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Lenvatinib: Drug information

Lenvatinib: Drug information
(For additional information see "Lenvatinib: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Lenvima (10 MG Daily Dose);
  • Lenvima (12 MG Daily Dose);
  • Lenvima (14 MG Daily Dose);
  • Lenvima (18 MG Daily Dose);
  • Lenvima (20 MG Daily Dose);
  • Lenvima (24 MG Daily Dose);
  • Lenvima (4 MG Daily Dose);
  • Lenvima (8 MG Daily Dose)
Brand Names: Canada
  • Lenvima (10 MG Daily Dose);
  • Lenvima (12 MG Daily Dose);
  • Lenvima (14 MG Daily Dose);
  • Lenvima (18 MG Daily Dose);
  • Lenvima (20 MG Daily Dose);
  • Lenvima (24 MG Daily Dose);
  • Lenvima (4 MG Daily Dose);
  • Lenvima (8 MG Daily Dose)
Pharmacologic Category
  • Antineoplastic Agent, Tyrosine Kinase Inhibitor;
  • Antineoplastic Agent, Vascular Endothelial Growth Factor (VEGF) Inhibitor
Dosing: Adult

Note: Lenvatinib is associated with a moderate or high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref). Prior to treatment initiation, correct electrolyte abnormalities and control BP. Withhold lenvatinib for at least 1 week prior to elective surgery; do not administer lenvatinib for at least 2 weeks following major surgery and until adequate wound healing. Prior to initiation, perform appropriate preventive dentistry and encourage good oral hygiene. Avoid invasive dental procedures in patients receiving lenvatinib, especially if at increased risk; withhold lenvatinib therapy for ≥1 week prior to scheduled dental surgery or invasive dental procedures.

Endometrial carcinoma, advanced, mismatch repair proficient or not microsatellite instability-high

Endometrial carcinoma, advanced, mismatch repair proficient or not microsatellite instability-high: Oral: 20 mg once daily (in combination with pembrolizumab), continue until disease progression or unacceptable toxicity (Ref).

Hepatocellular carcinoma, unresectable

Hepatocellular carcinoma, unresectable: Oral: 12 mg once daily (patients ≥60 kg [actual body weight]) or 8 mg once daily (patients <60 kg [actual body weight]) (Ref); continue until disease progression or unacceptable toxicity.

Renal cell carcinoma, advanced, first-line combination therapy

Renal cell carcinoma, advanced, first-line combination therapy:

In combination with pembrolizumab: Note: May be used in combination with pembrolizumab regardless of risk stratification (Ref); some experts may prefer this combination in patients with intermediate- or poor-risk disease who have symptomatic or life-threatening disease burden (Ref).

Oral: 20 mg once daily (in combination with pembrolizumab); continue until disease progression or unacceptable toxicity (Ref).

In combination with everolimus (off-label combination): Note: May be used in combination with everolimus regardless of risk stratification in patients who are ineligible for (or who decline) initial treatment with immunotherapy-based combinations (Ref).

Oral: 18 mg once daily (in combination with everolimus); continue until disease progression or unacceptable toxicity (Ref).

Renal cell carcinoma, advanced, previously treated, combination therapy

Renal cell carcinoma, advanced, previously treated, combination therapy:

In combination with everolimus: Note: May be used in combination with everolimus following prior antiangiogenic therapy, or in patients with progression after initial immunotherapy and who have not previously received antiangiogenic therapy, or after initial combination therapy (immunotherapy plus an antiangiogenic agent) (Ref).

Oral: 18 mg once daily (in combination with everolimus); continue until disease progression or unacceptable toxicity (Ref).

Thyroid cancer, differentiated

Thyroid cancer, differentiated: Oral: 24 mg once daily until disease progression or unacceptable toxicity (Ref).

Missed doses: Do not take a missed dose within 12 hours of the next dose (if within 12 hours, skip the missed dose and return to regular administration time).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

Note: CrCl calculated by Cockcroft-Gault equation (using actual body weight).

Preexisting renal impairment:

CrCl ≥30 mL/minute: No dosage adjustment necessary.

CrCl <30 mL/minute:

Endometrial carcinoma, advanced: 10 mg once daily.

Hepatocellular carcinoma, unresectable: There are no dosage adjustments provided in the manufacturer's labeling.

Renal cell cancer, advanced: 10 mg once daily.

Thyroid cancer, differentiated: 14 mg once daily.

End-stage renal disease: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Hemodialysis: Lenvatinib is not expected to be dialyzable (due to high protein binding).

Renal toxicity during treatment:

Nephrotic syndrome: Permanently discontinue lenvatinib.

Proteinuria ≥2 g proteinuria/24 hours: Withhold lenvatinib; resume lenvatinib at a reduced dose when improved to <2 g proteinuria/24 hours.

