Lenvatinib – Uses, Dosage, Side Effects, Interaction

Mechanism of Action

Lenvatinib is a receptor tyrosine kinase (RTK) inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). Lenvatinib also inhibits other RTKs that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1, 2, 3, and 4; the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET.

Lenvatinib acts as a multiple kinase inhibitor. It inhibits the three main vascular endothelial growth factor receptors VEGFR1, 2 and 3, as well as fibroblast growth factor receptors (FGFR) 1, 2, 3 and 4, platelet-derived growth factor receptor (PDGFR) alpha, c-Kit, and the RET proto-oncogene. Some of these proteins play roles in cancerogenic signalling pathways. VEGFR2 inhibition is thought to be the main reason for the most common side effect, hypertension.[rx]

Based on x-ray crystallography and kinetic interaction studies, lenvatinib binds to the adenosine 5′-triphosphate binding site of VEGFR2 and to a neighbouring region via a cyclopropane ring and thereby inhibits tyrosine kinase activity and associated signalling pathways.

Indications

  • Lenvatinib is indicated for the treatment of the following cancerous conditions: **Differentiated Thyroid Cancer (DTC)** – Treatment of locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer **Renal Cell Carcinoma (RCC)** – First-line treatment, in combination with [pembrolizumab], in adult patients with advanced renal cell carcinoma (RCC) – Treatment of advanced renal cell carcinoma, in combination with [everolimus], in adult patients who have previously tried ≥1 anti-angiogenic therapy **Hepatocellular Carcinoma (HCC)** – First-line treatment of patients with unresectable hepatocellular carcinoma **Endometrial Carcinoma** – Treatment of advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), in combination with [pembrolizumab], in patients who have experienced disease progression following prior systemic therapy and are not candidates for curative surgery or radiation
  • Lenvima is indicated as monotherapy for the treatment of adult patients with progressive, locally advanced or metastatic, differentiated (papillary/follicular/Hürthle cell) thyroid carcinoma (DTC), refractory to radioactive iodine (RAI).
  • Lenvima is indicated as monotherapy for the treatment of adult patients with advanced or unresectable hepatocellular carcinoma (HCC) who have received no prior systemic therapy. Kisplyx is indicated for the treatment of adults with advanced renal cell carcinoma (RCC): in combination with pembrolizumab, as first-line treatment. in combination with everolimus, following one prior vascular endothelial growth factor (VEGF)-targeted therapy.
  • Treatment of follicular thyroid cancer , Treatment of osteosarcoma, Treatment of papillary thyroid cancer
  • Treatment of all conditions included in the category of malignant neoplasms except haematopoietic and lymphoid tissue neoplasms, papillary thyroid cancer , follicular thyroid cancer and osteosarcoma.
  • Lenvima is indicated as monotherapy for the treatment of adult patients with progressive, locally advanced or metastatic, differentiated (papillary/follicular/Hürthle cell) thyroid carcinoma (DTC), refractory to radioactive iodine (RAI).
  • Lenvima is indicated as monotherapy for the treatment of adult patients with advanced or unresectable hepatocellular carcinoma (HCC) who have received no prior systemic therapy.
  • Lenvatinib mesylate is approved to be used alone or with other drugs to treat: Endometrial carcinoma that is advanced and got worse after other systemic therapies. It is used with pembrolizumab in patients whose cancer is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) and cannot be treated with surgery or radiation therapy. Hepatocellular carcinoma (a type of liver cancer). It is used as the first treatment in patients whose cancer cannot be removed by surgery. Renal cell carcinoma (a type of kidney cancer) that is advanced. It is used: With everolimus in adults who have received angiogenesis inhibitor therapy. With pembrolizumab as the first treatment in adults. Thyroid cancer in certain patients with progressive, recurrent, or metastatic cancer that does not respond to treatment with radioactive iodine.
  • Lenvatinib, is an anti-cancer medication for the treatment of certain kinds of thyroid cancer and for other cancers as well. It was developed by Eisai Co. and acts as a multiple kinase inhibitor against the VEGFR1VEGFR2 and VEGFR3 kinases.
  • Advanced Renal Cell Carcinoma
  • Endometrial Carcinoma
  • Unresectable Hepatocellular Carcinoma (HCC)
  • Progressive, locally advanced radioactive iodine-refractory Differentiated Thyroid Cancer (DTC)
  • Progressive, metastatic radioactive iodine-refractory Differentiated Thyroid Cancer (DTC)

