lenvatinib
Trade Name:Lenvima®
Appearance:capsule
in various strengths, shapes and colours
Monograph Name:lenvatinib
Monograph Body:
Lenvatinib is a multiple receptor tyrosine kinase inhibitor (TKI) that selectively inhibits vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR) and VEGFR3 (FLT4) as well as other proangiogenic and oncogenic pathway-related receptors.
Lenvatinib is rapidly absorbed with a tmax reached 1 to 4 hours post-dose. Food slows the rate of absorption, but does not affect the extent of absorption.
Bioavailability |
data from a mass-balance study suggests about 85% |
PPB |
98-99% (mainly to albumin) |
Active metabolites |
yes |
Inactive metabolites |
yes |
Plasma concentrations decline bi-exponentially following Cmax.
Half-life |
28 hours (terminal) |
Feces |
64% |
Urine |
25% |
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For the treatment of patients with locally recurrent or metastatic, progressive, radioactive-iodine refractory differentiated thyroid cancer (DTC).
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In combination with everolimus for the treatment of advanced renal cell carcinoma (RCC) following prior vascular endothelial growth factor (VEGF)-targeted therapy.
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For the first-line treatment of adult patients with unresectable hepatocellular carcinoma (HCC).*
*Efficacy and safety data for Child-Pugh Class B and Class C are not available.
Emetogenic Potential:
Extravasation Potential: Not applicable
The following table lists adverse effects that occurred in ≥5% of patients in the phase III SELECT trial in DTC patients comparing lenvatinib vs placebo, where there was at least a 5% difference between arms. Severe adverse events from other studies or post-marketing are also included.
ORGAN SITE | SIDE EFFECT* (%) | ONSET** | |||
---|---|---|---|---|---|
Cardiovascular | Arrhythmia (rare) | E | |||
Arterial thromboembolism (5%) (may be severe) | E | ||||
Bradycardia (11%) | E | ||||
Cardiotoxicity (5%) | E D | ||||
Hypertension (73%) (44% severe) | E | ||||
Hypotension (9%) | E | ||||
Other - Artery dissection or aneurysm (rare) | L | ||||
QT interval prolonged (12%) (2% severe) | E | ||||
Venous thromboembolism (3%) (severe) | E | ||||
Dermatological | Alopecia (12%) | E | |||
Hand-foot syndrome (32%) | E | ||||
Other (7%) - hyperkeratosis | E | ||||
Rash (19%) | E | ||||
Gastrointestinal | Abdominal pain (31%) | E | |||
Anorexia, weight loss (54%) | E | ||||
Constipation (29%) | E | ||||
Dehydration (9%) (may be severe) | E | ||||
Diarrhea (67%) (9% severe) | E | ||||
Dry mouth (17%) | E | ||||
Dyspepsia (13%) | E | ||||
GI obstruction (rare) | E | ||||
GI perforation (2% fistulas; may be severe) | E | ||||
Mucositis (41%) (5% severe) | E | ||||
Nausea, vomiting (47%) (may be severe) | E | ||||
General | Edema - limbs (21%) | E | |||
Fatigue (43%) | E | ||||
Wound dehiscence (rare) | E | ||||
Hematological | Hemorrhage (35%) (2% severe) | E | |||
Myelosuppression (14%) | E D | ||||
Hepatobiliary | ↓ albumin (49%) | E | |||
↑ Amylase / lipase (12%) (may be severe) | E | ||||
Cholecystitis (rare) | E | ||||
Hepatotoxicity (8%) (including hepatic encephalopathy) | E | ||||
↑ LFTs (52%) (4% severe) | E | ||||
Pancreatitis (rare) | E | ||||
Hypersensitivity | Hypersensitivity (rare) | E | |||
Infection | Infection (12%) | E | |||
Metabolic / Endocrine | Abnormal electrolyte(s) (40%) (low Ca, K, Na, Mg; 9% severe) | E | |||
Hyperglycemia (53%) (<1% severe) | E | ||||
Hypoglycemia (19%) (mild to moderate) | E | ||||
Hypothyroidism (21%) | E D | ||||
Other - ↑ TSH (61%) | E D | ||||
↑ Triglycerides (15%) | E | ||||
Musculoskeletal | Fracture (rare) | D L | |||
Musculoskeletal pain (26%) | E | ||||
Rhabdomyolysis (rare) | E | ||||
Neoplastic | Secondary malignancy (adenocarcinoma; rare) | D L | |||
Nervous System | Dizziness (15%) | E | |||
Dysgeusia (18%) | E | ||||
Headache (38%) | E | ||||
Insomnia (12%) | E | ||||
Posterior reversible encephalopathy syndrome (PRES) (rare) | E | ||||
Seizure (rare) | E | ||||
Ophthalmic | Retinal vascular disorder (retinal vein thrombosis; rare) | E | |||
Renal | Creatinine increased (87%) (3% severe) | E | |||
Proteinuria (34%) (may be severe) | E | ||||
Respiratory | Cough, dyspnea (24%) | E | |||
Dysphonia (31%) | E |
* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare"
may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal
reports.