Renal failure or impairment (grade 3 or 4): Withhold lenvatinib; if improves to ≤ grade 1 or baseline, depending on the severity and persistence, resume lenvatinib at a reduced dose or permanently discontinue therapy.

Dosing: Hepatic Impairment: Adult

Preexisting hepatic impairment:

Mild impairment (Child-Pugh class A): No dosage adjustment necessary.

Moderate impairment (Child-Pugh class B):

Endometrial carcinoma, advanced: No dosage adjustment necessary.

Hepatocellular carcinoma, unresectable: There are no dosage adjustments provided in the manufacturer's labeling.

Renal cell cancer, advanced: No dosage adjustment necessary.

Thyroid cancer, differentiated: No dosage adjustment necessary.

Severe impairment (Child-Pugh class C):

Endometrial carcinoma, advanced: 10 mg once daily.

Hepatocellular carcinoma, unresectable: There are no dosage adjustments provided in the manufacturer's labeling.

Renal cell cancer, advanced: 10 mg once daily.

Thyroid cancer, differentiated: 14 mg once daily.

Hepatotoxicity during treatment (grade 3 or 4): Withhold lenvatinib; if improves to ≤ grade 1 or baseline, depending on the severity and persistence, resume lenvatinib at a reduced dose or permanently discontinue therapy. Permanently discontinue lenvatinib for hepatic failure.

Dosing: Adjustment for Toxicity: Adult
Recommended Lenvatinib Dose Reductions for Adverse Reactions

Indication

Usual lenvatinib dosage

First dose reduction to:

Second dose reduction to:

Third dose reduction to:

a When used in combination with pembrolizumab, modify the dose of one or both drugs as appropriate; withhold, reduce dose, or discontinue lenvatinib as appropriate. Refer to pembrolizumab monograph for dosage modification information.

b When used in combination with everolimus, for adverse reactions of both lenvatinib and everolimus, withhold or reduce the lenvatinib dose first and then the everolimus dose (refer to Everolimus monograph for dosage modification information).

Endometrial carcinoma (advanced)a

20 mg once daily

14 mg once daily

10 mg once daily

8 mg once daily

Hepatocellular carcinoma (unresectable); ≥60 kg

12 mg once daily

8 mg once daily

4 mg once daily

4 mg once every other day

Hepatocellular carcinoma (unresectable); <60 kg

8 mg once daily

4 mg once daily

4 mg once every other day

Discontinue therapy

Renal cell carcinoma (advanced), first-line therapya

20 mg once daily

14 mg once daily

10 mg once daily

8 mg once daily

Renal cell carcinoma (advanced), previously treatedb

18 mg once daily

14 mg once daily

10 mg once daily

8 mg once daily

Thyroid cancer (differentiated)

24 mg once daily

20 mg once daily

14 mg once daily

10 mg once daily

Adverse Reactions Requiring Dose Modification of Lenvatinib

Adverse reaction

Severity

Lenvatinib dosage modification

a If lenvatinib is discontinued, a drop in BP is expected and antihypertensive therapy should be reduced and/or interrupted as clinically appropriate (ESC [Lyon 2022]).

Hypertension

If indicated, initiate appropriate antihypertensive therapya to reduce the risk for cardiovascular complications (ASCO [Armenian 2017]; ESC [Lyon 2022]).

Grade 3

Withhold lenvatinib for grade 3 hypertension that persists despite optimal antihypertensive therapy. When hypertension is controlled at ≤ grade 2, resume lenvatinib at a reduced dose.

Grade 4

Permanently discontinue lenvatinib.

Cardiac dysfunction

Grade 3

Withhold lenvatinib until improves to ≤ grade 1 or baseline. Depending on the severity and persistence of the cardiac dysfunction, resume lenvatinib at a reduced dose or discontinue.

Grade 4

Permanently discontinue lenvatinib.

QTc prolongation

>500 msec or >60 msec increase from baseline

Withhold lenvatinib until improves to ≤480 msec or baseline, then resume lenvatinib at a reduced dose.

Arterial thrombotic event

Any grade

Permanently discontinue lenvatinib. The safety of resuming therapy after an arterial thrombotic event has not been established.

GI perforation

Any grade

Permanently discontinue lenvatinib.

Fistula formation

Grade 3 or 4

Permanently discontinue lenvatinib.

Reversible posterior leukoencephalopathy syndrome

Any grade

Withhold lenvatinib until fully resolved; depending on severity and persistence of neurologic symptoms, resume lenvatinib at a reduced dose or discontinue.

Other adverse reactions

Persistent or intolerable grade 2 or 3 adverse reaction

Withhold lenvatinib until improves to ≤ grade 1 or baseline and then resume lenvatinib at a reduced dose.

Grade 4 laboratory abnormality

Withhold lenvatinib until improves to ≤ grade 1 or baseline and then resume lenvatinib at a reduced dose.

