lenvatinib

ROUTE		ONSET		PEAK		DURATION
PO		within 2 mo		8 mo		throughout treatment

Contraindicated in:

OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Hypertension (control BP before initiating treatment; may need to withhold/discontinue for life-threatening elevation);
History of HF (may need to withhold/discontinue for worsening HF);
History of congenital long QTc syndrome, HF, bradyarrhythmias, and concurrent use of drugs that prolong QTc, including Class Ia and III antiarrhythmics (↑ risk of further QTc prolongation and serious arrhythmias; may require interruption/discontinuation of lenvatinib);
Severe hepatic or renal impairment (↓ dose);
Dehydration/volume depletion (↑ risk of renal impairment; may need to withhold/discontinue for worsening renal function);
Hypocalcemia (replace calcium; if persistent may require dose adjustment/interruption);
History of reversible posterior leukoencephalopathy syndrome (may require dose adjustment/interruption);
Invasive dental procedures, concurrent use of bisphosphonates or denosumab, or dental disease (may ↑ risk of osteonecrosis of the jaw [ONJ]);
Rep: Women and men of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypertension, HF, hypotension, MI, QT interval prolongation

Derm: alopecia, palmar-plantar erythrodysesthesia syndrome, rash, hyperkeratosis, impaired wound healing

EENT: dysphonia, epistaxis

Endo: hyperglycemia, hypoglycemia, hypothyroidism

F and E: hypercalcemia, hyperkalemia, hypermagnesemia, hypocalcemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, dehydration

GI: ↓appetite, ↑amylase, ↑lipase, ↑liver enzymes, abdominal pain, diarrhea, dry mouth, nausea, stomatitis, vomiting, weight loss, GI PERFORATION/FISTULA FORMATION, HEPATOTOXICITY

GU: ↑serum creatinine, proteinuria, ↓fertility, NEPHROTIC SYNDROME

Hemat: anemia, bleeding, leukopenia, lymphopenia, neutropenia, thrombocytopenia

Metab: hypercholesterolemia, hypertriglyceridemia, hypoalbuminemia

MS: ↑CK, arthralgia/myalgia, osteonecrosis (primarily of jaw)

Neuro: dysgeusia, fatigue, headache, insomnia, CAROTID ARTERY HEMORRHAGE, REVERSIBLE POSTERIOR LEUKOENCEPHALOPATHY SYNDROME (RPLS), STROKE

Resp: cough

Interactions ⬆ ⬇

Drug-drug:

QT interval prolonging drugs, including Class Ia and III antiarrhythmics, may ↑ risk of further QTc prolongation and serious arrhythmias (may require interruption/discontinuation of lenvatinib).
Alendronate, denosumab, ibandronate, pamidronate, risedronate, or zoledronic acid may ↑ risk of ONJ.

Route/Dosage ⬆ ⬇

Differentiated Thyroid Cancer

PO (Adults ): 24 mg once daily until disease progression or unacceptable toxicity.

Renal Impairment

PO (Adults ): CCr <30 mL/min: 14 mg once daily until disease progression or unacceptable toxicity.

Hepatic Impairment

PO (Adults ): Severe hepatic impairment: 14 mg once daily until disease progression or unacceptable toxicity.

Renal Cell Carcinoma

PO (Adults ): First-line treatment of advanced renal cell carcinoma: 20 mg once daily (in combination with pembrolizumab) until disease progression, unacceptable toxicity, or up to 2 yr. After 2 yr of combination therapy, continue 20 mg once daily (as monotherapy) until disease progression or unacceptable toxicity. Previously treated renal cell carcinoma: 18 mg once daily until disease progression or unacceptable toxicity.

Renal Impairment

PO (Adults ): CCr <30 mL/min: First-line treatment of advanced renal cell carcinoma: 10 mg once daily (in combination with pembrolizumab) until disease progression, unacceptable toxicity, or up to 2 yr. After 2 yr of combination therapy, continue 10 mg once daily (as monotherapy) until disease progression or unacceptable toxicity. Previously treated renal cell carcinoma: 10 mg once daily until disease progression or unacceptable toxicity.

Hepatic Impairment

PO (Adults ): Severe hepatic impairment: 10 mg once daily until disease progression or unacceptable toxicity.

Hepatocellular Carcinoma

PO (Adults ≥60 kg): 12 mg once daily until disease progression or unacceptable toxicity.
PO (Adults <60 kg): 8 mg once daily until disease progression or unacceptable toxicity.

