Inlyta Special Precautions

Specific safety events should be monitored before initiation of, and periodically throughout, treatment with axitinib as described as follows.
Cardiac failure events: In clinical studies with axitinib for the treatment of patients with RCC, cardiac failure events (including cardiac failure, cardiac failure congestive, cardiopulmonary failure, left ventricular dysfunction, ejection fraction decreased, and right ventricular failure) were reported (see Adverse Reactions).
Signs or symptoms of cardiac failure should periodically be monitored throughout treatment with axitinib. Management of cardiac failure events may require temporary interruption or permanent discontinuation and/or dose reduction of axitinib therapy.
Hypertension: In a clinical studies with axitinib for the treatment of patients with RCC, hypertension was very commonly reported (see Adverse Reactions).
In a controlled clinical study, the median onset time for hypertension (systolic blood pressure >150 mmHg or diastolic blood pressure >100 mmHg) was within the first month of the start of axitinib treatment and blood pressure increases have been observed as early as 4 days after starting axitinib.
Blood pressure should be well-controlled prior to initiating axitinib. Patients should be monitored for hypertension and treated as needed with standard antihypertensive therapy. In the case of persistent hypertension, despite use of antihypertensive medicinal products, the axitinib dose should be reduced. For patients who develop severe hypertension, temporarily interrupt axitinib and restart at a lower dose once the patient is normotensive. If axitinib is interrupted, patients receiving antihypertensive medicinal products should be monitored for hypotension (see Dosage & Administration).
In case of severe or persistent arterial hypertension and symptoms suggestive of posterior reversible encephalopathy syndrome (PRES) (see as follows), a diagnostic brain magnetic resonance image (MRI) should be considered.
Thyroid dysfunction: In clinical studies with axitinib for the treatment of patients with RCC, events of hypothyroidism and, to a lesser extent, hyperthyroidism, were reported (see Adverse Reactions).
Thyroid function should be monitored before initiation of, and periodically throughout, treatment with axitinib. Hypothyroidism or hyperthyroidism should be treated according to standard medical practice to maintain euthyroid state.
Arterial embolic and thrombotic events: In clinical studies with axitinib, arterial embolic and thrombotic events (including transient ischemic attack, myocardial infarction, cerebrovascular accident and retinal artery occlusion) were reported (see Adverse Reactions).
Axitinib should be used with caution in patients who are at risk for, or who have a history of, these events. Axitinib has not been studied in patients who had an arterial embolic or thrombotic event within the previous 12 months.
Venous embolic and thrombotic events: In clinical studies with axitinib, venous embolic and thrombotic events (including pulmonary embolism, deep vein thrombosis, and retinal vein occlusion/thrombosis) were reported (see Adverse Reactions).
Axitinib should be used with caution in patients who are at risk for, or who have a history of, these events. Axitinib has not been studied in patients who had a venous embolic or thrombotic event within the previous 6 months.
Elevation of haemoglobin or haematocrit: Increases in haemoglobin or haematocrit, reflective of increases in red blood cell mass, may occur during treatment with axitinib (see Adverse Reactions, polycythaemia). An increase in red blood cell mass may increase the risk of embolic and thrombotic events.
Haemoglobin or haematocrit should be monitored before initiation of, and periodically throughout, treatment with axitinib. If haemoglobin or haematocrit becomes elevated above the normal level, patients should be treated according to standard medical practice to decrease haemoglobin or haematocrit to an acceptable level.
Haemorrhage: In clinical studies with axitinib, haemorrhagic events were reported (see Adverse Reactions).
Axitinib has not been studied in patients who have evidence of untreated brain metastasis or recent active gastrointestinal bleeding, and should not be used in those patients. If any bleeding requires medical intervention, temporarily interrupt the axitinib dose.
Aneurysms and artery dissections: The use of VEGF pathway inhibitors in patients with or without hypertension may promote the formation of aneurysms and/or artery dissections. Before initiating Inlyta, this risk should be carefully considered in patients with risk factors such as hypertension or history of aneurysm.
Gastrointestinal perforation and fistula formation: In clinical studies with axitinib, events of gastrointestinal perforation and fistulas were reported (see Adverse Reactions).
Symptoms of gastrointestinal perforation or fistula should be periodically monitored for throughout treatment with axitinib.
Wound healing complications: No formal studies of the effect of axitinib on wound healing have been conducted.
Treatment with axitinib should be stopped at least 24 hours prior to scheduled surgery. The decision to resume axitinib therapy after surgery should be based on clinical judgment of adequate wound healing.
Posterior reversible encephalopathy syndrome (PRES): In clinical studies with axitinib, events of PRES were reported (see Adverse Reactions).
PRES is a neurological disorder which 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 the diagnosis of PRES. In patients with signs or symptoms of PRES, temporarily interrupt or permanently discontinue axitinib treatment. The safety of reinitiating axitinib therapy in patients previously experiencing PRES is not known.
Proteinuria: In clinical studies with axitinib, proteinuria, including that of Grade 3 and 4severity, was reported (see Adverse Reactions).
Monitoring for proteinuria before initiation of, and periodically throughout, treatment with axitinib is recommended. For patients who develop moderate to severe proteinuria, reduce the dose or temporarily interrupt axitinib treatment (see Dosage & Administration). Axitinib should be discontinued if the patient develops nephrotic syndrome.
Liver-related adverse reactions: In a controlled clinical study with axitinib for the treatment of patients with RCC, liver-related adverse reactions were reported. The most commonly reported liver-related adverse reactions included increases in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and blood bilirubin (see Adverse Reactions). No concurrent elevations of ALT (>3 times the upper limit of normal [ULN]) and bilirubin (>2 times the ULN) were observed.
In a clinical dose-finding study, concurrent elevations of ALT (12 times the ULN) and bilirubin (2.3 times the ULN), considered to be drug-related hepatotoxicity, were observed in 1 patient who received axitinib at a starting dose of 20 mg twice daily (4 times the recommended starting dose).
Liver function tests should be monitored before initiation of, and periodically throughout, treatment with axitinib.
Hepatic impairment: In clinical studies with axitinib, the systemic exposure to axitinib was approximately two-fold higher in subjects with moderate hepatic impairment (Child-Pugh class B) compared to subjects with normal hepatic function. A dose decrease is recommended when administering axitinib to patients with moderate hepatic impairment (Child-Pugh class B) (see Dosage & Administration).
Axitinib has not been studied in patients with severe hepatic impairment (Child-Pugh class C) and should not be used in this population.
Elderly (≥65 years) and race: In a controlled clinical study with axitinib for the treatment of patients with RCC, 34% of patients treated with axitinib were ≥65 years of age. The majority of patients were White (77%) or Asian (21%). Although greater sensitivity to develop adverse reactions in some older patients and Asian patients cannot be ruled out, overall, no major differences were observed in the safety and effectiveness of axitinib between patients who were ≥65 years of age and non-elderly, and between White patients and patients of other races.
No dosage adjustment is required on the basis of patient age or race (see Dosage & Administration and Pharmacology: Pharmacokinetics under Actions).
Lactose: This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Effects on ability to drive and use machines: Axitinib has minor influence on the ability to drive and use machines. Patients should be advised that they may experience events such as dizziness and/or fatigue during treatment with axitinib.