Cabometyx

Cabozantinib

Monotherapy for advanced renal cell carcinoma (RCC) as 1st-line treatment of adults w/ intermediate or poor risk; adults following prior vascular endothelial growth factor-targeted therapy. In combination w/ nivolumab for 1st-line treatment of advanced renal cell carcinoma in adults. Monotherapy for hepatocellular carcinoma (HCC) in adults who have previously been treated w/ sorafenib. Monotherapy for locally advanced or metastatic differentiated thyroid carcinoma (DTC) in adults w/ refractory or ineligible to radioactive iodine who have progressed during or after prior systemic therapy.

Monotherapy for RCC, HCC & DTC 60 mg once daily, may be reduced to 40 mg daily then to 20 mg daily. In combination w/ nivolumab 40 mg once daily w/ nivolumab IV 240 mg every 2 wk or 480 mg every 4 wk. May be reduced to 20 mg once daily then to 20 mg every other day.

Should be taken on an empty stomach: Refrain from eating for at least 2 hr before & 1 hr after intake. Swallow whole, do not crush.

Hypersensitivity.

Discontinue use if GI perforation or fistula, acute MI or other clinically significant thromboembolic complication, nephrotic syndrome develops; in patients w/ wound healing complications requiring medical intervention, posterior reversible encephalopathy syndrome; if severe/persistent HTN or hypertensive crisis, osteonecrosis of the jaw occurs. Interrupt, reduce or discontinue use in case of persistent or recurrent significant GI ARs, biochemical lab test abnormalities. Not to be administered in patients who have or at risk for severe haemorrhage. Aneurysms &/or artery dissections; palmar-plantar erythrodysaesthesia syndrome (PPES); history of QT interval prolongation, relevant pre-existing cardiac disease, bradycardia or electrolyte disturbances. Regularly monitor platelet levels, urine protein & periodic monitoring w/ on-treatment ECGs & electrolytes (serum Ca, K & Mg) during treatment. Perform LFTs prior to initiation & monitor liver enzymes during treatment. Monitor for signs & symptoms of hepatic encephalopathy, thyroid dysfunction. Perform oral exam prior to initiation & ensure good oral practice during treatment. Discontinue use at least 28 days prior to scheduled surgery including dental surgery or invasive dental procedures. Not to be taken by patients w/ galactose intolerance, total lactase deficiency or glucose-galactose malabsorption. Avoid chronic use w/ strong CYP3A4 inducers. Concomitant use w/ strong CYP3A4 inhibitors; bisphosphonates; antiarrhythmics; P-gp substrate eg, fexofenadine, aliskiren, ambrisentan, dabigatran etexilate, digoxin, colchicine, maraviroc, posaconazole, ranolazine, saxagliptin, sitagliptin, talinolol, tolvaptan; MRP2 inhibitors eg, cyclosporine, efavirenz, emtricitabine. May affect ability to drive & use machines. Not recommended in severe hepatic (Child-Pugh C) & renal impairment. Moderate hepatic & mild to moderate renal impairment. May impair male & female fertility. Women of childbearing potential & male partners should use effective contraception during & at least 4 mth after last dose. Not to be used during pregnancy. Not to be used during lactation & at least 4 mth after treatment. Childn & adolescents <18 yr.

Anaemia, thrombocytopenia; hypothyroidism; decreased appetite; hypomagnesaemia, hypokalaemia; dysgeusia, headache, dizziness; HTN; dysphonia, dyspnoea, cough; diarrhoea, nausea, vomiting, stomatitis, constipation, abdominal pain, dyspepsia; PPES, rash; fatigue; decreased wt, increased serum ALT & AST. Monotherapy: hypoalbuminaemia; haemorrhage; pain in extremity; mucosal inflammation, asthenia, peripheral oedema. In combination w/ nivolumab: URTI; hyperthyroidism; pruritus; musculoskeletal pain, arthralgia, muscle spasm; proteinuria; pyrexia, oedema; hypophosphataemia, hypo-/hypercalcaemia, hypo-/hypernatraemia, hypo-/hyperglycaemia, lymphopaenia, increased alkaline phosphatase, lipase, amylase, creatinine & total bilirubin, leucopoenia, hyperkalaemia, neutropaenia, hypermagnesaemia.

Decreased clearance & increased plasma exposure w/ strong CYP3A4 inhibitors eg, ketoconazole, ritonavir, itraconazole, erythromycin, clarithromycin, grapefruit juice. Increased clearance & decreased plasma exposure w/ strong CYP3A4 inducers eg, phenytoin, carbamazepine, rifampicin, phenobarb, St. John's wort herbal-containing prep. Increased plasma conc w/ MRP2 inhibitors. Decreased exposure w/ bile salt-sequestering agents eg, cholestyramine, cholestagel. Monitor INR values w/ warfarin. Increased plasma conc of P-gp substrates eg, fexofenadine, aliskiren, ambrisentan, dabigatran, etexilate, digoxin, colchicine, maraviroc, posaconazole, ranolazine, saxagliptin, sitagliptin, talinolol, tolvaptan.

Targeted Cancer Therapy

L01EX07 - cabozantinib ; Belongs to the class of other protein kinase inhibitors. Used in the treatment of cancer.

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