Endometrial Carcinoma

PO (Adults ): 20 mg once daily until disease progression or unacceptable toxicity.

Renal Impairment

PO (Adults ): CCr <30 mL/min: 10 mg once daily until disease progression or unacceptable toxicity.

Hepatic Impairment

PO (Adults ): Severe hepatic impairment: 10 mg once daily until disease progression or unacceptable toxicity.

Availability ⬆ ⬇

Capsules: 4 mg; 10 mg

Assessment ⬆ ⬇

Assess BP before starting therapy and after 1 wk, then every 2 wk for 1st 2 mo, and then at least monthly thereafter during therapy. Control preexisting hypertension before starting therapy. If Grade 3 hypertension persists despite antihypertensive therapy, hold lenvatinib until BP is controlled or Grade ≤2; then resume therapy at ↓ dose. If life-threatening hypertension occurs, discontinue lenvatinib.
Monitor for clinical signs and symptoms of cardiac dysfunction (shortness of breath, swollen ankles) during therapy. If Grade 3 cardiac dysfunction occurs, hold lenvatinib until improved to Grade ≤1; then resume at ↓ dose or discontinue depending on severity and persistence of cardiac dysfunction.
Monitor for signs and symptoms of arterial thromboembolic events (chest pain, acute neurologic symptoms of MI or stroke) during therapy. If arterial thromboembolic events occurs, discontinue lenvatinib.
Assess for signs and symptoms of GI perforation or fistula formation (severe abdominal pain) during therapy. If GI perforation/fistula occurs, discontinue lenvatinib.
Monitor ECG for patients with congenital long QT syndrome, HF, bradyarrhythmias, or those taking QT interval prolonging medications. If QT interval >500 msec or ↑ by 60 msec from baseline, hold lenvatinib until QT interval ≤480 msec; then resume at ↓ dose.
Monitor for signs and symptoms of RPLS (severe headache, seizures, weakness, confusion, blindness or change in vision) during therapy. If signs/symptoms of RPLS occur, confirm diagnosis with MRI. If RPLS confirmed, hold lenvatinib until fully resolved; then resume at ↓ dose or discontinue depending on severity and persistence of neurologic symptoms.
Monitor for bleeding (severe and persistent nosebleeds, vomiting blood, red or black stools, coughing up blood or blood clots, heavy or new onset vaginal bleeding) during therapy. If Grade 3 hemorrhage occurs, hold lenvatinib until Grade ≤1; then resume at ↓ dose or discontinue depending on severity and persistence of hemorrhage. If Grade 4 hemorrhage occurs, discontinue lenvatinib.
Obtain an oral exam prior to and periodically during therapy. Hold lenvatinib for ≥1 wk before scheduled dental surgery or invasive dental procedures, if possible. Discontinuation of bisphosphonate therapy may ↓ risk of ONJ. Hold lenvatinib if ONJ develops and restart after adequate resolution.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.
For pMMR/not MSI-H advanced endometrial carcinoma, select patients for therapy with lenvatinib in combination with pembrolizumab based on MSI or MMR status in tumor specimens. Information on FDA-approved tests for patient selection is available at http://www.fda.gov/CompanionDiagnostics.
Monitor ALT and AST before starting therapy, every 2 wk for 1st 2 mo, and at least monthly thereafter during therapy. May cause hypoalbuminemia, ↑ alkaline phosphatase, and hyperbilirubinemia. Permanently discontinue for hepatic failure. If Grade 3–4 hepatotoxicity occurs, hold lenvatinib until ALT/AST ↓ Grade ≤1; then resume at ↓ dose.
Monitor for proteinuria prior to and periodically during therapy. If urine dipstick proteinuria ≥2+ is detected, obtain 24 hr urine protein. If ≥2 g proteinuria/24 hr occurs, hold lenvatinib until proteinuria <2 g/24 hr; then resume at ↓ dose. If nephrotic syndrome occurs, discontinue lenvatinib.
Monitor BUN and serum creatinine before starting and periodically during therapy. If Grade 3 or 4 renal failure/impairment occurs, hold lenvatinib until resolved to Grade ≤1; then resume at ↓ dose or discontinue depending on severity and persistence of renal impairment.
Monitor and correct electrolyte abnormalities. Monitor calcium at least monthly and replace calcium as needed during therapy. Interrupt and adjust lenvatinib dose based on severity, presence of ECG changes, and persistence of hypocalcemia. May cause hypokalemia, hypomagnesemia, hypoglycemia, hypercalcemia, and hyperkalemia.
Monitor TSH monthly and adjust thyroid replacement medication as needed in patients with ↓ thyroid levels.
May ↑ lipase and amylase and may cause hypercholesterolemia.
May cause anemia, neutropenia, leukopenia, and thrombocytopenia.