Grade 4 adverse reaction

Permanently discontinue lenvatinib.

Diarrhea

Initiate prompt management of diarrhea or dehydration/hypovolemia. Based on the severity, withhold lenvatinib and upon recovery, resume lenvatinib at a reduced dose or permanently discontinue.

Hemorrhage

Withhold lenvatinib; upon recovery (depending on severity), resume lenvatinib at a reduced dose or permanently discontinue treatment.

Hypocalcemia

Administer calcium replacement therapy as necessary; withhold lenvatinib and resume at a reduced dose or permanently discontinue lenvatinib depending on the severity.

Hypothyroidism

Manage hypothyroidism according to standard medical practice.

Osteonecrosis of the jaw

Withhold lenvatinib; restart after adequate resolution based on clinical judgement.

Wound healing complications

Permanently discontinue lenvatinib. The safety of resuming lenvatinib after resolution of wound healing complications has not been established.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Cardiovascular: Hypertension (45% to 73%; severe hypertension: 3%), peripheral edema (14% to 21%)

Dermatologic: Alopecia (12%), palmar-plantar erythrodysesthesia (27% to 32%), skin rash (14% to 21%)

Endocrine & metabolic: Hyponatremia (grades 3/4: 15%), hypothyroidism (21%), increased gamma-glutamyl transferase (grades 3/4: 17%), increased thyroid stimulating hormone level (57% to 70%), weight loss (31% to 51%)

Gastrointestinal: Abdominal pain (30% to 31%), constipation (16% to 29%), decreased appetite (34% to 54%), diarrhea (39% to 67%), dysgeusia (18%), dyspepsia (13%), nausea (20% to 47%), stomatitis (11% to 41%; grades 3/4: ≤5%), vomiting (16% to 36%), xerostomia (17%)

Genitourinary: Proteinuria (26% to 34%), urinary tract infection (11%)

Hematologic & oncologic: Hemorrhage (23%, including carotid artery hemorrhage; grades 3/4: 4% to 5%)

Hepatic: Ascites (15%; severe: 3%), increased serum aspartate aminotransferase (grades 3/4: 5% to 12%)

Nervous system: Dizziness (15%), fatigue (44% to 67%), headache (10% to 38%), insomnia (12%), mouth pain (25%), voice disorder (24% to 31%)

Neuromuscular & skeletal: Arthralgia (≤62%), myalgia (≤62%)

Renal: Renal insufficiency (7% to 14%)

Respiratory: Cough (24%), epistaxis (12%)

Miscellaneous: Fever (15%)

1% to 10%:

Cardiovascular: Arterial thromboembolism (2% to 5%), cardiac failure (grades ≥3: ≤3%), cardiomyopathy (grades ≥3: ≤3%), hypotension (9%), prolonged QT interval on ECG (8% to 9%; >500 msec: 2%), pulmonary embolism (3%), reduced ejection fraction (ejection fraction reduced by >20%: grades ≥3: ≤3%), ventricular dysfunction (grade ≥3: ≤3%; ventricular hypokinesia: grades ≥3: ≤3%)

Dermatologic: Hyperkeratosis (7%)

Endocrine & metabolic: Dehydration (9%; severe dehydration: 3%), hypercalcemia (>5%), hypercholesterolemia (>5%), hyperkalemia (>5%), hypoalbuminemia (>5%), hypocalcemia (grades 3/4: 9%), hypoglycemia (>5%), hypokalemia (grades 3/4: 3% to 6%), hypomagnesemia (>5%)

Gastrointestinal: Gastrointestinal fistula (≤2%), gastrointestinal perforation (≤2%), increased serum amylase (>5%), increased serum lipase (grades 3/4: 4% to 6%), infection of mouth (≤10%)

Hematologic & oncologic: Anemia (grades 3/4: 4%), lymphocytopenia (grades 3/4: 8%), neutropenia (grades 3/4: 7%), thrombocytopenia (grades 3/4: 2% to 10%)

Hepatic: Hepatic encephalopathy (≤8%; severe: 5%), hepatic coma (≤8%), hepatic failure (3%), hyperbilirubinemia (>5%), increased serum alanine aminotransferase (grades 3/4: 4% to 8%), increased serum alkaline phosphatase (>5%)

Nervous system: Encephalopathy (≤8%, including metabolic encephalopathy)

Renal: Increased serum creatinine (grades 3/4: 2% to 3%)

Respiratory: Pneumonia (4%)

<1%:

Hepatic: Hepatitis (acute), hepatorenal syndrome

Nervous system: Reversible posterior leukoencephalopathy syndrome

Neuromuscular & skeletal: Osteonecrosis of the jaw

Frequency not defined:

Genitourinary: Hematuria

Neuromuscular & skeletal: Asthenia

Postmarketing:

Cardiovascular: Aneurysm (arterial), aortic aneurysm, aortic dissection, coronary artery dissection, myocardial rupture (arterial rupture and aortic rupture)

Gastrointestinal: Cholecystitis, pancreatitis

Genitourinary: Nephrotic syndrome

Hematologic & oncologic: Tumor hemorrhage

Miscellaneous: Wound healing impairment

Contraindications

There are no contraindications listed in the manufacturer's US labeling.

