Version July 2025
Dosage guidance:
Safety: 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.
Clinical considerations: Lenvatinib is associated with a moderate or high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref). Refer to the protocol or institutional guidance for additional details of off-label dosing.
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: 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:
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:
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).
Thymic carcinoma, advanced or metastatic, relapsed or refractory (subsequent therapy) (alternative therapy) (off-label use): Note: Experts recommend treatment with lenvatinib in patients with thymic carcinoma who progress on chemotherapy and progress on (or are ineligible for) immunotherapy (Ref).
Oral: 24 mg once daily; continue until disease progression or unacceptable toxicity (Ref).
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.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Kenar D. Jhaveri, MD; Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Preexisting altered kidney function:
Note: CrCl calculated by Cockcroft-Gault equation (using actual body weight) (Ref).
CrCl ≥30 mL/minute: Oral: No dosage adjustment necessary (Ref).
CrCl <30 mL/minute: Oral:
Endometrial carcinoma, advanced: 10 mg once daily (Ref).
Hepatocellular carcinoma, unresectable: There are no dosage adjustments provided in the manufacturer's labeling.
Renal cell cancer, advanced: 10 mg once daily (Ref).
Thyroid cancer, differentiated: 14 mg once daily (Ref).
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2): Note: Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Young patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).
Oral: No dosage adjustment necessary (Ref).
Hemodialysis, intermittent (thrice weekly): Unlikely to be significantly dialyzable (highly protein bound): Oral: Dose as for CrCl <30 mL/minute (Ref).
Peritoneal dialysis: Oral: Dose as for CrCl <30 mL/minute (Ref).
CRRT: Dose as for CrCl <30 mL/minute (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): Dose as for CrCl <30 mL/minute (Ref).
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.
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.
|
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 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. | |
Refer to adult dosing.
An increased risk of fatal cardiac adverse effects has been reported with vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor therapy. Serious (grade ≥ 3) and fatal cardiac dysfunction, including cardiomyopathy, left or right ventricular dysfunction, heart failure, ventricular hypokinesia, and reduced ejection fraction occurred in lenvatinib-treated patients. Cardiotoxicity associated with inhibition of the VEGF pathway is often reversible (Ref). P rolonged QT interval on ECG has also occurred with lenvatinib, including events of >500 msec and increases of >60 msec. In a retrospective pharmacovigilance study, lenvatinib was associated with an increased rate of prolonged QT interval on ECG when compared to other antiangiogenic tyrosine kinase inhibitors (Ref).
Mechanism: Cardiomyopathy: Not clearly established; may be dose-related and related to pharmacologic action (ie, VEGF inhibition). VEGF inhibition contributes to microvascular dysfunction in cardiac tissue and induction of hypoxia and hypoxia-inducible factor in the myocardium (Ref). Prevention of cardiac remodeling has also been hypothesized (Ref).
Risk factors:
Drug-induced QTc prolongation/torsades de pointes (TdP) (in general):
• Age >65 years (Ref)
• Baseline QTc interval prolongation (eg, >500 msec) or lengthening of the QTc by ≥60 msec (Ref)
• Bradycardia (Ref)
• Concurrent administration of multiple medications (≥2) that prolong the QT interval or medications with drug interactions that increase serum concentrations of QT-prolonging medications (Ref)
• Congenital long QT syndrome (LQTS) (Ref)
• Electrolyte disturbances (eg, hypocalcemia, hypokalemia, hypomagnesemia) (Ref)
• Females (Ref)
• Genetic defects of cardiac ion channels (Ref)
• History of drug-induced TdP (Ref)
• Kidney impairment (Ref)
• Liver impairment (Ref)
• Loop diuretic use (Ref)
• Sepsis (Ref)
• Structural heart disease (eg, history of myocardial infarction or heart failure with reduced ejection fraction) (Ref)
Serious, and sometimes fatal, gastrointestinal perforation has occurred with inhibitors of the vascular endothelial growth factor (VEGF) pathway, including lenvatinib. Additionally, fistulae formation (including tracheoesophageal, bronchopleural, bladder, and bowel) have been observed in lenvatinib-treated patients (Ref).