Use in Cancer

Lenvatinib mesylate is approved to be used alone or with other drugs to treat:

  • Endometrial carcinoma is advanced and got worse after other systemic therapies. It is used with pembrolizumab in patients whose cancer is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) and cannot be treated with surgery or radiation therapy.
  • Hepatocellular carcinoma (a type of liver cancer). It is used as the first treatment in patients whose cancer cannot be removed by surgery.
  • Renal cell carcinoma (a type of kidney cancer) is advanced. It is used:
    • With everolimus in adults who have received angiogenesis inhibitor therapy.
    • With pembrolizumab as the first treatment in adults.
  • Thyroid cancer in certain patients with progressive, recurrent, or metastatic cancer that does not respond to treatment with radioactive iodine. Lenvatinib mesylate is also being studied in the treatment of other types of cancer.

Contraindications

  • Bleeding, thyroid cancer.
  • Hypertension.
  • Cardiomyopathy, heart failure.
  • Cardiac disease, coronary artery disease, myocardial infarction, stroke, thromboembolic disease.
  • Hepatic disease, hepatotoxicity.
  • Dehydration, hypovolemia, renal disease, renal failure, renal impairment
  • a condition with low thyroid hormone levels
  • low amount of calcium in the blood
  • low amount of potassium in the blood
  • high blood pressure
  • prolonged QT interval on EKG
  • chronic heart failure
  • abnormal EKG with QT changes from birth
  • a localized weakening and ballooning in an artery wall called an arterial aneurysm
  • obstruction of a blood vessel by a blood clot
  • bleeding
  • a gastrointestinal tract fistula
  • recent operation
  • elevation of proteins in the urine
  • pregnancy
  • a patient who is producing milk and breastfeeding
  • chronic kidney disease stage 4 (severe)
  • kidney disease with likely reduction in kidney function
  • dissection of artery
  • Child-Pugh class C liver impairment

Dosage

Strengths: 4 mg daily-dose; 8 mg daily-dose; 10 mg daily-dose; 12 mg daily-dose; 14 mg daily-dose; 18 mg daily-dose; 20 mg daily-dose; 24 mg daily-dose

Lenvaitnib is available in 4 mg and 10 mg capsule dosages for oral consumption.

Radioactive Iodine-refractory Differentiated Thyroid Cancer (DTC)

  • 24 mg orally once a day.

Advanced Renal Cell Carcinoma (RCC)

  • First-line treatment: 20 mg orally once a day in combination with pembrolizumab for up to two years; then can be given as monotherapy.
  • Previously treated disease: 18 mg orally once daily in combination with everolimus.

Unresectable Hepatocellular Carcinoma (HCC)  

The suggested dose should be determined based on the patient’s body weight:

  • 12 mg orally once a day for patients’ body weight greater than or equal to 60 kg.
  • 8 mg orally once a day for patients weighing less than 60 kg.

Advanced Endometrial Carcinoma

  • 20 mg orally once daily; for patients with non-microsatellite instability-high (MSI-H) or non-mismatch repair deficient (dMMR) progressive disease who are not candidates for X-ray therapy or curative surgery, use with pembrolizumab.

or

Thyroid Cancer

  • 24 mg orally once a day
  • Treatment should be continued until disease progression or unacceptable toxicity.
  • For the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (DTC)

Renal Cell Carcinoma

First-Line Treatment of Patients with Advanced Renal Cell Carcinoma:

  • 20 mg orally once a day given in combination with 200 mg IV pembrolizumab over 30 minutes every 3 weeks

Previously Treated Renal Cell Carcinoma:

  • 18 mg orally once a day given in combination with 5 mg everolimus orally once a day
  • Refer to everolimus prescribing information for recommended dosing information.
  • Refer to pembrolizumab prescribing information for recommended dosing information
  • Treatment with everolimus should be continued until disease progression or unacceptable toxicity.
  • Treatment with pembrolizumab should be continued until disease progression or unacceptable toxicity or up to 2 years.
  • After 2 years of combination with pembrolizumab, this drug may be administered as a single agent until disease progression or unacceptable toxicity.
  • In combination with everolimus for the treatment of patients with advanced renal cell carcinoma following one prior anti-angiogenic therapy
  • In combination with pembrolizumab for the first-line treatment of adult patients with advanced renal cell carcinoma

Hepatocellular Carcinoma

  • Weight less than 60 kg: 8 mg orally once a day
  • Weight 60 kg or greater: 12 mg orally once a day
  • Treatment should be continued until disease progression or unacceptable toxicity.
  • For the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC)

