of hemoptysis, cerebral hemorrhage, or clinically significant gastrointestinal hemorrhage in the past 6 months.
• The recommended course of action in case of a hemorrhagic event is to withhold pazopanib and then resume at a reduced dose or permanently discontinue based on the severity of the event 2. Key points to consider:
• Bleeding risk: Patients with a high risk of bleeding should be closely monitored.
• Dose modification: Pazopanib may need to be withheld or dose reduced in case of a hemorrhagic event.
• Contraindications: Pazopanib has not been studied in patients with certain types of bleeding history, and its use in these patients should be approached with caution.

From the Research

Pazopanib Bleeding Risk Considerations

• The use of pazopanib, a tyrosine kinase inhibitor, in patients with a high risk of bleeding requires careful consideration of its potential effects on bleeding risk 3, 4, 5.
• Studies have shown that pazopanib may reduce bleeding in certain conditions, such as hereditary hemorrhagic telangiectasia (HHT) 3, 5.
• In HHT patients, pazopanib has been shown to improve hemoglobin levels, reduce epistaxis severity, and decrease the need for red blood cell transfusions 3, 5.
• However, pazopanib has also been reported to inhibit platelet procoagulant activity, which may increase the risk of bleeding in some patients 4.
• The risk of bleeding with pazopanib may be dose-dependent, with higher doses potentially increasing the risk of bleeding 4.
• Patients with a high risk of bleeding should be closely monitored for signs of bleeding, and the dose of pazopanib should be adjusted accordingly 6.

Key Findings

• Pazopanib has been shown to be effective in reducing bleeding in HHT patients, with a significant improvement in hemoglobin levels and a reduction in epistaxis severity 3, 5.
• The use of pazopanib in patients with a high risk of bleeding requires careful consideration of its potential effects on bleeding risk, and close monitoring for signs of bleeding 4, 6.
• The dose of pazopanib should be adjusted based on the individual patient's risk of bleeding and response to treatment 6.

Patient Monitoring

• Patients with a high risk of bleeding should be closely monitored for signs of bleeding, including hemoglobin levels, epistaxis severity, and the need for red blood cell transfusions 3, 5.
• The dose of pazopanib should be adjusted based on the individual patient's risk of bleeding and response to treatment 6.
• Patients should be educated on the signs and symptoms of bleeding and the importance of reporting any changes to their healthcare provider 6.