lenvatinib (Rx)

Brand and Other Names:Lenvima
  • Print

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule

  • 4mg
  • 10mg

Thyroid Cancer

Indicated for locally recurrent or metastatic, progressive, radioactive iodine-refractory thyroid cancer (DTC)

24 mg (two 10 mg capsules and one 4 mg capsule) PO qDay

Renal Cell Carcinoma

In combination with everolimus, indicated for advanced renal cell carcinoma (RCC) following 1 prior antiangiogenic therapy

18 mg (one 10 mg capsule and two 4 mg capsules) plus everolimus 5 mg PO qDay

Continue until disease progression or until unacceptable toxicity

Hepatocellular Carcinoma

Indicated for first-line treatment of 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

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 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

DTC dose reductions

  • First occurrence
    • ≥60 kg: Reduce to 8 mg PO qDay
    • <60 kg: Reduce to 4 mg PO qDay
  • Second occurrence
    • ≥60 kg: Reduce to 4 mg PO qDay
    • <60 kg: Reduce to 4 mg PO every other day
  • Third occurrence
    • ≥60 kg: Reduce to 4 mg PO every other day
    • <60 kg: Discontinue

Hypertension or cardiac dysfunction

  • Grade 3: Hold drug; may resume at reduced dose after resolution of adverse effects to grades 0, 1, or 2
  • Grade 4: Discontinue, do not resume

Arterial thrombotic event

  • Any grade: Discontinue, do not resume

Hepatic impairment

  • Hepatotoxicity grade 3 or 4: Hold or discontinue; consider resuming at reduced dose if resolves to grade 0, 1, or baseline
  • Hepatic failure grade 3 or 4: Discontinue, do not resume

Proteinuria

  • ≥2 g/24 hr: Hold dose; may resume at reduced dose after resolution to <2 g/24 hr

Nephrotic syndrome

  • Discontinue; do not resume

GI toxicity

  • Nausea, vomiting, and diarrhea grade 3: Hold; may resume at reduced dose after resolution to grade 0, 1, or baseline
  • Vomiting and diarrhea grade 4: Discontinue, do not resume
  • GI perforation, any grade: Discontinue, do not resume
  • GI fistula grade 3 or 4: Discontinue, do not resume

Renal failure or impairment

  • Grade 3 or 4: Hold or discontinue; consider resuming at reduced dose if resolves to grade 0, 1, or baseline

QTc prolongation

  • >500 ms or >60 ms increase from baseline: Hold; may resume at reduced dose after resolution to <480 ms or baseline

Reversible posterior leukoencephalopathy syndrome (RPLS)

  • Any grade: Hold or discontinue; consider resuming at reduced dose if resolves to grade 0 to 1

Hemorrhage

  • Grade 3: Hold; may resume at reduced dose after resolution to grade 0 to 1
  • Grade 4: Discontinue, do not resume

Severe renal (CrCl <30 mL/min) or hepatic impairment (Child-Pugh C)

  • DTC: 14 mg PO qDay
  • RCC: 10 mg PO qDay

Safety and efficacy not established

Next:

Interactions

Interaction Checker

and lenvatinib

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 
            Previous
            Next:

            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

            Previous
            Next:

            Warnings

            Contraindications

            None

            Cautions

            NOTE: Please refer to Dose Section (Dosage Modifications) for information on withholding and/or reducing dose, and for information regarding discontinuing the drug

            Hypertension reported in 73% of lenvatinib-treated patients in clinical trials (grade 3 hypertension was 44%); control blood pressure prior to treatment; monitor blood pressure after 1 week, then q2weeks for the first 2 months, and then at least monthly thereafter; withhold and resume at a reduced dose when hypertension is controlled or permanently discontinue therapy based on severity

            Serious complications of poorly controlled hypertension reported

            Cardiac dysfunction, defined as decreased left or right ventricular function, cardiac failure, or pulmonary edema, was reported in 7% of treated patients; monitor for clinical symptoms or signs of cardiac decompensation; monitor patients for clinical symptoms or signs of cardiac dysfunction; withhold and resume at a reduced dose upon recovery or permanently discontinue therapy based on severity

            Arterial thromboembolic events reported in 5% of treated patients; discontinue drug following a thromboembolic event; permanently discontinue therapy following an arterial thrombotic event (see Dosage Modifications)

            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 34% of lenvatinib-treated patients in clinical trials (grade 3 proteinuria was 11%); 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-hour 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 in 14% (grade ≥3 [3%]); the 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; for Grade 3 diarrhea, resume at reduced dose when diarrhea resolves to Grade 1 or baseline; permanently discontinue therapy for Grade 4 diarrhea despite medical management; withhold and resume at a reduced dose upon recovery or permanently discontinue therapy

            Gastrointestinal (GI) perforation or fistula reported (2%); 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 (9%); 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; withhold therapy for development of QTc interval prolongation >500 ms; resume therapy at reduced dose when QTc prolongation resolves to baseline

            Hypocalcemia reported (Grade ≥3 [9%]); 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; withhold and resume at a reduced dose upon recovery or permanently discontinue therapy depending on severity and persistence of neurologic symptoms

            Hemorrhagic events occurred in 35% of treated patients; consider risk of severe or fatal hemorrhage associated with tumor invasion or infiltration of major blood vessels (e.g. carotid artery); withhold and resume at reduced dose upon recovery or permanently discontinue therapy based on the severity

            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)

            Wound healing complications, including fistula formation and wound dehiscence, can occur; withhold lenvatinib for at least 6 days prior to scheduled surgery; resumed treatment after surgery based on clinical judgment of adequate wound healing; permanently discontinue drug in patients with wound healing complications

            Drug interactions overview

            • Avoid coadministration of lenvatinib with drugs known to prolong QT/QTc interval
            Previous
            Next:

            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.

            Previous
            Next:

            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

            Previous
            Next:

            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)

            Previous
            Next:

            Images

            Previous
            Next:

            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
            Additional Offers
            Email to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Email Forms to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Previous
            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.