Endometrial Carcinoma

  • 20 mg orally once daily in combination with pembrolizumab 200 mg IV over 30 minutes every 3 weeks
  • Refer to the pembrolizumab prescribing information for other dosing information.
  • Treatment should be continued until disease progression or unacceptable toxicity.65483

Renal Dose Adjustments

Mild (CrCl 60-89 mL/min) or moderate renal impairment (CrCl 30-59 mL/min): No dose adjustment recommended

Severe renal impairment (CrCl less than 30 mL/min):

  • Differentiated thyroid cancer (DTC): Reduce the starting dose to 14 mg orally once a day
  • Renal cell carcinoma (RCC): Reduce the starting dose to 10 mg orally once a day
  • Endometrial carcinoma: Reduce the starting dose to 10 mg orally once a day
  • Hepatocellular Carcinoma (HCC): Data not available
  • End stage renal disease: Data not available

Liver Dose Adjustments

  • Mild (Child-Pugh A) to moderate (Child-Pugh B) hepatic impairment: No dose adjustment recommended

Severe hepatic impairment (Child-Pugh C):

  • Differentiated thyroid cancer (DTC): Reduce the starting dose to 14 mg orally once a day
  • Renal cell carcinoma (RCC): Reduce the starting dose to 10 mg orally once a day
  • Endometrial carcinoma: Reduce the starting dose to 10 mg orally once a day
  • Hepatocellular Carcinoma (HCC): Data not available

Dose Adjustments

  • When administering this drug in combination with everolimus, reduce the dose of this drug first and then the everolimus dose for adverse reactions of both drugs. Refer to the everolimus prescribing information for additional dose modification information.
  • When administering this drug in combination with pembrolizumab, modify the dosage of one or both drugs as appropriate, interrupt, or reduce of discontinue the dose of this drug as appropriate. Refer to pembrolizumab prescribing information for additional dose modification information.

DOSE REDUCTION BASED ON THE PREVIOUS DOSE LEVEL:
DIFFERENTIATED THYROID CANCER (DTC):
Initial dose level of 24 mg orally once a day:

  • First occurrence: Reduce dose to 20 mg orally once a day.
  • Second occurrence: Reduce dose to 14 mg orally once a day.
  • Third occurrence: Reduce dose to 10 mg orally once a day.

RENAL CELL CARCINOMA (RCC):
Initial dose level of 18 mg orally once a day:

  • First occurrence: Reduce dose to 14 mg orally once a day.
  • Second occurrence: Reduce dose to 10 mg orally once a day.
  • Third occurrence: Reduce dose to 8 mg orally once a day.

ENDOMETRIAL CARCINOMA:
Initial dose level of 20 mg orally once a day:

  • First occurrence: Reduce dose to 14 mg orally once a day.
  • Second occurrence: Reduce dose to 10 mg orally once a day.
  • Third occurrence: Reduce dose to 8 mg orally once a day.

HEPATOCELLULAR CARCINOMA (HCC):
Initial dose level of 12 mg orally once a day:

  • First occurrence: Reduce dose to 8 mg orally once a day.
  • Second occurrence: Reduce dose to 4 mg orally once a day.
  • Third occurrence: Reduce dose to 4 mg orally every other day.

Initial dose level of 8 mg orally once a day:

  • First occurrence: Reduce dose to 4 mg orally once a day.
  • Second occurrence: Reduce dose to 4 mg orally every other day.
  • Third occurrence: Discontinue therapy.

RECOMMENDED DOSE MODIFICATIONS FOR ADVERSE REACTIONS:
HYPERTENSION:
Grade 3:

  • Withhold for Grade 3 that persists despite optimal antihypertensive therapy.
  • Resume at reduced dose when hypertension is controlled at Grade 2 or less.

Grade 4:

  • Permanently discontinue therapy.

CARDIAC DYSFUNCTION:
Grade 3:

  • Withhold until improves to Grade 0 to 1 or baseline.
  • Resume at reduced dose or discontinue depending on the severity and persistence of adverse reaction.

Grade 4:

  • Permanently discontinue therapy.

ARTERIAL THROMBOEMBOLIC EVENT:
Any Grade:

  • Permanently discontinue therapy.

HEPATOTOXICITY:
Grade 3 or 4:

  • Withhold until improves to Grade 0 to 1 or baseline.
  • Either resume at a reduced dose or discontinue depending on severity and persistence of hepatotoxicity.
  • Permanently discontinue for hepatic failure.

