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cabozantinib (Rx)Brand and Other Names:Cometriq, Cabometyx

 
 
 

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule (Cometriq)

  • 20mg
  • 80mg

tablet (Cabometyx)

  • 20mg
  • 40mg
  • 60mg
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Medullary Thyroid Cancer

Cometriq: Indicated for treatment of progressive, metastatic medullary thyroid cancer

140 mg PO qDay on empty stomach (see Administration)

Renal Cell Carcinoma

Cabometyx: Indicated for advanced renal cell carcinoma (RCC) in patients who have received prior antiangiogenic therapy

60 mg PO qDay

Dosage Modifications

CYP3A4 inhibitors

  • Avoid coadministration with strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole)
  • Cometriq
    • If strong CYP3A4 inhibitor required, decrease cabozantinib dose by 40 mg/day
    • Resume previous dose 2-3 days after strong CYP3A4 inhibitor discontinued
  • Cabometyx
    • If strong CYP3A4 inhibitor required, decrease cabozantinib dose by 20 mg/day
    • Resume previous dose 2-3 days after strong CYP3A4 inhibitor discontinued

CYP3A4 inducers

  • Avoid coadministration of strong CYP3A4 inducers (eg, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, St. John’s wort)
  • Cometriq
    • If strong CYP3A4 inducer required, increase dose by 40 mg/day
    • Resume previous dose 2-3 days after strong CYP3A4 inducer discontinued
    • Do not exceed 180 mg/day
  • Cabometyx
    • If strong CYP3A4 inducer required, increase dose by 20 mg/day
    • Resume previous dose 2-3 days after strong CYP3A4 inducer discontinued
    • Do not exceed 80 mg/day

Hepatic impairment

  • Moderate-to-severe (Cometriq): Not recommended
  • Cabometyx
    • Mild-to-moderate: Reduce starting dose to 40 mg/day
    • Severe: Not recommended

Withhold dose

  • Withhold dose for Grade 4 hematologic adverse reactions, ≥Grade 3 nonhematologic adverse reactions, or intolerable Grade 2 adverse reactions
  • Upon resolution (ie, reutrn to baseline or Grade 1), reduce dose as follows:
  • Cometriq
    • If previous daily dose 140 mg, resume at 100 mg/day
    • If previous daily dose 100 mg, resume at 60 mg/day
    • If previous daily dose 60 mg, resume at 60 mg if tolerated, otherwise, discontinue
  • Cabometyx
    • If previous daily dose 60 mg, resume at 40 mg/day
    • If previous daily dose 40 mg, resume at 20 mg/day
    • If previous daily dose 20 mg, resume at 20 mg if tolerated, otherwise, discontinue

Patients undergoing surgery

  • Stop drug at least 28 days prior to scheduled surgery, including dental surgery (see Cautions)

Permanently discontinue

  • Development of visceral perforation or fistula formation
  • Severe hemorrhage
  • Serious arterial thromboembolic event (eg, myocardial infarction, cerebral infarction)
  • Nephrotic syndrome
  • Malignant hypertension, hypertensive crisis, persistent uncontrolled hypertension despite optimal medical management
  • Osteonecrosis of the jaw
  • Reversible posterior leukoencephalopathy syndrome

Safety and efficacy not established

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Interactions

Interaction Checker

cabozantinib and

No Results

     
     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10% (Cometriq)

            All grades

            AST, ALT increased (86%)

            Diarrhea (63%)

            Hypertension, treatment-emergent (61%)

            Increased TSH (57%)

            Lymphopenia (53%)

            ALP increased (52%)

            Hypocalcemia (52%)

            Stomatitis (51%)

            Palmar-plantar erythrodysesthesia syndrome (50%; ≥Grade 3, 13%)

            Weight decreased (48%)

            Appetite decreased (46%)

            Nausea (43%)

            Fatigue (41%)

            Oral pain (36%)

            Neutropenia (35%)

            Thrombocytopenia (35%)

            Dysgeusia (34%)

            Hair color changes, depigmentation, graying (34%)

            Hypertension (33%)

            Hypophosphatemia (28%)

            Constipation (27%)

            Abdominal pain (27%)

            Hypobilirubinemia (25%)

            Vomiting (24%)

            Asthenia (21%)

            Dysphonia (20%)

            Rash (19%)

            Dry skin (19%)

            Hypomagnesemia (19%)

