Axitinib

Cardiac failure, including fatal events, has been observed rarely. Monitor for signs/symptoms of cardiac failure throughout therapy; management may require permanent therapy discontinuation.

Gastrointestinal perforation and fistulas (including a fatality) have been reported. Monitor for signs/symptoms throughout treatment.

Hemorrhagic events (cerebral hemorrhage, gastrointestinal hemorrhage, hematuria, hemoptysis, and melena) have been reported (with some fatalities). Temporarily interrupt treatment with any hemorrhage requiring medical intervention.

May cause hypertension; the median onset is within the first month, and has been observed as early as 4 days after treatment initiation. Hypertensive crisis has been reported. Blood pressure should be well-controlled prior to treatment initiation. Monitor blood pressure and treat with standard antihypertensive therapy. Persistent hypertension (despite antihypertensive therapy) may require dose reduction; discontinue if severe and persistent despite concomitant antihypertensives (or dose reduction), or with evidence of hypertensive crisis. Monitor for hypotension if on antihypertensive therapy and axitinib is withheld or discontinued.

Proteinuria is associated with use. Monitor for proteinuria at baseline and periodically throughout therapy. If moderate or severe proteinuria occurs, reduce dose or temporarily withhold treatment.

Cases of RPLS have been reported. Symptoms of RPLS include confusion, headache, hypertension (mild-to-severe), lethargy, seizure, blindness and/or other vision or neurologic disturbances; interrupt treatment and manage hypertension. MRI is recommended to confirm RPLS diagnosis. Discontinue axitinib if RPLS is confirmed. The safety of reinitiating axitinib in patients previously experiencing RPLS is unknown.

Arterial thrombotic events (cerebrovascular accident, MI, retinal artery occlusion, and transient ischemic attack), with fatalities, have been reported. Venous thrombotic events, including pulmonary embolism, deep vein thrombosis, retinal vein occlusion and retinal vein thrombosis, have been observed (with some fatalities). Use with caution in patients with a history of or risks for arterial or venous thrombotic events; has not been studied in patients within 12 months of an arterial thrombotic event or within 6 months of a venous thrombotic event.

Hypothyroidism occurs commonly with tyrosine kinase inhibitors, including axitinib. Hyperthyroidism has also been reported. Monitor thyroid function at baseline and periodically throughout therapy. Thyroid disorders should be treated according to standard practice to achieve/maintain euthyroid state.

Although the effect on wound healing has not been studied with axitinib, vascular endothelial growth factor (VEGF) receptor inhibitors are associated with impaired wound healing. Discontinue treatment at least 24 hours prior to scheduled surgery; treatment reinitiation should be guided by clinical judgment and wound assessment. Disease-related concerns:

Has not been studied in patients with evidence of untreated brain metastases; use is not recommended.

Has not been studied in patients with recent active gastrointestinal bleeding; use is not recommended.

Systemic exposure to axitinib is increased in patients with moderate impairment (Child-Pugh class B); dose reductions are recommended. Has not been studied in patients with severe impairment (Child-Pugh class C). Increases in ALT have been observed; monitor liver function tests prior to therapy initiation and periodically throughout treatment. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.