RENAL IMPAIRMENT OR FAILURE:
Grade 3 or 4:

  • Withhold until improves to Grade 0 to 1 or baseline.
  • Resume at a reduced dose or discontinue depending on severity and persistence of renal impairment.

PROTEINURIA:
2 grams or greater proteinuria in 24 hours:

  • Withhold until less than or equal to 2 grams of proteinuria per 24 hours.
  • Resume at a reduced dose.
  • Permanently discontinue for nephrotic syndrome.

GI PERFORATION:
Any Grade:

  • Permanently discontinue therapy.

FISTULA FORMATION:
Grade 3 or 4:

  • Permanently discontinue therapy.

QT PROLONGATION:
Greater than 500 ms or greater than 60 ms increase from baseline:

  • Withhold until improves to less than or equal to 480 ms or baseline.
  • Resume at a reduced dose.

REVERSIBLE POSTERIOR LEUKOENCEPHALOPATHY SYNDROME (RPLS):
Any Grade:

  • Withhold until fully resolved.
  • Resume at a reduced dose or discontinue depending on severity and persistence of neurologic symptoms.

OTHER ADVERSE REACTIONS:
Persistent or intolerable Grade 2 or 3 adverse reaction or Grade 4 laboratory abnormality:

  • Withhold until improves to Grade 0 to 1 or baseline.
  • Resume at reduced dose.

Grade 4 adverse reaction:

  • Permanently discontinue therapy.

Administration advice:

  • Capsules can be swallowed whole or dissolved in a small glass of liquid.
  • This drug can be given with or without food.
  • This drug should be taken at the same time each day.
  • If a dose is missed and cannot be taken within 12 hours, skip that dose and take the next dose at the usual time.
  • Cardiovascular: Blood pressure, bleeding, signs and symptoms of cardiac dysfunction, ECG
  • Endocrine: TSH levels
  • Hepatic: ALT, AST
  • Metabolic: Serum electrolytes, blood calcium levels
  • Neurologic: New onset or worsening neurological function
  • Renal: Proteinuria, regular laboratory renal tests
  • Advise the patient to read the FDA-approved patient labeling.
  • Advise patients regarding good oral hygiene practices and to have preventive dentistry performed prior to and throughout treatment.
  • Advise patients that this drug can increase the risk for bleeding.
  • Advise patients that this drug can increase the risk of fistula formation or gastrointestinal perforation and to seek immediate medical attention for severe abdominal pain.
  • Advise patients that this drug to report any clinical symptom of cardiac dysfunction.
  • Advise patients to inform their healthcare provider of any planned surgical procedure.
  • Advise females of reproductive potential to use effective contraception during treatment and for at least 30 days after the last dose.
  • Advise women to discontinue breastfeeding during treatment and for at least 1 week after the last dose.

Side Effects

The Most Common

  • fatigue or tiredness
  • rash, redness, itching, or peeling of skin on palms and sole(s) of the feet
  • diarrhea
  • nausea
  • constipation
  • heartburn
  • decreased appetite
  • weight loss
  • change in ability to taste food
  • cough
  • hoarseness
  • mouth sores
  • dry mouth
  • headache
  • joint and muscle pain
  • difficulty falling asleep or staying asleep
  • hair loss
  • fever
  • burning during urination
  • rash
  • shortness of breath or trouble breathing
  • swelling of legs and ankles
  • chest pain
  • numbness or weakness of the face, arm, or leg on one side of your body
  • pain in arms, back, neck, or jaw
  • sudden, severe headache
  • slow or difficult speech
  • sudden changes in vision
  • yellowing of the skin or eyes
  • stomach pain
  • dark (tea-colored) urine
  • light-colored stools
  • seizures
  • weakness
  • confusion
  • severe and persistent nose bleeds
  • bloody vomit
  • black, tarry, or bloody stools
  • coughing up blood or blood clots
  • heavy menstrual bleeding
  • vomiting, diarrhea, or signs of dehydration
  • wounds that do not heal

