Dosing & Uses
Dosage Forms & Strengths
capsule
- 4mg
- 10mg
Differentiated Thyroid Cancer
Indicated for patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (DTC)
24 mg (two 10 mg capsules and one 4 mg capsule) PO qDay
Advanced Renal Cell Carcinoma
Indicated in combination with everolimus for the treatment of patients with advanced renal cell carcinoma (RCC) following one prior anti-angiogenic therapy
Lenvatinib 18 mg (one 10 mg capsule and two 4 mg capsules) PO qDay PLUS
Everolimus 5 mg PO qDay
Continue until disease progression or until unacceptable toxicity
Hepatocellular Carcinoma
Indicated for first-line treatment of patients with unresectable hepatocellular carcinoma (HCC)
Dose based on actual body weight
- <60 kg: 8 mg PO qDay
- ≥60 kg: 12 mg PO qDay
- Continue until disease progression or until unacceptable toxicity
Endometrial Cancer
Indicated in combination with pembrolizumab for 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
20 mg PO qDay, PLUS pembrolizumab 200 mg IV q3weeks
Continue until disease progression or unacceptable toxicity
Refer to pembrolizumab prescribing information for recommended dosing information
Dosage Modifications
DTC dose reductions
- First occurrence: Reduce to 20 mg PO qDay
- Second occurrence: Reduce to 14 mg PO qDay
- Third occurrence: Reduce to 10 mg PO qDay
RCC or endometrial carcinoma dose reductions
- First occurrence: Reduce to 14 mg PO qDay
- Second occurrence: Reduce to 10 mg PO qDay
- Third occurrence: Reduce to 8 mg PO qDay
-
Dose modification of everolimus in RCC
- Reduce lenvatinib dose first and then the everolimus dose for adverse reactions of both lenvatinib and everolimus
- Refer to the everolimus prescribing information for additional dose modification information
-
Dose modification of pembrolizumab in endometrial carcinoma
- Interrupt one or both drugs or reduce lenvatinib when appropriate
- No dose reductions are recommended for pembrolizumab
- Refer to pembrolizumab prescribing information for additional dose modification information
HCC dose reductions
-
First occurrence
- <60 kg: Reduce to 4 mg PO qDay
- ≥60 kg: Reduce to 8 mg PO qDay
-
Second occurrence
- <60 kg: Reduce to 4 mg PO every other day
- ≥60 kg: Reduce to 4 mg PO qDay
-
Third occurrence
- <60 kg: Discontinue
- ≥60 kg: Reduce to 4 mg PO every other day
Hypertension
- Grade 3: Withhold if persists despite optimal antihypertensive therapy; resume at reduced dose when hypertension is controlled at Grade ≤2
- Grade 4: Permanently discontinue
Cardiac dysfunction
- Grade 3: Withhold until improved Grade≤1or baseline; resume at reduced dose or discontinue depending on severity and persistence of adverse reaction
- Grade 4: Permanently discontinue
Arterial thrombotic event
- Any grade: Permanently discontinue
Hepatoxicity
- Grade 3 or 4: Withhold until improved Grade ≤1 or baseline; resume at reduced dose or discontinue depending on severity and persistence of adverse reaction
- Hepatic failure: Permanently discontinue
Proteinuria
- ≥2 g/24 hr: Withhold; resume at reduced dose after resolution to <2 g/24 hr
- Nephrotic syndrome: Permanently discontinue
GI toxicity
- Grade 3 nausea, vomiting, and diarrhea: Withhold; resume at reduced dose after resolution to Grade ≤1 or baseline
- Grade 4 nausea, vomiting, and diarrhea: Permanently discontinue
- GI perforation, any grade: Permanently discontinue
- Grade 3 or 4 GI fistula: Permanently discontinue
Renal failure or impairment
- Grade 3 or 4: Withhold until improved Grade ≤1 or baseline; resume at reduced dose or discontinue depending on severity and persistence of adverse reaction
QTc prolongation
- >500 ms or >60 ms increase from baseline: Withhold; resume at reduced dose after resolution to ≤480 ms or baseline
Reversible posterior leukoencephalopathy syndrome (RPLS)
- Any grade: Withhold until fully resolved, resume at reduced dose or discontinue depending on severity and persistence of neurologic symptoms
Other adverse reactions
- Persistent or intolerable Grade 2 or 3 adverse reaction, or Grade 4 laboratory abnormality: Withhold until improves to Grade ≤1 or baseline; resume at reduced dose
- Grade 4 adverse reaction: Permanently discontinue
Renal impairment
- Mild-to-moderate (CrCl ≥30 mL/min): No dosage adjustment necessary
-
Severe (CrCl <30 mL/min)
- DTC: 14 mg PO qDay
- RCC and endometrial carcinoma: 10 mg PO qDay
Hepatic impairment
- Mild-to-moderate (Child-Pugh A or B): No dosage adjustment necessary