** I = immediate (onset in hours to days)
E = early (days to weeks)
D = delayed (weeks to months)
L = late (months to years)
The most common side effects for lenvatinib include creatinine increased, hypertension, diarrhea, anorexia, weight loss, hyperglycemia, ↑ LFTs, ↓ albumin, nausea, vomiting, fatigue and mucositis.
Hypertension was commonly reported and may be severe. Median time to onset was 16-35 days. Serious complications, including aortic dissection, have been reported secondary to poorly controlled hypertension.
Cardiac failure was reported in in less than 1% of DTC patients, but decreases in left ventricular ejection fraction (LVEF) were seen in 5% of DTC patients and 10% of RCC patients receiving combination treatment. Arterial thromboembolic events were reported as well, including fatal cases.
Severe cases of artery dissection (with or without hypertension) and artery aneurysm (including rupture) have been reported in patients using VEGFR TKIs.
QT prolongation has been reported and may lead to severe ventricular arrhythmias, including Torsades de pointes.
Grade 3 or 4 renal failure was reported in up to 3% of patients, with the primary risk factor being dehydration secondary to diarrhea or vomiting. HCC Patients with baseline renal impairment had a higher incidence of fatigue, hypothyroidism, dehydration, diarrhea, decreased appetite, proteinuria and hepatic encephalopathy. These patients also had a higher incidence of renal reactions and arterial thromboembolic events.
Proteinuria was common and may be severe. The median time to onset for RCC patients was 6 weeks for any grade and 20 weeks for grades 3 or 4.
Lenvatinib impairs exogenous thyroid suppression and may elevate thyroid stimulating hormone (TSH) levels in both DTC and RCC patients. TSH should be monitored regularly and thyroid medication adjusted as required.
Diarrhea was reported more commonly in RCC patients on combination treatment (81%; 19% grade 3, 4).
Serious gastrointestinal perforation or fistulas have been reported, mainly in patients with prior surgery or radiotherapy. Reports of non-GI fistulae (e.g. respiratory, genitourinary, cutaneous) have been observed across various indications.
Wound healing complications, including fistula formation and wound dehiscence, may occur.
Severe tumour-related hemorrhage, including fatal intracranial hemorrhage in patients with brain metastases has been reported. Epistaxis and hematuria were the most frequently reported hemorrhagic events.
Posterior-reversible encephalopathy syndrome (PRES) has been reported rarely and may be associated with hypertension.
Refer to protocol by which the patient is being treated.
Lenvatinib is associated with a moderate emetic potential; antiemetics may be considered to prevent nausea and vomiting.
Blood pressure should be well controlled and electrolyte abnormalities should be corrected prior to starting treatment.
Adequate washout period is required between lenvatinib and other systemic anticancer treatments (e.g. sorafenib). In DTC and RCC studies, the minimum washout period was 3 weeks. In HCC, washout period from prior locoregional therapies was 4 weeks.
DTC patients:
lenvatinib 24 mg PO daily
RCC patients:
lenvatinib 18 mg PO daily in combination with everolimus 5 mg PO daily
HCC patients:
In patients with body weight (BW) of ≥60 kg: lenvatinib 12 mg PO daily
In patients with body weight (BW) of <60 kg: lenvatinib 8 mg PO daily
The dosing and dose modifications described here relate to lenvatinib use only.
Refer to the everolimus drug monograph for dosage modifications for RCC patients. For toxicities related to both lenvatinib and everolimus, reduce the lenvatinib dose first and then the everolimus dose.
Reduced doses should not be increased.
Dose Levels:
Dose level |
Lenvatinib DTC / RCC monotherapy dose (mg daily) |
Lenvatinib RCC dose when in combination with everolimus (mg daily) |
≥60 kg BW Lenvatinib HCC dose (mg daily, unless otherwise stated) |
<60 kg BW Lenvatinib HCC dose (mg daily, unless otherwise stated) |
0 | 24 | 18 | 12 | 8 |
-1 | 20 | 14 | 8+ | 4+ |
-2 | 14 | 10 | 4 | 4 every other day |
-3 | 10 | 8 | 4 every other day | Discontinue |
-4 | Discontinue | N/A |
+ No dose adjustment required for first occurrence of hematologic toxicity or proteinuria
No recommendations are available for resuming lenvatinib in patients with grade 4 adverse reactions that resolve.