            Hypokalemia (18%)

            Headache (18%)

            Alopecia (16%)

            Dizziness (14%)

            Arthralgia (14%)

            Dysphagia (13%)

            Muscle spasms (12%)

            Dyspepsia (11%)

            Erythema (11%)

            >10% (Cabometyx)

            Diarrhea, all grades (74%)

            AST increased, all grades (74%)

            ALT increased, all grades (68%)

            Creatinine increased, all grades (58%)

            Fatigue, all grades (56%)

            Triglycerides increased, all grades (53%)

            Nausea, all grades (50%)

            Hypophosphatemia, all grades (48%)

            Decreased appetite, all grades (46%)

            Palmar-plantar erythrodysesthesia syndrome, all grades (42%)

            Hypertension, all grades (39%)

            Hyperglycemia, all grades (37%)

            Hypoalbuminemia, all grades (36%)

            ALP increased, all grades (35%)

            WBCs decreased, all grades (35%)

            Vomiting, all grades (32%)

            Hypomagnesemia, all grades (31%)

            Weight decreased, all grades (31%)

            ANC decreased, all grades (31%)

            Hgb decreased, all grades (31%)

            Hyponatremia, all grades (30%)

            GGT increased, all grades (27%)

            Constipation, all grades (25%)

            Lymphocytes decreased, all grades (25%)

            Platelets decreased, all grades (25%)

            Dysgeusia, all grades (24%)

            Abdominal pain, all grades (23%)

            Rash, all grades (23%)

            Stomatitis, all grades (22%)

            Hypothyroidism, all grades (21%)

            Dysphonia, all grades (20%)

            Dyspnea, all grades (19%)

            Mucosal inflammation, all grades (19%)

            Asthenia, all grades (19%)

            Cough, all grades (18%)

            Anemia, all grades (17%)

            Hypertension, grades 3-4 (16%)

            Muscle spasms, all grades (13%)

            Dyspepsia, all grades (12%)

            Proteinuria, all grades (12%)

            Diarrhea, grades 3-4 (11%)

            Dry skin, grades 3-4 (11%)

            Headache, all grades (11%)

            Dizziness, all grades (11%)

            Arthralgia, all grades (11%)

            1-10% (Cometriq)

            Hyponatremia (10%)

            Hemorrhoids (9%)

            Musculoskeletal chest pain (9%)

            Anxiety (9%)

            Paresthesia (7%)

            Peripheral sensory neuropathy (7%)

            Dehydration (7%)

            Hyperkeratosis (7%)

            Hypotension (7%)

            Venous thromboembolism (6%)

            eripheral neuropathy (5%)

            Non-GI fistula (4%)

            GI perforation (3%)

            Arterial thromboembolism (2%)

            Proteinuria (2%)

            GI fistula (1%)

            Osteonecrosis of the jaw (1%)

            1-10% (Cabometyx)

            Fatigue, grades 3-4 (9%)

            Palmar-plantar erythrodysesthesia syndrome, grades 3-4 (8%)

            Hyponatremia, grades 3-4 (8%)

            Hypophosphatemia, grades 3-4 (8%)

            Hypomagnesemia, grades 3-4 (7%)

            Lymphocytes decreased, grades 3-4 (7%)

            Anemia, grades 3-4 (5%)

            GGT decreased, grades 3-4 (5%)

            Nausea, grades 3-4 (4%)

            Asthenia, grades 3-4 (4%)

            Abdominal pain, grades 3-4 (4%)

            Hgb decreased, grades 3-4 (4%)

            Triglycerides increased, grades 3-4 (4%)

            ALT increased, grades 3-4 (3%)

            AST increased, grades 3-4 (3%)

            Dyspnea, grades 3-4 (3%)

            Decreased appetite, grades 3-4 (3%)

            Proteinuria, grades 3-4 (2%)

            Vomiting, grades 3-4 (2%)

            Stomatitis, grades 3-4 (2%)

            ANC decreased, grades 3-4 (2%)

            ALP decreased, grades 3-4 (2%)

            Hypoalbuminemia, grades 3-4 (2%)

            Hyperglycemia, grades 3-4 (2%)

            <1%

            Reversible posterior leukoencephalopathy syndrome (RPLS)

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            Warnings

            Black Box Warnings

            Perforations and fistulas (Cometriq)