-
Severe (Child-Pugh C)
- DTC: 14 mg PO qDay
- RCC and endometrial carcinoma: 10 mg PO qDay
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>10%
Percentages are for all grades of adverse effects unless otherwise noted
Hypertension (73%)
Diarrhea (67%)
Fatigue (67%)
Arthralgia/myalgia (62%)
Decreased appetite (54%)
Weight decreased (51%)
Nausea (47%)
Hypertension, grades 3-4 (44%)
Stomatitis (41%)
Headache (38%)
Vomiting (36%)
Proteinuria (34%)
Palmar-plantar erythrodysesthesia (32%)
Abdominal pain (31%)
Dysphonia (31%)
Constipation (29%)
Oral pain (25%)
Cough (24%)
Peripheral edema (21%)
Rash (21%)
Dysgeusia (18%)
Dry mouth (17%)
Dizziness (15%)
Dyspepsia (13%)
Alopecia (12%)
Epistaxis (12%)
Insomnia (12%)
Urinary tract infection (11%)
1-10%
Percentages are for all grades of adverse effects unless otherwise noted
Dental infections (10%)
Hypotension (9%)
Diarrhea, grades 3-4 (9%)
Dehydration (9%)
Prolonged QT interval (9%)
Hypocalcemia (9%)
Decreased appetite, grades 3-4 (7%)
Hyperkeratosis (7%)
Hypokalemia (6%)
AST increased (5%)
ALT increased (4%)
Lipase increased (4%)
Creatinine increased (3%)
Nausea, grades 3-4 (2%)
Platelet count decreased (2%)
Postmarketing Reports
Pancreatitis
Amylase increased
Cholecystitis
Impaired wound healing
Fistula
Aortic dissection
Nephrotic syndrome
Arterial (including aortic) aneurysms, dissections, and rupture
Warnings
Contraindications
None
Cautions
Hypertension reported in clinical trials; control blood pressure before treatment; monitor blood pressure after 1 week, then q2weeks for the first 2 months, and then at least monthly thereafter
Serious complications of poorly controlled hypertension reported
Cardiac dysfunction, defined as decreased left or right ventricular function, cardiac failure, or pulmonary edema, was reported; monitor for clinical symptoms or signs of cardiac decompensation; monitor patients for clinical symptoms or signs of cardiac dysfunction
Arterial thromboembolic events reported; discontinue drug following a thromboembolic event; permanently discontinue therapy following an arterial thrombotic event
Serious hepatic adverse reactions reported; 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 therapy based on severity; increased ALT and/or AST observed; rare reports of hepatic failure, including fatalities, were also reported
Proteinuria reported in clinical trials; monitor for proteinuria before initiation of, and periodically throughout, treatment; if urine dipstick proteinuria greater than or equal to 2+ is detected, obtain a 24-hr urine protein; withhold and resume at a reduced dose upon recovery or permanently discontinue therapy on severity
Serious including fatal renal failure or impairment can occur with therapy; initiate prompt management of diarrhea or dehydration/hypovolemia; withhold and resume at a reduced dose upon recovery or permanently discontinue therapy for renal failure or impairment based on severity; renal failure and impairment reported; primary risk factor for severe renal impairment was dehydration/hypovolemia due to diarrhea and vomiting; initiate active management of diarrhea and any other gastrointestinal symptoms Grade 1 events
Diarrhea may occur; initiate prompt medical management for diarrhea; monitor for dehydration; interrupt therapy for Grade 3 or 4 diarrhea
Gastrointestinal (GI) perforation or fistula reported; discontinue if patient develops a GI perforation or life-threatening fistula; permanently discontinue therapy in patients who develop gastrointestinal perforation of any severity or Grade 3 or 4 fistula
QT prolongation reported; monitor ECG in patients with congenital long QT syndrome, CHF, bradyarrhythmias, or those who are taking drugs known to prolong the QT interval, including class Ia and III antiarrhythmics; monitor and correct electrolyte abnormalities in all patients; monitor electrocardiograms in patients with congenital long QT syndrome; congestive heart failure, bradyarrhythmias, or those who are taking drugs known to prolong QT interval, including Class Ia and III antiarrhythmics
Hypocalcemia reported; monitor blood calcium levels at least monthly and replace calcium as necessary during treatment; withhold and resume at reduced dose upon recovery or permanently discontinue therapy depending on severity
Reversible posterior leukoencephalopathy syndrome (RPLS) reported rarely; confirm diagnosis of RPLS with magnetic resonance imaging