Toxicity | Severity | Action |
Hypertension | ≥ 140/90 | Treat with anti-hypertensives |
Grade 3 that persists despite optimal antihypertensive therapy | Hold until recovery to ≤ grade 2; resume at 1 dose level ↓.* | |
Grade 4, life-threatening | Discontinue | |
Cardiotoxicity or hemorrhage | Grade 3 | Hold until recovery to ≤ grade 1 or baseline; resume at 1 dose level ↓* or discontinue depending on severity and persistence. |
Grade 4 | Discontinue | |
Nephrotoxicity or hepatotoxicity | Grade 3 | Hold until recovery to ≤ grade 1 or baseline; resume at 1 dose level ↓* or discontinue depending on severity and persistence. |
Grade 4 | Discontinue | |
Hepatic failure | Grade 3 or 4 | Discontinue |
Proteinuria | ≥ 2 g proteinuria / 24 h (≥ 2+ on urine dipstick) | Hold until proteinuria < 2 g / 24 h; resume at 1 dose level ↓.*† |
Nephrotic syndrome | Discontinue | |
Nausea, vomiting, diarrhea** |
Persistent and intolerable Grade 2 or Grade 3 |
Hold until recovery to ≤ grade 1 or baseline; resume at 1 dose level ↓. |
Grade 4 despite medical management | Discontinue | |
QT prolongation | Grade 3 or 4 | Hold until recovery to ≤ grade 1 or baseline; resume at 1 dose level ↓.* |
PRES | Any | Hold until resolved; resume at 1 dose level ↓* or discontinue depending on the severity and persistence of neurologic symptoms. |
Arterial thromboembolism | Discontinue | |
GI perforation or fistula | ||
Wound healing complications | ||
Other treatment-related toxicity |
Persistent and intolerable Grade 2 Or Grade 3 Or Grade 4 lab abnormalities considered non-life-threatening |
Medically manage. Hold until recovery to ≤ grade 1 or baseline; resume at 1 dose level ↓.*† |
Grade 4 (except lab abnormalities considered non-life-threatening) |
Discontinue | |
Major surgery | Hold at least 6 days prior to scheduled surgery, resume after adequate wound healing. |
*For each occurrence of toxicity, reduce dose in succession based on the previous dose level (see dose levels table).
**Initiate prompt medical management in order to reduce the risk of development of renal impairment or failure.
†For patients with HCC and hematologic toxicity or proteinuria, may restart when recovery to ≤ Grade 2.
Lenvatinib exposure increases in severe hepatic impairment.
Childs classification of hepatic impairment |
Starting dose DTC / RCC monotherapy (mg daily) |
Starting dose RCC when in combination with everolimus (mg daily) |
Starting Dose HCC (≥60 kg BW) (mg daily) |
Starting Dose HCC (<60 kg BW) (mg daily) |
A |
24 |
18 | 12 | 8 |
B |
24 |
18 | No data | |
C |
14 |
10 | No data: not recommended for use |
Lenvatinib exposure increases with severe renal impairment.
Creatinine clearance (ml/min) |
Starting dose DTC / RCC monotherapy (mg daily) |
Starting dose RCC when in combination with everolimus (mg daily) |
Starting Dose HCC (≥60 kg BW) (mg daily) |
Starting Dose HCC (<60 kg BW) (mg daily) |
50-80 |
24 |
18 | 12 | 8 |
30-49 |
24 |
18 | 12 | 8 |
< 30 |
14 |
10 | No data | |
End stage renal failure |
No data: not recommended for use |
No dosage adjustment is recommended. Use with caution and monitor patients closely.
In the DTC study, patients aged 75 and older had a higher incidence of toxicity, including severe and fatal adverse events, compared to younger patients, leading to treatment discontinuation (21% vs 14%). Patients 75 years or older were more likely to experience grade 3-4 hypertension, proteinuria, decreased appetite, and dehydration compared to patients < 65 years old.
In the RCC, study patients aged 65 and older had a higher incidence of cough, dyspnea, lethargy, nausea, peripheral swelling and vomiting compared to younger patients.
In the HCC study, patients ≥75 years appeared to have lower tolerability and were more likely to experience hypertension, proteinuria, decreased appetite, asthenia, dehydration, dizziness and hepatic encephalopathy. Arterial thromboembolic events also occurred at an increased incidence in this age group.
Body weight
In patients with DTC and RCC, no adjustment of starting dose is required based on body weight. In the DTC study, patients with body weight <60 kg had a higher incidence of hand-foot syndrome, proteinuria, severe electrolyte abnormalities and a trend towards severe anorexia.
Lenvatinib PK was affected by body weight in patients with HCC. Refer to the dosing section for starting doses.
No adjustment of starting dose is required based on gender.
In the DTC study, females had a higher incidence of hypertension (including severe hypertension), proteinuria and hand-foot syndrome, while males had a higher incidence of cardiotoxicity, GI perforation and fistulas.