More common

  • Bladder pain
  • bleeding gums
  • bloating or swelling of the face, arms, hands, lower legs, or feet
  • blood in the urine or stools
  • blurred vision or other change in vision
  • chest pain or discomfort
  • chills
  • cloudy urine
  • confusion
  • constipation
  • cough
  • coughing up blood
  • decreased frequency or amount of urine
  • depressed mood
  • diarrhea
  • difficulty with breathing or swallowing
  • dilated neck veins
  • dizziness, fainting, or lightheadedness when getting up suddenly from a lying or sitting position
  • dry skin and hair
  • feeling cold
  • fever
  • hair loss
  • heavy jaw feeling
  • hoarseness or husky voice
  • increase in heart rate
  • increased menstrual flow or vaginal bleeding
  • loosening of a tooth
  • lower back or side pain
  • muscle cramps in the hands, arms, feet, legs, or face
  • muscle stiffness
  • nervousness
  • nosebleeds
  • numbness and tingling around the mouth, fingertips, or feet
  • pain, swelling, or numbness in the mouth, or jaw
  • painful or difficult urination
  • pale skin
  • paralysis
  • pinpoint red spots on the skin
  • pounding in the ears
  • prolonged bleeding from cuts
  • rapid or irregular breathing
  • rapid weight gain
  • red or black, tarry stools
  • red or dark brown urine
  • redness, swelling, or pain of the skin
  • scaling of the skin on the hands and feet
  • severe headache
  • slow or fast heartbeat
  • sore throat
  • stomach pain and bloating
  • swelling of the face, fingers, feet, or lower legs
  • tingling of the hands or feet
  • tremor
  • ulceration of the skin
  • ulcers, sores, or white spots in the mouth
  • unusual bleeding or bruising
  • unusual tiredness or weakness
  • unusual weight gain or loss
  • vomiting
  • wrinkled skin

Rare

  • Clay-colored stools
  • difficulty with speaking
  • heartburn or indigestion
  • inability to move the arms, legs, or facial muscles
  • pain or discomfort in the arms, jaw, back, or neck
  • severe stomach pain, cramping, or burning
  • stomach tenderness
  • vomiting of material that looks like coffee grounds
  • yellow eyes or skin
  • Abnormal small opening
  • loss of appetite
  • severe nausea or vomiting
  • slow wound healing
  • Belching
  • change or loss of taste
  • decreased weight
  • dry mouth
  • hair loss or thinning of the hair
  • itching, skin rash
  • muscle or joint pain
  • swelling or inflammation of the mouth
  • trouble sleeping
  • voice changes

Drug Interactions

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Pregnancy and Lactation

AU TGA pregnancy category: D
US FDA pregnancy category: Not assigned.

Pregnancy

Based on its mechanism of action and data from animal reproduction studies, LENVIMA can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, oral administration of lenvatinib during organogenesis at doses below the recommended human doses resulted in embryotoxicity, fetotoxicity, and teratogenicity in rats and rabbits (see Data). There are no available human data informing the drug-associated risk. Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Lactation

No information is available on the clinical use of lenvatinib during breastfeeding. Because lenvatinib is more than 98% bound to plasma proteins, the amount in milk is likely to be low. However, its half-life is about 28 hours and it might accumulate in the infant. The manufacturer recommends that breastfeeding be discontinued during lenvatinib therapy and for at least 1 week after the last dose.

Why is this medication prescribed?

Lenvatinib is used to treat a certain type of thyroid cancer that has returned or that has spread to other parts of the body and cannot be treated with radioactive iodine. Lenvatinib is also used along with everolimus (Afinitor, Zortress) to treat renal cell carcinoma (RCC, a type of cancer that begins in the kidney) in people who have previously received treatment with another chemotherapy medication. Lenvatinib is also used along with pembrolizumab (Keytruda) as an initial treatment for advanced renal cell carcinoma. Lenvatinib is also used to treat hepatocellular carcinoma (HCC; a type of liver cancer) that cannot be treated with surgery. Lenvatinib is also used along with pembrolizumab (Keytruda) to treat a certain type of cancer of the endometrium (lining of the uterus) that has spread to other parts of the body or worsened during or after treatment with chemotherapy medications or that cannot be treated with surgery or radiation therapy. Lenvatinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps stop the spread of cancer cells.

How should this medicine be used?

Lenvatinib comes as a capsule to take by mouth. It is usually taken once daily with or without food. Take lenvatinib at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take lenvatinib exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Swallow the capsules whole; do not open, chew, or crush them.

If you are unable to swallow the capsules, put them into a small glass and add about one tablespoon of water or apple juice. Do not break or crush the capsules. Leave the capsules in the liquid for at least 10 minutes and then stir the contents for at least 3 minutes. Drink the mixture. After drinking the mixture, add another 1 tablespoon of water or apple juice to the glass. Swirl the contents a few times and swallow the mixture.

