What are the precautions for Pazopanib?

Patients should pay attention to hepatotoxicity, QT prolongation and torsade de pointes, cardiac dysfunction, bleeding, In the event of arterial and venous thromboembolism, thrombotic microangiopathy, gastrointestinal perforation and fistula, interstitial lung disease/pneumonia, posterior reversible encephalopathy syndrome, hypertension, impaired wound healing, hypothyroidism, proteinuria, tumor lysis syndrome, infection and other events, the administration may be interrupted, reduced or discontinued according to the severity of the condition.

1. Hepatotoxicity: manifested byincreased ALT, aspartate aminotransferase (AST) and bilirubin. This liver toxicity can be severe and fatal. Patients over 65 years of age are at greater risk for hepatotoxicity. At weeks 3, 5, 7, and 9; at months 3 and 4; and then as regularly as clinically indicated. Increase weekly monitoring of patients with elevated ALT until ALT returns to Grade 1 or baseline levels. Discontinue this product and continue weekly monitoring at a reduced dose for 8 weeks, or permanently discontinue weekly monitoring until resolution based on severity of hepatotoxicity.

2. QT prolongation and torsade de pointes: Monitor patients who are at significant risk for QTc interval prolongation, including patients with a history of QT prolongation, patients who are taking antiarrhythmic drugs or other drugs that may prolong the QT interval, and patients with preexisting related cardiac disease. Correct hypokalemia, hypomagnesemia, and hypocalcemia before initiating pazopanib and during treatment.

3. Heart dysfunction: including reduced left ventricular ejection fraction (LVEF) and congestive heart failure. Monitor blood pressure and manage appropriately, monitor for clinical signs or symptoms of congestive heart failure, and perform baseline and periodic assessments of LVEF.

4. Bleeding: The most common bleeding events were hematuria (4%), epistaxis (2%), hemoptysis (2%), and rectal bleeding (1%). Pazopanib has not been studied in patients with a history of hemoptysis, cerebral hemorrhage, or clinically significant gastrointestinal bleeding in the past 6 months.

5. Arterial and venous thromboembolism: Venous thromboembolic events include venous thrombosis and fatal pulmonary embolism, which occur in patients receiving pazopanib. If an arterial thromboembolic event occurs, permanently discontinue pazopanib.

6. Thrombotic microangiopathy: including thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). Pazopanib is not suitable for use in combination with other medications. Six of the 7 cases of TMA occurred within 90 days of starting treatment. Improvement of TMA was observed after cessation of treatment.

7. Gastrointestinal perforation and fistulas: In the renal cell carcinoma trial, the incidence of fatal perforation in these patients0.3%, fatal perforation occurred in 0.3% of these patients in the soft tissue sarcoma trial. Monitor for signs and symptoms of gastrointestinal perforation or fistula. Pazopanib should be discontinued if grade 2 or 3 gastrointestinal fistula occurs, and permanently if gastrointestinal perforation or grade 4 gastrointestinal fistula occurs.

8. Interstitial lung disease/pneumonia: Among patients treated with pazopanib , 0.1% developed ILD/pneumonitis. Monitor patients for the development of pulmonary symptoms indicative of ILD/pneumonitis. Pazopanib should be permanently discontinued in patients who develop ILD or pneumonitis.

9. Posterior reversible encephalopathy syndrome (PRES): can manifest as headache, seizures, drowsiness, confusion, blindness, and other visual and neurological disorders. Mild to severe hypertension may be present. The diagnosis of PRES is confirmed by magnetic resonance imaging. Pazopanib should be permanently discontinued in patients who develop PRES.

10. Hypertension: Hypertension (systolic blood pressure ≥150mmHg or diastolic blood pressure ≥100mmHg) and hypertensive crisis have been observed in patients treated with pazopanib. Do not use pazopanib in patients with uncontrolled hypertension. Optimize blood pressure before starting medication. Monitor blood pressure as clinically indicated and initiate and adjust antihypertensive therapy as appropriate.

11. Impaired wound healing: Patients receiving drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway may develop complications from wound healing disorders. Pazopanib should be discontinued at least one week before elective surgery and should not be administered for at least 2 weeks after major surgery until the wound is completely healed.

12. Proteinuria: Baseline and periodic urinalysis during treatment, and follow-up measurement of 24-hour urine protein as clinically indicated Then, depending on the severity of the proteinuria, reduce the dose or permanently discontinue the drug. The drug should be permanently discontinued in patients with nephrotic syndrome.

13. Tumor lysis syndrome (TLS): Patients may be at risk for TLS if they have rapidly growing tumors, high tumor burden, renal dysfunction, or dehydration. Monitor at-risk patients closely, consider appropriate precautions, and treat as clinically indicated.

14. Infection: Serious infections (with or without neutropenia) have been reported, including some fatal outcomes. Monitor patients for signs and symptoms of infection. Initiate appropriate anti-infective treatment promptly and consider interrupting or discontinuing treatment for serious infections.