In the RCC study, females had a higher incidence of hepatotoxicity, while males had a higher incidence of hemorrhage, nephrotoxicity, proteinuria and hand-foot syndrome.
In HCC patients, females had a higher incidence of hypertension, fatigue and ECG QT prolongation. Hepatic failure events were observed in male patients only.
No adjustment of starting dose is required based on race.
In the DTC study, Asian patients had a higher incidence of peripheral edema, hypertension, fatigue, hand-foot syndrome, proteinuria, thrombocytopenia and elevated TSH levels compared to Caucasian patients.
In HCC patients, Asian patients had a higher incidence of proteinuria and hand-foot syndrome compared to Caucasian patients, while Caucasian patients had a higher incidence of fatigue, hepatic encephalopathy and acute kidney injury, anxiety, asthenia, thrombocytopenia, and vomiting.
Safety and efficacy have not been established in pediatric patients. Animal studies suggest the potential for impaired bone growth in children. Lenvatinib should not be used in children younger than 2 years of age.
-
Lenvatinib should be taken at the same time daily, with or without food.
-
Capsules should be swallowed whole with water.
-
If the patient has difficulty swallowing, capsule(s) may be added (without breaking or crushing) to a tablespoon of water or apple juice in a small glass. Capsule(s) should be left in the liquid for at least 10 minutes and stirred for at least 3 minutes to allow the capsule shell(s) to dissolve. The entire suspension should then be swallowed. After drinking, the glass should be filled with the same amount of water or apple juice, swirled a few times, then additional liquid should be swallowed.
-
If a dose is missed and it cannot be taken within 12 hours, then that dose should be skipped and the next dose should be taken at the usual time.
-
Lenvatinib should be stored between 15-30oC.
- Patients who have a hypersensitivity to this drug or to any ingredient in the formulation or component of the container.
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The degree of tumour invasion of major blood vessels should be considered prior to treatment given the potential risk of hemorrhage associated with tumour shrinkage.
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Lenvatinib is not recommended in patients with congenital long QT syndrome or those who are taking medications known to prolong the QT interval.
-
Use with caution in patients at risk of prolonged QT, including females, aged ≥ 65 years, family history of sudden cardiac death at < 50 years of age, pre-existing cardiac disease, history of arrhythmias, electrolyte disturbances or conditions leading to electrolyte disturbances, bradycardia, acute neurological events, diabetes mellitus and autonomic neuropathy.
-
Use lenvatinib with caution in patients who are at risk for, or have a history of cardiac events or arterial thromboembolism. The drug has not been studied in patients who have had an arterial thromboembolic event within the previous 6 months.
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Patients with prior surgery or radiotherapy are at increased risk of GI perforation or fistulas.
Other Drug Properties:
-
Carcinogenicity:
Unknown
Carcinogenicity studies have not been conducted.
-
Embryotoxicity:
Yes
-
Fetotoxicity:
Yes
-
Teratogenicity:
Yes
Lenvatinib is not recommended for use in pregnancy as it's likely to cause fetal harm. Highly effective contraception (including barrier method) should be used by both sexes during treatment, and for at least 1 month after the last dose.
-
Excretion into breast milk:
Likely
Observed in animal studies.
Breastfeeding is not recommended.
-
Fertility effects:
Likely
Animal studies suggest decreased male and female fertility.
Lenvatinib is extensively metabolized by CYP3A4. In vitro studies indicate that lenvatinib inhibits CYP 2C8, 1A2, 2B6, 2C9, 2C19, 2D6 and 3A4. Lenvatinib inhibited UGT1A1 and UGT1A4 as well as OAT1, OAT3, OCT1, OCT2, OATP1B1 and BSEP. It is not considered a strong inducer or inhibitor P450 or UGT enzymes.
Lenvatinib may be co-administered with CYP3A4 inhibitors and inducers, PGP inducers and inhibitors, BRCP inhibitors and drugs that effect gastric pH without dosage adjustment.
