Lenvatinib

Lenvatinib is a prescription medication used to treat Differentiated Thyroid Cancer, Renal Cell Carcinoma, Hepatocellular Carcinoma, Endometrial Cancer. 

• Lenvatinib is available under the following different brand names: Lenvima.

Adult dosage

Capsule

• 4mg
• 10mg

Differentiated Thyroid Cancer

Adult dosage

• 24 mg (two 10 mg capsules and one 4 mg capsule) orally once daily

Renal Cell Carcinoma

Adult dosage

• Combination therapy with everolimus
• Levatinib 18 mg (one 10 mg capsule and two 4 mg capsules) orally once daily plus
• Everolimus 5 mg orally once daily

Combination therapy with pembrolizumab

• Levatinib 20 mg orally once daily, plus
• Pembrolizumab 200 mg IV every 3 weeks or 400 mg every 6 weeks

Hepatocellular Carcinoma

Adult dosage

• Weight less than 60 kg: 8 mg orally once daily
• Weight 60 kg or greater: 12 mg orally once daily

Endometrial Cancer

Adult dosage

• 20 mg orally once daily, plus pembrolizumab 200 mg IV every 3 weeks

Dosage Considerations – Should be Given as Follows: 

• See "Dosages."

Common side effects of Lenvatinib include:

• bleeding, 
• stomach pain, 
• nausea, 
• vomiting, 
• diarrhea, 
• loss of appetite, 
• weight loss, 
• abnormal thyroid function tests, 
• muscle or joint pain, 
• swelling in the arms and legs, 
• mouth sores, 
• rash, 
• redness, itching, or peeling skin on the hands or feet, 
• headache, 
• tiredness, 
• cough, 
• trouble breathing, and
• hoarse voice 

Serious side effects of Lenvatinib include:

• hives, 
• difficulty breathing, 
• swelling of the face, lips, tongue, or throat, 
• severe stomach pain, 
• chocking or gagging while eating or drinking, 
• severe diarrhea, 
• headache, 
• confusion, 
• change in mental status, 
• vision loss, 
• seizure, 
• little or no urination, 
• nosebleeds, 
• heavy menstrual bleeding, 
• any bleeding that will not stop,
• severe headache, 
• blurred vision, 
• pounding in the neck or ears, 
• jaw pain or numbness, 
• red or swollen gums, 
• loose teeth, 
• slow healing after dental work, 
• bloody or tarry stools, 
• coughing up blood, 
• vomit that looks like coffee grounds, 
• chest pain, 
• pain in the jaw or shoulder, 
• swelling, 
• rapid weight gain, 
• shortness of breath, 
• sudden numbness or weakness, 
• problems with vision or speech, 
• dark urine, 
• clay-colored stools, 
• yellowing of the skin or eyes (jaundice), 
• muscle spasms or contractions, and
• numbness or tingling feeling (around the mouth, or in the fingers or toes)

Rare side effects of Lenvatinib include:

• none 

This is not a complete list of side effects and other serious side effects or health problems may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

• Lenvatinib has severe interactions with the following drug:
  • elagolix
• Lenvatinib has serious interactions with at least 27 other drugs. 
• Lenvatinib has moderate interactions with at least 127 other drugs. 
• Lenvatinib has minor interactions with the following drug:
  • atopepant

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this drug, tell your doctor or pharmacist of all the drugs you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Lenvatinib?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Lenvatinib?”