Mechanism: Not clearly established; may be dose-related and related to pharmacologic action (ie, VEGF inhibition) resulting in regression of capillaries of intestinal villi (Ref). Additional proposed mechanisms include submucosal inflammation and loss of vascular integrity secondary to disturbance of platelet and endothelial cell interactions; exacerbation of existing diverticulitis or ulcers; tumor necrosis; and ischemic perforation of normal bowel or anastomotic sites (Ref).
Onset: Delayed; average time to fistula was 10.4 weeks in one retrospective study in thyroid cancer (Ref).
Risk factors:
• Abdominal carcinomatosis (Ref)
• Bowel obstruction (Ref)
• Diverticulitis (Ref)
• Histologic diagnosis of papillary thyroid cancer or poorly differentiated thyroid cancer (Ref)
• History of aerodigestive, pelvic, or abdominal irradiation (Ref)
• Intra-abdominal abscess (Ref)
• Previous bowel surgery (Ref)
• Recent history of sigmoidoscopy or colonoscopy (Ref)
• Tumor invasion at fistula/perforation site (Ref)
Diarrhea occurred in ~50% of patients receiving lenvatinib monotherapy in clinical trials, including grade 3 events. When used in combination with everolimus for the management of renal cell carcinoma, diarrhea was the most frequent cause of dose interruption and/or reduction, and diarrhea recurred despite dose reduction. Higher rates of diarrhea are observed in multikinase inhibitors, such as lenvatinib, when compared to pure vascular endothelial growth factor (VEGF) inhibitors (Ref).
Mechanism: Not clearly established; multiple mechanisms have been proposed, including direct local irritation by excreted metabolites (Ref); transient lactose intolerance (Ref); inhibition of microcirculation in GI tract secondary to VEGF inhibition (Ref); and intestinal microbiome changes (Ref).
Onset: Varied; most events occurred beyond the first month of treatment with lenvatinib. Median time to first onset of diarrhea ranged from 4.8 to 20 weeks in various studies (Ref).
Serious and fatal hemorrhagic events may occur with lenvatinib. Hemorrhage (any grade) occurred in over 25% of patients treated with lenvatinib monotherapy or in combination with everolimus; epistaxis and hematuria were the most 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 hemorrhage-related events (including cases of fatal hemorrhage) have also 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. In one retrospective study, intratumoral and intraperitoneal bleeding occurred in 7.4% of patients with hepatocellular cancer (Ref).
Mechanism: Not clearly established; may be dose-related and related to pharmacologic action (ie, vascular endothelial growth factor and platelet-derived growth factor receptor inhibition). Possible mechanisms include blood vessel destabilization, loss of vascular integrity, and thrombocytopenia (Ref).
Onset: Varied; 2 to 11 days has been reported for hepatocellular cancer (Ref). Average onset to tumor-related bleeding was 10.4 weeks in one retrospective study in thyroid cancer (Ref). Onset of grade 4 and 5 (fatal) hemorrhage occurred at ~7 to 238 days in renal cell cancer, thyroid cancer, and glioma clinical trials (Ref).
Risk factors:
• Anaplastic thyroid carcinoma
• Concomitant anticoagulant (Ref)
• Heptocellular tumor diameter >90 mm (Ref)
• Preexisting high-risk esophagogastric varices (Ref)
• Tumor invasion or infiltration of major blood vessels (eg, carotid artery)
Serious hepatic events (including fatalities) were observed in patients with malignancies (other than hepatocellular carcinoma [HCC]) treated with lenvatinib. Fatal adverse events included hepatic failure, acute hepatitis, and hepatorenal syndrome. In HCC patients, hepatic encephalopathy (including encephalopathy, metabolic encephalopathy, and hepatic coma) and hepatic failure, including grade 3 to 5 events, occurred, requiring treatment modification and discontinuation. Hyperbilirubinemia, increased gamma-glutamyl transferase, increased serum alanine aminotransferase, increased serum aspartate aminotransferase, and increased serum alkaline phosphatase have also occurred.
Onset: Delayed; median time to first hepatic event in HCC was 6.4 weeks in one literature review (Ref).