AGENT | EFFECT | MECHANISM | MANAGEMENT |
---|---|---|---|
Use of lenvatinib immediately following sorafenib or other anticancer drugs | Potential for additive toxicities | Additive | For DTC and RCC, use a minimum washout period of 3 weeks. For HCC, use a minimum washout period of 4 weeks after locoregional therapies |
Drugs decrease heart rate and/or prolong PR interval (e.g. antiarrhythmics, beta blockers, non-dihydropyridine Ca channel blockers, digoxin, some HIV protease inhibitors, sphingosine-1 phosphate receptor modulators) | Decreased heart rate, prolonged PR interval | Additive | Avoid if possible; monitor closely if used together |
Drugs that may prolong QT (i.e. amiodarone, procainamide, sotalol, venlafaxine, amitriptyline, sunitinib, methadone, chloroquine, clarithromycin, haloperidol, fluconazole, moxifloxacin, domperidone, ondansetron, etc) | Prolonged QT, Torsades de pointes | Additive | Avoid if possible; monitor closely if used together |
CYP3A4 substrates (e.g. cyclosporine, pimozide, tacrolimus, triazolo-benzodiazepines, dihydropyridine calcium-channel blockers, certain HMG-CoA reductase inhibitors) | Reduced efficacy of substrate | Lenvatinib may induce CYP3A4 | Use with caution with substrates that have a narrow therapeutic index |
P-glycoprotein substrates (i.e. verapamil, digoxin, morphine, ondansetron) | Reduced efficacy of substrate | Lenvatinib may induce PgP | Use with caution with substrates that have a narrow therapeutic index |
Drugs that disrupt electrolyte levels (i.e. loop/thiazide diuretics, laxatives, amphotericin B, high dose corticosteroids) | Increased risk of arrhythmias | Additive | Avoid if possible; monitor closely if used together |
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
Monitor Type | Monitor Frequency |
---|---|
Blood pressure |
Baseline, after 1 week, then every 2 weeks for the first 2 months, monthly thereafter while on treatment |
CBC |
Baseline and at each visit |
ECG |
Baseline and as clinically indicated |
Liver function tests |
Baseline, every 2 weeks for the first 2 months, then monthly during treatment |
Renal function tests |
Baseline and at each visit |
Urine protein |
Baseline and at each visit |
TSH levels |
Baseline and monthly during treatment |
Serum calcium and electrolytes |
Baseline, at least monthly and as clinically indicated |
Clinical toxicity assessment for GI effects, infection, wound healing complications, bleeding, hypertension, thromboembolism, cardiac and neurologic effects |
At each visit |
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
Exceptional Access Program (EAP Website)
- lenvatinib - For the treatment of patients with locally recurrent or metastatic, progressive, radioactive-iodine-refractory differentiated thyroid cancer (DTC) according to criteria
- lenvatinib - For the treatment of unresectable advanced hepatocellular carcinoma according to clinical criteria
- lenvatinib - In Combination with Pembrolizumab for First-Line Advanced or Metastatic Renal Cell Carcinoma
- lenvatinib - In Combination with Pembrolizumab for Advanced Endometrial Cancer
Lenvatinib product monograph, Eisai Limited. December 19, 2018
Schlumberger M, Tahara M, Wirth LJ, et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med. 2015 Feb 12;372(7):621-30.
Scott LJ. Lenvatinib: first global approval. Drugs 2015;75:553-560
Product Monograph Update: Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKIs). Health Canada InfoWatch, June 2020.
September 2023 Updated elimination section
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.
Lenvatinib product monograph, Eisai Limited. December 19, 2018
Schlumberger M, Tahara M, Wirth LJ, et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med. 2015 Feb 12;372(7):621-30.
Scott LJ. Lenvatinib: first global approval. Drugs 2015;75:553-560
Product Monograph Update: Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKIs). Health Canada InfoWatch, June 2020.
lenvatinib (patient)
Info Sheet Introduction:- For treating certain types of thyroid, kidney or liver cancers, and may be used to treat other types of cancer
Other Name: Lenvima
in various strengths, shapes and colours
- For treating certain types of thyroid, kidney or liver cancers, and may be used to treat other types of cancer
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Tell your health care team if you have or had significant medical condition(s), especially if you have or had:
-
high blood pressure
-
liver, kidney or heart problems (including an irregular heartbeat)
-
diabetes or nerve problems,
-
headaches, seizures, or vision problems
-
any bleeding problems
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a history of blood clots, including stroke
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a history of a tear in your stomach or intestine
-
previous radiotherapy or
-
any allergies.
-
-
Tell your health care team if you have an eating disorder, are following a strict diet, or have conditions that may change salt levels in your blood such as severe vomiting or diarrhea.
-
Tell your health care team if you have recently had or will have surgery.
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Your blood pressure should be well controlled before starting lenvatinib. Your health care team will check your blood pressure regularly when you start treatment.
Remember to:
-
Tell your health care team about all of the other medications you are taking.
-
Keep taking other medications that have been prescribed for you, unless you have been told not to by your health care team.
You will have a blood test to check for hepatitis B before starting treatment. See the Hepatitis B and Cancer Medications pamphlet for more information.
Talk to your health care team about:
-
How this medication may affect your sexual health.
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How this medication may affect your ability to have a baby, if this applies to you.
This medication may harm an unborn baby. Tell your health care team if you or your partner are pregnant, become pregnant during treatment, or are breastfeeding.
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If there is any chance of pregnancy happening, you and your partner together must use 2 effective forms of birth control at the same time for at least 1 month after your last dose. Talk to your health care team about which birth control options are best for you.
-
Do not breastfeed while using this medication.
- This medication may affect fertility (ability to get pregnant).