            • GI perforations occurred in 3% and fistula formation in 1%
            • Non-GI fistulas (eg, tracheal, esophageal) reported in 4%
            • Discontinue if perforation or fistula formation occurs

            Hemorrhage (Cometriq)

            • Severe, sometimes fatal, hemorrhage including hemoptysis and GI hemorrhage occurred in 3%
            • Monitor for signs and symptoms of bleeding
            • Do not administer with severe hemorrhage

            Contraindications

            None

            Cautions

            GI perforations and fistulas reported (see Black Box Warnings for Cometriq); monitor for symptoms and discontinue Cabometyx in patients who experience a fistula which cannot be appropriately managed or a GI perforation

            Serious and sometimes fatal hemorrhage reported (see Black Box Warnings for Cometriq); do not administer Cabometyx to patients with risk for severe hemorrhage

            Thromboembolic events reported; discontinue if acute MI or any other arterial thromboembolic event develops

            May impair wound healing; stop treatment at least 28 days prior to schedules surgery; withhold with dehiscence or wound healing complications requiring medical intervention

            Osteonecrosis of the jaw reported (rare); discontinue at least 28 days prior to invasive dental procedures

            Increases risk of treatment-emergent hypertension; discontinue for severe hypertension that cannot be controlled with antihypertensive therapy

            Palmar-plantar erythrodysesthesia syndrome reported; withhold treatment if needed (see Dosage Modifications)

            Proteinuria may occur

            Diarrhea commonly reported (see Adverse Effects)

            Reversible posterior leukoencephalopathy syndrome (RPLS) reported (rare)

            Avoid coadministration with strong CYP3A4 inhibitors or inducers; if unable to avoid, dose adjustment required (see Dosage Modifications)

            Hepatic impairment

            • Cometriq: Not recommended with moderate-to-severe hepatic impairment
            • Cabometyx: Not recommended with severe hepatic impairment; dosage adjustment required with mild-to-moderate impairment (see Dosage Modifications)
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            Pregnancy & Lactation

            Pregnancy

            Based on its mechanism of action, can cause fetal harm when administered to pregnant women

            Advise females of reproductive potential to use effective contraception during treatment and for 4 months after the final dose

            May impair male and female fertility

            Lactation

            Unknown whether distributed in breast milk

            Because of potential for serious adverse reactions in a breastfed infant from cabozantinib, advise females of reproductive potential to not breastfeed during treatment and for 4 months after the final dose

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

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            Pharmacology

            Mechanism of Action

            Tyrosine kinase inhibitor that targets RET, MET, VEGFR-1, -2, and -3, KIT, TrkB, FLT-3, AXL, and TIE-2 pathways; these tyrosine kinases are involved in both normal cellular function and pathologic processes (eg, oncogenesis, metastasis, tumor angiogenesis, and maintenance of tumor microenvironment)

            Absorption

            Peak Plasma Time: 2-5 hr; (Cometriq); 2-3 hr (Cabometyx)

            A 19% increase in the peak plasma concentration of the tablet formulation (Cabometyx) compared with the capsule formulation (Cometriq)

            High fat meal increases Cmax and AUC by 41% and 57% respectively compared to fasted conditions

            Steady-state achieved: Day 15

            Distribution

            Protein Bound: ≥99.7%

            Vd: 349 L (Cometriq); 319 L (Cabometyx)

            Metabolism

            Metabolized via hepatic CYP3A4

            Metabolites: XL184 N-oxide

            CYP3A4 substrate; CYP2C8 inhibitor (noncompetitive), CYP2C9 and CYP2C19 inhibitor (mixed), CYP3A4 (weak competitive); CYP1A1 inducer

            P-gp transport inhibitor

            Elimination

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

            Total body clearance: 4.4 L/hr (Cometriq); 2.2 L/hr (Cabometyx)

            Excretion: 54% feces, 27% urine

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            Administration

            Oral Administration

            Do not substitute Cabometyx tablets and Cometriq capsules for one another

            Take on empty stomach, do not eat for at least 2 hr before or 1 hr after administration

            Swallow capsule or tablet whole; do not chew or empty contents of capsule; do not crush tablet

            Do not take a missed dose within 12 hr of the next dose

            Do not ingest foods (eg, grapefruit, grapefruit juice) or nutritional supplements known to affect CYP3A4 substrates (eg, St. John’s wort)

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            Images

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            Formulary

            FormularyPatient Discounts

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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