Canadian labeling: Hypersensitivity to lenvatinib or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Cardiac effects: Hypertension commonly occurred in patients treated with lenvatinib in clinical trials (including grade 3 and 4 events); the median time to onset of new or worsening hypertension was 16 to 35 days. Serious complications have been reported secondary to poorly controlled hypertension. Serious (≥ grade 3) and fatal cardiac dysfunction has been reported with lenvatinib, including cardiomyopathy, left or right ventricular dysfunction, decreased left or right ejection fraction (>20% from baseline), heart failure, cardiac failure, or ventricular hypokinesia. QT/QTc prolongation was also observed in lenvatinib-treated patients, including prolongation >500 msec and increases >60 msec from baseline.

• Fistula formulation/GI perforation: Fistulas and GI perforations have been reported with lenvatinib.

• GI toxicity: Diarrhea has commonly occurred in patients receiving lenvatinib; grade 3 events have been reported. When used in combination with everolimus, diarrhea was the most frequent cause of dose interruption and/or reduction, and diarrhea recurred despite dose reduction.

• Hemorrhage: Serious and fatal hemorrhagic events may occur with lenvatinib. Hemorrhagic events (any grade) occurred in over 25% of patients treated with lenvatinib (either as a single agent or in combination with everolimus); epistaxis and hematuria were the most frequently reported hemorrhagic events. Fatal intracranial hemorrhage was observed in a patient who had CNS metastases at baseline and received lenvatinib; cerebral hemorrhage has been reported in patients who received lenvatinib in combination with everolimus (including rare fatal cases). Serious tumor-related bleeding events (including cases of fatal hemorrhage) have been observed. Serious and fatal carotid artery hemorrhages were reported more frequently in patients with anaplastic thyroid carcinoma (ATC) than with other tumor types. Safety and efficacy of lenvatinib have not been established in the treatment of ATC. Consider the risk of severe or fatal hemorrhage associated with tumor infiltration/invasion of major blood vessels.

• Hepatotoxicity: Serious hepatic adverse reactions were observed in patients with malignancies other than hepatocellular cancer (HCC) who received lenvatinib; fatal events, including hepatic failure, acute hepatitis, and hepatorenal syndrome, have occurred. Hepatic encephalopathy (including hepatic encephalopathy, encephalopathy, metabolic encephalopathy, and hepatic coma) have been reported in lenvatinib-treated patients with HCC, including ≥ grade 3 events and hepatic failure.

• Hypocalcemia: Grade 3 to 4 hypocalcemia has occurred in patients receiving lenvatinib; in most cases, hypocalcemia improved or resolved following calcium supplementation, with or without treatment interruption or dosage reduction.

• Hypothyroidism: Lenvatinib impairs exogenous thyroid suppression. Most patients with differentiated thyroid cancer (DTC) had a baseline thyroid stimulating hormone (TSH) level ≤0.5 milliunits/L, however, in patients with DTC with a normal baseline TSH, elevation of TSH level >0.5 milliunits/L was commonly observed. Grade 1 or 2 hypothyroidism also occurred in patients receiving lenvatinib for other indications; an elevation of TSH was commonly observed in patients with a normal or low TSH at baseline.

• Osteonecrosis of the jaw: Osteonecrosis of the jaw (ONJ), also referred to as medication-related osteonecrosis of the jaw (MRONJ), has been reported with lenvatinib. Risk factors for ONJ include bisphosphonate or denosumab therapy, dental disease, and/or invasive dental procedures. Discontinuing bisphosphonate therapy in patients requiring invasive dental procedures may reduce the risk of ONJ. According to a position paper by the American Association of Maxillofacial Surgeons (AAOMS), MRONJ has been associated with other antiangiogenic agents used as anticancer therapy. Angiogenic agents, when given concomitantly with antiresorptive agents, are associated with an increased risk of ONJ. The AAOMS suggests that if medically permissible, delay the initiation of antiangiogenic agents for cancer therapy until optimal dental health is attained (if extractions are required, antiangiogenesis therapy should be delayed until the extraction site has mucosalized or until after adequate osseous healing). Once antiangiogenic therapy for oncologic disease is initiated, procedures that involve direct osseous injury and placement of dental implants should be avoided. Patients developing ONJ during therapy should receive care by an oral surgeon (AAOMS [Ruggiero 2014]).