-
This medication is usually taken once daily by mouth, with or without food. Talk to your health care team about how and when to take your medication.
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Swallow lenvatinib capsules whole with a glass of water. Do NOT open, chew, crush, or split the capsules.
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If you have trouble swallowing capsules, talk to your health care team about how to make a lenvatinib mixture in a small glass of water or apple juice without crushing or breaking the capsules.
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You may be given this treatment along with other medication(s) to prevent nausea and vomiting. Make sure you take them as directed by your doctor
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If you miss a dose of lenvatinib, take it if it is within 12 hours of the missed dose. Do not take lenvatinib if it has been more than 12 hours since you missed your dose. Take your next dose as scheduled. Do not double the dose to make up for the forgotten one.
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If you vomit (throw up) after taking your medication, talk to your health care team about what to do.
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If you take too much of your medication by accident, or if you think a child or a pet may have swallowed your medication, you must call the Ontario Poison Control Center right away.
Will this medication interact with other medications or natural health products?
-
This medication can interact with other medications, vitamins, foods and natural health products. Interactions can make the treatment not work as well or cause severe side effects.
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Tell your health care team about all of your:
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prescription and over-the-counter (non-prescription) medications and all other drugs, such as marijuana (medical or recreational)
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natural health products such as vitamins, herbal teas, homeopathic medicines, and other supplements
-
-
Check with your health care team before starting or stopping any of them.
If you take medication(s) to help with your blood pressure, your health care team may monitor your blood pressure and may change your dose.
What should I do if I feel unwell, have pain, a headache or a fever?
-
Always check your temperature to see if you have a fever before taking any medications for fever or pain (such as acetaminophen (Tylenol) or ibuprofen (Advil)).
-
Fever can be a sign of infection that may need treatment right away.
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If you take these medications before you check for fever, they may lower your temperature and you may not know you have an infection.
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How to check for fever:
Keep a digital (electronic) thermometer at home and take your temperature if you feel hot or unwell (for example, chills, headache, mild pain).
- You have a fever if your temperature taken in your mouth (oral temperature) is:
- 38.3°C (100.9°F) or higher at any time
OR
- 38.0°C (100.4°F) or higher for at least one hour.
- 38.3°C (100.9°F) or higher at any time
If you do have a fever:
- Try to contact your health care team. If you are not able to talk to them for advice, you MUST get emergency medical help right away.
- Ask your health care team for the Fever pamphlet for more information.
If you do not have a fever but have mild symptoms such as headache or mild pain:
-
Ask your health care team about the right medication for you. Acetaminophen (Tylenol®) is a safe choice for most people.
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Talk to your health care team before you start taking Ibuprofen (Advil®, Motrin®), naproxen (Aleve®) or ASA (Aspirin®), as they may increase your chance of bleeding or interact with your cancer treatment.
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Talk to your health care team if you already take low dose aspirin for a medical condition (such as a heart problem). It may still be safe to take.
What to DO while on this medication:
- DO check with your health care team before getting any vaccinations, surgery, dental work or other medical procedures. You may need to stop this drug before surgery (lenvatinib might affect how your wounds heal). Only take it again after surgery once you have been told to do so by your health care team.
- DO talk to your health care team about your risk of getting other cancers and heart problems after this treatment.
What NOT to DO while on this medication:
- DO NOT smoke or drink alcohol while on treatment without talking to your health care team first. Smoking and drinking can make side effects worse and make your treatment not work as well.
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Do not throw out any unused medications at home. Bring them to your pharmacy to be thrown away safely.
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Keep this medication in the original packaging at room temperature in a dry place, away from heat and light. Keep out of sight and reach of children and pets.
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How to safely touch oral anti-cancer medications
If you are a patient:
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Wash your hands before and after touching your oral anti-cancer medication.
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Swallow each pill whole. Do not crush or chew your pills.
If you are a caregiver:
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Wear nitrile or latex gloves when touching tablets, capsules or liquids.
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Wash your hands before putting on your gloves and after taking them off, even if your skin did not touch the oral anti-cancer medication.
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Throw out your gloves after each use. Do not re-use gloves.
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Do not touch oral anti-cancer medications if you are pregnant or breastfeeding.
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What to do if oral anti-cancer medication gets on your skin or in your eyes
If medication gets on your skin:
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Wash your skin with a lot of soap and water.
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If your skin gets red or irritated, talk to your health care team.
If medication gets in your eyes:-
Rinse your eyes with running water right away. Keep water flowing over your open eyes for at least 15 minutes.
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The following table lists side effects that you may have when getting lenvatinib. The table is set up to list the most common side effects first and the least common last.
It is unlikely that you will have all of the side effects listed and you may have some that are not listed. Read over the side effect table so that you know what to look for and when to get help. Keep this paper during your treatment so that you can refer to it if you need to.
