- Cabometyx: Treatment of advance renal cell carcinoma (RCC) in patients who have previously received anti-angiogenic therapy.
- Cometriq: Treatment of progressive, metastatic medullary thyroid cancer (MTC).
Inhibits tyrosine kinase, resulting in disruption of cellular function including tumor formation and progression.
- Improved survival with RCC.
- Decreased spread of MTC.
Absorption: Well absorbed following oral administration; food significantly enhances absorption.
Distribution: Extensively distributed to tissues.
Protein Binding: >99.7%.
Metabolism and Excretion: Highly metabolized, mostly by the CYP3A4 system. 54% excreted in feces, 27% in urine (as metabolites).
Half-life: 55 hr (Cometriq); 99 hr (Cabometyx).
TIME/ACTION PROFILE (improved survival)
|PO||within 2 mo||unknown||14.7–21.4 mo|
- Moderate to severe hepatic impairment (Cometriq)
- Severe hepatic impairment (Cabometyx);
- Concurrent foods/nutritional supplements that are CYP3A4 inhibitors;
- OB: May cause fetal harm;
- Lactation:Avoid breastfeeding.
Use Cautiously in:
- Concurrent use of strong CYP3A4 inhibitors/inducers should be avoided if possible; if unavoidable, dosage adjustments are necessary
- Severe renal impairment;
- Elective surgical procedures (discontinue 28 days prior, if possible);
- Hypertension (control prior to treatment)
- Rep: Women of reproductive potential should use effective contraception;
- Pedi: Safety and effectiveness not established.
Adverse Reactions/Side Effects
CNS: REVERSIBLE POSTERIOR LEUKOENCEPHALOPATHY SYNDROME (RPLS), dizziness, fatigue, headache
CV: ARTERIAL THROMBOEMBOLISM, VENOUS THROMBOEMBOLISM (DVT, PE), hypertension
GI: GASTROINTESTINAL PERFORATION/FISTULA, abdominal pain, altered taste, ↓ appetite, constipation, diarrhea, dyspepsia, ↑ liver enzymes, nausea, oral pain, stomatitis, vomiting, weight loss
Derm: dry skin, hair color changes, palmar-plantar erythrodysesthesia syndrome, rash, wound complications
F and E: hypocalcemia, hypophosphatemia, hypokalemia, hypomagnesemia, hyponatremia
GU: proteinuria, infertility, nephrotic syndrome
Hemat: BLEEDING, lymphocytopenia, neutropenia, thrombocytopenia, anemia
MS: arthralgia, muscle spasms, osteonecrosis of the jaw
Resp: cough, dyspnea
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- Levels and risk of toxicity are ↑ by strong CYP3A4 inhibitors, including atazanavir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, 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, saquinavir, and tenofovir.
- Levels and risk of toxicity are ↑ by grapefruit juice; avoid concurrent use.
- Levels and effectiveness may be ↓ by chronic concurrent use of St. John's wort ; avoid concurrent use.
Capsules and tablets are not interchangeable
PO: (Adults) 60 mg once daily. Concurrent use of strong CYP3A4 inhibitor– ↓ daily dose by 20 mg; resume full dose 2–3 days after discontinuing inhibitor. Concurrent use of strong CYP3A4 inducer– ↑ daily dose by 20 mg; resume full dose 2–3 days after discontinuing inducer. Daily dose should not exceed 80 mg.
(Adults) Mild or moderate hepatic impairment– 40 mg once daily.
PO: (Adults) 140 mg once daily. Concurrent CYP3A4 inhibitors– ↓ daily dose by 40 mg, resume full dose 4 days after discontinuing inhibitor. Concurrent CYP3A4 inducers– ↑ daily dose by 40 mg, resume full dose 2–3 days after discontinuing inducer. Daily dose should not exceed 180 mg.
(Adults) Mild or moderate hepatic impairment– 80 mg once daily.
