Lenvima

Monotherapy in adults w/ progressive, locally advanced or metastatic, differentiated (papillary/follicular/Hürthle cell) thyroid carcinoma (DTC), refractory to radioactive iodine; advanced or unresectable hepatocellular carcinoma (HCC) who have received no prior systemic therapy. In combination w/ pembrolizumab for 1st-line treatment of patients w/ advanced renal cell carcinoma (RCC); advanced endometrial carcinoma (EC) in patients w/ disease progression following prior systemic therapy in any setting & are not candidates for curative surgery or radiation. In combination w/ everolimus for adults w/ advanced RCC following 1 prior vascular endothelial growth factor (VEGF)-targeted therapy.

DTC 24 mg (two 10-mg cap & one 4-mg cap) once daily. Dose modification: 1st dose reduction: 20 mg (two 10-mg cap) once daily, 2nd dose reduction: 14 mg (one 10-mg cap & one 4-mg cap) once daily, 3rd dose reduction: 10 mg once daily. RCC Initially 20 mg (two 10-mg cap) once daily + pembrolizumab 200 mg as IV infusion over 30 min every 3 wk in 1st-line treatment of patients w/ advanced RCC. Initially 18 mg (one 10-mg cap & two 4-mg cap) once daily + everolimus 5 mg once daily in previously treated RCC. Dose modification: 1st dose reduction: 14 mg (one 10-mg cap & one 4-mg cap) once daily, 2nd dose reduction: 10 mg once daily, 3rd dose reduction: 8 mg (two 4-mg cap) once daily. HCC Patient weighing ≥60 kg 12 mg (three 4-mg cap) once daily. Dose modification: 1st dose reduction: 8 mg (two 4-mg cap) once daily, 2nd dose reduction: 4 mg once daily, 3rd dose reduction: 4 mg every other day; <60 kg 8 mg (two 4-mg cap) once daily. Dose modification: 1st dose reduction: 4 mg once daily, 2nd dose reduction: 4 mg every other day. EC 20 mg (two 10-mg cap) once daily + pembrolizumab 200 mg as IV infusion over 30 min every 3 wk until unacceptable toxicity or disease progression. Dose modification: 1st dose reduction: 14 mg (one 10-mg cap & one 4-mg cap) once daily, 2nd dose reduction: 10 mg once daily, 3rd dose reduction: 8 mg (two 4-mg cap) once daily. Patient w/ severe hepatic (Child-Pugh C) & renal impairment DTC Initially 14 mg once daily. RCC Initially 10 mg once daily in combination w/ everolimus once daily. EC 10 mg once daily.

May be taken with or without food. Do not open cap, swallow whole. May disperse whole cap & administer susp orally or via feeding tube. Take immediately.

Hypersensitivity. Lactation.

