Description

Lenvatinib is a kinase inhibitor that is indicated: Differentiated Thyroid Cancer: Lenvatinib is indicated for the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (DTC). Renal Cell Carcinoma: Lenvatinib is indicated in combination with Everolimus for the treatment of patients with advanced renal cell carcinoma (RCC) following one prior anti-angiogenic therapy. Hepatocellular Carcinoma: Lenvatinib is indicated for the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC). Endometrial Carcinoma: Lenvatinib, in combination with Pembrolizumab, is indicated for the treatment of patients with advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), who have disease progression following prior systemic therapy and are not candidates for curative surgery or radiation.

Lenvatinib capsules can be swallowed whole or dissolved in a small glass of liquid. To dissolve in liquid, put capsules into 1 tablespoon of water or apple juice without breaking or crushing the capsules. Leave the capsules in the water or apple juice for at least 10 minutes. Stir for at least 3 minutes. After drinking the mixture, add 1 tablespoon of water or apple juice to the glass, swirl the contents a few times and swallow the water or apple juice.

Drugs That Prolong the QT Interval: Lenvatinib has been reported to prolong the QT/QTc interval. Avoid coadministration of Lenvatinib with medicinal products with a known potential to prolong the QT/QTc interval.

It is contraindicated in patients with known hypersensitivity to Lenvatinib or to any component of the formulation.

Hypertension, cardiac dysfunction, arterial thromboembolic events, hepatotoxicity, renal failure and impairment, proteinuria, diarrhea, fistula formation and gastrointestinal perforation, QT Interval Prolongation, hypocalcemia, reversible posterior leukoencephalopathy syndrome, hemorrhagic events, impairment of thyroid stimulating hormone suppression/thyroid dysfunction, wound healing complications.

Use in Pregnancy: Based on the mechanism of action, Lenvatinib can cause embryo-fetal harm when administered to a pregnant female. Pregnant women should be advised of the potential risk to a fetus. Females of reproductive potential should be advised to use effective contraception during treatment with Lenvatinib and for at least 30 days after the last dose. Use in Lactation: It is not known whether Lenvatinib is present in human milk. Because of the potential for serious adverse reactions in breastfed infants, women should be advised to discontinue breastfeeding during treatment with Lenvatinib and for at least 1 week after the last dose.

Hypertension: 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. Cardiac Dysfunction: 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. Arterial Thromboembolic Events: 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. Hepatotoxicity: 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. Renal Failure or Impairment: Withhold and resume at a reduced dose upon recovery or permanently discontinue Lenvatinib for renal failure or impairment based on severity. Proteinuria: 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. Diarrhea: 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. Fistula Formation and Gastrointestinal Perforation: Permanently discontinue Lenvatinib in patients who develop gastrointestinal perforation of any severity or Grade 3 or 4 fistula. QT Interval Prolongation: 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. Hypocalcemia: Hypocalcemia improved or resolved following calcium supplementation, with or without dose interruption or dose reduction. Reversible Posterior Leukoencephalopathy Syndrome: Withhold and resume at a reduced dose upon recovery or permanently discontinue Lenvatinib depending on severity and persistence of neurologic symptoms. Hemorrhagic Events: 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. Impairment of Thyroid Stimulating Hormone Suppression/Thyroid Dysfunction: Monitor thyroid function prior to initiating Lenvatinib and at least monthly during treatment. Treat hypothyroidism according to standard medical practice. Wound Healing Complications: 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.

Dosage Modifications for Severe Renal Impairment: The recommended dosage of Lenvatinib for patients with DTC, RCC, or endometrial carcinoma and severe renal impairment (creatinine clearance less than 30 mL/min calculated by Cockcroft-Gault equation using actual body weight) is: Differentiated thyroid cancer: 14 mg orally once daily Renal cell carcinoma: 10 mg orally once daily Endometrial carcinoma: 10 mg orally once daily Dosage Modifications for Severe Hepatic Impairment: The recommended dosage of Lenvatinib for patients with DTC, RCC, or endometrial carcinoma and severe hepatic impairment (Child-Pugh C) is: Differentiated thyroid cancer: 14 mg taken orally once daily Renal cell carcinoma: 10 mg taken orally once daily Endometrial carcinoma: 10 mg orally once daily Or as directed by the registered physician. Pediatric Use: The safety and effectiveness in pediatric patients have not been established.