Lenvatinib oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of lenvatinib.
Drugs List
Therapeutic Indications
Uses
Advanced renal cell carcinoma progressing on/after VEGF-targeted therapy
Hepatocellular carcinoma
Treatment of locally advanced or metastatic differentiated thyroid cancer
Treatment of progressive, locally advanced or metastatic differentiated (papillary/follicular/Hurthle cell) thyroid carcinoma, refractory to radioactive iodine (RAI). Treatment of patients with advanced renal cell carcinoma (RCC) following one prior vascular endothelial growth factor (VEGF)- targeted therapy when used in combination with everolimus. Treatment of advanced or unresectable hepatocellular carcinoma (HCC) in patients who have not had previous systemic therapy.
Dosage
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
Adults
Differentiated thyroid cancer
24mg once a day, taken at the same time each day.
Renal cell carcinoma
18mg once a day in combination with 5mg of everolimus once a day.
Hepatocellular carcinoma
Bodyweight equal to or more than 60kg
12mg once a day. Modify dose according to dose/toxicity plan.
Bodyweight less than 60kg
8mg once a day. Modify dose according to dose/toxicity plan.
Patients with Renal Impairment
Differentiated thyroid cancer
Severe renal impairment: 14mg once a day.
Renal cell carcinoma
Severe renal impairment: 10mg once a day.
Patients with Hepatic Impairment
Differentiated thyroid cancer
Severe hepatic impairment (Child-Pugh C): 14mg once a day.
Renal cell carcinoma
Severe hepatic impairment (Child-Pugh C): 10mg lenvatinib once a day. Only to be used if potential benefits of treatment outweigh the risks.
Additional Dosage Information
Missed Dose
Advise patient if a dose is missed to take if within 12 hours of the normal dose. If remembered after 12 hours, the patient must skip the missed dose and resume the usual dose regime.
Blood pressure
Systolic BP greater than or equal to 140mmHg and less than 160mmHg or diastolic BP greater than or equal to 90mmHg and less than 100mmHg:
Continue treatment and initiate antihypertensive treatment if patient not already receiving. If the patient is already receiving antihypertensive therapy, increase dose of current antihypertensive treatment or initiate an additional antihypertensive treatment.
Systolic BP greater than or equal to 160mmHg or diastolic BP 100mmHg despite antihypertensive treatment:
Suspend treatment of lenvatinib until systolic BP less than or equal to 150mmHg and diastolic BP less than or equal to 95mmHg and patient has been on a stable dose of antihypertensive for 48 hours. Resume lenvatinib at a reduced dose.
Malignant hypertension, neurological deficit or hypertensive crisis:
Discontinue treatment of lenvatinib and institute appropriate medical management.
Dose Modification
Dose modification is not generally required for mild to moderate adverse reactions (Grade 1 or 2) unless intolerable to the patient. Severe adverse reactions (Grade 3) may require interruption of therapy until improvement of the adverse reaction symptom(s) occurs to Grade 0 or 1. Treatment should then be resumed at a reduced dose.
Treatment should be discontinued for any life threatening (grade 4) adverse reactions except for laboratory abnormalities judged to be non-life threatening, which should be managed as grade 3 adverse reactions.
Differentiated thyroid cancer - Dose modification levels
1st reduction: 20mg once a day.
2nd reduction: 14mg once a day.
3rd reduction: 10mg once a day.
Doses lower than 10mg should be considered on an individual patient basis. At the time of writing there are limited data available on doses lower than 10mg once a day.
Renal cell carcinoma - Dose modification levels
1st reduction: 14mg once a day.
2nd reduction: 10mg once a day.
3rd reduction: 8mg once a day.
Hepatocellular carcinoma
Bodyweight equal to or more than 60kg
1st occurrence: 8mg once a day
2nd occurrence: 4mg once a day
3rd occurrence: 4mg every other day
Bodyweight less than 60kg
1st occurrence: 4mg once a day
2nd occurrence: 4mg every other day
3rd occurrence: Discontinue
The following lenvatinib dose modifications for toxicity related to lenvatinib are recommended. For toxicities relating to everolimus, refer to everolimus product literature. For toxicities related to both lenvatinib and everolimus, reduce lenvatinib before reducing everolimus.
