GI perforation: GI perforation has been reported (rare); monitor
patients for signs/symptoms (abdominal pain, constipation, or vomiting);
discontinue treatment if gastrointestinal perforation occurs
• Bleeding: Increased risk of bleeding may occur; consider permanently
discontinuing with serious bleeding events (eg, requires medical
intervention). Fatal bleeding events have been reported. Thyroid cancer
patients with tracheal, bronchial, and esophageal infiltration should be
treated with local therapy prior to administering sorafenib due to the
potential bleeding risk.
- Cardiovascular events: May cause cardiac ischemia or infarction;
consider discontinuation (temporary or permanent) in patients who
develop these conditions. Use in patients with unstable coronary artery
disease or recent myocardial infarction has not been studied. Heart
failure has been reported in multiple clinical studies. In a scientific
statement from the American Heart Association, sorafenib has been
determined to be an agent that may exacerbate underlying myocardial
dysfunction (magnitude: minor)
- Dermatologic toxicity: Hand-foot skin reaction and rash (generally
grades 1 or 2) are the most common drug-related adverse events, and
typically appear within the first 6 weeks of treatment; usually managed
with topical treatment, treatment delays, and/or dose reductions.
Consider permanently discontinuing with severe or persistent
- Hepatotoxicity: Sorafenib-induced hepatitis (characterized by a
hepatocellular pattern of liver damage with significant increases of
transaminases) which may result in hepatic failure and death has been
observed. Bilirubin elevations and INR increases may also occur. Severe
drug-induced liver injury (transaminase elevations >20 times ULN or
with significant clinical sequelae [eg, elevated INR, ascites,
transplantation or fatality]) occurred rarely. Monitor liver function
tests regularly. Discontinue sorafenib if significantly increased
transaminases occur without alternative explanation (eg, viral hepatitis
or progressing underlying malignancy).
- Hypertension: May cause hypertension (generally mild-to-moderate),
especially in the first 6 weeks of treatment; monitor. Use caution in
patients with underlying or poorly-controlled hypertension. Consider
discontinuing (temporary or permanent) in patients who develop severe or
persistent hypertension while on appropriate antihypertensive therapy.
- QT prolongation: QT prolongation has been observed; may increase the
risk for ventricular arrhythmia. Avoid use in patients with congenital
long QT syndrome. Monitor electrolytes and ECG in patients with heart
failure, bradyarrhythmias, and concurrent medications know to prolong
the QT interval. Correct electrolyte (calcium, magnesium, potassium)
imbalances. Interrupt treatment for QTc interval >500 msec or for ≥60
msec increase from baseline.
- Thyroid impairment: Sorafenib impairs exogenous thyroid suppression. TSH
level elevations were commonly observed in the thyroid cancer study;
monitor TSH levels monthly and as clinically necessary, and adjust
thyroid replacement as needed.
- Wound healing complications: May complicate wound healing; temporarily
withhold treatment for patients undergoing major surgical procedures.
The appropriate timing to resume sorafenib after major surgery has not