Risk factors:
• Hepatic encephalopathy or hepatic failure in HCC:
- Age ≥75 years (Ref)
- Worsened hepatic impairment and/or tumor burden at baseline (Ref)
Hypertension is associated with inhibitors of the vascular endothelial growth factor (VEGF) pathway (eg, lenvatinib), including grade ≥3 events. Serious complications have been reported secondary to poorly controlled hypertension associated with lenvatinib; uncontrolled hypertension may contribute to the development of angina, subarachnoid/intracerebral hemorrhage, myocardial infarction, heart failure, sudden cardiac death, ischemic stroke, kidney failure, and peripheral arterial disease (Ref). Risk of hypertension appears to be greater with lenvatinib when compared to other inhibitors of the VEGF pathway secondary to more potent inhibition of VEGFR2 (Ref). Hypertension associated with inhibition of the VEGF pathway appears to be reversible and usually resolves upon discontinuation of therapy (Ref).
Mechanism: Not clearly established; may be dose-related and related to pharmacologic action (ie, VEGF inhibition, fibroblast growth factor receptor inhibition). Multiple mechanisms have been proposed, including endothelial vasoconstriction and vascular resistance through reduction in nitric oxide and prostacyclin synthesis and increases in circulating endothelin-1 (Ref); interruption of survival signaling in endothelial cells and decreased angiogenesis, leading to cellular apoptosis, reduced microvascular density (rarefaction), and ultimately an increase in vascular resistance (Ref); and regulation of endothelial cell function in the renal glomeruli (Ref).
Onset: Varied; most cases occur within the first 6 weeks of treatment initiation; median time to first onset of new or worsening hypertension in clinical trials with lenvatinib monotherapy is 16 to 35 days.
Risk factors:
• Advanced age (Ref)
• History of smoking (Ref)
• Hyperlipidemia (Ref)
• Japanese ethnicity (Ref)
• Longer treatment duration (Ref)
• Obesity (Ref)
• Preexisting hypertension or cardiovascular disease (Ref)
• Previous treatment with an anthracycline (Ref)
Treatment with lenvatinib is associated with the development of hypocalcemia, including grade 3 to 4 events. In patients with differentiated thyroid cancer, hypocalcemia improved or resolved following oral or IV calcium supplementation, with or without dose modification of lenvatinib.
Mechanism: Not clearly established; multiple mechanisms have been proposed, including postsurgical hypoparathyroidism following thyroidectomy (Ref); vitamin D and/or magnesium malabsorption secondary to adverse effects (eg, nausea, vomiting, diarrhea, anorexia) (Ref); tumor lysis syndrome (Ref); and direct effect on bone metabolism via vascular endothelial growth factor inhibitory effects on osteoblasts and osteoclasts (Ref).
Onset: Delayed; median time to onset from treatment initiation in a retrospective cohort study in advanced thyroid cancer was 3 months (range: 0.5 to 13 months) (Ref); hypocalcemia was observed as early as 2 weeks postinitiation in a single case report (Ref).
Osteonecrosis of the jaw (ONJ), also referred to as medication-related osteonecrosis of the jaw, has been reported in patients receiving lenvatinib and is characterized in oncology patients by nonhealing (persistence >8 weeks) exposed or necrotic bone in the maxillofacial region in patients with current or previous treatment with bone modifying agents or angiogenic inhibitors and no history of radiation or metastatic disease to the jaw (Ref).
Mechanism: Dose-related; related to pharmacologic action (ie, vascular endothelial growth factor inhibition) resulting in wound healing impairment, and effects on bone remodeling (Ref).
Risk factors:
• Concomitant exposure to antiresorptive therapy (eg, bisphosphonates, denosumab) (Ref)
• Concomitant exposure to alternative anticancer therapies (eg, everolimus, glucocorticoids) (Ref)
• Dental disease (Ref)
• Invasive dental procedures (Ref)
Dermatologic toxicity may occur with lenvatinib therapy, particularly palmar-plantar erythrodysesthesia.
Mechanism: Not clearly established; impaired vascular repair in high friction areas (hands and feet) secondary to combined vascular endothelial growth factor and platelet-derived growth factor receptor inhibition has been proposed (Ref). Alternatively, dermatologic toxicity may be related to epidermal cell apoptosis (Ref).