Hypertension Grade 3 despite antihypertensive therapy: Interrupt until Grade 0, 1 or 2. Grade 4: Discontinue and do not resume. Proteinuria Greater than or equal to 2gm per 24 hours: Interrupt until resolves to less than 2gm per 24 hours. QT prolongation Greater than 500msec: Interrupt until resolves to less than 480msec or baseline. The dose should be adjusted or interrupted depending on the severity and persistence of hypocalcaemia, and the presence of ECG changes.
Contraindications
Children under 18 years
Fistula
Breastfeeding
End stage renal disease
Long QT syndrome
Pregnancy
Torsade de pointes
Uncontrolled hypertension
Precautions and Warnings
Asian ancestry
Family history of long QT syndrome
Females of childbearing potential
History of radiotherapy
Patients over 75 years
Recent surgery
Risk of haemorrhage
Tobacco smoking
Weight below 60kg
Behcet's disease
Cerebrovascular disorder
Decompensated cardiac failure
Dehydration
Diabetes mellitus
Electrolyte imbalance
Giant cell arteritis
History of aneurysm
History of torsade de pointes
Hyperlipidaemia
Hypertension
Hypovolaemia
Ischaemic heart disease
Marfan syndrome
Occlusive peripheral arterial disease
Proteinuria
Recent arterial thromboembolic disorder
Severe hepatic impairment
Severe renal impairment
Takayasu arteritis
Vascular Ehlers-Danlos syndrome
Correct electrolyte disorders before treatment
Reduce dose in patients with severe hepatic impairment
Reduce dose in patients with severe renal impairment
Advise ability to drive/operate machinery may be affected by side effects
Consider a dental exam & appropriate preventive dentistry before treatment
Ensure hypertension is controlled prior to treatment
May increase risk of fistula occurring
Not all available brands are licensed for all indications
Treatment to be initiated and supervised by a specialist
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Monitor thyroid stimulating hormone (TSH) before & during treatment
Monitor blood pressure after 1week, every 2 weeks for 2 months then monthly
Monitor calcium levels at least monthly
Monitor ECG in patients at risk of QT prolongation
Monitor for gastrointestinal toxicity
Monitor for protein in urine
Monitor for symptoms of gastrointestinal perforation or fistula
Monitor liver function before, every 2 weeks for 2 months & then monthly
Monitor patients for signs and symptoms of cardiac failure
Monitor serum electrolytes
Advise patient to report diarrhoea
Advise patient to report headaches, seizures, confusion, visual disturbance
May increase the risk of tumour associated haemorrhage
Treatment may adversely affect wound healing
Consider dose modification if proteinuria greater than or equal to 2+
Consider interrupting treatment if symptoms of cardiac dysfunction occur
Discontinue if arterial thromboembolism develops
Discontinue if grade 4 toxicity occurs
Discontinue if nephrotic syndrome occurs
Discontinue if posterior reversible encephalopathy syndrome (PRES) develops
Discontinue if renal failure develops
Discontinue if severe haemorrhage occurs
Discontinue permanently if any grade 4 fistula occurs
Discontinue permanently if grade 4 diarrhoea occurs
Interrupt treatment and/or reduce dose for any grade 3 toxicity
Interrupt treatment if QTc exceeds 500msec and consider dose modification
Female:Non-hormonal contraception advised until 1 month after treatment
Advise patient on giving up smoking
Patients with pre-existing hypertension should be on a stable dose of antihypertensive treatment 1 week prior to treatment. Antihypertensive treatment should be initiated as soon as an elevated blood pressure is confirmed. The degree of tumour invasion/infiltration of major blood vessels should be considered because of the potential risk of severe haemorrhage associated with tumour shrinkage or necrosis following lenvatinib therapy. Arterial thromboembolism has been reported in patients receiving lenvatinib, caution should be used in patients who have had an arterial thromboembolism within the previous 6 months. Patients aged 75 years or over, of Asian race and with comorbidities (hypertension, hepatic or renal impairment) and/or have a body weight of less than 60kg appear to have a reduced tolerability to lenvatinib. These patients excluding those with renal and hepatic impairment should initiate treatment at the normal recommended dose, which should then be modified based on patient tolerability. Posterior Reversible Encephalopathy Syndrome (PRES) also known as Reversible Posterior Leucoencephalopathy Syndrome (RPLS) Posterior reversible encephalopathy syndrome (PRES) has been reported in some patients. If patients present with symptoms indicating PRES such as headache, altered mental state, seizures and visual disturbances, an MRI should be performed. If PRES is diagnosed, treatment should be discontinued and adequate blood pressure control is advisable. The safety of reinstating treatment in patients previously experiencing PRES is unknown. Risk factors for aneurysm and artery dissection Use of systemic VEGF inhibitors may promote the formation of aneurysms or artery dissections, mainly in relation to aortic aneurysm rupture and aortic dissection. It is therefore important to consider the risk of aneurysm and artery dissection in patients with risk factors such as hypertension, history of aneurysm, smoking, diabetes, coronary, cerebrovascular or peripheral arterial disease, and hyperlipidaemia. Other risk factors include Marfan syndrome, vascular Ehlers-Danlos syndrome, Takayasu arteritis, and the use of fluoroquinolones. In patients receiving VEGF inhibitors, any modifiable risk factors such as smoking and hypertension should be reduced as far as possible.
