, haemorrhagic events were reported (see section 4.8).
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.
Gastrointestinal perforation and fistula formation
In clinical studies with axitinib, events of gastrointestinal perforation and fistulas were reported (see section 4.8).
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
In clinical studies with axitinib, events of posterior reversible encephalopathy syndrome (PRES) were reported (see section 4.8).
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 severity, was reported (see section 4.8).
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 section 4.2).
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 section 4.8). 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 section 4.2).
Axitinib has not been studied in patients with severe hepatic impairment (Child-Pugh class C) and should not be used in this population.
Older people (≥ 65 years) and rac |