Very Common Side Effects (50 or more out of 100 people) | |
Side effects and what to do | When to contact health care team |
Abnormal kidney lab tests (Rarely may be severe) Your health care team may check your kidney function regularly with a blood test What to look for?
What to do?
|
Talk to your health care team if it does not improve or if it is severe |
High blood pressure (may be severe) What to look for?
What to do?
If you have a severe headache get emergency help right away as it may be a sign your blood pressure is too high. |
Talk to your health care team if it does not improve or if it is severe |
Diarrhea (may be severe) What to look for?
What to do? If you have diarrhea:
|
Talk to your health care team if no improvement after 24 hours of taking diarrhea medication or if severe (more than 7 times in one day) |
Changes in thyroid activity Thyroid changes may happen weeks to months after you receive your treatment. Your health care team may check your thyroid activity regularly with a blood test. What to look for? Underactive thyroid (uncommon):
What to do? Your health care team may give you prescription medication to treat your underactive thyroid. If you have weight changes along with any of the other symptoms listed, talk to your health care team as soon as possible. |
Talk to your health care team as soon as possible. |
Low appetite What to look for?
Ask your health care team for the Loss of Appetite pamphlet for more information. |
Talk to your health care team if it does not improve or if it is severe |
High blood sugar What to look for?
|
Talk to your health care team as soon as possible |
Liver problems (may be severe) Your health care team may check your liver function with a blood test. The liver changes do not usually cause any symptoms.
If you have any symptoms of liver problems, get emergency medical help right away. |
Get emergency medical help right away |
Common Side Effects (25 to 49 out of 100 people) | |
Side effects and what to do | When to contact health care team |
Low amounts of protein (albumin) in your blood This may be caused by protein loss in your pee Your doctor may monitor for protein in your pee regularly What to look for?
What to do?
|
Talk to your health care team as soon as possible |
Nausea and vomiting What to look for?
What to do? To help prevent nausea:
|
Talk to your healthcare team if nausea lasts more than 48 hours or vomiting lasts more than 24 hours or if it is severe |
Fatigue What to look for?
What to do?
Ask your health care team for the Fatigue pamphlet for more information. |
Talk to your health care team if it does not improve or if it is severe |
Mouth sores What to look for?
To help prevent mouth sores:
Ask your health care team for the Oral Care (Mouth Care) pamphlet for more information. |
Talk to your health care team as soon as you notice mouth or lip sores or if it hurts to eat, drink or swallow |
Too much or too little salt in your body What to look for?
What to do? Get emergency medical help right away for severe symptoms. |
Get emergency medical help right away for severe symptoms |
Headache; mild joint, muscle pain or cramps What to look for?
What to do?
Ask your health care team for the Pain pamphlet for more information. |
Talk to your health care team if it does not improve or if it is severe |
Unusual bleeding or bruising (may be severe) It may be due to low platelets (a type of blood cell). When platelets are low, you are at risk for bleeding and bruising. Ask your health care team for the Low Platelet Count pamphlet for more information. What to look for?
What to do? If your health care team has told you that you have low platelets:
If you have signs of bleeding:
If you have bleeding that does not stop or is severe (very heavy), you must get emergency medical help right away. |
Talk to your health care team if you have any signs of bleeding. If you have bleeding that doesn’t stop or is severe, you MUST get emergency medical help right away |
Proteins in Urine (may be severe) Your health care team may do urine tests to check for proteins in your pee. What to look for?
What to do? Talk to your health care team if it does not improve or if it is severe. |
Talk to your health care team if it does not improve or if it is severe |
Rash on your hands and feet (hand-foot syndrome) What to look for?
What to do? To help prevent Hand-foot syndrome:
Ask your health care team for the Hand-foot syndrome pamphlet for more information. |
Talk to your health care team if it does not improve or if it is severe |
Pains or cramps in the belly What to look for?
|
Talk to your health care team if it does not improve or if it is severe |
Hoarseness (raspy voice) What to look for?
What to do? Talk to your health care team if it does not improve or if it is severe. |
Talk to your health care team if it does not improve or if it is severe |
Constipation What to look for?
What to do? To help prevent constipation:
To help treat constipation:
Ask your health care team for the Constipation Pamphlet for more information. |
Talk to your health care team if it does not improve or if it is severe |
Less Common Side Effects (10 to 24 out of 100 people) | |
Side effects and what to do | When to contact health care team |
Cough and feeling short of breath (may rarely be severe) What to look for?
What to do?
|
Talk to your health care team. If you are not able to talk to your health care team for advice, and you have a fever or severe symptoms, you MUST get emergency medical help right away |
Mild swelling What to look for?
What to do?
|
Talk to your health care team if it does not improve or if it is severe |
Low blood sugar What to look for?