Pregnancy and Lactation
Pregnancy
Lenvatinib is contraindicated during pregnancy.
The manufacturer does not recommend using lenvatinib during pregnancy unless clearly necessary and after careful consideration of the needs of the mother and risk to the foetus. Animal studies have shown teratogenic effects. Human data is limited and as such a potential risk cannot be ruled out.
Lactation
Lenvatinib is contraindicated during breastfeeding.
Use of lenvatinib when breastfeeding is contraindicated by the manufacturer. Animal data reports levels of lenvatinib in the breast milk, however presence in human breast milk is unknown. Effects on exposed infants are unknown.
Counselling
Advise patient to swallow whole with water at the same time each day. OR Alternatively, whole capsules may be added to a tablespoon of water or apple juice in a small glass to produce a suspension. Leave the whole capsules in the liquid for at least 10 minutes and then stir for at least 3 minutes to dissolve the capsule shells. Swallow the suspension. After drinking, add the same amount of water or apple juice to the same glass to swirl and swallow.
Advise patient to report headaches, seizures, confusion and visual disturbances.
Advise patient to report diarrhoea.
Advise female patients to use a non-hormonal contraceptive during and for 1 month after treatment.
Advise patient ability to drive/operate machinery may be affected by side effects.
Side Effects
Alopecia
Aneurysm
Arterial thrombosis
Artery dissection
Arthralgia
Asthenia
Back pain
Cardiac failure
Cerebrovascular accident
Cholecystitis
Constipation
Decreased appetite
Decreased ejection fraction
Dehydration
Diarrhoea
Dizziness
Dry mouth
Dysgeusia
Dyspepsia
Dysphonia
Elevated amylase levels
Elevated serum lipase
Elevated TSH
Fatal intracranial haemorrhage
Fatigue
Fistulae
Flatulence
Gamma glutamyl transferase (GGT) increased
Gastro-intestinal pain
Gastro-intestinal perforation
Haemorrhage
Headache
Hepatic impairment
Hepatitis
Hepatotoxicity
Hypercholesterolaemia
Hyperkeratosis
Hypertension
Hypoalbuminaemia
Hypocalcaemia
Hypokalaemia
Hypomagnesaemia
Hypotension
Hypothyroidism
Impaired healing
Increase in alkaline phosphatase
Increase in blood urea or creatinine
Increase in serum ALT/AST
Insomnia
Intracranial bleeding
Leukopenia
Lymphopenia
Malaise
Monoparesis
Musculoskeletal pain
Myalgia
Myocardial infarction
Nausea
Nephrotic syndrome
Neutropenia
Non-gastrointestinal fistula
Oral mucositis
Oral pain
Osteonecrosis (primarily of the jaw)
Painful extremities
Palmar-Plantar Erythrodysaesthesia syndrome
Pancreatitis
Perineal abscess
Peripheral oedema
Pneumothorax
Posterior reversible encephalopathy syndrome (PRES)
Prolongation of QT interval
Proteinuria
Pulmonary embolism
Rash
Renal failure
Renal impairment
Serum bilirubin increased
Splenic infarction
Stomatitis
Thrombocytopenia
Transient ischaemic attack
Urinary tract infections
Vomiting
Weight loss
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: April 2021
Reference Sources
MHRA Drug Safety Update July 2020
Available at: https://www.gov.uk/drug-safety-update/systemically-administered-vegf-pathway-inhibitors-risk-of-aneurysm-and-artery-dissection
Last accessed: 07 April 2021
Summary of Product Characteristics: Kisplyx 4mg and 10mg hard capsules. Eisai Ltd. Revised February 2021.
Summary of Product Characteristics: Lenvima 4mg and 10mg capsules. Eisai Ltd. Revised March 2021.
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.