Names and pronunciation
(ka-boe-zan′ti-nib) Cabometyx, Cometriq
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Drug reference
(ka-boe-zan′ti-nib) Cabometyx, Cometriq
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Func. class.: Antineoplastic, biologic response modifier, signal transduction inhibitor
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Chem. class.: Multi-tyrosine kinase inhibitor
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ACTION: Blocks abnormal tyrosine kinase proteins (RET, MET, VEGFR-1, VEGFR-2, VEGFR-3, KIT, TRKB, FLT-3, AXL, TIE-2, ROS1, TYRO3, and MER); inhibits these receptor tyrosine kinases (RTKs) that are responsible for the con- trol of cell migration, metabolism, prolif- eration, and differentiation
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USES: In patients with progressive, met- astatic medullary thyroid cancer, advanced renal cell cancer (RCC) who have received prior anti-angiogenic therapy
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CONTRAINDICATIONS: Hyper- sensitivity, pregnancy
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Black Box Warning: Bleeding, fistula, GI perforation Precautions: Breastfeeding, contracep- tion requirements, dental disease, dental work, diarrhea, encephalopathy, GI bleeding, hypertension, infertility, MI, proteinuria, reproductive risk, skin dis- ease, surgery, thromboembolic disease, wound dehiscence Black Box Warning: GI perforation/ bleeding: some cases have been fatal, usually occurs in those using NSAIDs, taxanes, or those with diverticulitis or peptic ulcer disease, discontinue if these occur • Serious arterial and venous throm- boembolic disease: some have been fatal, permanently discontinue if myo- cardial infarction or any other arterial thromboembolic complication occurs • Wound dehiscence: temporary suspen- sion of therapy is recommended at least 28 days before scheduled surgery, including dental surgery. Resume based on adequate wound healing. Hold in those who develop wound dehiscence or wound healing com- plications • Hypertension: monitor BP prior to and regularly during treatment, hold in those not adequately controlled; resume at a reduced dose. Permanently discon- tinue if malignant hypertension, hyper- tensive crisis, or persistent uncontrolled hypertension despite optimal manage- ment • Dental disease: oral examination prior to starting therapy to evaluate for dental disease; good oral hygiene prac- tices should be encouraged. Discontinue at least 28 days before invasive dental work or surgery. Osteonecrosis of the jaw (ONJ) has been reported; permanently discontinue capsules (Cometriq) in those who develop ONJ • Palmar-plantar erythrodysesthesia (hand and foot syndrome): hold in those who develop intolerable grade 2 or grade 3 or 4 hand and foot syndrome, resume at a reduced dose when toxicity has im- proved to grade 1 • Proteinuria: monitor urine protein regularly; permanently discontinue in nephrotic syndrome • Severe diarrhea: those with preexist- ing diarrhea should be treated prior to receiving this product; hold (Cabome- tyx) therapy for intolerable grade 2 diarrhea, for grade 3 or higher diar- rhea that cannot be managed with stan- dard antidiarrheal treatments until improvement to grade 1 or less; a dose reduction may be necessary. Fluid and electrolyte replacement if dehy- drated • Reversible posterior leukoencepha- lopathy syndrome (RPLS): assess for seizures, headache, visual disturbances, confusion, and altered mental status. Dis- continue if RPLS is suspected or diag- nosed; confirm by MRI • Pregnancy/breastfeeding: assess if pregnancy is planned or suspected. Fe- males of reproductive potential should avoid becoming pregnant during treat- ment; women who become pregnant while receiving product should be ap- prised of the potential hazard to the fe- tus • Counsel patients about the reproduc- tive risk and contraception require- ments. Females and men with female partners who are able to become preg- nant should avoid pregnancy and use effective contraception during and for ≥4 mo after the last dose. Obtain pregnancy testing prior to initiation; do not breast- feed
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SIDE EFFECTS RESP: Cough, dyspnea CNS: Dizziness, headache, fatigue CV: Hypertension, hypertriglyceridemia EENT: Rash, erythema, hair discolor- ation, oral ulceration, stomatitis META: Hyperbilirubinemia, hyperglyce- mia, hypocalcemia, hypokalemia, hypo- albuminemia, hypomagnesemia, hypona- tremia, hypophosphatemia MISC: Arthralgia, asthenia, dysgeusia, hand and foot syndrome, hypothyroid- ism, dysphonia GI: Anorexia, nausea, vomiting, weight loss, abdominal pain, diarrhea, constipa- tion, dyspepsia HEMA: Thrombocytopenia, lymphopenia, neutropenia, anemia
