What are the precautions for taking Lenvatinib?

In clinical studies of lenvatinib , hypertension, cardiac dysfunction, arterial thromboembolic events, hepatotoxicity, renal failure and damage, proteinuria, diarrhea, fistula formation, and gastrointestinal perforation have occurred,Warnings and precautions such as QT prolongation, hypocalcemia, reversible posterior leukoencephalopathy syndrome, bleeding events, impaired thyroid-stimulating hormone suppression/thyroid dysfunction, impaired wound healing, osteonecrosis of the jaw, embryo-fetal toxicity. Discontinue and resume at a reduced dose upon recovery, or permanently discontinue lenvatinib based on severity.

1. Hypertension: This is the most reported side effect of lenvatinib. It is recommended to conduct routine blood pressure checks. Monitor blood pressure after 1 week, then every 2 weeks in the first 2 months, and then at least once a month during treatment. Early detection may be possible through 24-hour blood pressure monitoring while taking lenvatinib. Before initiating treatment, patients with underlying hypertension should have their blood pressure controlled and maintained within a stable range. When hypertension is controlled, the medication is discontinued and continued at a reduced dose.

2. Cardiac dysfunction: Including cardiomyopathy, left ventricular or right ventricular dysfunction, congestive heart failure, heart failure, ventricular hypokinesis, or a decrease in left ventricular or left ventricular ejection fraction by more than 20% compared to baseline. Monitor patients for clinical signs or symptoms of cardiac dysfunction.

3. Arterial thromboembolic events: Arterial thromboembolic events of any severity, including myocardial infarction and cerebrovascular accidents, have occurred in patients receiving lenvatinib in combination with other drugs. Permanently discontinue lenvatinib after an arterial thrombotic event. The safety of resuming lenvatinib after an arterial thrombotic event has not been established.

4. Hepatotoxicity: including hepatic encephalopathy, encephalopathy, metabolic encephalopathy and hepatic coma. Fatal liver poisoning events include liver failure, acute hepatitis, and hepatorenal syndrome. Monitor liver function before initiating lenvatinib treatment, then every two weeks for the first two months, and at least monthly thereafter during treatment. Monitor patients with hepatocellular carcinoma (HCC) closely for signs of liver failure, including hepatic encephalopathy.

5. Renal failure and damage: Lenvatinib can cause severe renal failure or damage, including fatal renal failure. Treat diarrhea or dehydration/hypovolemia promptly. Depending on severity, discontinue lenvatinib due to renal failure or injury and continue at a reduced dose or permanently discontinue after recovery.

6. Proteinuria: Monitor proteinuria before and regularly during lenvatinib treatment. If urine dipstick proteinuria was detected to be greater than or equal to 2+, 24-hour urine protein was obtained.

7. Diarrhea: Diarrhea is the most common reason for dose interruption/reduction, and diarrhea recurs despite dose reduction. Patients should promptly initiate treatment for diarrhea.

8. Fistula formation and gastrointestinal perforation: Permanently discontinue lenvatinib in patients who develop gastrointestinal perforation of any severity orGrade 3 or 4 fistulas.

9. QT interval prolongation: Monitor and correct electrolyte abnormalities regularly at baseline and during treatment. Monitor ECGs in patients with congenital long QT syndrome, congestive heart failure, bradyarrhythmias, or patients taking drugs known to prolong the QT interval, including Class Ia and III antiarrhythmic drugs.

10. Hypocalcemia: In clinical studies, patients will develop hypocalcemia. After calcium supplementation, the hypocalcemia is improved or alleviated regardless of whether the dose is interrupted or reduced. Patients should monitor blood calcium levels at least monthly and replace calcium as needed during treatment.

11. Reversible posterior leukoencephalopathy syndrome (RPLS): Use magnetic resonance imaging to confirm the diagnosis of RPLS. Depending on the severity and persistence of neurological symptoms, discontinue and continue lenvatinib at a reduced dose after recovery, or permanently discontinue lenvatinib.

12. Bleeding Events: Serious tumor-related bleeding has occurred in patients treated with lenvatinib in clinical trials and in the postmarketing setting. The most commonly reported bleeding events were epistaxis and hematuria, including fatal bleeding events. During postmarketing surveillance, severe and fatal carotid bleeding was more common in patients with anaplastic thyroid cancer (ATC) than other tumor types. Consider the risk of severe or fatal bleeding associated with tumor invasion or infiltration of major vessels (such as the carotid artery).

13. Impaired suppression of thyroid-stimulating hormone/Thyroid dysfunction: Lenvatinib impairs exogenous thyroid suppression, and the thyroid-stimulating hormone (TSH) level is ≤0.5mU/L. Among patients with normal TSH at baseline, 57% of lenvatinib-treated patients had an increase in TSH levels >0.5 mU/L after baseline. Monitor thyroid function before initiating lenvatinib therapy and at least monthly during treatment. Treat hypothyroidism according to standard medical practice.

14. Impaired wound healing: Discontinue lenvatinib at least1 week before elective surgery. Do not give this medication for at least 2 weeks after major surgery and until the wound has completely healed. The safety of resuming lenvatinib after resolution of wound healing complications has not been established.

15. Osteonecrosis of the jaw (ONJ): Simultaneous exposure to other risk factors, such as bisphosphonates, denosumab, dental disease, or invasive dental surgery, may increase the risk of ONJ. Have an oral examination before treatment with lenvatinib and periodically during treatment. Advise patients on good oral hygiene practices. If possible, avoid invasive dental procedures, especially in higher-risk patients. Discontinue lenvatinib for at least 1 week before scheduled dental surgery or invasive dental procedures. For patients who require invasive dental procedures, stopping bisphosphonate treatment can reduce the risk of ONJ.

16. Embryo-Fetotoxicity: According to the mechanism of action of lenvatinib and data from animal reproduction studies, administration to pregnant women can cause harm to the fetus. In animal reproduction studies, oral administration of lenvatinib during organogenesis resulted in embryotoxicity, fetotoxicity, and teratogenicity in rats and rabbits at doses lower than the recommended clinical dose. Inform pregnant women of potential risks to the fetus. Advise females of childbearing potential to use effective contraception during treatment with lenvatinib and for 30 days after the last dose.