Onset: Varied; most cases occurred within the first 3 months of treatment (Ref). Median time to first onset of palmar-plantar erythrodysesthesia was 5.1 to 5.9 weeks in hepatocellular carcinoma and thyroid carcinoma (differentiated), respectively (Ref) and 8.1 to 9.7 weeks in combination with pembrolizumab for endometrial carcinoma (Ref).
Risk factors:
• Japanese ethnicity (Ref)
• Age <75 years (Ref)
• Longer duration of therapy (Ref)
Proteinuria, including grade 3 events, has occurred with lenvatinib. Lenvatinib produces proteinuria at a higher frequency than other vascular endothelial growth factor (VEGF) inhibitors given more potent inhibitory properties (Ref). Hypertension does not appear to contribute to the pathogenesis associated with proteinuria secondary to lenvatinib (Ref). In studies with other VEGF inhibitor therapy, proteinuria is typically asymptomatic and decreases following discontinuation (Ref).
Mechanism: Not clearly established; may be dose-related and related to pharmacologic action (ie, VEGF inhibition) resulting in renal podocyte dysfunction (Ref).
Onset: Varied; median time to first onset of proteinuria: 6.1 weeks in hepatocellular carcinoma and thyroid carcinoma, differentiated (Ref) and 3.2 to 5.1 weeks in combination with pembrolizumab in endometrial carcinoma and renal cell carcinoma (Ref).
Risk factors:
• Advanced age (Ref)
• Diabetes mellitus (Ref)
• Hypertension (Ref)
• Preexisting grade 1 proteinuria (Ref)
• Japanese ethnicity (Ref)
Reversible posterior leukoencephalopathy syndrome (RPLS) has been reported with lenvatinib; signs and symptoms include cerebral edema, headache, visual loss, seizure, hypertension, and encephalopathy (Ref). RPLS symptoms and associated white matter changes may be reversible upon lenvatinib discontinuation (Ref).
Mechanism: Dose-related; exact mechanism is unknown, likely secondary to pharmacologic action (ie, vascular endothelial growth factor inhibition) and related hypertension and endothelial dysfunction (Ref).
Onset: Varied; diagnosis within 1 month of initiating therapy has been reported (Ref); another reported case occurred 7 months after initiation of therapy (Ref).
Lenvatinib is associated with an increased risk of arterial thromboembolism; data on venous thromboembolism are conflicting (Ref); however, pulmonary embolism was observed in clinical trials. In a retrospective pharmacovigilance study, lenvatinib was associated with a higher rate of ischemic heart disease and cerebral ischemia compared to other antiangiogenic tyrosine kinase inhibitors (Ref). The safety of resuming lenvatinib following an arterial thromboembolic event has not been established.
Mechanism: Not clearly established; likely dose-related and related to pharmacologic action (ie, vascular endothelial growth factor inhibition). Proposed mechanisms include endothelial cell apoptosis creating a prothrombotic state; lack of endothelial cell renewal resulting in exposure of the extracellular matrix to circulating blood and platelet activation through exposure to collagen and von Willebrand factor; increased tissue factor expression; reduced nitric oxide and thrombomodulin expression; and direct platelet activation (Ref).
Lenvatinib is associated with effects on thyroid function. In patients with normal baseline thyroid stimulating hormone levels, 50% to 70% had increased thyroid stimulating hormone following treatment with lenvatinib, both as monotherapy and when used in combination with everolimus. Grade 1 or 2 hypothyroidism occurred in approximately one-quarter of patients treated with lenvatinib. Thyrotoxicosis occurred in 10% of hepatocellular carcinoma patients treated with lenvatinib (Ref).
Mechanism: Not clearly established; multiple mechanisms have been proposed, including destructive thyroiditis secondary to apoptosis of thyroid follicular cells; and prevention of vascular endothelial growth factor binding to normal thyroid cells, inhibition of thyroid blood flow, and tissue ischemia (Ref).
Onset: Varied; hypothyroidism occurred as early as 2 weeks from initiation of lenvatinib in one retrospective study (Ref). Median time to first onset of hypothyroidism (lenvatinib in combination with pembrolizumab) ranged from 6.1 to 14.3 weeks in various studies (Ref). Thyrotoxicosis generally occurred within 8 weeks of lenvatinib initiation; onset within 1 week of therapy has also been reported (Ref).
