Cabometyx:

• Advanced renal cell carcinoma (RCC).First-line treatment of advanced RCC (in combination with nivolumab).Hepatocellular carcinoma (HCC) in patients previously treated with sorafenib.
• Locally advanced or metastatic differentiated thyroid cancer (DTC) that has progressed following prior vascular endothelial growth factor (VEGF) receptor-targeted therapy in patients who are refractory to or ineligible to receive radioactive iodine.

Cometriq:

• Progressive, metastatic medullary thyroid cancer (MTC).

Contraindicated in:

• Severe hepatic impairment
• Concurrent foods/nutritional supplements that are CYP3A4 inhibitors
• OB: Pregnancy
• Lactation: Lactation.

Use Cautiously in:

• Concurrent use of strong CYP3A4 inhibitors/inducers should be avoided if possible; if unavoidable, dosage adjustments are necessary
• Moderate hepatic impairment (Cabometyx)
• Severe renal impairment
• Elective surgical procedures (discontinue 28 days prior, if possible)
• Hypertension (control prior to treatment)
• Women of reproductive potential
• Pedi: Safety and effectiveness not established in children <12 yr (DTC) or children <18 yr (all other indications).

CNS: dizziness, fatigue, headache, POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (PRES).

CV: hypertension, THROMBOTIC EVENTS.

Derm: dry skin, hair color changes, palmar-plantar erythrodysesthesia, rash, impaired wound healing.

Endo: hypothyroidism, ADRENAL INSUFFICIENCY (IN COMBINATION WITH NIVOLUMAB).

F and E: hypocalcemia, hypophosphatemia, hypokalemia, hypomagnesemia, hyponatremia.

GI: abdominal pain, altered taste, ↓appetite, constipation, diarrhea, dyspepsia, hepatotoxicity (in combination with nivolumab), ↑liver enzymes, nausea, oral pain, stomatitis, vomiting, weight loss, GASTROINTESTINAL PERFORATION/FISTULA.

GU: proteinuria, infertility, nephrotic syndrome.

Hemat: lymphocytopenia, neutropenia, thrombocytopenia, anemia, BLEEDING.

MS: arthralgia, muscle spasms, osteonecrosis of the jaw.

Resp: cough, dyspnea.

Drug-Drug:

• Levels and risk of toxicity are ↑ by strong CYP3A4 inhibitors, including atazanavir, clarithromycin, conivaptan, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, and voriconazole; concurrent use should be avoided if possible. If unavoidable, cabozantinib daily dose should be ↓; routine dose may be resumed 4 days following discontinuation of inhibitor.
• Levels and effectiveness may be ↓ by chronic concurrent use of strong CYP3A4 inducers, including carbamazepine, dexamethasone, phenobarbital, phenytoin, rifabutin, rifampin, and rifapentine; concurrent use should be avoided if possible. If unavoidable, cabozantinib daily dose should be ↑; routine dose may be resumed 2–3 days following discontinuation of inducer.
• Levels and risk of toxicity are ↑ by MRP2 inhibitors, including abacavir, adefovir, cidofovir, furosemide, lamivudine, nevirapine, ritonavir, probenecid, and tenofovir.

Drug-Natural Products:

• Levels and effectiveness may be ↓ by chronic concurrent use of St. John's wort ; avoid concurrent use.

Drug-Food:

• Levels and risk of toxicity are ↑ by grapefruit juice; avoid concurrent use.