• Renal toxicity: Proteinuria (including grade 3 toxicity) was commonly observed in clinical studies. Serious renal impairment or failure may also occur (including ≥ grade 3 events and fatal renal failure); a primary risk factor for renal impairment is dehydration or hypovolemia due to diarrhea and vomiting.

• Reversible posterior leukoencephalopathy syndrome: Reversible posterior leukoencephalopathy syndrome has occurred (rarely).

• Thromboembolic events: Arterial thromboembolic events, including ≥ grade 3 events, have been reported. Myocardial infarction and cerebrovascular events have occurred. Lenvatinib has not been studied in patients who have had an arterial thromboembolic event within the preceding 6 months.

• Wound healing impairment: Vascular endothelial growth factor receptor inhibitors, including lenvatinib, are associated with impaired wound healing.

Special populations:

• Older adult: Patients ≥75 years of age appeared to have reduced tolerability for lenvatinib in some studies.

Other warnings/precautions:

• Appropriate use: For mismatch repair proficient (pMMR) or not microsatellite instability-high (MSI-H) advanced endometrial carcinoma, select patients for treatment based on tumor specimen pMMR or MSI-H status. Information on approved tests may be found at http://www.fda.gov/companiondiagnostics.

Dosage Forms Considerations

Each Lenvima Therapy Pack contains a 30 day supply of dosage units

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule Therapy Pack, Oral:

Lenvima (10 MG Daily Dose): 10 mg (30 ea)

Lenvima (12 MG Daily Dose): 3x4 mg (15 ea, 90 ea)

Lenvima (14 MG Daily Dose): 10 mg & 4 mg (60 ea)

Lenvima (18 MG Daily Dose): 10 mg & 2x4 mg (15 ea, 90 ea)

Lenvima (20 MG Daily Dose): 2x10 mg (60 ea)

Lenvima (24 MG Daily Dose): 2x10 mg & 4 mg (90 ea)

Lenvima (4 MG Daily Dose): 4 mg (5 ea, 30 ea)

Lenvima (8 MG Daily Dose): 2x4 mg (10 ea, 60 ea)

Generic Equivalent Available: US

No

Pricing: US

Capsule Therapy Pack (Lenvima (10 MG Daily Dose) Oral)

10 mg (per each): $970.20

Capsule Therapy Pack (Lenvima (12 MG Daily Dose) Oral)

3 x 4 mg (per each): $323.40

Capsule Therapy Pack (Lenvima (14 MG Daily Dose) Oral)

10 & 4 mg (per each): $485.10

Capsule Therapy Pack (Lenvima (18 MG Daily Dose) Oral)

10 MG &2 x 4 MG (per each): $323.40

Capsule Therapy Pack (Lenvima (20 MG Daily Dose) Oral)

2 x 10 mg (per each): $485.10

Capsule Therapy Pack (Lenvima (24 MG Daily Dose) Oral)

2 x 10 MG &4 MG (per each): $323.40

Capsule Therapy Pack (Lenvima (4 MG Daily Dose) Oral)

4 mg (per each): $970.20

Capsule Therapy Pack (Lenvima (8 MG Daily Dose) Oral)

2 x 4 mg (per each): $485.10

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule Therapy Pack, Oral:

Lenvima (10 MG Daily Dose): 10 mg (30 ea)

Lenvima (12 MG Daily Dose): 3 x 4 MG (6 ea, 90 ea)

Lenvima (14 MG Daily Dose): 10 & 4 MG (60 ea)

Lenvima (18 MG Daily Dose): 10 MG & 2 x 4 MG (90 ea)

Lenvima (20 MG Daily Dose): 2 x 10 MG (60 ea)

Lenvima (24 MG Daily Dose): 2 x 10 MG & 4 MG (90 ea)

Lenvima (4 MG Daily Dose): 4 mg (30 ea)

Lenvima (8 MG Daily Dose): 2 x 4 MG (60 ea)

Prescribing and Access Restrictions

Lenvatinib is available only through specialty pharmacies. For further information on patient assistance, product availability, and prescribing instructions, please refer to the following website: http://www.eisaireimbursement.com/patient/lenvima

Administration: Adult

Lenvatinib is associated with a moderate or high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref).

Oral: Administer at the same time each day. May be administered with or without food. Swallow capsules whole.

For patients unable to swallow whole capsules, a suspension may be prepared for oral administration or for feeding tube administration: Place dose (up to a maximum of 5 capsules) in a small container (~20 mL capacity) or a 20 mL syringe; do not break or crush capsules. Add 3 mL of liquid (use water or apple juice for oral administration; use water only for feeding tube administration) to the container or syringe and wait 10 minutes for the capsule shell (outer surface) to disintegrate, then stir or shake mixture for 3 minutes until capsules are fully disintegrated. Administer contents. Using a second syringe or dropper, add an additional 2 mL liquid to the container or syringe and swirl or shake and then administer; repeat this step at least once and until there is no more visible residue to ensure the full dose is administered. If 6 capsules are required for the dose, follow the above instructions using 3 capsules at a time. Suspension may be stored refrigerated in a covered container for up to 24 hours (discard if not administered within 24 hours). Compatibility has been confirmed for polypropylene syringes and for feeding tubes of at least 5 French diameter (PVC or polyurethane tube) or 6 French diameter (silicone tube).