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INTERACTIONS • Increase: GI bleeding—warfarin, NSAIDs • Increase: cabozantinib effects— CYP3A4 inhibitors (amprenavir, bocena- vir, delavirdine, ketoconazole, indinavir, itraconazole, dalfopristin/quinupristin, ritonavir, tipranavir, fluconazole, isonia- zid, miconazole) • Decrease: cabozantinib effects— CYP3A4 inducers (rifAMPin, rifapentine, rifabutin, primadone, phenytoin, pheno- barbital, nevirapine, nafcillin, modafinil, griseofulvin, etravirine, efavirenz, barbi- turates, bexarotene, bosentan, carBAMaz epine, enzalutamide, dexamethasone) Drug/Food Increase: cabozantinib effects— grapefruit juice Drug/Herb Decrease: cabozantinib effects—St. John’s wort Drug/Smoking Decrease: cabozantinib effects—smoking, dose may need to be increased Drug/Lab Increase: INR, PT, AST, ALT, bilirubin C
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DOSAGE AND ROUTES Progressive, metastatic medullary thyroid cancer (capsules only; do not substitute with tablets): • Adult: PO 140 mg daily on an empty stomach until disease progression or un- acceptable toxicity occurs Advanced RCC in patients who have received prior anti-angiogenic ther- apy (tablets only; do not substitute with capsules): • Adult: PO 60 mg daily on an empty stomach until disease progression or un- acceptable toxicity Hepatic dose Cometriq capsules: • Mild or moderate hepatic impairment (Child-Pugh class A or B): reduce the starting dose to 80 mg daily; severe hepatic impairment (Child-Pugh class C): do not use Cabometyx tablets: • Mild or moderate hepatic impairment (Child-Pugh class A or B): reduce the starting dose to 40 mg daily; severe hepatic impairment (Child-Pugh class C): do not use
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Available forms: Capsules 60, 100, 140 mg; tablets 20, 40, 60 mg
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Administer: • Do not substitute tablets with capsules • Take on an empty stomach; do not eat for at least 2 hr prior to and at least 1 hr after taking, swallow capsules and tablets whole; do not open or crush • Do not take with grapefruit juice or nutritional supplements that are known to inhibit CYP450 • Do not take a missed dose within 12 hr of the next dose. If the next dose is in 12 hr or more, take the missed dose; if the next dose is in <12 hr, skip and take the next dose at the scheduled time Cometriq capsules: • Strong CYP3A4 inhibitors: Avoid concomitant use if possible. If a strong CYP3A4 inhibitor is required, reduce the daily dose by 40 mg; resume the prior dose after 2 to 3 days if the strong CYP3A4 inhibitor is discontin- ued • Strong CYP3A4 inducers: If a strong CYP3A4 inducer is required, increase the daily dose by 40 mg as tolerated. Max 180 mg/day. Resume the prior dose after 2 to 3 days if the strong CYP3A4 inducer is discontinued Cabometyx tablets: • Strong CYP3A4 inhibitors: Reduce the daily dose by 20 mg; resume the prior dose after 2 to 3 days if the strong CYP3A4 inhibitor is discontinued • Strong CYP3A4 inducers: Increase the daily dose by 20 mg as tolerated. Max 80 mg/day. Resume the prior dose after 2 to 3 days if the strong CYP3A4 inducer is discontinued
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Assess:
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Evaluate: • Therapeutic response: decreased spread of cancer
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • To report adverse reactions immedi- ately, SOB, severe abdominal pain, per- sistent diarrhea, severe hypertension, bleeding • About reason for treatment, expected results • To use reliable contraception during treatment and for ≥4 mo after treat- ment HIGH ALERT
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PHARMACOKINETICS Protein binding ≥99.7%, half-life 55 hr, excretion 54% feces (43% as unchanged drug), 21% urine, peak 2-5 hr • Metabolized in the liver and is a sub- strate of CYP3A4
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• Adult: PO 140 mg daily on an empty stomach until disease progression or un- acceptable toxicity occurs Advanced RCC in patients who have received prior anti-angiogenic ther- apy (tablets only; do not substitute with capsules):
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• Adult: PO 60 mg daily on an empty stomach until disease progression or un- acceptable toxicity Hepatic dose Cometriq capsules:
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• Mild or moderate hepatic impairment (Child-Pugh class A or B): reduce the starting dose to 80 mg daily; severe hepatic impairment (Child-Pugh class C): do not use Cabometyx tablets:
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• Mild or moderate hepatic impairment (Child-Pugh class A or B): reduce the starting dose to 40 mg daily; severe hepatic impairment (Child-Pugh class C): do not use
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