ases of pulmonary embolism were observed in approximately 1.3% of patients with GIST and in approximately 0.8% of patients with MRCC, who received sunitinib in Phase 3 studies (see section 4.4 - Venous thromboembolic events). No treatment-related pulmonary embolism was reported for patients with pNET who received sunitinib in the phase 3 study. Rare cases with fatal outcome have been observed in post-marketing setting (see section 4.8).
Thyroid Dysfunction
Baseline laboratory measurement of thyroid function is recommended in all patients. Patients with pre-existing hypothyroidism or hyperthyroidism should be treated as per standard medical practice prior to the start of sunitinib treatment. During sunitinib treatment, routine monitoring of thyroid function should be performed every 3 months. In addition, patients should be observed closely for signs and symptoms of thyroid dysfunction during treatment, and patients who develop any signs and/or symptoms suggestive of thyroid dysfunction should have laboratory testing of thyroid function performed as clinically indicated. Patients who develop thyroid dysfunction should be treated as per standard medical practice.
Hypothyroidism has been observed to occur early as well as late during treatment with sunitinib.
Hypothyroidism was reported as an adverse event in 7 patients (4%) receiving sunitinib across the two cytokine-refractory MRCC studies; in 61 patients (16%) on sunitinib and three patients (<1%) in the IFN-α arm in the treatment-naïve MRCC study. Additionally, TSH elevations were reported in 4 cytokine-refractory MRCC patients (2%). Overall, 7% of the MRCC population had either clinical or laboratory evidence of treatment-emergent hypothyroidism. Treatment-emergent acquired hypothyroidism was noted in 8 GIST patients (4%) on sunitinib versus 1 (1%) on placebo. In the phase 3 pNET study treatment-related hypothyroidism was reported in 5 patients (6%) receiving sunitinib and in one patient (1%) on placebo.
Rare cases of hyperthyroidism, some followed by hypothyroidism, have been reported in clinical trials and through post-marketing experience.
Pancreatitis
Increases in serum lipase and amylase activities were observed in patients with various solid tumours who received sunitinib. Increases in lipase activities were transient and were generally not accompanied by signs or symptoms of pancreatitis in subjects with various solid tumours. Pancreatitis has been observed uncommonly (<1%) in patients receiving sunitinib for GIST or MRCC.
Cases of serious pancreatic events, some with fatal outcome, have been reported. If symptoms of pancreatitis are present, patients should have sunitinib discontinued and be provided with appropriate supportive care.
No treatment-related pancreatitis was reported in the phase 3 pNET study.
Hepatotoxicity
Hepatotoxicity has been observed in patients treated with sunitinib. Cases of hepatic failure, some with a fatal outcome, were observed in <1% of solid tumor patients treated with sunitinib. Monitor liver function tests (alanine transaminase [ALT], aspartate transaminase [AST], bilirubin levels) before initiation of treatment, during each cycle of treatment, and as clinically indicated. If signs or symptoms of hepatic failure are present, sunitinib should be discontinued and appropriate supportive care should be provided.
Renal function
Cases of renal impairment, renal failure and/or acu |
