cabozantinib

cabozantinib

(ka-boe-zan-ti-nib) ,

Cometriq

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: kinase inhibitors
Pregnancy Category: D

Indications

Treatment of progressive, metastatic medullary thyroid cancer (MTC).

Action

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

Therapeutic effects

Decreased spread of MTC.

Pharmacokinetics

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

Time/action profile (improved survival)

ROUTEONSETPEAKDURATION
POwithin 2 mounknown14.7 mos

Contraindications/Precautions

Contraindicated in: Moderate to severe hepatic impairment; Concurrent foods/nutritional supplements that are CYP3A4 inhibitors; Obstetric / Lactation: Pregnancy or lactation.
Use Cautiously in: Concurrent medications that are CYP3A4 inhibitors/inducers should be avoided if possible; if unavoidable, dosage adjustments are necessary; Elective surgical procedures (discontinue 28 days prior if possible); Reproductive potential; Hypertension (control prior to treatment); Pediatric: Safe and effective use in children has not been established.

Adverse Reactions/Side Effects

Central nervous system

  • fatigue (most frequent)
  • reversible posterior leukoencephalopathy syndrome

Cardiovascular

  • thrombotic events (life-threatening)
  • hypertension

Gastrointestinal

  • gastrointestinal perforation/fistula (life-threatening)
  • abdominal pain (most frequent)
  • ↓ appetite (most frequent)
  • altered taste (most frequent)
  • diarrhea (most frequent)
  • nausea (most frequent)
  • oral pain (most frequent)
  • stomatitis (most frequent)
  • ↑ transaminases (most frequent)
  • constipation

Dermatologic

  • hair color changes (most frequent)
  • palmar-plantar erythrodysesthesia syndrome
  • wound complications

Fluid and Electrolyte

  • hypocalcemia (most frequent)
  • hypophosphatemia (most frequent)

Genitourinary

  • nephrotic syndrome

Hematologic

  • bleeding (life-threatening)
  • lymphopenia (most frequent)
  • neutropenia (most frequent)
  • thrombocytopenia (most frequent)

Musculoskeletal

  • osteonecrosis of the jaw

Interactions

Drug-Drug interaction

Levels and risk of toxicity are ↑ by CYP3A4 inhibitors including atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazdone, nelfinavirritonavir, saquinavir, telithromycin, and voriconazole ; concurrent use should be avoided if possible. If unavoidable, cabozantinib daily dose should be ↓ by 40 mg; routine dose may be resumed 4 days following discontinuation of inhibitor.Levels and effectiveness may be ↓ by chronic concurrent use of CYP3A4 inducers including carbamazepine, dexamethasone, phenobarbital, phenytoin, rifabutin, rifampin, and rifapentine and should be avoided. If unavoidable, daily dose should be ↑ by 40 mg; routine dose may be resumed 2–3 days following discontinuation of inducer.St. John's wort ↓ levels and effectiveness, concurrent use should be avoided.

Route/Dosage

Oral (Adults) 140 mg once daily; adjustments required for hematologic toxicity and/or interacting medications. 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.

Availability

Capsules: 20 mg, 80 mg

Nursing implications

Nursing assessment

  • Monitor BP prior to and periodically during therapy. Withhold cabozantinib if BP is not adequately controlled with medications; resume at a reduced dose. Discontinue carbozantinib 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.
  • 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.
    • May cause ↑AST, ↑ALT, ↑ALP, hypocalcemia, hypophosphatemia, hyperbilirubinemia, hypomagnesemia, hypokalemia, hyponatremia, lymphopenia, neutropenia, and thrombocytopenia.

Potential Nursing Diagnoses

Diarrhea (Adverse Reactions)

Implementation

  • Stop treatment at least 28 days before scheduled surgery. Resume therapy postoperatively based on clinical judgement of adequate wound healing. Withhold in patients with dehiscence or wound healing complications.
  • Oral: Administer 140 mg dose as one 80-mg and 3 20-mg capsules, on an empty stomach at least 1hr 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.

Patient/Family Teaching

  • 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 hr-s 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, 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.
  • 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 is teratogenic. Advise female and male patients with female partners who may become pregnant to use effective contraception during and for at least 4 mo after completion of therapy and to avoid breastfeeeding.

Evaluation/Desired Outcomes

  • Decreased spread of metastatic MTC.
References in periodicals archive ?
Newer agents, such as the VEGF/Met inhibitor cabozantinib (3) or the next-generation immunotherapy PD-1 inhibitor nivolumab, have arisen.
Of these, five are in the subclass of tyrosine kinase inhibitors (trade name; indication): axitinib (Inlyta; renal cancer), bosutinib (Bosulif; leukemia), cabozantinib (Cometriq; thyroid cancer), ponatinib (Iclusig; leukemia), and ziv-aflibercept (Zal-trap; colorectal cancer).
GlobalData has released its new PharmaPoint Drug Evaluation report, Cabozantinib (Prostate Cancer) - Forecast and Market Analysis to 2022.
They found 76 percent of patients saw some or all of their tumors shrink on bone scans following treatment with Cabozantinib.
Subject : Cell free DNA (cfDNA) to monitor clonal evolution in patients (pts) with KRAS wild-type (WT) metastatic colorectal cancer (mCRC): Preliminary results of a phase I/II clinical trial of the anti-MET multi-kinase inhibitor cabozantinib (C) plus the anti-EGFR monoclonal antibody panitumumab (P)Lead Author : John H.
No OS benefit of cabozantinib among men with prior docetaxel and abiraterone or enzalutamide
Morrissey will review the company's development plans and priorities for cabozantinib in 2013.
Announced in early January 2013 that Exelixis plans to initiate phase 3 pivotal trials of cabozantinib in advanced hepatocellular cancer (HCC) and metastatic renal cell cancer (RCC).
METEOR, Phase 3 Pivotal Trial Of Cabozantinib -- On July 20, 2015 Exelixis, Inc announced positive top-line results from the primary analysis of METEOR, the phase 3 pivotal trial of Cabozantinib.
Co-administration of strong CYP3A4 inhibitors can increase cabozantinib exposure.
Exelixis has five Phase III trials for various cancer treatments using Cabozantinib and Cobimetinib.
During the webcast, Exelixis management will discuss the Company's financial results, financial outlook, and development program and plans for cabozantinib, and also provide a general business update.