<p><strong>Hypertension</strong>: Control blood pressure prior to initiating Lenvatinib. Monitor blood pressure after 1 week, then every 2 weeks for the first 2 months, and then at least monthly thereafter during treatment. Withhold and resume at a reduced dose when hypertension is controlled or permanently discontinue Lenvatinib is based on severity.<br />
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<strong>Cardiac Dysfunction</strong>: Serious and fatal cardiac dysfunction can occur with Lenvatinib. Monitor patients for clinical symptoms or signs of cardiac dysfunction. Withhold and resume at a reduced dose upon recovery or permanently discontinue Lenvatinib based on severity.<br />
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<strong>Arterial Thromboembolic Events</strong>: Permanently discontinue Lenvatinib following an arterial thrombotic event. The safety of resuming Lenvatinib after an arterial thromboembolic event has not been established and Lenvatinib has not been studied in patients who have had an arterial thromboembolic event within the previous 6 months.<br />
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<strong>Hepatotoxicity</strong>: Monitor liver function prior to initiating Lenvatinib, then every 2 weeks for the first 2 months, and at least monthly thereafter during treatment. Monitor patients with HCC closely for signs of hepatic failure, including hepatic encephalopathy. Withhold and resume at a reduced dose upon recovery or permanently discontinue Lenvatinib based on severity.<br />
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<strong>Renal Failure or Impairment</strong>: Withhold and resume at a reduced dose upon recovery or permanently discontinue Lenvatinib for renal failure or impairment based on severity.<br />
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<strong>Proteinuria</strong>: Monitor for proteinuria prior to initiating Lenvatinib and periodically during treatment. If urine dipstick proteinuria greater than or equal to 2+ is detected, obtain a 24-hour urine protein. Withhold and resume at a reduced dose upon recovery or permanently discontinue Lenvatinib based on severity.<br />
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<strong>Diarrhea</strong>: Diarrhea was the most frequent cause of dose interruption/reduction and diarrhea recurred despite dose reduction. Promptly initiate management of diarrhea. Withhold and resume at a reduced dose upon recovery or permanently discontinue Lenvatinib based on severity.<br />
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<strong>Fistula Formation and Gastrointestinal Perforation</strong>: Permanently discontinue Lenvatinib in patients who develop gastrointestinal perforation of any severity or Grade 3 or 4 fistula.<br />
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<strong>QT Interval Prolongation</strong>: Monitor and correct electrolyte abnormalities at baseline and periodically during treatment. Monitor electrocardiograms in patients with congenital long QT syndrome, congestive heart failure, bradyarrhythmias, or those who are taking drugs known to prolong the QT interval, including Class Ia and III antiarrhythmics. Withhold and resume at a reduced dose of Lenvatinib upon recovery based on severity.<br />
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<strong>Hypocalcemia</strong>: Hypocalcemia improved or resolved following calcium supplementation, with or without dose interruption or dose reduction.<br />
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<strong>Reversible Posterior Leukoencephalopathy Syndrome</strong>: Withhold and resume at a reduced dose upon recovery or permanently discontinue Lenvatinib depending on severity and persistence of neurologic symptoms.<br />
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<strong>Hemorrhagic Events</strong>: Consider the risk of severe or fatal hemorrhage associated with tumor invasion or infiltration of major blood vessels (e.g. carotid artery). Withhold and resume at reduced dose upon recovery or permanently discontinue Lenvatinib based on the severity.<br />
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<strong>Impairment of Thyroid Stimulating Hormone Suppression/Thyroid Dysfunction</strong>: Monitor thyroid function prior to initiating Lenvatinib and at least monthly during treatment. Treat hypothyroidism according to standard medical practice.<br />
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<strong>Wound Healing Complications</strong>: Wound healing complications, including fistula formation and wound dehiscence, can occur with Lenvatinib. Withhold Lenvatinib for at least 6 days prior to scheduled surgery. Resume Lenvatinib after surgery based on clinical judgment of adequate wound healing. Permanently discontinue Lenvatinib in patients with wound healing complications.</p>