Vascular endothelial growth factor (VEGF) receptor inhibitors, including lenvatinib, are associated with wound healing impairment. Life-threatening and fatal outcomes related to delayed wound healing have occurred (Ref). Reports of bleeding and fistula enlargement at previous surgical site are attributed to initiation of lenvatinib months after transesophageal puncture prosthetic placement (to facilitate resonant speech) (Ref). The safety of resuming lenvatinib following resolution of wound healing complications has not been established.
Mechanism: Not clearly established; likely dose-related and related to pharmacologic action (ie, VEGF inhibition). Proposed mechanisms include platelet dysfunction and decreased expression of endothelial tissue factor (Ref).
Onset: Varied; time to delayed wound healing from tissue injury or surgery was 4 to 58 days in one study (Ref); time to procedural site bleeding or fistula expansion after start of lenvatinib was 6 to 9 months in 2 case reports (Ref).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Cardiovascular: Hypertension (45% to 73%; severe hypertension: 3%) (table 1), peripheral edema (14% to 21%)
|
Drug (Lenvatinib) |
Comparator (Sorafenib) |
Placebo |
Dose |
Indication |
Number of Patients (Lenvatinib) |
Number of Patients (Sorafenib) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
73% |
N/A |
16% |
24 mg once daily |
Differentiated thyroid cancer |
261 |
N/A |
131 |
|
45% |
31% |
N/A |
12 mg once daily (patients ≥60 kg) or 8 mg once daily (patients <60 kg) |
Hepatocellular carcinoma |
476 |
475 |
N/A |
Dermatologic: Alopecia (12%), palmar-plantar erythrodysesthesia (27% to 32%) (table 2), skin rash (14% to 21%)
|
Drug (Lenvatinib) |
Comparator (Sorafenib) |
Placebo |
Dose |
Indication |
Number of Patients (Lenvatinib) |
Number of Patients (Sorafenib) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
32% |
N/A |
1% |
24 mg once daily |
Differentiated thyroid cancer |
261 |
N/A |
131 |
|
27% |
52% |
N/A |
12 mg once daily (patients ≥60 kg) or 8 mg once daily (patients <60 kg) |
Hepatocellular carcinoma |
476 |
475 |
N/A |
Endocrine & metabolic: Hyponatremia (grades 3/4: 15%), hypothyroidism (21%), 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%; grades 3/4: 4% to 9%) (table 3), dysgeusia (18%), dyspepsia (13%), mouth pain (25%), nausea (20% to 47%; grades 3/4: 1% to 2%), stomatitis (11% to 41%; grades 3/4: ≤5%), vomiting (16% to 36%; grades 3/4: 1% to 2%), xerostomia (17%)
|
Drug (Lenvatinib) |
Comparator (Sorafenib) |
Placebo |
Dose |
Indication |
Number of Patients (Lenvatinib) |
Number of Patients (Sorafenib) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
All grades: 67% |
N/A |
All grades: 17% |
24 mg once daily |
Differentiated thyroid cancer |
261 |
N/A |
131 |
|
Grades 3/4: 9% |
N/A |
Grades 3/4: 0% |
24 mg once daily |
Differentiated thyroid cancer |
261 |
N/A |
131 |
|
All grades: 39% |
All grades: 46% |
N/A |
12 mg once daily (patients ≥60 kg) or 8 mg once daily (patients <60 kg) |
Hepatocellular carcinoma |
476 |
475 |
N/A |
|
Grades 3/4: 4% |
Grades 3/4: 4% |
N/A |
12 mg once daily (patients ≥60 kg) or 8 mg once daily (patients <60 kg) |
Hepatocellular carcinoma |
476 |
475 |
N/A |
Genitourinary: Proteinuria (26% to 34%), urinary tract infection (11%)
Hematologic & oncologic: Hemorrhage (23%, including carotid artery hemorrhage; grades 3/4: 4%) (table 4)
|
Drug (Lenvatinib) |
Comparator (Sorafenib) |
Dose |
Indication |
Number of Patients (Lenvatinib) |
Number of Patients (Sorafenib) |
