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, 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: hypothyroidism

F and E: dehydration, hypocalcemia, hypokalemia

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

GU: proteinuria, renal impairment, ↓fertility, NEPHROTIC SYNDROME

Hemat: bleeding, thrombocytopenia

Metab: ↓weight

MS: 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:

Concurrent use of 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).
Concurrent use of 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 or 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 or 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 prior to and after 1 wk, then every 2 wk for first 2 mo, and then at least monthly thereafter during therapy. Initiate or adjust medication management to control BP. Hold lenvatinib for Grade 3 hypertension that persists despite antihypertensive therapy. Resume at a reduced dose (1st occurrence: 20 mg/day; 2nd occurrence: 14 mg/day; 3rd occurrence: 10 mg/day) when hypertension is controlled or ≤Grade 2). Discontinue lenvatinib for life-threatening hypertension.
Monitor for clinical signs and symptoms of cardiac dysfunction (shortness of breath, swollen ankles) during therapy. Hold lenvatinib for Grade 3 cardiac dysfunction until improved to Grade 0 or 1 or baseline. Resume at reduced dose (1st occurrence: 20 mg/day; 2nd occurrence: 14 mg/day; 3rd occurrence: 10 mg/day) 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. Discontinue lenvatinib if event occurs.
Assess for signs and symptoms of gastrointestinal perforation or fistula formation (severe abdominal pain) during therapy. Discontinue lenvatinib if gastrointestinal perforation or fistula occurs.
Monitor ECG for patients with congenital long QT syndrome, congestive heart failure, bradyarrhythmias, or those taking drugs known to prolong QT interval. Hold lenvatinib for development of QT interval prolongation >500 msec or >60 msec increase from baseline. Hold until improves to ≤480 msec or baseline. Resume at reduced dose (1st occurrence: 20 mg/day; 2nd occurrence: 14 mg/day; 3rd occurrence: 10 mg/day) when QT prolongation resolves to Grade 0 or 1.
Monitor for signs and symptoms of RPLS (severe headache, seizures, weakness, confusion, blindness or change in vision) during therapy. If symptoms occur, confirm diagnosis with MRI. Hold lenvatinib for RPLS until fully resolved. Resume at reduced dose (1st occurrence: 20 mg/day; 2nd occurrence: 14 mg/day; 3rd occurrence: 10 mg/day) or discontinue depending on severity and persistence of neurologic symptoms.
Monitor for bleeding (severe and persistent nose bleeds, vomiting blood, red or black stools, coughing up blood or blood clots, heavy or new onset vaginal bleeding) during therapy. Hold lenvatinib for Grade 3 hemorrhage until resolved to Grade 0 or 1. Resume at reduced dose (1st occurrence: 20 mg/day; 2nd occurrence: 14 mg/day; 3rd occurrence: 10 mg/day) or discontinue depending on severity and persistence of hemorrhage. Discontinue lenvatinib if Grade 4 hemorrhage occurs.
Obtain an oral exam prior to and periodically during therapy. Hold lenvatinib for at least 1 wk before scheduled dental surgery or invasive dental procedures, if possible. Discontinuation of bisphosphonate therapy may reduce the risk of ONJ. Hold lenvatinib if ONJ develops and restart after adequate resolution.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.For the pMMR/not MSI-H advanced endometrial carcinoma indication, 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. An FDA-approved test for selection of patients who are not MSI-H is not currently available.Monitor serum ALT and AST levels for hepatotoxicity prior to and every 2 wk for first 2 mo, and at least monthly thereafter during therapy. Hold lenvatinib for Grade 3 cardiac dysfunction until improved to Grade 0 or 1 or baseline. Resume at reduced dose (1st occurrence: 20 mg/day; 2nd occurrence: 14 mg/day; 3rd occurrence: 10 mg/day) or discontinue depending on severity and persistence of hepatotoxicity. May cause hypoalbuminemia, ↑ alkaline phosphatase, and hyperbilirubinemia.
- Monitor for proteinuria prior to and periodically during therapy. If urine dipstick proteinuria ≥2+ is detected, obtain 24 hr urine protein. Hold lenvatinib for ≥2 g proteinuria/24 hr and resume at reduced dose (1st occurrence: 20 mg/day; 2nd occurrence: 14 mg/day; 3rd occurrence: 10 mg/day) when proteinuria <2 g/24 hr. Discontinue lenvatinib for nephrotic syndrome.
- Monitor BUN and serum creatinine prior to and periodically during therapy. Hold lenvatinib for Grade 3 or 4 renal failure/impairment until resolved to Grade 0 or 1 or baseline. Resume at reduced dose (1st occurrence: 20 mg/day; 2nd occurrence: 14 mg/day; 3rd occurrence: 10 mg/day) or discontinue depending on severity and persistence of renal impairment.
- Monitor and correct electrolyte abnormalities. Monitor serum calcium levels 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 levels monthly and adjust thyroid replacement medication as needed in patients with ↓ thyroid levels.
- May cause ↑ serum lipase and amylase, hypercholesterolemia, and ↓ platelet count.

Implementation ⬆ ⬇

Hold therapy for at least 1 wk before elective surgery and for at least 2 wk after major surgery and until adequate wound healing occurs.
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 of water or apple juice and put capsule in liquid without breaking or crushing. Leave capsule in liquid for at least 10 min. Stir for at least 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 minutes 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 second 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 ⬆ ⬇

Instruct patient to take lenvatinib 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. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
Advise patient to notify health care professional 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 1 side of body; trouble talking; sudden severe headache; sudden vision changes), liver problems (yellow skin or whites of eyes, dark tea colored urine, light-colored bowel movements), severe stomach pain, RPLS, or bleeding occur.
Instruct patient to notify health care professional of therapy before any elective surgery or dental procedure. Lenvatinib must be stopped at least 1 wk before and for at least 2 wk after major surgery and until wound healing occurs.
Advise patient to practice good mouth care during therapy and to notify health care professional if signs and symptoms of ONJ (jaw pain, toothache, sores on gums) occur.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception during and for at least 30 days following last dose of therapy and to notify health care professional if pregnancy is suspected. Advise patient to avoid breastfeeding during and for at least 1 wk after last dose. May impair fertility in males and females.
Emphasize importance of lab tests to monitor for adverse reactions.

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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 ⬆