Cabometyx

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: Swallow whole, do not crush. Take at least 2 hr before or 1 hr after a meal.

Hypersensitivity.

Closely evaluate patient during 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. Possible vanishing bile duct syndrome in patients who have received immune checkpoint inhibitors either before or concurrently w/ treatment. Monitor for signs & symptoms of hepatic encephalopathy; perforations & 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 requiring medical intervention; 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 history of VTE including pulmonary embolism & arterial thromboembolism. Higher risk of portal vein thrombosis in patients w/ history of portal vein invasion. Carefully evaluate patients who have history of severe bleeding prior to treatment initiation. Not to be administered to patients who have or are 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 ability to drive & use machines. Mild or moderate renal impairment. Moderate hepatic impairment. Not recommended in patients w/ severe renal or hepatic impairment. Advise women of childbearing potential to avoid pregnancy during therapy. Effective contraception 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.

Monotherapy: 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, pneumonia; 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. In combination w/ nivolumab: URTI; hypothyroidism, hyperthyroidism; decreased appetite; dysgeusia, dizziness, headache; HTN; dysphonia, dyspnoea, cough; diarrhoea, vomiting, nausea, constipation, stomatitis, abdominal pain, dyspepsia; PPES, rash, pruritus; musculoskeletal pain, arthralgia, muscle spasm; proteinuria; fatigue, pyrexia, oedema; increased ALT & AST, alkaline phosphatase, lipase, amylase, creatinine & total bilirubin, hypophosphataemia, hypocalcaemia, hypomagnesaemia, hyponatraemia, hyperglycaemia, lymphopaenia, thrombocytopaenia, anaemia, leucopoenia, hyperkalaemia, neutropaenia, hypercalcaemia, hypoglycaemia, hypokalaemia, hypermagnesaemia, hypernatraemia, decreased wt. Pneumonia; eosinophilia; hypersensitivity, adrenal insufficiency; dehydration; peripheral neuropathy; tinnitus; dry eyes, blurred vision; atrial fibrillation, tachycardia; thrombosis; pneumonitis, pulmonary embolism, epistaxis, pleural effusion; colitis, gastritis, oral pain, dry mouth, haemorrhoids; hepatitis; alopecia, dry skin, erythema, hair colour change; arthritis; renal failure, acute kidney injury; pain, chest pain; increased blood cholesterol, hypertriglyceridaemia.

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