|---|---|---|---|---|---|
|
All grades: 23% |
All grades: 15% |
12 mg once daily (patients ≥60 kg) or 8 mg once daily (patients <60 kg) |
Hepatocellular carcinoma |
476 |
475 |
|
Grades 3/4: 4% |
Grades 3/4: 4% |
12 mg once daily (patients ≥60 kg) or 8 mg once daily (patients <60 kg) |
Hepatocellular carcinoma |
476 |
475 |
Hepatic: Ascites (15%; severe: 3%), hyperbilirubinemia (grades 3/4: 13%) (table 5), increased gamma-glutamyl transferase (grades 3/4: 17%), increased serum aspartate aminotransferase (grades 3/4: 5% to 12%) (table 6)
|
Drug (Lenvatinib) |
Comparator (Sorafenib) |
Dose |
Indication |
Number of Patients (Lenvatinib) |
Number of Patients (Sorafenib) |
|---|---|---|---|---|---|
|
Grades 3/4: 13% |
Grades 3/4: 10% |
12 mg once daily (patients ≥60 kg) or 8 mg once daily (patients <60 kg) |
Hepatocellular carcinoma |
476 |
475 |
|
Drug (Lenvatinib) |
Comparator (Sorafenib) |
Placebo |
Dose |
Indication |
Number of Patients (Lenvatinib) |
Number of Patients (Sorafenib) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
Grades 3/4: 5% |
N/A |
Grades 3/4: 0% |
24 mg once daily |
Differentiated thyroid cancer |
261 |
N/A |
131 |
|
Grades 3/4: 12% |
Grades 3/4: 18% |
N/A |
12 mg once daily (patients ≥60 kg) or 8 mg once daily (patients <60 kg) |
Hepatocellular carcinoma |
476 |
475 |
N/A |
Nervous system: Dizziness (15%), fatigue (44% to 67%), headache (10% to 38%), insomnia (12%), voice disorder (24% to 31%)
Neuromuscular & skeletal: Arthralgia (≤62%), myalgia (≤62%)
Renal: Kidney impairment (7% to 14%)
Respiratory: Cough (24%), epistaxis (12%)
Miscellaneous: Fever (15%)
1% to 10%:
Cardiovascular: Arterial thromboembolism (2% to 5%), cardiomyopathy (grades ≥3: ≤3%), heart failure (grades ≥3: ≤3%), hypotension (9%), prolonged QT interval on ECG (8% to 9%; >500 msec: 2%) (table 7), pulmonary embolism (3%) (table 8), reduced ejection fraction (ejection fraction reduced by >20%: grades ≥3: ≤3%), ventricular dysfunction (grades ≥3: ≤3%; ventricular hypokinesia: grades ≥3: ≤3%)
|
Drug (Lenvatinib) |
Placebo |
Dose |
Indication |
Number of Patients (Lenvatinib) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|
|
9% |
2% |
24 mg once daily |
Differentiated thyroid cancer |
261 |
131 |
N/A |
|
2% |
N/A |
24 mg once daily |
Differentiated thyroid cancer |
261 |
131 |
>500 msec |
|
8% |
N/A |
12 mg once daily (patients ≥60 kg) or 8 mg once daily (patients <60 kg) |
Hepatocellular carcinoma |
476 |
N/A |
>60 msec |
|
2% |
N/A |
12 mg once daily (patients ≥60 kg) or 8 mg once daily (patients <60 kg) |
Hepatocellular carcinoma |
476 |
N/A |
>500 msec |
|
Drug (Lenvatinib) |
Placebo |
Dose |
Indication |
Number of Patients (Lenvatinib) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
3% |
2% |
24 mg once daily |
Differentiated thyroid cancer |
261 |
131 |
Dermatologic: Hyperkeratosis (7%)
Endocrine & metabolic: Dehydration (9%; severe dehydration: 3%), hypercalcemia (>5%), hypercholesterolemia (>5%), hyperkalemia (>5%), hypoalbuminemia (>5%), hypocalcemia (grades 3/4: 9%) (table 9), hypoglycemia (>5%), hypokalemia (grades 3/4: 3% to 6%), hypomagnesemia (>5%)
|
Drug (Lenvatinib) |
Placebo |
Dose |
Indication |
Number of Patients (Lenvatinib) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
Grades 3/4: 9% |
Grades 3/4: 2% |
24 mg once daily |
Differentiated thyroid cancer |
261 |
131 |
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%; including encephalopathy, hepatic coma, and metabolic encephalopathy) (table 10), hepatic failure (grades ≥3: 3%) (table 11), increased serum alanine aminotransferase (grades 3/4: 4% to 8%) (table 12), increased serum alkaline phosphatase (>5%)
