Lenvima

Lenvatinib

Locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (DTC). In combination w/ everolimus for advanced renal cell carcinoma (RCC) following 1 prior vascular endothelial growth factor (VEGF)-targeted therapy. 1st-line treatment of unresectable hepatocellular carcinoma (HCC). In combination w/ pembrolizumab for 1st-line treatment of advanced RCC; for adult patients w/ advanced or recurrent endometrial carcinoma (EC) who have disease progression on or following prior treatment w/ platinum-containing therapy in any setting & are not candidates for curative surgery or radiation.

Adult DTC 24 mg once daily. RCC 18 mg once daily in combination w/ everolimus 5 mg or 20 mg once daily in combination w/ pembrolizumab 200 mg every 3 wk or 400 mg every 6 wk IV infusion over 30 min. HCC Patient weighing ≥60 kg 12 mg once daily, <60 kg 8 mg once daily. EC 20 mg once daily in combination w/ pembrolizumab 200 mg every 3 wk or 400 mg every 6 wk IV infusion over 30 min. Severe hepatic & renal impairment DTC Initially 14 mg once daily. RCC & EC Initially 10 mg once daily.

May be taken with or without food: Take at the same time each day. Swallow whole w/ liqd. Alternatively, add the cap to a tbsp of water or apple juice in a small glass to produce a susp. Do not crush/break the cap. Leave for at least 10 min. Stir susp for at least 3 min & drink immediately. Rinse glass w/ another 1 tbsp of water or apple juice. Swirl a few times & swallow the additional liqd.

Hypersensitivity.

Monitor BP after 1 wk of treatment then every 2 wk for the 1st 2 mth & mthly thereafter. W/hold treatment if w/ systolic BP ≥160 mmHg or diastolic BP ≥100 mmHg despite optimal antihypertensive therapy. Discontinue treatment & institute appropriate medical management if life-threatening consequences (malignant HTN, neurological deficit or hypertensive crisis) occur. Possible artery dissection in patients using VEGF receptor tyrosine kinase inhibitors w/ or w/o HTN. Regularly monitor urine protein. Discontinue use if nephrotic syndrome occurs. Actively manage GI toxicity to reduce the risk of developing renal impairment or failure. Monitor for clinical symptoms or signs of cardiac decompensation. Dose interruption, adjustment or discontinuation may be necessary in patients w/ signs or symptoms of posterior reversible encephalopathy syndrome. Possible serious tumour-related bleeds including fatal haemorrhagic events. Patients w/ arterial thromboembolic event w/in the previous 6 mth. GI perforation & fistula formation may occur. Do not start in patients w/ fistula; permanently discontinue in patients w/ oesophageal or tracheobronchial tract involvement & any Grade 4 fistula. Monitor ECG in all patients w/ special attention for those w/ congenital long QT syndrome, CHF, bradyarrhythmias & those taking QT interval-prolonging drugs including class Ia & III antiarrhythmics. Increased risk of QT prolongation caused by electrolyte disturbances (eg, hypokalaemia, hypocalcaemia or hypomagnesaemia). Consider periodic monitoring of ECG & electrolytes (Mg, K & Ca) during treatment. Regularly monitor TSH levels. Discontinue use in the event of persistent grade 4 diarrhoea. W/hold use at least 1 wk prior to elective surgery; do not administer for at least 2 wk following major surgery & until adequate wound healing. Possible osteonecrosis of the jaw. Simultaneous or sequential treatment w/ antiresorptive therapy &/or other angiogenesis inhibitors. Consider dental exam & appropriate preventive dentistry prior to treatment; avoid invasive dental procedures in patients who have previously received or are receiving IV biphosphonates. Patients of ethnic origin other than Caucasian or Asian. Potential risk of additive toxicities w/ sorafenib or other anticancer treatments. Not recommended in patients w/ ESRD. Monitor LFTs before initiation of treatment then every 2 wk for the 1st 2 mth & mthly thereafter during treatment. Adjust initial dose in patients w/ severe renal or hepatic impairment. Closely monitor patients w/ HCC for signs of hepatic failure including hepatic encephalopathy. May cause fatigue & dizziness which may affect ability to drive or operate machines. Women of childbearing potential must use highly effective contraception while on treatment & for at least 1 mth after finishing treatment. Pregnancy. Contraindicated during breastfeeding. Childn 2 to <18 yr; not to be used in childn <2 yr. Elderly ≥75 yr.

UTI; thrombocytopenia, lymphopenia, leukopenia, neutropenia; hypothyroidism, increased blood TSH; hypocalcaemia, hypokalaemia, hypercholesterolaemia, decreased appetite & wt; insomnia; dizziness, headache, dysgeusia; haemorrhage, HTN, hypotension; dysphonia; diarrhoea, GI & abdominal pains, vomiting, nausea, oral inflammation & pain, constipation, dyspepsia, dry mouth, increased lipase & amylase; hypoalbuminaemia, increased blood bilirubin, AST & ALT, blood alkaline phosphatase, γ-glutamyl transferase; palmar-plantar erythrodysaesthesia syndrome, rash, alopecia; back pain, arthralgia, myalgia, pain in extremity, musculoskeletal pain; proteinuria, increased blood creatinine; fatigue, asthenia, peripheral oedema. Anaemia; hyperthyroidism. Dehydration, hypomagnesaemia; CVA; MI, cardiac failure, prolonged ECG QT, decreased ejection fraction; pulmonary embolism; anal fistula, flatulence; hepatic failure & encephalopathy, abnormal hepatic function, cholecystitis; hyperkeratosis; renal failure & impairment, increased blood urea; malaise.

May reduce effectiveness of hormonal contraceptives.

Targeted Cancer Therapy

L01EX08 - lenvatinib ; Belongs to the class of other protein kinase inhibitors. Used in the treatment of cancer.

POM