Implementation ⬆ ⬇

Recommended Dose Modifications: Differentiated thyroid cancer:1st dose reduction: 20 once daily; 2nd dose reduction: 14 mg once daily; 3rd dose reduction: 10 mg once daily. Renal cell carcinoma and endometrial carcinoma: 1st dose reduction: 14 mg once daily; 2nd dose reduction: 10 mg once daily; 3rd dose reduction: 8 mg once daily. Hepatocellular carcinoma (weight ≥60 kg): 1st dose reduction: 8 mg once daily; 2nd dose reduction: 4 mg once daily; 3rd dose reduction: 4 mg every other day. Hepatocellular carcinoma (weight <60 kg): 1st dose reduction: 4 mg once daily; 2nd dose reduction: 4 mg every other day; 3rd dose reduction: Discontinue lenvatinib.
Hold therapy for ≥1 wk before elective surgery and for ≥2 wk after major surgery, until adequate wound healing occurs.
During administration and when preparing tablets, wear double chemotherapy gloves, protective gown, and hair and shoe covers. Respiratory (N95) protection and eye/face protection is needed if there is risk of patient vomiting or spitting up. Single chemotherapy gloves are appropriate if handling and administering intact tablets from a unit-dose package. Health care providers who are actively trying to conceive, who are pregnant or may become pregnant, and who are breastfeeding should avoid handling lenvatinib.
PO: Administer two 10-mg capsules and one 4-mg capsule to make 24 mg at the same time each day without regard to food. DNC: Swallow capsules whole; do not open, crush, or chew. For patients with difficulty swallowing, measure 1 tablespoon (about 15 mL) of water or apple juice and put capsule in liquid without breaking or crushing. Leave capsule in liquid for ≥10 min. Stir for ≥3 min; then drink mixture. After drinking, add same amount (1 tablespoon) of water or apple juice to glass. Swirl contents and swallow additional liquid. For administration via feeding tube: Place required number of capsules, up to a maximum of 5, in a small container (20 mL capacity) or syringe (20 mL). Do not break or crush capsules. Add 3 mL of liquid to container or syringe. Wait 10 min for the capsule shell (outer surface) to disintegrate; then stir or shake mixture for 3 min until capsules are fully disintegrated and administer the entire contents. Add an additional 2 mL of liquid to container or syringe using a 2nd syringe or dropper, swirl or shake, and administer. Repeat this step at least once and until there is no visible residue to ensure all of the medication is taken. Suspension is stable for 24 hr if covered and refrigerated; discard suspension after 24 hr.

Patient/Family Teaching ⬆ ⬇

Explain the purpose a side effects of lenvatinib. Instruct patient to take as directed at the same time each day. Take missed dose within 12 hr or omit and take next dose at usual time; do not double doses. Keep out of children’s reach. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
Explain need for continued medical follow-up to assess effectiveness and possible side effects of medication. Emphasize importance of lab tests to monitor for adverse reactions.
Advise patient to immediately report signs and symptoms of hepatotoxicity (fatigue, nausea, upper abdominal pain, yellowing of skin or eyes, dark urine, light-colored stools).
Advise patient to notify health care provider promptly if signs and symptoms of high BP, heart problems, blood clots (severe chest pain or pressure; pain in arms, back, or jaw; shortness of breath; numbness or weakness on one side of body; trouble talking; sudden severe headache; sudden vision changes), severe stomach pain, RPLS, or bleeding occur.
Instruct patient to notify health care provider of therapy before any elective surgery or dental procedure. Lenvatinib must be stopped ≥1 wk before and for ≥2 wk after major surgery until wound healing occurs.
Advise patient to practice good mouth care during therapy and to notify health care provider if signs and symptoms of ONJ (jaw pain, toothache, sores on gums) occur.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications.
Rep: May cause fetal harm. Advise women of reproductive potential to use effective contraception during and for ≥30 days following last dose of therapy and to notify health care provider if pregnancy is suspected. Advise patient to avoid breastfeeding during and for ≥1 wk after last dose. May impair fertility in men and women.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