Hazardous Drugs Handling Considerations

This medication is not on the NIOSH (2016) list; however, it may meet the criteria for a hazardous drug. Lenvatinib may be teratogenic, cause reproductive toxicity, and has a structural/toxicity profile similar to existing hazardous agents.

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).

Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.

Use: Labeled Indications

Endometrial carcinoma, advanced: Treatment of advanced endometrial carcinoma (in combination with pembrolizumab) that is mismatch repair proficient (as determined by an approved test), or not microsatellite instability-high, in patients who have disease progression following prior systemic therapy (in any setting) and are not candidates for curative surgery or radiation.

Hepatocellular carcinoma, unresectable: First-line treatment of unresectable hepatocellular carcinoma (HCC).

According to guidelines from the American Society of Clinical Oncology for systemic therapy for advanced HCC, lenvatinib is a first-line option for select patients with advanced HCC with Child-Pugh class A hepatic impairment, performance status of 0 or 1, and with contraindications to atezolizumab and/or bevacizumab therapy. Lenvatinib is a second-line therapy option in patients who received first-line therapy with atezolizumab and bevacizumab (ASCO [Gordan 2020]).

Renal cell carcinoma, advanced:

First-line treatment of advanced renal cell carcinoma (RCC) (in combination with pembrolizumab) in adults.

Treatment of advanced RCC (in combination with everolimus) in adults following 1 prior anti-angiogenic therapy.

Thyroid cancer, differentiated: Treatment of locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer.

Medication Safety Issues
Sound-alike/look-alike issues

Lenvatinib may be confused with cabozantinib, enasidenib, lapatinib, larotrectinib, lonafarnib, lorlatinib, neratinib, sorafenib, tivozanib, vandetanib

Lenvima may be confused with Lynparza

High alert medication

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its lists of drug classes which have a heightened risk of causing significant patient harm when used in error.

Metabolism/Transport Effects

Substrate of BCRP/ABCG2, CYP3A4 (minor), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Amiodarone: QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of Amiodarone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Amisulpride (Oral): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Amisulpride (Oral). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even greater risk. Risk D: Consider therapy modification

Androgens: Hypertension-Associated Agents may enhance the hypertensive effect of Androgens. Risk C: Monitor therapy

Azithromycin (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Azithromycin (Systemic). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Carbetocin: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Chloroquine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Chloroquine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Citalopram: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Citalopram. Risk X: Avoid combination

Clarithromycin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Clarithromycin. Risk X: Avoid combination

Clofazimine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Clofazimine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

ClomiPRAMINE: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

CloZAPine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of CloZAPine. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Dabrafenib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Dasatinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Dasatinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy

Domperidone: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Domperidone. Risk X: Avoid combination

Doxepin-Containing Products: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Doxepin-Containing Products. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Dronedarone: QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of Dronedarone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

DroPERidol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of DroPERidol. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Encorafenib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Entrectinib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk X: Avoid combination

Escitalopram: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Escitalopram. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Etelcalcetide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Fexinidazole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk X: Avoid combination

Fingolimod: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias (including TdP) with a continuous overnight ECG when fingolimod is combined with QT prolonging drugs. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Flecainide: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Flecainide. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Fluorouracil Products: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Fluorouracil Products. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Flupentixol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Flupentixol. Risk X: Avoid combination

Gadobenate Dimeglumine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Gadobenate Dimeglumine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Gemifloxacin: QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of Gemifloxacin. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Gilteritinib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. If use is necessary, monitor for QTc interval prolongation and arrhythmias. Risk D: Consider therapy modification

Halofantrine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Halofantrine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Haloperidol: QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of Haloperidol. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

HydrOXYzine: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk C: Monitor therapy

Imipramine: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Inotuzumab Ozogamicin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Inotuzumab Ozogamicin. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Ketoconazole (Systemic): May enhance the QTc-prolonging effect of Lenvatinib. Ketoconazole (Systemic) may increase the serum concentration of Lenvatinib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Levofloxacin-Containing Products (Systemic): QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of Levofloxacin-Containing Products (Systemic). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Levoketoconazole: QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of Levoketoconazole. Risk X: Avoid combination

Lofexidine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Lofexidine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Meglumine Antimoniate: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Methadone: QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of Methadone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Midostaurin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Midostaurin. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Moxifloxacin (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Moxifloxacin (Systemic). Risk X: Avoid combination

Nilotinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Nilotinib. Risk X: Avoid combination

OLANZapine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of OLANZapine. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Ondansetron: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Ondansetron. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Osimertinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Osimertinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Oxytocin: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Pacritinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pacritinib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

PAZOPanib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of PAZOPanib. Risk X: Avoid combination

Pentamidine (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pentamidine (Systemic). Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Pilsicainide: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pilsicainide. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Pimozide: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pimozide. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk X: Avoid combination

Piperaquine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Piperaquine. Risk X: Avoid combination

Probucol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Probucol. Risk X: Avoid combination

Propafenone: May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Propofol: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-prolonging Agents (Indeterminate Risk - Avoid): May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Agents (Indeterminate Risk - Caution): May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Class IA Antiarrhythmics (Highest Risk): QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-prolonging Class III Antiarrhythmics (Highest Risk): QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of QT-prolonging Class III Antiarrhythmics (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-Prolonging Inhalational Anesthetics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-prolonging Kinase Inhibitors (Highest Risk): May enhance the QTc-prolonging effect of other QT-prolonging Kinase Inhibitors (Highest Risk). Risk X: Avoid combination

QT-prolonging Miscellaneous Agents (Highest Risk): QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Kinase Inhibitors (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk). Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Kinase Inhibitors (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QUEtiapine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of QUEtiapine. Risk X: Avoid combination

Quizartinib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Ribociclib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Ribociclib. Risk X: Avoid combination

RisperiDONE: QT-prolonging Agents (Highest Risk) may enhance the CNS depressant effect of RisperiDONE. QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of RisperiDONE. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Sertindole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk X: Avoid combination

Solriamfetol: May enhance the hypertensive effect of Hypertension-Associated Agents. Risk C: Monitor therapy

Sparfloxacin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Sparfloxacin. Risk X: Avoid combination

SUNItinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of SUNItinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Terbutaline: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Thioridazine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Thioridazine. Risk X: Avoid combination

Toremifene: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Toremifene. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Vemurafenib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Vemurafenib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Warfarin: Lenvatinib may enhance the anticoagulant effect of Warfarin. Risk C: Monitor therapy

Food Interactions

Administration with a high fat meal (~900 calories; ~55% from fat, ~15% from protein, and ~30% from carbohydrates) decreased the rate of absorption and delayed the median Tmax from 2 hours to 4 hours, but did not affect the extent of absorption. May be administered with or without food.

Reproductive Considerations

Verify pregnancy status prior to lenvatinib initiation in patients who could become pregnant. Patients who could become pregnant should use effective contraception during lenvatinib treatment and for 30 days after the last lenvatinib dose.

Pregnancy Considerations

Based on the mechanism of action and findings from animal reproduction studies, lenvatinib may cause fetal harm if administered in pregnancy.

Breastfeeding Considerations

It is not known if lenvatinib is present in breast milk. Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends discontinuing breastfeeding during lenvatinib treatment and for 1 week after the last lenvatinib dose.

Monitoring Parameters

Mismatch repair proficient status or not microsatellite instability-high status (in advanced endometrial carcinoma). LFTs (at baseline, every 2 weeks for 2 months, and at least monthly thereafter); renal function; electrolytes (baseline and periodically); serum calcium at least monthly; thyroid function (TSH levels) at baseline and monthly or as clinically indicated; monitor for proteinuria at baseline and periodically during treatment (urine dipstick; if 2+ then obtain a 24-hour urine protein). Verify pregnancy status prior to treatment initiation (in patients who could become pregnant). Monitor BP after 1 week, then every 2 weeks for 2 months, and at least monthly thereafter. Dental exam prior to and periodically during treatment. ECG in select patients (congenital long QT syndrome, heart failure, bradyarrhythmias, or in those on concomitant medications known to prolong the QT interval). Monitor for clinical signs/symptoms of cardiac dysfunction, arterial thrombosis, reversible posterior leukoencephalopathy syndrome (confirm with MRI), fistula formation, GI perforation, bleeding/hemorrhagic events, diarrhea, dehydration, and wound healing complications; monitor patients with hepatocellular carcinoma closely for signs of hepatic failure, including hepatic encephalopathy. Monitor adherence.

Additional cardiovascular monitoring: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (ASCO [Armenian 2017]; ESC [Lyon 2022]). BP at each clinical visit (as well as daily home monitoring for first cycle, after dose increases, and every 2 to 3 weeks thereafter); ECG and QTc assessment in patients at moderate- or high-risk of QTc prolongation (assess QTc monthly during the first 3 months and every 3 to 6 months thereafter); baseline echocardiography in high- and very high-risk patients (repeat every 3 months during the first year and every 6 to 12 months thereafter); consider baseline echocardiography in low- and moderate-risk patients (consider repeating every 4 months during the first year for moderate-risk patients and every 6 to 12 months thereafter) (ESC [Lyon 2022]).