|
Drug (Lenvatinib) |
Comparator (Sorafenib) |
Dose |
Indication |
Number of Patients (Lenvatinib) |
Number of Patients (Sorafenib) |
|---|---|---|---|---|---|
|
8% |
3% |
12 mg once daily (patients ≥60 kg) or 8 mg once daily (patients <60 kg) |
Hepatocellular carcinoma |
476 |
475 |
|
Drug (Lenvatinib) |
Comparator (Sorafenib) |
Dose |
Indication |
Number of Patients (Lenvatinib) |
Number of Patients (Sorafenib) |
|---|---|---|---|---|---|
|
Grades ≥3: 3% |
Grades ≥3: 3% |
12 mg once daily (patients ≥60 kg) or 8 mg once daily (patients <60 kg) |
Hepatocellular carcinoma |
476 |
475 |
|
Drug (Lenvatinib) |
Comparator (Sorafenib) |
Placebo |
Dose |
Indication |
Number of Patients (Lenvatinib) |
Number of Patients (Sorafenib) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
Grades 3/4: 4% |
N/A |
Grades 3/4: 0% |
24 mg once daily |
Differentiated thyroid cancer |
261 |
N/A |
131 |
|
Grades 3/4: 8% |
Grades 3/4: 9% |
N/A |
12 mg once daily (≥60 kg) or 8 mg once daily (patients <60 kg) |
Hepatocellular carcinoma |
476 |
475 |
N/A |
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 (table 13)
|
Drug (Lenvatinib) |
Placebo |
Dose |
Indication |
Number of Patients (Lenvatinib) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
0.4% |
0% |
24 mg once daily |
Differentiated thyroid cancer |
261 |
131 |
Frequency not defined:
Genitourinary: Hematuria
Nervous system: Asthenia
Postmarketing:
Cardiovascular: Aneurysm (arterial), aortic aneurysm, aortic dissection, coronary artery dissection, ischemic heart disease (Ref), myocardial rupture (arterial rupture and aortic rupture)
Dermatologic: Dermal ulcer (Ref), pyoderma gangrenosum (Ref)
Endocrine & metabolic: Thyroiditis (Ref), thyrotoxicosis (Ref)
Gastrointestinal: Cholecystitis, colitis (Ref), gallbladder perforation (Ref), pancreatitis (including acute pancreatitis) (Ref)
Hematologic & oncologic: Polycythemia (Ref), tumor hemorrhage (Ref), tumor lysis syndrome (Ref)
Nervous system: Cerebral ischemia (Ref)
Renal: Nephrotic syndrome (including focal segmental glomerulosclerosis) (Ref)
Respiratory: Interstitial pneumonitis (Ref), pneumothorax (Ref)
Miscellaneous: Wound healing impairment (Ref)
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to lenvatinib or any component of the formulation.
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.
Each Lenvima Therapy Pack contains a 30 day supply of dosage units
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 (15 ea, 90 ea)
Lenvima (14 MG Daily Dose): 10 mg & 4 mg (60 ea)
Lenvima (18 MG Daily Dose): 10 mg & 2 x 4 mg (15 ea, 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 (5 ea, 30 ea)
Lenvima (8 MG Daily Dose): 2 x 4 mg (10 ea, 60 ea)
No
Capsule Therapy Pack (Lenvima (10 MG Daily Dose) Oral)
10 mg (per each): $999.32
Capsule Therapy Pack (Lenvima (12 MG Daily Dose) Oral)
3 x 4 mg (per each): $333.11
Capsule Therapy Pack (Lenvima (14 MG Daily Dose) Oral)
10 & 4 mg (per each): $499.66
Capsule Therapy Pack (Lenvima (18 MG Daily Dose) Oral)
10 MG &2 x 4 MG (per each): $333.11
Capsule Therapy Pack (Lenvima (20 MG Daily Dose) Oral)
2 x 10 mg (per each): $499.66
Capsule Therapy Pack (Lenvima (24 MG Daily Dose) Oral)
2 x 10 MG &4 MG (per each): $333.11
Capsule Therapy Pack (Lenvima (4 MG Daily Dose) Oral)
4 mg (per each): $999.32
Capsule Therapy Pack (Lenvima (8 MG Daily Dose) Oral)
2 x 4 mg (per each): $499.66
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.
