Cabometyx

Cabozantinib

Advanced renal cell carcinoma (RCC) as monotherapy, as 1st-line treatment of adult patients w/ intermediate or poor risk & in adults following prior vascular endothelial growth factor-targeted therapy; as 1st-line treatment in combination w/ nivolumab. Monotherapy for hepatocellular carcinoma (HCC) in adults previously treated w/ sorafenib. Monotherapy for locally advanced or metastatic differentiated thyroid carcinoma (DTC), refractory or not eligible to radioactive iodine in adults who have progressed during or after prior systemic therapy.

RCC, HCC & DTC Monotherapy: 60 mg once daily. May reduce dose to 40 mg daily then 20 mg daily if necessary. 1st-line advanced RCC Combination therapy w/ nivolumab: 40 mg once daily. May reduce dose to 20 mg once daily then 20 mg every other day.

Should be taken on an empty stomach.

Hypersensitivity.

Closely evaluate patients during the 1st 8 wk of treatment to determine if dose modifications are warranted. Management of suspected AR may require temporary dose interruption or reduction. Perform LFTs (eg, ALT, AST & bilirubin) before treatment initiation; closely monitor during treatment. Monitor liver enzymes before initiation & periodically throughout treatment. Monitor for signs & symptoms of hepatic encephalopathy; perforation & fistulas including abscesses & sepsis. Discontinue use if unmanageable GI perforation or fistula is experienced; develop acute MI or other clinically significant arterial thromboembolic complication; ≥28 days prior to scheduled surgery including dental surgery or invasive dental procedures & in those w/ wound healing complications; hypertensive crisis, severe & persistent HTN despite antihypertensive therapy & dose reduction of cabozantinib; osteonecrosis of the jaw (ONJ); nephrotic syndrome; posterior reversible encephalopathy syndrome. Institute prompt medical management to prevent dehydration, electrolyte imbalances & wt loss. Consider dose interruption or reduction, or permanent discontinuation in persistent or recurrent significant GI AR. Patients who are at risk for, or who have a history of VTE including pulmonary embolism & arterial thromboembolism. Patients w/ history of severe bleeding; not to be administered to patients who have or at risk for severe haemorrhage. Patients w/ risk factors eg, HTN or history of aneurysm. Monitor platelet levels during treatment. Control BP prior to initiating treatment; monitor for HTN. Perform oral exam prior to initiation & periodically during therapy; advise patients regarding oral hygiene practice. Patients receiving ONJ-associated agents (eg, bisphosphonates). Possible palmar-plantar erythrodysaesthesia syndrome (PPES); consider treatment interruption in severe PPES. Regularly monitor urine protein during treatment. Patients w/ history of QT interval prolongation, those taking antiarrhythmics or w/ relevant pre-existing cardiac disease, bradycardia or electrolyte disturbances. Consider periodic monitoring of patients w/ on-treatment ECGs & electrolytes (serum Ca, K & Mg). Treat patients w/ pre-existing hypo- or hyperthyroidism prior to starting treatment. Closely observe for signs & symptoms of thyroid dysfunction during treatment; periodically monitor thyroid function. Possible hypocalcaemia in patients w/ thyroid cancer. Monitor biochemical parameters during treatment & institute appropriate replacement therapy according to standard clinical practice if required. Concurrent administration w/ strong CYP3A4 inhibitors & inducers, P-gp substrates, MRP2 inhibitors (eg, cyclosporine, efavirenz, emtricitabine). Not to be taken by patients w/ rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption. Contains Na <1 mmol. Patients w/ cardiac impairment. Minor influence on the ability to drive & use machines. Patients w/ mild or moderate renal or hepatic impairment. Not recommended in patients w/ severe renal or hepatic impairment. Advise women of childbearing potential to avoid pregnancy during therapy. Effective contraceptive methods should be used by male or female patients & their partners during therapy & for at least 4 mth after completion. Pregnancy. Discontinue breastfeeding during treatment & for at least 4 mth after completion. Childn & adolescents <18 yr.

Anaemia, thrombocytopenia; hypothyroidism; decreased appetite, hypomagnesaemia, hypokalaemia, hypoalbuminaemia; dysgeusia, headache, dizziness; HTN, haemorrhage; dysphonia, dyspnoea, cough; diarrhoea, nausea, vomiting, stomatitis, constipation, abdominal pain, dyspepsia; PPES, rash; pain in extremity; fatigue, mucosal inflammation, asthenia, peripheral oedema; decreased wt, increased serum ALT & AST. Abscess; neutropenia, lymphopenia; dehydration, hypophosphataemia, hyponatraemia, hypocalcaemia, hyperkalaemia, hyperbilirubinemia, hyperglycaemia, hypoglycaemia; peripheral neuropathy; tinnitus; venous thrombosis; pulmonary embolism; GI perforation, pancreatitis, fistula, GERD, haemorrhoids, oral pain, dry mouth, dysphagia; hepatic encephalopathy; pruritus, alopecia, dry skin, dermatitis acneiform, hair colour change, hyperkeratosis, erythema; muscle spasms, arthralgia; proteinuria; increased GGT, amylase, lipase, blood ALP, creatinine, cholesterol & triglycerides.

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 or herbal prep containing St. John's Wort). Plasma conc may be increased by MRP2 inhibitors. Potentially decrease exposure w/ bile salt-sequestering agents (eg, cholestyramine & cholestagel). May not guarantee unchanged contraceptive effect; additional contraceptive method (eg, barrier method) is recommended. Possible interaction w/ warfarin; monitor INR values. Potentially increase 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.

POM