Drug Interaction:
Cabozantinib is a CYP3A4 substrate .
Coadministration of strong CYP3A4 inhibitors can increase
cabozantinib exposure
Chronic co-administration of strong CYP3A4 inducers can reduce
cabozantinib exposure. DRUG INTERACTIONS
Cabozantinib is a CYP3A4 substrate .
Coadministration of strong CYP3A4 inhibitors can increase
cabozantinib exposure
Chronic co-administration of strong CYP3A4 inducers can reduce
cabozantinib exposure.
Indication:
COMETRIQ. (cabozantinib) capsules, for oral use
Initial U.S. Approval: 2012
WARNING: PERFORATIONS AND FISTULAS, and
HEMORRHAGE
See full prescribing information for complete boxed warning.
Perforations and Fistulas: Gastrointestinal perforations
occurred in 3% and fistula formation in 1% of COMETRIQ treated patients.
Discontinue COMETRIQ in patients with perforation or fistula.
Hemorrhage: Severe, sometimes fatal, hemorrhage including hemoptysis
and gastrointestinal hemorrhage occurred in 3% of COMETRIQ-treated
patients. Monitor patients for signs and symptoms of bleeding.
Do not administer COMETRIQ to patients with severe hemorrhage.
Drug Name- Cometriq
Active Ingredient - Cabozantinib
To treat medullary thyroid cancer that has spread to other parts of the
body (metastasized)
Indication-
To treat medullary thyroid cancer that has spread to other parts of the
body (metastasized)
Approved by FDA on 29-11--2012 (Ref- FDA approved List- 2012)
Adverse Reaction:
The most commonly reported adverse drug reactions (.25%) are
diarrhea, stomatitis, palmar-plantar erythrodysesthesia syndrome(PPES),
decreased weight, decreased appetite, nausea, fatigue, oral pain,
hair color changes, dysgeusia, hypertension, abdominal pain,
and constipation.
The most common laboratory abnormalities (.25%)
are increased AST, increased ALT, lymphopenia, increased alkaline
phosphatase, hypocalcemia, neutropenia, thrombocytopenia,
hypophosphatemia, and hyperbilirubinemia.
Contra-Indications:
CONTRAINDICATIONS
None
WARNINGS AND PRECAUTIONS
Thrombotic Events: Discontinue COMETRIQ for myocardial infarction,
cerebral infarction, or other serious arterial thromboembolic events.
Wound Complications: Withhold COMETRIQ for dehiscence or
complications requiring medical intervention.
Hypertension: Monitor blood pressure regularly. Discontinue
COMETRIQ for hypertensive crisis.
Osteonecrosis of the jaw: Discontinue COMETRIQ.
Palmar-plantar Erythrodysesthesia syndrome (PPES): Interrupt
COMETRIQ, decrease dose.
Proteinuria: Monitor urine protein. Discontinue for nephrotic
syndrome.
Reversible posterior leukoencephalopathy syndrome (RPLS):
Discontinue COMETRIQ.
Embryofetal toxicity: Can cause fetal harm. Advise women of
potential risk to a fetus.
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
COMETRIQ is a kinase inhibitor indicated for the treatment of
patients with progressive, metastatic medullary thyroid cancer
DOSAGE AND ADMINISTRATION
Recommended Dose: 140 mg orally, once daily.
Instruct patients not to eat for at least 2 hours before and at least
1 hour after taking COMETRIQ. .
DOSAGE FORMS AND STRENGTHS
20 mg and 80 mg capsules.
Patient Information:
PATIENT COUNSELING INFORMATION
See FDA-approved patient labeling (Patient Information and Instructions for Use).
Inform patients of the following:
COMETRIQ often causes diarrhea which may be severe in some cases.
Inform patients of the need to contact their healthcare provider if severe diarrhea
occurs during treatment with COMETRIQ.
COMETRIQ often causes palmar plantar erythrodysesthesia syndrome. Advise
patients to contact their healthcare provider for progressive or intolerable rash.
COMETRIQ often causes sores in the mouth, oral pain, changes in taste, nausea
or vomiting. Advise patients to contact their healthcare provider if any of these
symptoms are severe or prevent patients from eating and drinking.
COMETRIQ often causes weight loss which may be significant in some cases.
Advise patients to report significant weight loss.
To contact their healthcare provider before any planned surgeries, including
dental procedures.
COMETRIQ may interact with other drugs; advise patients to inform their
healthcare provider of all prescription or nonprescription medication or
herbal products that they are taking.
Patients of childbearing potential must use effective contraception during
therapy and for at least four months following their last dose of COMETRIQ.
Breast-feeding mothers must discontinue nursing while receiving COMETRIQ
therapy.
COMETRIQ should not be taken with food. Instruct patients not to eat for
at least 2 hours before and at least 1 hour after taking COMETRIQ.
COMETRIQ capsules should not be opened or crushed but should be taken
with a full glass (at least 8 ounces) of water.
Patients should not consume grapefruits or grapefruit juice while taking COMETRIQ
treatment.
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
In vitro biochemical and/or cellular assays have shown that cabozantinib inhibits the
tyrosine kinase activity of RET, MET, VEGFR-1, -2 and -3, KIT, TRKB, FLT-3, AXL,
and TIE-2.
These receptor tyrosine kinases are involved in both normal cellular function and
pathologic processes such as oncogenesis, metastasis, tumor angiogenesis,
and maintenance of the tumor microenvironment.
2. Pharmacokinetics
A population pharmacokinetic analysis of cabozantinib was performed using data
collected from patients with solid tumors including MTC following oral
administration of 140 mg daily doses.
The predicted effective half-life is approximately 55 hours, the oral volume of
distribution (V/F) is approximately 349 L, and the clearance (CL/F) at steady-state
is estimated to be 4.4 L/hr.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Pregnancy Category D
Risk Summary
Based on its mechanism of action, COMETRIQ can cause fetal harm when
administered to a pregnant woman.
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 hazar
to the fetus.
2. Nursing Mothers
It is unknown whether cabozantinib or its metabolites are excreted in human milk.
Because many drugs are excreted in human milk and because of the potential
for serious adverse reactions in nursing infants from COMETRIQ, a decision
should be made whether to discontinue nursing or to discontinue the drug,
taking into account the importance of the drug to the mother.
3. Pediatric Use
The safety and effectiveness of COMETRIQ in pediatric patients have not been
studied.
4. Geriatric Use
Clinical studies of COMETRIQ did not include sufficient numbers of patients
aged 65 years and over to determine whether they respond differently from
younger patients
Manufacturer Details