Cabozantinib

Cabozantinib
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aparna Vuppala, M.B.B.S. [2]

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Overview

Cabozantinib is a multikinase inhibitor that is FDA approved for the treatment of patients with progressive, metastatic medullary thyroid cancer (MTC).. Common adverse reactions include .

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Medullary thyroid cancer

• COMETRIQ is indicated for the treatment of patients with progressive, metastatic medullary thyroid cancer (MTC)

Recommended Dose

• The recommended daily dose of COMETRIQ is 140 mg (one 80-mg and three 20-mg capsules). Do not administer COMETRIQ with food. Instruct patients not to eat for at least 2 hours before and at least 1 hour after taking COMETRIQ. Continue treatment until disease progression or unacceptable toxicity occurs.
• Swallow COMETRIQ capsules whole. Do not open COMETRIQ capsules.
• Do not take a missed dose within 12 hours of the next dose.
• Do not ingest foods (e.g., grapefruit, grapefruit juice) or nutritional supplements that are known to inhibit cytochrome P450 during COMETRIQ treatment.

Dosage Adjustments

• For Adverse Reactions

• Withhold COMETRIQ for NCI CTCAE Grade 4 hematologic adverse reactions, Grade 3 or greater non-hematologic adverse reactions or intolerable Grade 2 adverse reactions.
• Upon resolution/improvement of the adverse reaction (i.e., return to baseline or resolution to Grade 1), reduce the dose as follows:
• If previously receiving 140 mg daily dose, resume treatment at 100 mg daily (one 80-mg and one 20-mg capsule)
• If previously receiving 100 mg daily dose, resume treatment at 60 mg daily (three 20-mg capsules)
• If previously receiving 60 mg daily dose, resume at 60 mg if tolerated, otherwise, discontinue COMETRIQ

• Permanently discontinue COMETRIQ for any of the following:

• Development of visceral perforation or fistula formation
• severe hemorrhage
• serious arterial thromboembolic event (e.g., 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

• In Patients with Hepatic Impairment

• COMETRIQ is not recommended for use in patients with moderate and severe hepatic impairment [see WARNINGS AND PRECAUTIONS (5.11) and USE IN SPECIFIC POPULATIONS (8.6)].

• In Patients Taking CYP3A4 Inhibitors

• Avoid the use of concomitant strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole) in patients receiving COMETRIQ.
• For patients who require treatment with a strong CYP3A4 inhibitor, reduce the daily COMETRIQ dose by 40 mg (for example, from 140 mg to 100 mg daily or from 100 mg to 60 mg daily). Resume the dose that was used prior to initiating the CYP3A4 inhibitor 2 to 3 days after discontinuation of the strong inhibitor.

• In Patients Taking Strong CYP3A4 Inducers

• Avoid the chronic use of concomitant strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital) if alternative therapy is available [see WARNINGS AND PRECAUTIONS (5.10) and DRUG INTERACTIONS (7.2)].
• Do not ingest foods or nutritional supplements (e.g., St. John’s Wort (Hypericum perforatum)) that are known to induce cytochrome P450 activity.
• For patients who require treatment with a strong CYP3A4 inducer, increase the daily COMETRIQ dose by 40 mg (for example, from 140 mg to 180 mg daily or from 100 mg to 140 mg daily) as tolerated. Resume the dose that was used prior to initiating the CYP3A4 inducer 2 to 3 days after discontinuation of the strong inducer. The daily dose of COMETRIQ should not exceed 180 mg.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

Condition1

• Developed by:

• Class of Recommendation:

• Strength of Evidence:

• Dosing Information

• Dosage

Condition2

There is limited information regarding Off-Label Guideline-Supported Use of Cabozantinib in adult patients.

Non–Guideline-Supported Use

Condition1

• Dosing Information

• Dosage

Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Cabozantinib in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Condition1

• Dosing Information

• Dosage

Condition2

There is limited information regarding FDA-Labeled Use of Cabozantinib in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

Condition1

• Developed by:

• Class of Recommendation:

• Strength of Evidence:

• Dosing Information

• Dosage

Condition2

There is limited information regarding Off-Label Guideline-Supported Use of Cabozantinib in pediatric patients.

Non–Guideline-Supported Use

Condition1

• Dosing Information

• Dosage

Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Cabozantinib in pediatric patients.

Contraindications

• None

Warnings

Perforations and Fistulas

• Gastrointestinal (GI) perforations and fistulas were reported in 3% and 1% of COMETRIQ-treated patients, respectively. All were serious and one GI fistula was fatal (< 1%). Non-GI fistulas including tracheal/esophageal were reported in 4% of COMETRIQ-treated patients. Two (1%) of these were fatal.
• Monitor patients for symptoms of perforations and fistulas. Discontinue COMETRIQ in patients who experience a perforation or a fistula.

Hemorrhage

• Serious and sometimes fatal hemorrhage occurred with COMETRIQ. The incidence of Grade ≥3 hemorrhagic events was higher in COMETRIQ-treated patients compared with placebo (3% vs. 1%).
• Do not administer COMETRIQ to patients with a recent history of hemorrhage or hemoptysis.

Thrombotic Events

• COMETRIQ treatment results in an increased incidence of thrombotic events (venous thromboembolism: 6% vs. 3% and arterial thromboembolism: 2% vs. 0% in COMETRIQ-treated and placebo-treated patients, respectively).
• Discontinue COMETRIQ in patients who develop an acute myocardial infarction or any other clinically significant arterial thromboembolic complication.

