n its mechanism of action and data from animal reproduction studies, LENVIMA can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, oral administration of lenvatinib during organogenesis at doses below the recommended human dose resulted in embryotoxicity, fetotoxicity, and teratogenicity in rats and rabbits. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with LENVIMA and for at least 2 weeks following completion of therapy [see Use in Specific Populations (8.1, 8.3)].
6 ADVERSE REACTIONS
The following adverse reactions are discussed elsewhere in the label:
Hypertension [see WARNINGS AND PRECAUTIONS (5.1)]
Cardiac Dysfunction [see WARNINGS AND PRECAUTIONS (5.2)]
Arterial Thromboembolic Events [see WARNINGS AND PRECAUTIONS (5.3)]
Hepatotoxicity [see WARNINGS AND PRECAUTIONS (5.4)]
Proteinuria [see WARNINGS AND PRECAUTIONS (5.5)]
Diarrhea [see WARNINGS AND PRECAUTIONS (5.6)]
Renal Failure and Impairment [see WARNINGS AND PRECAUTIONS (5.7)]
Gastrointestinal Perforation and Fistula Formation [see WARNINGS AND PRECAUTIONS (5.8)]
QT Interval Prolongation [see WARNINGS AND PRECAUTIONS (5.9)]
Hypocalcemia [see WARNINGS AND PRECAUTIONS (5.10)]
Reversible Posterior Leukoencephalopathy Syndrome [see WARNINGS AND PRECAUTIONS (5.11)]
Hemorrhagic Events [see WARNINGS AND PRECAUTIONS (5.12)]
Impairment of Thyroid Stimulating Hormone Suppression/Thyroid Dysfunction [see WARNINGS AND PRECAUTIONS (5.13)]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data in the Warnings and Precautions section reflect exposure to LENVIMA as a single agent in 261 DTC patients (Study 1) and LENVIMA + everolimus in 62 RCC patients (Study 2). Safety data obtained in 1160 patients with advanced solid tumors who received LENVIMA as a single agent across multiple clinical studies was used to further characterize the risks of serious adverse reactions [see Warnings and Precautions (5.4, 5.10, 5.11)]. In the entire single agent population, the median age was 60 years (range 21-89 years), the dose range was 0.2 mg to 32 mg, and the median duration of exposure was 5.5 months.
Differentiated Thyroid Cancer
The safety data described below are derived from Study 1 which randomized (2:1) patients with radioactive iodine-refractory differentiated thyroid cancer (RAI-refractory DTC) to LENVIMA (n=261) or placebo (n=131) [see CLINICAL STUDIES (14.1)]. The median treatment duration was 16.1 months for LENVIMA and 3.9 months for placebo. Among 261 patients who received LENVIMA in Study 1, median age was 64 years, 52% were women, 80% were White, 18% were Asian, and 2% were Black; 4% identified themselves as having Hispanic or Latino ethnicity.
In Study 1, the most common adverse reactions observed in LENVIMA-treated patients (greater than or equal to 30%) were, in order of decreasing frequency, hypertension, fatigue, diarrhea, arthralgia/myalgia, decreased appetite, weight decreased, nausea, stomatitis, headache, vomiting, proteinuria, palmar-plantar erythrodysesthesia (PPE) syndrome, abdominal pain |
