Axitinib

DAE Class; Rx

Common Brand Names; Inlyta

• Antineoplastics, Tyrosine Kinase Inhibitors; 
• Antineoplastics, VEGF Inhibitor

Oral tyrosine kinase inhibitor
Used for renal cell cancer, as monotherapy or in combination with avelumab or pembrolizumab
Do not give axitinib for at least 2 days before elective surgery, and for at least 2 weeks after major surgery and until adequate wound healing

Indicated for advanced renal cell carcinoma (RCC) in patients who failed 1 prior systemic therapy

Combination therapy with avelumab

• Indicated in combination with avelumab for first-line treatment of advanced RCC

Combination therapy with pembrolizumab

• Indicated in combination with pembrolizumab for first-line treatment of advanced RCC

None

Diarrhea (55%)

Hypertension (40%)

Fatigue (39%)

Decreased appetite (34%)

Nausea (32%)

Dysphonia (31%)

Palmar-plantar erythrodysesthesia syndrome (27%)

Weight decreased (25%)

Vomiting (24%)

Asthenia (21%)

Constipation (20%)

Hypothyroidism (19%)

Cough (15%)

Mucosal inflammation (15%)

Arthralgia (15%)

Stomatitis (15%)

Dyspnea (15%)

Abdominal pain (14%)

Headache (14%)

Extremity pain (13%)

Rash (13%)

Proteinuria (11%)

Dysgeusia (11%)

Hypertension and hypertensive crisis reported in clinical trials, typically within the first month of treatment; blood pressure increases may appear as early as 4 days after initiating; blood pressure should be well controlled before starting therapy; dosage modification or discontinuation of treatment may be required; monitor patients for hypertension and treat as needed with standard anti-hypertensive therapy; withhold and then dose reduce or permanently discontinue based on severity of hypertension (see Dosage Modification)

Although rare, arterial thromboembolic events (including deaths) reported during clinical trials; permanently discontinue if an arterial thromboembolic event occurs during treatment

Venous thromboembolic events (eg, DVT, PE, retinal vein occlusion, retinal vein thrombosis) reported, including deaths; monitor for signs and symptoms of VTE and PE; withhold therapy and then resume at same dose or permanently discontinue based on severity of VTE

Hemorrhagic events (eg, cerebral hemorrhage, hematuria, hemoptysis, GI bleeding, melena) may occur; not studied in patients who have evidence of untreated brain metastasis or recent active gastrointestinal bleeding; should not be used in those patients; withhold and then dose reduce or discontinue based on severity and persistence of hemorrhage

Rare occurrences of GI perforation and fistula formation reported

May cause thyroid dysfunction; monitor thyroid function before initiating and periodically throughout therapy; treat hypothyroidism and hyperthyroidism according to standard medical practice to maintain euthyroid state

Stop treatment 24 hr before scheduled surgery

May cause proteinuria; monitor proteinuria before initiating and periodically throughout therapy; for patients who develop moderate to severe proteinuria, withhold and then dose reduce therapy

Elevated liver enzymes reported; monitor ALT, AST, and bilirubin; when used as single agent, monitor ALT, aspartate aminotransferase (AST), and bilirubin before initiation of and periodically throughout treatment

Moderate hepatic impairment requires dose reduction (see Dosage modification)

Coadministration with strong CYP3A4/5 inhibitors or inducers should be avoided if possible (see Dosage modifications)

Reversible posterior leukoencephalopathy syndrome (RPLS) reported; RPLS is a neurological disorder that can present with headache, seizure, lethargy, confusion, blindness and other visual and neurologic disturbances; mild to severe hypertension may be present; magnetic resonance imaging is necessary to confirm diagnosis of RPLS; permanently discontinue therapy in patients developing RPLS; safety of reinitiating therapy in patients previously experiencing RPLS not known

Cardiac failure reported with axitinib use; monitor for signs or symptoms of cardiac failure throughout treatment; may require permanent discontinuation of axitinib; may require dose reduction, dose interruption or permanent discontinuation of therapy

Pregnancy

Based on mechanism of action and findings from animal studies, drug can cause fetal harm when administered to a pregnant woman; there are no available human data to inform drug-associated risk; in developmental toxicity studies in mice, axitinib was teratogenic, embryotoxic and fetotoxic at maternal exposures that were lower than human exposures at recommended clinical dose

When used in combination with avelumab or pembrolizumab, refer to full prescribing information of avelumab or pembrolizumab for pregnancy information

Lactation

There are no data on presence of drug in human milk, or effects on breastfed child or on milk production; because of potential for serious adverse reactions in a breastfed child, advise lactating women not to breastfeed during treatment and for 2 weeks after final dose

When used in combination with avelumab or pembrolizumab, refer to full prescribing information of avelumab or pembrolizumab for lactation information

Adults

20 mg/day PO.

Geriatric

20 mg/day PO.

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

Axitinib