Cautions

• Serious and fatal cardiac dysfunction may occur; Grade 3 cardiac dysfunction or greater (including cardiomyopathy, left or right ventricular dysfunction, congestive heart failure [CHF], cardiac failure, ventricular hypokinesia, or decrease in left or right ventricular EF over 20% from baseline) reported; monitor for symptoms or signs of cardiac decompensation and/or dysfunction
• Arterial thromboembolic events reported; permanently discontinue therapy following a thromboembolic event; safety of resuming after an arterial thromboembolic event not established om patients who had an arterial thromboembolic event within the previous 6 months
• Serious hepatic adverse reactions reported; monitor patients with HCC closely for signs of hepatic failure, including hepatic encephalopathy; withhold and resume at a reduced dose upon recovery or permanently discontinue therapy based on severity; increased ALT and/or AST observed; rare reports of hepatic failure, including fatalities, were also reported
• Proteinuria reported; monitor for proteinuria before initiation and during treatment; if urine dipstick proteinuria greater than 2+ is detected, obtain a 24-hour urine protein; withhold and resume at a reduced dose upon recovery or permanently discontinue therapy on severity
• Serious including fatal renal failure or impairment can occur; initiate prompt management of diarrhea or dehydration/hypovolemia; withhold and resume at a reduced dose upon recovery or permanently discontinue therapy for renal failure or impairment based on severity; primary risk factor for severe renal impairment was dehydration/hypovolemia due to diarrhea and vomiting; initiate active management of diarrhea and any other gastrointestinal symptoms Grade 1 events
• Diarrhea may occur; initiate prompt medical management for diarrhea; monitor for dehydration; interrupt therapy for Grade 3 or 4 diarrhea
• Gastrointestinal (GI) perforation or fistula reported; discontinue if patient develops a GI perforation or life-threatening fistula; permanently discontinue therapy in patients who develop gastrointestinal perforation of any severity or Grade 3 or 4 fistula
• Hypocalcemia reported; monitor blood calcium levels at least monthly and replace calcium as necessary during treatment; withhold and resume at reduced dose upon recovery or permanently discontinue therapy depending on severity
• Reversible posterior leukoencephalopathy syndrome (RPLS) reported rarely; confirm diagnosis of RPLS with magnetic resonance imaging
• Hemorrhagic events occurred; consider risk of severe or fatal hemorrhage associated with tumor invasion or infiltration of major blood vessels (eg, carotid artery)
• Impairs exogenous thyroid suppression; monitor TSH levels monthly and adjust thyroid replacement medication as needed; monitor thyroid function before initiating therapy and at least monthly during treatment; treat hypothyroidism according to standard medical practice
• May cause fetal harm when administered to pregnant females
• Impaired wound healing reported in patients who received therapy; withhold therapy for at least 1 week prior to elective surgery; do not administer for at least 2 weeks following major surgery and until adequate wound healing; safety of resumption of therapy after resolution of wound healing complications not established; permanently discontinue drug in patients with wound healing complications
• Hypertension
  • Hypertension reported
  • Control blood pressure (BP) before treatment; monitor BP after 1 week, then every 2weeks for the first 2 months, and then at least monthly thereafter
  • Serious complications of poorly controlled hypertension reported
• Osteonecrosis of the jaw
  • Osteonecrosis of the Jaw (ONJ) reported; concomitant exposure to other risk factors, such as bisphosphonates, denosumab, dental disease, or invasive dental procedures, may increase risk of ONJ
  • Perform an oral examination prior to treatment and periodically during treatment; advise patients regarding good oral hygiene practices; avoid invasive dental procedures, if possible, while on treatment, particularly in patients at higher risk
  • Withhold therapy for at least 1 week prior to scheduled dental surgery or invasive dental procedures, if possible
  • For patients requiring invasive dental procedures, discontinuation of bisphosphonate treatment may reduce risk of ONJ; withhold therapy if ONJ develops and restart based on clinical judgment of adequate resolution
• QT prolongation
  • QT prolongation reported
  • Monitor ECG in patients with congenital long QT syndrome, CHF, bradyarrhythmias, or those who are taking drugs known to prolong the QT interval, including class Ia and III antiarrhythmics
  • Monitor and correct electrolyte abnormalities in all patients
  • Monitor electrocardiograms in patients with congenital long QT syndrome; CHF, bradyarrhythmias, or those who are taking drugs known to prolong QT interval, including Class Ia and III antiarrhythmics

Pregnancy and Lactation

• Based on its mechanism of action and data from animal reproduction studies, lenvatinib can cause fetal harm when administered to a pregnant woman; verify the pregnancy status of females of reproductive potential prior to initiating
• In animal reproduction studies, oral administration during organogenesis at doses below the recommended human dose (approximately 0.14 times the recommended human dose based on body surface area) resulted in embryotoxicity, fetotoxicity, and teratogenicity in rats and rabbits
• There are no available human data informing the drug-associated risk
• Advise pregnant women of the potential risk to a fetus
• Contraception
  • Advise females of reproductive potential to use effective contraception during treatment and for at least 30 days after last dose
• Infertility
  • Females: May result in reduced fertility in females of reproductive potential
  • Males: May result in damage to male reproductive tissues, leading to reduced fertility of unknown duration
• Lactation: Unknown if distributed in human breast milk; because of the potential for serious adverse reactions in nursing infants, advise women to discontinue breastfeeding during treatment and for at least 1 week after the last dose.