Table 7: Grade 3-4 Laboratory Abnormalities in ≥ 3% of Patients in the LENVIMA + Everolimus Arma,b
Laboratory Abnormality LENVIMA 18 mg
+ Everolimus 5 mg
N=62 Everolimus 10 mg

N=50
Grades 3-4
(%) Grades 3-4
(%)
Chemistry
Aspartate aminotransferase (AST) increased 3 0
Alanine aminotransferase (ALT) increased 3 2
Alkaline phosphatase increased 3 0
Hyperkalemia 6 2
Hypokalemia 6 2
Hyponatremia 11 6
Hypocalcemia 6 2
Hypophosphatemia 11 6
Hyperglycemia 3 16
Hypertriglyceridemia 18 18
Elevated cholesterol 11 0
Creatine kinase increased 3 4
Lipase increased 13 12
Hematology
Hemoglobin decreased 8 16
Platelet count decreased 5 0
Lymphocyte count decreased 10 20
a With at least 1 grade increase from baseline
b Subject with at least 1 post baseline laboratory value
6.2 Postmarketing Experience
The following adverse reactions have been identified during post approval use of LENVIMA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Gastrointestinal Disorders: amylase increased, pancreatitis
Hepatobiliary Disorders: cholecystitis
7 DRUG INTERACTIONS
7.1  Effect of Other Drugs on Lenvatinib
No dose adjustment of LENVIMA is recommended when co-administered with CYP3A, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP) inhibitors and CYP3A and P-gp inducers [see CLINICAL PHARMACOLOGY (12.3)].
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
Based on its mechanism of action and data from animal reproduction studies, LENVIMA can cause fetal harm when administered to a pregnant woman [see CLINICAL PHARMACOLOGY (12.1)]. 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 [see DATA]. There are no available human data informing the drug-associated risk. Advise pregnant women of the potential risk to a fetus.
The background risk of major birth defects and miscarriage for the indicated population is unknown; however, the background risk in the U.S. general population of major birth defects is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies.
Data
Animal Data
In an embryofetal development study, daily oral administration of lenvatinib mesylate at doses greater than or equal to 0.3 mg/kg [approximately 0.14 times the recommended human dose based on body surface area (BSA)] to pregnant rats during organogenesis resulted in dose-related decreases in mean fetal body weight, delayed fetal ossificat