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Before using lenvatinib, please carefully read the following precautions and strictly administer the medication under the guidance of a physician to ensure medication safety and effective management of potential risks.
Hypertension is a common adverse reaction in patients receiving lenvatinib treatment, mostly presenting as grade 3 severe hypertension. This adverse reaction usually occurs early in the treatment course; the median time to onset of new-onset hypertension or exacerbation of pre-existing hypertension after medication initiation is 16–26 days.
Blood pressure must be evaluated and controlled prior to the start of lenvatinib treatment. Blood pressure should be monitored 1 week after treatment initiation, once every 2 weeks during the first 2 months of treatment, and at least once a month thereafter. During treatment, pharmacological interventions (i.e., antihypertensive drugs) should be used to control blood pressure based on the patient’s condition. Depending on the severity of hypertension, treatment may be temporarily suspended, and resumption may occur at a reduced dose after blood pressure is controlled, or permanent discontinuation may be required.
Lenvatinib may cause severe, even fatal, cardiac dysfunction. Clinical trials have shown that 3% of patients receiving lenvatinib developed grade 3 or higher cardiac dysfunction (including cardiomyopathy, left or right ventricular dysfunction, congestive heart failure, decreased ventricular contractility, and a >20% reduction in left or right ventricular ejection fraction from baseline).
Patients should be monitored for clinical manifestations of cardiac dysfunction. Based on the severity of cardiac dysfunction, treatment may be temporarily suspended, and resumption may occur at a reduced dose after the patient recovers, or permanent discontinuation may be required.
Arterial thromboembolic events have been reported in patients receiving lenvatinib treatment.
In the event of an arterial thromboembolic event, lenvatinib must be permanently discontinued. The safety of reinitiating lenvatinib after such an event has not been established, and the drug has not been evaluated in patients who experienced an arterial thromboembolic event within the previous 6 months.
Severe hepatic adverse reactions are rarely reported in patients with malignant tumors other than hepatocellular carcinoma who receive lenvatinib treatment, though some cases may be fatal.
Liver function must be tested prior to treatment initiation; liver function should be monitored once every 2 weeks during the first 2 months of treatment, and at least once a month thereafter.
Patients with hepatocellular carcinoma should be closely monitored for signs of liver failure. Depending on the severity of hepatotoxicity, treatment may be temporarily suspended, and resumption may occur at a reduced dose after the patient recovers, or permanent discontinuation may be required.
Proteinuria has been reported in patients receiving lenvatinib treatment.
Proteinuria should be regularly monitored before and during treatment. If urine dipstick testing shows proteinuria ≥2+, a 24-hour urine collection should be performed to measure urinary protein quantification. Based on the severity of proteinuria, treatment may be temporarily suspended, and resumption may occur at a reduced dose after the patient recovers, or permanent discontinuation may be required.
Renal impairment (including severe cases) and renal failure have been reported in patients receiving lenvatinib treatment.
Diarrhea or dehydration/hypovolemia should be managed promptly. Depending on the severity of renal impairment, treatment may be temporarily suspended, and resumption may occur at a reduced dose after the patient recovers, or permanent discontinuation may be required.
Diarrhea is a common adverse reaction in patients receiving lenvatinib treatment and is the leading cause of dose interruption or reduction; in some patients, diarrhea may recur even after dose reduction.
Symptomatic treatment for diarrhea should be administered promptly. Depending on the severity of diarrhea, treatment may be temporarily suspended, and resumption may occur at a reduced dose after the patient recovers, or permanent discontinuation may be required.
Gastrointestinal perforation and fistula formation have been reported in patients receiving lenvatinib or other tyrosine kinase inhibitors.
In the event of gastrointestinal perforation of any severity, or grade 3 or 4 fistula formation, lenvatinib must be permanently discontinued.
QT interval prolongation has been reported in patients receiving lenvatinib treatment.
All patients should undergo regular monitoring of serum electrolyte levels (including potassium, magnesium, and calcium) at baseline and during treatment, with timely correction of electrolyte imbalances.