Permanently discontinue treatment in patients w/ oesophageal or tracheobronchial tract involvement & any Grade 4 fistula. Discontinue treatment in case of life-threatening consequences (malignant HTN, neurological deficit or hypertensive crisis); nephrotic syndrome; persistent Grade 4 diarrhoea despite medical management; life-threatening (Grade 4) reactions; arterial thrombotic event. Withhold therapy if w/ ≥160 mmHg systolic BP or ≥100 mmHg diastolic BP despite optimal antihypertensive therapy; QT interval prolongation >500 ms develops & resume at reduced dose when resolved to <480 ms or baseline. Interrupt, adjust or discontinue dose if urine dipstick proteinuria ≥2+ is detected; in case of hepatotoxicity, bleeding, or GI perforation of fistula; in patients w/ signs or symptoms of posterior reversible encephalopathy syndrome (PRES); depending on severity, presence of ECG changes, & persistence of hypocalcaemia. Consider temporary interruption in patients undergoing major surgical procedures. Not to be started in patients w/ fistula. HTN; proteinuria; increased ALT, AST & blood bilirubin; hepatic failure (in patients w/ progressive metastatic liver disease) & failure, acute hepatitis; renal impairment & failure; diarrhoea; cardiac failure & decreased left ventricular ejection fraction; PRES also known as reversible posterior leucoencephalopathy syndrome; arterial thromboembolisms (CVA, transient ischaemic attack & MI); serious tumour related bleeds including fatal haemorrhagic events; bleeding secondary to tumour shrinkage & fistula formation; fatal intracranial haemorrhage in patients w/ or w/o metastases; GI perforation or fistulae in patients w/ risk factors eg, prior surgery or RT; QT/QTC interval prolongation; hypothyroidism; impaired wound healing; osteonecrosis of the jaw (ONJ). Increased risk for development of fistulae when treated for DTC. Patients who had arterial thromboembolism w/in the previous 6 mth; receiving agents associated w/ ONJ eg, bisphosphonates & denosumab. Asian patients. Control BP & ensure stable antihypertensive therapy dose in hypertensive patients for at least 1 wk prior to treatment. Monitor BP after 1 wk of treatment, then every 2 wk for 1st 2 mth, & mthly thereafter; urine protein regularly; LFTs before treatment initiation, then every 2 wk for 1st 2 mth & mthly thereafter during treatment; liver function worsening including hepatic encephalopathy in patients w/ HCC; clinical symptoms or signs of cardiac decompensation; ECG at baseline & periodically during treatment especially in patients w/ congenital long QT syndrome, CHF, bradyarrhythmias & those taking QT prolonging medicinal products eg, class Ia & III antiarrhythmics; electrolytes (eg, Mg, K & Ca) periodically during treatment for any abnormalities & correct before treatment; blood Ca levels at least mthly & replace Ca as necessary during treatment; thyroid function before initiation of & periodically throughout treatment; TSH levels regularly. Manage diarrhoea to prevent dehydration. Perform screening & subsequent treatment of oesophageal varices in patients w/ liver cirrhosis before treatment. Consider oral dental exam & appropriate preventive dentistry prior to treatment. Avoid invasive dental procedures during treatment. RCC patients receiving agents acting on the renin-angiotensin aldosterone system. May affect ability to drive & use machines. Not recommended in severe renal & hepatic (Child-Pugh C) impairment; ESRD. Women of childbearing potential must use highly effective contraception during treatment & for 1 mth after stopping treatment. Not to be used during pregnancy. Contraindicated during breastfeeding. Patients weighing <60 kg w/ RCC. Not to be used in childn <2 yr. Childn 2 to <18 yr. Elderly ≥75 yr.

UTI, nasopharyngitis; thrombocytopenia, leukopenia, neutropenia, anemia; hypo-/hyperthyroidism, increased blood TSH; hypocalcaemia, hypercholesterolaemia, hypokalaemia, hypertriglyceridaemia, decreased appetite & wt; insomnia; dizziness, headache, dysgeusia; haemorrhage, HTN, hypotension; dysphonia, cough, dyspnea; diarrhoea, GI & abdominal pains, vomiting, nausea, oral inflammation & pain, constipation, dyspepsia, dry mouth, stomatitis, pancreatitis; hypoalbuminaemia, increased AST, ALT & blood bilirubin; palmar-plantar erythrodysaesthesia syndrome, palmar erythema, rash, alopecia, pruritus; back pain, arthralgia, myalgia, pain in extremity, musculoskeletal pain & disorders; proteinuria; fatigue, asthenia, pyrexia, peripheral oedema. Lymphopenia; dehydration, hypomagnesaemia; CVA; MI, cardiac failure, prolonged ECG QT, decreased ejection fraction; pulmonary embolism; anal fistula, flatulence, increased lipase & amylase; hepatic failure, hepatic encephalopathy, increased blood alkaline phosphatase & γ-glutamyltransferase, abnormal hepatic function, cholecystitis; hyperkeratosis; renal failure & impairment, increased blood creatinine & 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.

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