The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Mechanism of Action

Lenvatinib is a multitargeted tyrosine kinase inhibitor of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), VEGFR3 (FLT4), fibroblast growth factor (FGF) receptors FGFR1, 2, 3, and 4, platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET. Inhibition of these receptor tyrosine kinases leads to decreased tumor growth and slowing of cancer progression. In hepatocellular carcinoma cell lines dependent on activated FGFR signaling (with a concurrent inhibition of FGF-receptor substrate 2α phosphorylation), lenvatinib exhibited antiproliferative activity. Combining lenvatinib with everolimus has demonstrated increased antiangiogenic and antitumor activity by decreasing human endothelial cell proliferation, tube formation, and VEGF signaling (in vitro) compared to either drug alone.

Pharmacokinetics (Adult Data Unless Noted)

Absorption: Administration with a high fat meal (~900 calories; ~55% from fat, ~15% from protein, and ~30% from carbohydrates) decreased the rate of absorption and delayed the median Tmax from 2 hours to 4 hours, but did not affect the extent of absorption.

Distribution: Vdss: 97 L.

Protein binding: 97% to 99%.

Metabolism: Primarily enzymatic through CYP3A and aldehyde oxidase; nonenzymatic metabolism also occurs.

Half-life elimination: ~28 hours.

Time to peak: 1 to 4 hours.

Excretion: Feces (~64%); urine (~25%).

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Hepatic function impairment: In a single 10 mg dose study of lenvatinib in patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment, or a single 5 mg dose in patients with severe (Child-Pugh class C) hepatic impairment, the dose-adjusted AUC of lenvatinib was 119%, 107%, and 180%, respectively, as compared to patients with normal hepatic function.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (PR) Puerto Rico: Lenvima;
  • (QA) Qatar: Lenvima
  1. <800> Hazardous Drugs–Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 43-NF 38). Rockville, MD: United States Pharmacopeia Convention; 2020:74-92.
  2. Armenian SH, Lacchetti C, Barac A, et al. Prevention and monitoring of cardiac dysfunction in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2017;35(8):893-911. [PubMed 27918725]
  3. George D. Systemic therapy of advanced clear cell renal carcinoma. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 23, 2022.
  4. Gordan JD, Kennedy EB, Abou-Alfa GK, et al. Systemic therapy for advanced hepatocellular carcinoma: ASCO guideline. J Clin Oncol. 2020;38(36):4317-4345. doi:10.1200/JCO.20.02672 [PubMed 33197225]
  5. Hesketh PJ, Kris MG, Basch E, et al. Antiemetics: ASCO guideline update. J Clin Oncol. 2020;38(24):2782-2797. doi:10.1200/JCO.20.01296 [PubMed 32658626]
  6. Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. 2020;38(31):3698-3715. doi:10.1200/JCO.20.01757 [PubMed 32716741]
  7. Kudo M, Finn RS, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018. pii: S0140-6736(18)30207-30211. doi:10.1016/S0140-6736(18)30207-1 [PubMed 29433850]
  8. Lenvima (lenvatinib) [prescribing information]. Woodcliff Lake, NJ: Eisai Inc; November 2022.
  9. Lenvima (lenvatinib) [product monograph]. Mississauga, Ontario, Canada: Eisai Limited; May 2022.
  10. Lyon AR, López-Fernández T, Couch LS, et al. 2022 ESC guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022;43(41):4229-4361. doi:10.1093/eurheartj/ehac244 [PubMed 36017568]
  11. Makker V, Colombo N, Casado Herráez A, et al; Study 309–KEYNOTE-775 Investigators. Lenvatinib plus pembrolizumab for advanced endometrial cancer. N Engl J Med. Published online January 19, 2022. doi:10.1056/NEJMoa2108330 [PubMed 35045221]
  12. Motzer R, Alekseev B, Rha SY, et al; CLEAR Trial Investigators. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N Engl J Med. 2021;384(14):1289-1300. doi:10.1056/NEJMoa2035716 [PubMed 33616314]
  13. Motzer RJ, Hutson TE, Glen H, et al. Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial. Lancet Oncol. 2015;16(15):1473-1482. doi:10.1016/S1470-2045(15)00290-9 [PubMed 26482279]
  14. Ruggiero SL, Dodson TB, Fantasia J, et al; American Association of Oral and Maxillofacial Surgeons. American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw--2014 update. J Oral Maxillofac Surg. 2014;72(10):1938-1956. doi:10.1016/j.joms.2014.04.031 [PubMed 25234529]
  15. Schlumberger M, Tahara M, Wirth LJ, et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med. 2015;372(7):621-630. [PubMed 25671254]
  16. US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. https://www.cdc.gov/niosh/docs/2016-161/default.html. Updated September 2016. Accessed October 5, 2016.
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