What to do?
|
Talk to your health care team if it does not improve or if it is severe |
Rash; dry, itchy skin What to look for?
What to do? To prevent and treat dry skin:
Rash may be severe in some rare cases and cause your skin to blister or peel. If this happens, get emergency medical help right away. |
Talk to your health care team if it does not improve or if it is severe |
Taste changes What to look for?
What to do?
|
Talk to your health care team if it does not improve or if it is severe |
Dry mouth What to look for?
What to do?
See our Mouth Care pamphlet for more information. Talk to your health care team if your dry mouth does not improve or if it is severe. |
Talk to your health care team if it does not improve or if it is severe |
Higher than normal cholesterol or fat levels in the blood What to look for?
What to do?
|
Talk to your health care team if it does not improve or if it is severe |
Dizziness What to look for?
|
Talk to your health care team if it does not improve or if it is severe |
Low neutrophils (white blood cells) in the blood (neutropenia) When neutrophils are low, you are at risk of getting an infection more easily. Ask your health care team for the Neutropenia (Low white blood cell count) pamphlet for more information. What to look for?
You have a fever if your temperature taken in your mouth (oral temperature) is:
What to do? If your health care team has told you that you have low neutrophils:
If you have a fever: If you have a fever, try to contact your health care team. If you are unable to talk to the team for advice, you must get emergency medical help right away. |
If you have a fever, try to contact your health care team. If you are unable to talk to the team for advice, you MUST get emergency medical help right away. |
Heartburn; stomach upset; bloating What to look for?
What to do?
|
Talk to your health care team if it does not improve or if it is severe |
Higher than normal levels of pancreas enzymes in your blood (lipase, amylase) What to look for?
What to do?
If you have any symptoms, get emergency medical help right away. |
Talk to your health care team if it does not improve or if it is severe |
Hair thinning or loss What to look for?
What to do?
|
Talk to your health care team if this bothers you |
Trouble Sleeping Your medications may cause trouble sleeping. It may get better once your body gets used to the medication or when your treatment ends. What to look for?
What to do? Talk to your health care team if it does not improve or if it is severe |
Talk to your health care team if it does not improve or if it is severe |
Heart problems What to look for?
What to do? Get emergency medical help right away. |
Get emergency medical help right away |
Other rare, but serious side effects are possible.
If you experience ANY of the following, speak to your cancer health care provider or get emergency medical help right away:
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Sudden severe pain in the neck, face, back or belly. Unusual pulsating feeling in your chest or belly
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Sudden weakness on one side of your body
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Bloating or feeling of fullness in the belly and severe constipation
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Pain, swelling or hardening of a vein in your arm or leg
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Feeling confused, severe headache, problems with your vision, trouble speaking, swallowing or using your arms or legs
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Severe or unusual bone pain especially in your back, hips and wrist
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Severe muscle pain or weakness with dark pee
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Signs of an allergy such as fever, itchiness, rash, swollen lips, face or tongue, chest and throat tightness
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Wounds that do not heal well or take too long to heal
Who do I contact if I have questions or need help?My cancer health care provider is: ______________________________________________ During the day I should contact:________________________________________________ Evenings, weekends and holidays:______________________________________________
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Other Notes:
____________________________________________________________________________
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____________________________________________________________________________
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March 2023 Modified "What should I do before I have this medication" section
For more links on how to manage your symptoms go to www.cancercareontario.ca/symptoms.
The information set out in the medication information sheets, regimen information sheets, and symptom management information (for patients) contained in the Drug Formulary (the "Formulary") is intended to be used by health professionals and patients for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or side effects of a certain drug, nor should it be used to indicate that use of a particular drug is safe, appropriate or effective for a given condition.
A patient should always consult a healthcare provider if he/she has any questions regarding the information set out in the Formulary. The information in the Formulary is not intended to act as or replace medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.



- lenvatinib - For the treatment of patients with locally recurrent or metastatic, progressive, radioactive-iodine-refractory differentiated thyroid cancer (DTC) according to criteria
- lenvatinib - For the treatment of unresectable advanced hepatocellular carcinoma according to clinical criteria
- lenvatinib - In Combination with Pembrolizumab for First-Line Advanced or Metastatic Renal Cell Carcinoma
- lenvatinib - In Combination with Pembrolizumab for Advanced Endometrial Cancer
len VA ti nib
Cancer Type: Endocrine Thyroid Gastrointestinal Hepatobiliary / Liver / Bile Duct Genitourinary Renal cell / Kidney Gynecologic Endometrial Type of Content: Drug Monograph Status: Null Info Sheet Status: Null Global Date: Lundi, septembre 18, 2023 Universal Date: 2023-09-18 00:00:00 AddThis: Title URL: lenvatinib Drug Display Status: Active Revision Summary:Drug Monograph: Updated elimination section