What are the precautions for axitinib/axitinib?

In clinical studies of axitinib/axitinib (Axitinib) in the treatment of various renal cancers, warnings and precautions such as hypertension, arterial thromboembolic events, venous thromboembolic events, bleeding, heart failure, gastrointestinal perforation and fistula formation, thyroid dysfunction, impaired wound healing, reversible posterior leukoencephalopathy syndrome, proteinuria, hepatotoxicity, liver damage, major adverse cardiovascular events, embryonic-fetal toxicity have emerged. Discontinue and resume at reduced dose upon recovery, or permanently discontinue based on severity.

1. Hypertension: Patients receiving axitinib treatment developed hypertension (systolic blood pressure>150mmHg or diastolic blood pressure>100mmHg). Before starting treatment with axitinib, ensure that blood pressure is well controlled. Monitor patients for hypertension and treat with standard antihypertensive therapy as needed.

2. Arterial thromboembolic events: Arterial thromboembolic events (including transient ischemic attack, cerebrovascular accident, myocardial infarction, and retinal artery occlusion), including death, have been reported in clinical trials. Patients with an arterial thromboembolic event within the past 12 months have not been studied. If an arterial thromboembolic event occurs during treatment, permanently discontinue axitinib.

3. Venous thromboembolic events: These include pulmonary embolism, deep vein thrombosis, retinal vein occlusion and retinal vein thrombosis; patients who have experienced venous thromboembolic events within the previous 6 months have not been studied; monitor for symptoms and signs of VTE and pulmonary embolism.

4. Bleeding: including cerebral hemorrhage, hematuria, hemoptysis, lower gastrointestinal bleeding and melena; axitinib has not been studied in patients with untreated brain metastases or evidence of recent active gastrointestinal bleeding and should not be used in these patients.

5. Heart failure: Monitor for signs or symptoms of heart failure throughout the entire course of treatment with axitinib.

6. Gastrointestinal perforation and fistula formation: During treatment with axitinib, regularly monitor for symptoms of gastrointestinal perforation or fistula.

7. Thyroid dysfunction: Monitor thyroid function regularly before starting axitinib treatment and throughout the treatment. Treat hypothyroidism and hyperthyroidism according to standard medical practice to maintain euthyroidism.

8. Impaired wound healing: Patients receiving drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway may experience impaired wound healing. Therefore, axitinib has the potential to adversely affect wound healing. Stop taking this product at least 2 days before elective surgery. Do not give this medication for at least 2 weeks after major surgery and until the wound has completely healed.

9. Reversible posterior leukoencephalopathy syndrome (RPLS): RPLS is a neurological disorder that can present with headaches, seizures, drowsiness, confusion, blindness, and other visual and neurological impairments. Mild to severe hypertension may be present. Magnetic resonance imaging is necessary to confirm the diagnosis of RPLS. Axitinib should be permanently discontinued in patients with RPLS disease.

10. Proteinuria: It is recommended to monitor proteinuria regularly before starting axitinib treatment and throughout the treatment process. In patients who develop moderate to severe proteinuria, this product should be discontinued and the dose should be reduced.

11. Hepatic impairment: When used as a single agent, monitor alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin before starting axitinib and periodically throughout treatment. Systemic exposure to axitinib was higher in subjects with moderate hepatic impairment (Child-Pugh class B) compared with subjects with normal hepatic function. A dose reduction of axitinib is recommended in patients with moderate hepatic impairment (Child-Pugh class B). Axitinib has not been studied in patients with severe hepatic impairment (Child-Pugh class C).

12. Major Adverse Cardiovascular Events (MACE): Consider baseline and periodic assessment of left ventricular ejection fraction. Monitor for signs and symptoms of cardiovascular events. Optimize management of cardiovascular risk factors such as hypertension, diabetes, or dyslipidemia. For grade 3-4 cardiovascular events, permanently discontinue axitinib and avelumab.

13. Embryonic-Fetal toxicity: Based on its mechanism of action and animal study results, axitinib can cause fetal harm when used in pregnant women. There are no human data available to describe drug-related risks. In developmental toxicity studies in mice, axitinib was teratogenic, embryotoxic, and fetotoxic at recommended clinical doses at maternal exposures lower than human exposures.

Inform females of reproductive potential of the potential risk to the fetus and to use effective contraception during treatment with axitinib and for 1 week after the last dose Advise men with female partners of reproductive potential to use an effective method of contraception during treatment and for 1 week after the last dose.

Reference materials:https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=84137882-e000-47da-bd5b-fa76ab3c76f9##