Capsules (Cometriq): 20 mg, 80 mg
Tablets (Cabometyx): 20 mg, 40 mg, 60 mg
- Monitor BP prior to and periodically during therapy. Withhold cabozantinib if BP is not adequately controlled with medications; resume at a reduced dose. Discontinue cabozantinib for uncontrolled hypertension.
- Monitor for symptoms of perforations and fistulas (severe abdominal pain, coughing, gagging, choking especially when eating or drinking). Discontinue cabozantinib if symptoms occur.
- Monitor for diarrhea. May require dose reductions if severe.
- Perform an oral examination for inflammation, infection, or ulceration prior to and periodically during therapy.
- Evaluate patients with seizures, headache, visual disturbances, confusion, or altered mental status for reversible posterior leukoencephalopathy syndrome via MRI. Discontinue therapy if confirmed.
Lab Test Considerations: Monitor urine protein periodically during therapy; discontinue therapy in patients with nephrotic syndrome.
- Monitor CBC and platelet count periodically during therapy. May cause ↓ WBC, ANC, hemoglobin, lymphocytes, and platelets.
- May cause ↑AST, ↑ALT, ↑ALP, hypocalcemia, hypophosphatemia, hyperbilirubinemia, hypomagnesemia, hypokalemia, hyponatremia, lymphopenia, neutropenia, and thrombocytopenia.
- Diarrhea (Adverse Reaction)
- Do not substitute tablets and capsules.
- Stop treatment at least 28 days before scheduled surgery, including dental surgery. Resume therapy postoperatively based on clinical judgement of adequate wound healing. Withhold in patients with dehiscence or wound healing complications.
- PO: Cometriq : Administer 140 mg dose as one 80-mg and 3 20-mg capsules, on an empty stomach at least 1 hr before or 2 hr after meals. Swallow capsules whole; do not open, crush, or chew. Avoid foods or nutritional supplements that inhibit cytochrome P450 during therapy.
- Withhold dose for Grade 4 hematologic, ≥Grade 3 non-hematologic or intolerable Grade 2 adverse reactions. Upon return to baseline or resolution to Grade 1, reduce dose. If previously receiving 140 mg daily, resume at 100 mg daily (one 80-mg and one 20-mg capsule). If previously receiving 100 mg daily, resume at 60 mg daily (3 20-mg capsules). If previously receiving 60 mg daily, resume at 60 mg daily if tolerated, otherwise, discontinue.
- Permanently discontinue if development of visceral perforation or fistula formation, severe hemorrhage, serious arterial thrombotic event (MI, cerebral infarction), nephrotic syndrome, malignant hypertension, hypertensive crisis, persistent uncontrolled hypertension despite medical management, osteonecrosis of the jaw, reversible posterior leukoencephalopathy syndrome occur.
- PO: Cabometyx : Administer tablet on an empty stomach at least 1 hr before or 2 hr after meals. Swallow tablet whole; do not break, crush, or chew.
- Withhold dose for Grade 4 hematologic and Grade 3 or intolerable Grade 2 adverse reactions not managed by dose reductions or supportive care. Upon return to baseline or resolution to Grade 1, reduce dose. If previously receiving 60 mg daily, resume at 40 mg daily. If previously receiving 40 mg daily, resume at 30 mg daily. If previously receiving 20 mg daily, resume at 20 mg daily if tolerated, otherwise, discontinue.
- Permanently discontinue if development of visceral perforation or fistula formation, severe hemorrhage, serious arterial thrombotic event (MI, cerebral infarction), nephrotic syndrome, malignant hypertension, hypertensive crisis, persistent uncontrolled hypertension despite medical management, reversible posterior leukoencephalopathy syndrome occur.
- 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) 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.
- Rep: Cabozantinib is teratogenic. Advise female 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 breastfeeeding during and for 4 mo following last dose. May impair fertility in male and female patients.
- Decreased spread of metastatic MTC.
- Improved survival with RCC.
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