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 (90 ea)
Lenvima (14 MG Daily Dose): 10 mg & 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)
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
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 whole; do not crush or chew capsules.
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 agent (NIOSH 2024 [table 2]).
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 2023; NIOSH 2024; 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.
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, in patients with contraindications to immune check point inhibitor (ICI) combination therapy, lenvatinib may be offered as a first-line treatment option for select patients with advanced HCC with Child-Pugh class A hepatic impairment and performance status of 0 or 1. Lenvatinib is a second-line therapy option in patients who received first-line ICI combination therapy (ASCO [Gordan 2024]).
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 in adults.
Thymic carcinoma, advanced or metastatic, relapsed or refractory
Lenvatinib may be confused with cabozantinib, enasidenib, lapatinib, larotrectinib, lonafarnib, lorlatinib, neratinib, sorafenib, tivozanib, vandetanib
Lenvima may be confused with Lynparza
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
Substrate of BCRP, CYP3A4 (Minor), P-glycoprotein (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
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 drug interactions program by clicking on the “Launch drug interactions program” link above.
Amiodarone: QT-prolonging Kinase Inhibitors (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase hypertensive effects of Androgens. Risk C: Monitor
Azithromycin (Systemic): QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects of Citalopram. Risk X: Avoid
Clarithromycin: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Clarithromycin. Risk X: Avoid
Clofazimine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase hyponatremic effects of Desmopressin. Risk C: Monitor
Domperidone: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Domperidone. Risk X: Avoid
Doxepin-Containing Products: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Risk X: Avoid
Escitalopram: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Risk X: Avoid
Fingolimod: May increase QTc-prolonging effects 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
Flecainide: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects of Flupentixol. Risk X: Avoid
Gadobenate Dimeglumine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Risk C: Monitor
Imipramine: May increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects of Lenvatinib. Ketoconazole (Systemic) may increase 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
Levofloxacin-Containing Products (Systemic): QT-prolonging Kinase Inhibitors (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects of Levoketoconazole. Risk X: Avoid
Lofexidine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects of Moxifloxacin (Systemic). Risk X: Avoid
Nilotinib: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Nilotinib. Risk X: Avoid
OLANZapine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects 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
PAZOPanib: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of PAZOPanib. Risk X: Avoid
Pentamidine (Systemic): QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects 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
Piperaquine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Piperaquine. Risk X: Avoid
Probucol: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Probucol. Risk X: Avoid
Propafenone: May increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects 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
QT-prolonging Agents (Indeterminate Risk - Caution): May increase QTc-prolonging effects 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
QT-prolonging Class IA Antiarrhythmics (Highest Risk): QT-prolonging Kinase Inhibitors (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects of QT-prolonging Kinase Inhibitors (Highest Risk). Risk X: Avoid
QT-prolonging Miscellaneous Agents (Highest Risk): QT-prolonging Kinase Inhibitors (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase 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 increase QTc-prolonging effects of QUEtiapine. Risk X: Avoid
Quizartinib: May increase QTc-prolonging effects 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 increase QTc-prolonging effects of Ribociclib. Risk X: Avoid
RisperiDONE: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of RisperiDONE. QT-prolonging Agents (Highest Risk) may increase CNS depressant effects 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 increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Risk X: Avoid
Solriamfetol: May increase hypertensive effects of Hypertension-Associated Agents. Risk C: Monitor
Sparfloxacin: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Sparfloxacin. Risk X: Avoid
SUNItinib: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects of Thioridazine. Risk X: Avoid
Toremifene: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase anticoagulant effects of Warfarin. Risk C: Monitor
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.
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.
Based on the mechanism of action and findings from animal reproduction studies, lenvatinib may cause fetal harm if administered in pregnancy.
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.
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.
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.
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%).
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.
