Lenvatinib
Cytostatic · Kinase Inhibitor
Indications
For the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (DTC). In combination with pembrolizumab. For the first line treatment of adult patients with advanced renal cell carcinoma (RCC). In combination with everolimus, for the treatment of adult patients with advanced renal cell carcinoma (RCC) following one prior anti angiogenic therapy. For the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC). In combination with pembrolizumab, for the treatment of patients with advanced endometrial carcinoma (EC) that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
Dosage
Adults: Single Agent Therapy: DTC: 24 mg once daily. HCC: The recommended dosage is based on actual body weight: 12 mg once daily for patients greater than or equal to 60 kg or 8 mg once daily for patients less than 60 kg. Combination Therapy: EC: 20 mg once daily in combination with pembrolizumab 200 mg administered as an IV infusion over 30 minutes every 3 weeks. RCC: 20 mg once daily with pembrolizumab 200 mg administered as an IV infusion over 30 minutes every 3 weeks. 18 mg once daily with everolimus 5 mg once daily. Modify the recommended daily dose for certain patients with renal or hepatic impairment. Children: Not recommended.
Adverse Effects
In DTC: Hypertension, fatigue, diarrhea, arthralgia/myalgia, decreased appetite, decreased weight, nausea, stomatitis, headache, vomiting, proteinuria, palmar-plantar erythrodysesthesia syndrome, abdominal pain, and dysphonia. In RCC: For lenvatinib and pembrolizumab are fatigue, diarrhea, musculoskeletal pain, hypothyroidism, hypertension, stomatitis, decreased appetite, rash, nausea, decreased weight, dysphonia, proteinuria, palmar-plantar erythrodysesthesia syndrome, abdominal pain, hemorrhagic events, vomiting, constipation, hepatotoxicity, headache, and acute kidney injury. For lenvatinib and everolimus are diarrhea, fatigue, arthralgia/myalgia, decreased appetite, vomiting, nausea, stomatitis/oral inflammation, hypertension, peripheral edema, cough, abdominal pain, dyspnea, rash, decreased weight, hemorrhagic events, and proteinuria. In HCC: For lenvatinib are hypertension,…
Risk Factor (Pregnancy/Lactation)
Pregnancy: Contraindicated in pregnancy. Lactation: Contraindicated or not recommended. Precautions: Monitor, control or withhold or discontinue for any of the following: Blood pressure, cardiac dysfunction, arterial thromboembolic event, hepatotoxicity, Renal Failure or Impairment, Proteinuria, Diarrhea, Fistula Formation and Gastrointestinal Perforation, QT Interval Prolongation, Hypocalcemia, Reversible Posterior Leukoencephalopathy Syndrome (RPLS), Hemorrhagic Events, Impairment of Thyroid Stimulating Hormone Suppression/Thyroid Dysfunction, Impaired Wound Healing. Osteonecrosis of the Jaw: Consider preventive dentistry prior to treatment, avoid invasive dental procedures, if possible, particularly in patients at higher risk. Advise use of effective contraception.
Interactions
Metabolism/Transport Effects Substrate of BCRP/ABCG2, CYP3A4 (minor), P-glycoprotein/ABCB1 (minor), Citalopram, Clarithromycin, Domperidone, Entrectinib, Fexinidazole (INT), Flupentixol, Moxifloxacin (Systemic), Nilotinib, Pimozide, Piperaquine, Probucol, QT-prolonging Kinase Inhibitors (Highest Risk): QUEtiapine, Ribociclib, Sparfloxacin, Thioridazine.
Advice to Patient
Advise patients to undergo regular blood pressure monitoring. Advise patients to report any clinical symptoms of cardiac dysfunction. Advise patients to seek immediate medical attention for new onset chest pain or acute neurologic symptoms consistent with myocardial infarction or stroke. Advise patients that they will need to undergo regular laboratory tests to monitor liver function, calcium levels, kidney function and protein in the urine, thyroid function. Diarrhea: Advise patients when to start standard anti-diarrheal therapy and to maintain adequate hydration. Advise patients that Lenvatinib can increase the risk of fistula formation or gastrointestinal perforation and to seek immediate medical attention for severe abdominal pain. Advise patients who are at risk for QTc prolongation that they will need to undergo regular ECGs, to undergo laboratory tests to monitor…
Pharmacokinetics
Absorption: Administration with a high fat meal (~900 calories: ~55% from fat, ~15% from protein, and ~30% from carbohydrates) decreased the rate of absorption and delayed the median Tmax from 2 hours to 4 hours, but did not affect the extent of absorption. Metabolism: Primarily enzymatic through CYP3A and aldehyde oxidase; nonenzymatic metabolism also occurs. Half-life elimination: ~28 hours. Time to peak: 1 to 4 hours. Excretion: Faces (~64% urine (~25%)
Compiled by Healify Pharmacy from published drug references. How we compile it →
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