Your doctor may decrease your dose of lenvatinib or tell you to stop taking the medication for a time or permanently if you experience serious side effects. Be sure to talk to your doctor about how you are feeling during your treatment with lenvatinib.

The length of your treatment depends on how well you respond to the medication and the side effects you experience. Continue to take lenvatinib even if you feel well. Do not stop taking lenvatinib without talking to your doctor. Ask your pharmacist or doctor for a copy of the manufacturer’s information for the patient. This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

What special precautions should I follow?

Before taking lenvatinib,

  • tell your doctor and pharmacist if you are allergic to lenvatinib, any other medications, or any of the ingredients in lenvatinib capsules. Ask your pharmacist for a list of the ingredients.
  • tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: certain medications for irregular heartbeat including amiodarone (Nexterone, Pacerone), disopyramide (Norpace), dofetilide (Tikosyn), dronedarone (Multaq), procainamide, quinidine (in Nuedexta), and sotalol (Betapace, Betapace AF, Sorine, Sotylize), ketoconazole, or rifampin (Rifadin,Rimactane). Also tell your doctor if you are taking or have taken alendronate (Binosto, Fosamax), denosumab (Prolia, Xgeva), ibandronate (Boniva), pamidronate, romosozumab-aqqg (Evenity), risedronate (Actonel, Atelvia), or zoledronic acid injection (Reclast, Zometa). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
  • tell your doctor if you have or have ever had seizures; high blood pressure; a stroke; a heart attack; headaches; changes in vision, especially those due to blood clots; a fistula (abnormal connection between 2 organs inside your body or between an organ and the outside of your body); a tear in the wall of your stomach or intestine; QT interval prolongation (an irregular heart rhythm that can lead to fainting, loss of consciousness, seizures, or sudden death); heart failure; low levels of calcium, potassium, or magnesium in your blood; bleeding problems; problems with your mouth, teeth, or gums; thyroid problems; or heart, kidney, or liver disease. Also tell your doctor if you have severe diarrhea or vomiting or you think you may be dehydrated.
  • you should know that lenvatinib may decrease fertility in men and women. However, you should not assume that you or your partner cannot become pregnant. Tell your doctor if you are pregnant or plan to become pregnant. You will need to have a pregnancy test before you begin treatment with lenvatinib. If you can become pregnant, you should use birth control during your treatment with lenvatinib and for at least 30 days after your final dose. If you become pregnant while you are taking lenvatinib, call your doctor immediately. Lenvatinib may harm the fetus.
  • tell your doctor if you are breastfeeding or plan to breastfeed. You should not breastfeed while taking lenvatinib
  • tell your doctor if you are planning to have any surgery, including dental surgery. Your doctor will probably tell you to stop your treatment with lenvatinib at least 7 days before your scheduled surgery because it can affect wound healing. Your doctor will tell you when to start taking lenvatinib again after your surgery.
  • you should know that your blood pressure may increase during your treatment with lenvatinib. Your doctor will probably monitor your blood pressure during your treatment.
  • you should know that lenvatinib may cause osteonecrosis of the jaw (ONJ, a serious condition of the jaw bone), especially if you have dental surgery or treatment while you are taking the medication. A dentist should examine your teeth and perform any needed treatments, including cleaning or fixing ill-fitted dentures, before you start to take lenvatinib. Be sure to brush your teeth and clean your mouth properly while you are taking lenvatinib. Tell your doctor or dentist if you have or have had mouth, teeth, or jaw pain; mouth sores or swelling; numbness or a feeling of heaviness in the jaw; or any loose teeth. Talk to your doctor before having any dental treatments while you are taking this medication. Your doctor will probably tell you to stop your treatment with lenvatinib at least 7 days before your scheduled dental procedure.

What special dietary instructions should I follow?

Unless your doctor tells you otherwise, continue your normal diet.

What should I do if I forget a dose?

If your next dose is due in 12 hours or more, take the missed dose as soon as you remember it. However, if the next dose will be taken in less than 12 hours, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

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  30. https://dailymed.nlm.nih.gov/dailymed/browse-drug-classes.cfm
  31. https://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/ucm162549.htm
  32. https://www.nlm.nih.gov/copyright.html
  33. https://www.ncbi.nlm.nih.gov/books/n/livertox/Lenvatinib/
  34. https://www.cancer.gov/policies/copyright-reuse
  35. https://ncithesaurus.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=ncit&code=C95124
  36. https://ncit.nci.nih.gov