Electrocardiogram monitoring is required for patients with congenital long QT syndrome, congestive heart failure, bradyarrhythmias, and those taking other drugs known to prolong the QT interval.
If QT interval prolongation occurs, temporary treatment suspension may be necessary, followed by resumption at a reduced dose.
Hypocalcemia has been reported in patients receiving lenvatinib treatment; some patients may require calcium supplementation, along with temporary treatment suspension or dose reduction.
Serum calcium levels should be monitored at least once a month during treatment, with calcium supplementation administered as needed.
In the event of hypocalcemia, the decision to resume treatment at a reduced dose after temporary suspension or to discontinue treatment permanently should be based on the patient’s electrocardiogram changes, as well as the severity and duration of hypocalcemia.
In clinical trials, 3 cases of reversible posterior leukoencephalopathy syndrome were reported in patients receiving lenvatinib treatment; diagnosis of this condition requires confirmation by magnetic resonance imaging (MRI).
If reversible posterior leukoencephalopathy syndrome occurs, treatment must be suspended until the patient’s symptoms resolve completely. After symptom resolution, the decision to resume treatment at a reduced dose or to discontinue permanently should be based on the severity and duration of neurological symptoms.
Hemorrhagic events have been reported in patients receiving lenvatinib treatment, with epistaxis being the most common; some hemorrhagic events may be fatal. Post-marketing surveillance data indicate that patients with anaplastic thyroid carcinoma have a higher incidence of severe and fatal carotid artery hemorrhage compared to patients with other tumor types. The safety and efficacy of lenvatinib in patients with anaplastic thyroid carcinoma have not been established.
During treatment, attention should be paid to the risk of severe, even fatal, hemorrhagic events caused by tumor invasion or infiltration of major blood vessels. Depending on the severity of the hemorrhagic event, treatment may be temporarily suspended, and resumption may occur at a reduced dose after the patient recovers, or permanent discontinuation may be required.
Lenvatinib may inhibit the suppressive effect of exogenous thyroid hormones.
Elevations in thyroid-stimulating hormone levels from baseline normal or low levels have been observed in patients receiving lenvatinib treatment.
Thyroid function should be monitored before treatment initiation and at least once a month during treatment; dosage adjustments or thyroid hormone replacement therapy should be implemented as needed.
Lenvatinib may impair a patient’s wound healing ability.
Patients scheduled for elective surgery should discontinue lenvatinib at least 1 week before the procedure; for major surgeries, lenvatinib should be discontinued for at least 2 weeks, and medication resumption should only occur after complete wound healing.
The safety of reinitiating lenvatinib after resolution of wound healing-related complications has not been established.
Lenvatinib may cause osteonecrosis of the jaw, and the risk is increased in patients exposed to other risk factors (e.g., bisphosphonate or denosumab therapy, oral diseases, invasive dental procedures).
Dental examinations should be performed regularly before and during treatment. During treatment, invasive dental procedures should be avoided if possible, especially in patients at high risk of osteonecrosis of the jaw. If a patient plans to undergo dental surgery or invasive dental procedures, lenvatinib should be discontinued at least 1 week in advance if feasible; for patients concurrently receiving bisphosphonate therapy, bisphosphonates should be discontinued. If osteonecrosis of the jaw occurs, treatment should be suspended, and the decision to resume medication should be made only after clinical evaluation confirms adequate resolution of the condition.
Lenvatinib may cause fetal harm; animal studies have confirmed the teratogenic, embryotoxic, and fetotoxic effects of this drug.
Pregnancy should be avoided during treatment. The pregnancy status of females of reproductive potential must be verified before initiating lenvatinib treatment. Females of reproductive potential should use effective contraceptive measures during lenvatinib treatment and for 30 days after discontinuing the drug. If a patient becomes pregnant during treatment or accidentally becomes pregnant while taking the drug, the patient should be informed of the potential risks of the drug to the fetus.
from FDA，2024.06