• Capsules (Cometriq): 20 mg; 80 mg;
• Tablets (Cabometyx): 20 mg; 40 mg; 60 mg;

Cabometyx

• PO (Adults): As monotherapy — 60 mg once daily until disease progression or unacceptable toxicity. With nivolumab — 40 mg once daily until disease progression or unacceptable toxicity.Concurrent use of strong CYP3A4 inhibitor (as monotherapy) — 40 mg once daily until disease progression or unacceptable toxicity (resume full dose 2–3 days after discontinuing inhibitor). Concurrent use of strong CYP3A4 inhibitor (with nivolumab) — 20 mg once daily until disease progression or unacceptable toxicity (resume full dose 2–3 days after discontinuing inhibitor). Concurrent use of strong CYP3A4 inducer (as monotherapy) — 80 mg once daily until disease progression or unacceptable toxicity (resume full dose 2–3 days after discontinuing inducer). Concurrent use of strong CYP3A4 inducer (with nivolumab) — 60 mg once daily until disease progression or unacceptable toxicity (resume full dose 2–3 days after discontinuing inducer).

Cometriq

• PO (Adults): 140 mg once daily until disease progression or unacceptable toxicity. Concurrent use of strong CYP3A4 inhibitor — 100 mg once daily until disease progression or unacceptable toxicity (resume full dose 4 days after discontinuing inhibitor). Concurrent use of strong CYP3A4 inducer — 180 mg once daily until disease progression or unacceptable toxicity (resume full dose 2–3 days after discontinuing inducer).

Cabometyx, Cometriq

• Inhibits tyrosine kinase, resulting in disruption of cellular function including tumor formation and progression.

• Improved survival with RCC and HCC.
• Decreased spread of MTC.
• Improved progression free survival with DTC.

Therapeutic Classification: antineoplastics

Pharmacologic Classification: kinase inhibitors

Absorption: Well absorbed following oral administration; food significantly enhances absorption.

Distribution: Extensively distributed to tissues.

Protein Binding: >99.7%.

Metabolism/Excretion: Highly metabolized by the liver, mostly by the CYP3A4 isoenzyme. 54% excreted in feces, 27% in urine (as metabolites).

Half-life: 55 hr (Cometriq); 99 hr (Cabometyx).

(improved survival)

• Instruct patient to take cabozantinib as directed on an empty stomach with at least 8 oz of water. Take missed doses as soon as remembered if within 12 hrs of dose; take next dose at regularly scheduled time. If >12 hrs omit dose and text next dose at normal time; do not double doses.
• Advise patient to avoid grapefruit, grapefruit juice and any foods or supplements that contain grapefruit during therapy.
• Caution patient to notify health care professional immediately if signs and symptoms of hemorrhage (coughing up blood or blood clots, vomiting blood or coffee-ground like vomit, red or black tarry stools, menstrual bleeding heavier than usual, any unusual or heavy bleeding); perforation or fistula (abdominal pain or tenderness); stroke or heart attack (swelling or pain in hands, arms, feet, or legs; shortness of breath; unusual sweating; numbness or weakness of face, arm or leg especially on one side of body; sudden confusion, trouble speaking, or understanding; sudden trouble seeing in one or both eyes; sudden trouble walking; dizziness, loss of balance or coordination; sudden severe headache); diarrhea; PPE (rashes, redness, pain, swelling, or blisters on palms or soles of feet); swelling in hands, arms, legs, or feet; jaw pain, toothache, or sores on gums; or reversible posterior leukoencephalopathy syndrome occur.
• Instruct patient to notify health care professional if signs and symptoms of hand-foot skin reactions (progressive or intolerable rash, redness, pain, swelling, blisters on hands or soles of feet); severe diarrhea; mouth sores, oral pain, changes in taste, nausea or vomiting severe or preventing from eating or drinking; or weight loss occur.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially St. John's Wort.
• Instruct patient to maintain good oral hygiene and regular dentist exams during therapy. If jaw pain, toothache, or sores on gums occur, notify health care professional.
• Advise patient to notify health care professional of medication regimen prior to treatment or surgery. Therapy must be stopped 28 days before planned surgery, including dental procedures.
• Cabozantinib may cause fetal harm. Advise females of reproductive potential and male patients with female partners with reproductive potential to use effective contraception during and for at least 4 mo after completion of therapy and to avoid breastfeeding during and for 4 mo following last dose. May impair fertility in male and female patients.

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