Wound Complications

• Wound complications have been reported with COMETRIQ. Stop treatment with COMETRIQ at least 28 days prior to scheduled surgery. Resume COMETRIQ therapy after surgery based on clinical judgment of adequate wound healing. Withhold COMETRIQ in patients with dehiscence or wound healing complications requiring medical intervention.

Hypertension

• COMETRIQ treatment results in an increased incidence of treatment-emergent hypertension with Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (modified JNC criteria) stage 1 or 2 hypertension identified in 61% in COMETRIQ-treated patients compared with 30% of placebo-treated patients in the randomized trial. Monitor blood pressure prior to initiation and regularly during COMETRIQ treatment. Withhold COMETRIQ for hypertension that is not adequately controlled with medical management; when controlled, resume COMETRIQ at a reduced dose. Discontinue COMETRIQ for severe hypertension that cannot be controlled with anti-hypertensive therapy.

Osteonecrosis of the Jaw

• Osteonecrosis of the jaw (ONJ) occurred in 1% of COMETRIQ-treated patients. ONJ can manifest as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration or erosion, persistent jaw pain or slow healing of the mouth or jaw after dental surgery. Perform an oral examination prior to initiation of COMETRIQ and periodically during COMETRIQ therapy. Advise patients regarding good oral hygiene practices. For invasive dental procedures, withhold COMETRIQ treatment for at least 28 days prior to scheduled surgery, if possible.

Palmar-Plantar Erythrodysesthesia Syndrome

• Palmar-plantar erythrodysesthesia syndrome (PPES) occurred in 50% of patients treated with COMETRIQ and was severe (≥ Grade 3) in 13% of patients. Withhold COMETRIQ in patients who develop intolerable Grade 2 PPES or Grade 3-4 PPES until improvement to Grade 1; resume COMETRIQ at a reduced dose.

Proteinuria

• Proteinuria was observed in 4 (2%) of patients receiving COMETRIQ, including one with nephrotic syndrome, as compared to none of the patients receiving placebo. Monitor urine protein regularly during COMETRIQ treatment. Discontinue COMETRIQ in patients who develop nephrotic syndrome.

Reversible Posterior Leukoencephalopathy Syndrome

• Reversible Posterior Leukoencephalopathy Syndrome (RPLS), a syndrome of subcortical vasogenic edema diagnosed by characteristic finding on MRI, occurred in one (<1%) patient. Perform an evaluation for RPLS in any patient presenting with seizures, headache, visual disturbances, confusion or altered mental function. Discontinue COMETRIQ in patients who develop RPLS.

Drug Interactions

• Avoid administration of COMETRIQ with agents that are strong CYP3A4 inducers or inhibitors [see DOSAGE AND ADMINISTRATION (2.1) and DRUG INTERACTIONS (7.1, 7.2)].

Hepatic Impairment

• COMETRIQ is not recommended for use in patients with moderate or severe hepatic impairment [see USE IN SPECIFIC POPULATIONS (8.6)].

Embryo-fetal Toxicity

• COMETRIQ can cause fetal harm when administered to a pregnant woman. Cabozantinib was embryolethal in rats at exposures below the recommended human dose, with increased incidences of skeletal variations in rats and visceral variations and malformations in rabbits. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Clinical Trial Experience of Cabozantinib in the drug label.

Body as a Whole

Cardiovascular

Digestive

Endocrine

Hematologic and Lymphatic

Metabolic and Nutritional

Musculoskeletal

Neurologic

Respiratory

Skin and Hypersensitivy Reactions

Special Senses

Urogenital

Miscellaneous

Postmarketing Experience

There is limited information regarding Postmarketing Experience of Cabozantinib in the drug label.

Body as a Whole

Cardiovascular

Digestive

Endocrine

Hematologic and Lymphatic

Metabolic and Nutritional

Musculoskeletal

Neurologic

Respiratory

Skin and Hypersensitivy Reactions

Special Senses

Urogenital

Miscellaneous

Drug Interactions

• Drug

• Description

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

• Pregnancy Category

Pregnancy Category (AUS):

• Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Cabozantinib in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Cabozantinib during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Cabozantinib with respect to nursing mothers.

Pediatric Use

There is no FDA guidance on the use of Cabozantinib with respect to pediatric patients.

Geriatic Use

There is no FDA guidance on the use of Cabozantinib with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Cabozantinib with respect to specific gender populations.

Race

There is no FDA guidance on the use of Cabozantinib with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Cabozantinib in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Cabozantinib in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Cabozantinib in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Cabozantinib in patients who are immunocompromised.

Administration and Monitoring

Administration

• Oral

• Intravenous

Monitoring

There is limited information regarding Monitoring of Cabozantinib in the drug label.

• Description

IV Compatibility

There is limited information regarding IV Compatibility of Cabozantinib in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

• Description

Management

• Description

Chronic Overdose

There is limited information regarding Chronic Overdose of Cabozantinib in the drug label.

Pharmacology

There is limited information regarding Cabozantinib Pharmacology in the drug label.

Mechanism of Action

Structure

This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Cabozantinib in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Cabozantinib in the drug label.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Cabozantinib in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Cabozantinib in the drug label.

How Supplied

Storage

There is limited information regarding Cabozantinib Storage in the drug label.

Images

Drug Images

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Patient Counseling Information

There is limited information regarding Patient Counseling Information of Cabozantinib in the drug label.

Precautions with Alcohol

• Alcohol-Cabozantinib interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

• ®

Look-Alike Drug Names

• A® — B®

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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