Drug information of lenvatinib

lenvatinib


Antineoplastic

Mechanism of effect

Receptor tyrosine kinase (RTK) inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4

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 (PDGFR-alpha), KIT, and RET

Pharmacodynamic

Endometrial carcinoma, advanced

Hepatocellular carcinoma, unresectable

Renal cell carcinoma, advanced

Thyroid cancer, differentiated

Pharmacokinetics

Peak plasma time: 1-4 hr after PO administration

Administration with food does not affect the extent of absorption but can delay the mean peak plasma time from 2 hr to 4 hr

Protein bound: 98-99%

Metabolized by the CYP3A enzymes and aldehyde oxidase

Half-life: 28 hr

Excretion (10 days after single dose): 64% feces; 25% urine

Drug indications

advanced renal cell carcinoma , hepatocellular carcinoma , Thyroid Cancer , Endometrial Carcinoma

Endometrial carcinoma, advanced
Hepatocellular carcinoma, unresectable
Renal cell carcinoma, advanced
Thyroid cancer, differentiated

Dosage

Endometrial carcinoma, advanced: Oral: 20 mg once daily (in combination with pembrolizumab), continue until disease progression or unacceptable toxicity .

Hepatocellular carcinoma, unresectable: Oral: 12 mg once daily (patients ≥60 kg [actual body weight]) or 8 mg once daily (patients <60 kg [actual body weight]) continue until disease progression or unacceptable toxicity.

Renal cell carcinoma, advanced: Oral: 18 mg once daily (in combination with everolimus), continue until disease progression or unacceptable toxicity .

Thyroid cancer, differentiated: Oral: 24 mg once daily until disease progression or unacceptable toxicity .

Missed doses: Do not take a missed dose within 12 hours of the next dose (if within 12 hours, skip the missed dose and return to regular administration time).

Dosage adjustment for surgery: Temporarily withhold lenvatinib treatment for at least 1 week prior to elective surgery; do not reinitiate therapy for ≥2 weeks following major surgery and until adequate wound healing.

Drug contraindications

Hypersensitivity to this drug

Hypersensitivity to lenvatinib or any component of the formulation

Side effects

Diarrhea , Proteinuria , hemorrhage , liver failure , ECG prolonged QT , renal failure , cardiac failure , tiredness , swelling of the face, mouth, hands, or feet , Fistulas

Hypertension , peripheral edema ,Fatigue , headache , voice disorder , mouth pain , dizziness , insomnia ,Palmar-plantar erythrodysesthesia , skin rash , alopecia ,Increased thyroid stimulating hormone level , weight loss , hypothyroidism , increased gamma-glutamyl transferase , hyponatremia ,Diarrhea , decreased appetite , nausea , stomatitis , vomiting , abdominal pain ,constipation , dysgeusia , xerostomia , dyspepsia ,Proteinuria , urinary tract infection , Hemorrhage ,Increased serum aspartate aminotransferase ,Arthralgia , myalgia ,Renal insufficiency ,Cough ,epistaxis ,Fever ,Hypotension , prolonged QT interval on ECG , cardiac failure , ventricular dysfunction , arterial thromboembolism , cardiac abnormality , pulmonary embolism , reduced ejection fraction ,Hyperkeratosis ,Dehydration , hypocalcemia , hypokalemia , hypercalcemia , hypercholesterolemia , hypoalbuminemia , hypoglycemia , hypomagnesemia ,Infection of mouth , increased serum lipase , increased serum amylase , gastrointestinal fistula , gastrointestinal perforation ,Thrombocytopenia , lymphocytopenia , neutropenia , anemia ,Hepatic encephalopathy , hyperbilirubinemia , increased serum alanine aminotransferase , increased serum alkaline phosphatase , hepatic failure ,Increased serum creatinine ,Pulmonary edema , pneumonia ,Aortic dissection, cholecystitis, hepatitis, nephrotic syndrome, pancreatitis, pneumothorax, reversible posterior leukoencephalopathy syndrome, tumor hemorrhage, wound healing impairment

 

Doxepin-Containing Products

Fexinidazole

Gadobenate Dimeglumine

(Levofloxacin-Containing Products (Systemic

Pilsicainide

Piperaquine

QT-prolonging Agents (Indeterminate Risk – Avoid

QT-prolonging Class IA Antiarrhythmics (Highest Risk

QT-prolonging Class III Antiarrhythmics (Highest Risk

QT-prolonging Kinase Inhibitors (Highest RiskQT-prolonging Miscellaneous Agents (Highest Risk

QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk

QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk

Sodium Stibogluconate

Alerts

-Hypertension reported in clinical trials

-Cardiac dysfunction, defined as decreased left or right ventricular function, cardiac failure, or pulmonary edema, was reported;-

-Arterial thromboembolic events reported; discontinue drug following a thromboembolic event

-Serious hepatic adverse reactions reported

-Proteinuria reported in clinical trials

-Serious including fatal renal failure or impairment can occur with therapy

-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

-QT prolongation reported

-Hypocalcemia reported

-Reversible posterior leukoencephalopathy syndrome (RPLS) reported rarely

-Hemorrhagic events occurred

-Impairs exogenous thyroid suppression

-Impaired wound healing been reported in patients who received therapy

- May result in reduced fertility in females of reproductive potential and damage to male reproductive tissues, leading to reduced fertility of unknown duration

Points of recommendation

-control blood pressure before treatment; monitor blood pressure after 1 week, then q2weeks for the first 2 months, and then at least monthly thereafter

- monitor for clinical symptoms or signs of cardiac decompensation

- monitor for proteinuria before initiation of, and periodically throughout, treatment;

-monitor ECG in patients with congenital long QT syndrome, CHF, bradyarrhythmias, or those who are taking drugs known to prolong the QT interval

-monitor blood calcium levels at least monthly and replace calcium as necessary during treatment

-monitor TSH levels monthly and adjust thyroid replacement medication as needed

- Advise females of reproductive potential to use effective contraception during treatment and for at least 30 days after last dose

Pregnancy level

Based on the mechanism of action and findings from animal reproduction studies, lenvatinib may cause fetal harm if administered in pregnancy.

Advise pregnant women of the potential risk to a fetus

Breast feeding warning

 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 last dose

Related drugs

Regorafenib

Drug forms

Lenvima

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