Hemorrhagic events occurred; consider risk of severe or fatal hemorrhage associated with tumor invasion or infiltration of major blood vessels (eg, carotid artery)
Impairs exogenous thyroid suppression; monitor TSH levels monthly and adjust thyroid replacement medication as needed; monitor thyroid function prior to initiating therapy and at least monthly during treatment; treat hypothyroidism according to standard medical practice
Based on its mechanism of action and data from animal reproduction studies, lenvatinib can cause fetal harm when administered to a pregnant woman (see Pregnancy)
Impaired wound healing been reported in patients who received therapy; withhold therapy for at least 1 week prior to elective surgery; do not administer for at least 2 weeks following major surgery and until adequate wound healing; safety of resumption of therapy after resolution of wound healing complications has not been established; permanently discontinue drug in patients with wound healing complications
Drug interactions overview
- Avoid coadministration of lenvatinib with drugs known to prolong QT/QTc interval
Pregnancy & Lactation
Pregnancy
Based on its mechanism of action and data from animal reproduction studies, lenvatinib can cause fetal harm when administered to a pregnant woman; verify the pregnancy status of females of reproductive potential prior to initiating
In animal reproduction studies, oral administration during organogenesis at doses below the recommended human dose (approximately 0.14 times the recommended human dose based on body surface area) resulted in embryotoxicity, fetotoxicity, and teratogenicity in rats and rabbits
There are no available human data informing the drug-associated risk
Advise pregnant women of the potential risk to a fetus
Contraception
- Advise females of reproductive potential to use effective contraception during treatment and for at least 30 days after last dose
Infertility
- Females: May result in reduced fertility in females of reproductive potential
- Males: May result in damage to male reproductive tissues, leading to reduced fertility of unknown duration
Lactation
Unknown if distributed in human breast milk; because of the potential for serious adverse reactions in nursing infants, advise women to discontinue breastfeeding during treatment and for at least 1 week after last dose
Lenvatinib and its metabolites are excreted in rat milk at concentrations higher than in maternal plasma (~2 times higher [based on AUC]) in milk compared with maternal plasma
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Receptor tyrosine kinase (RTK) inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4)
Also inhibits other RTKs that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1, 2, 3, and 4; the platelet-derived growth factor receptor alpha (PDGFR-alpha), KIT, and RET
Absorption
Peak plasma time: 1-4 hr after PO administration
Administration with food does not affect the extent of absorption but can delay the mean peak plasma time from 2 hr to 4 hr
Distribution
Protein bound: 98-99%
Substrate of P-gp and BCRP
Metabolism
Metabolized by the CYP3A enzymes and aldehyde oxidase
Elimination
Half-life: 28 hr
Excretion (10 days after single dose): 64% feces; 25% urine
Administration
Oral Administration
Swallow capsule whole
May take with or without food
Take at the same time each day
Missed dose: If a dose is missed and cannot be taken within 12 hr, skip that dose and take the next dose at the usual time of administration
If unable to swallow capsule
- Capsules can be dissolved in a small glass of liquid
- Measure 1 tablespoon of water or apple juice and put the capsules into the liquid without breaking or crushing them
- Leave the capsules in the liquid for at least 10 minutes
- Stir for at least 3 minutes, and then drink the mixture
- After drinking, add the same amount (1 tablespoon) of water or apple juice to the glass; swirl the contents a few times and swallow the additional liquid
Storage
Store at room temperature, between 68-77°F (20-25°C)
Images
Patient Handout
Formulary
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Adding plans allows you to:
- View the formulary and any restrictions for each plan.
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- Compare formulary status to other drugs in the same class.
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