Drug information of Cabozantinib

Cabozantinib


Cabozantinib is used to treat advanced kidney cancer, or thyroid cancer that has spread to other parts of the body
Cabozantinib is also used to treat liver cancer in people who have been previously treated with sorafenib (Nexavar

Mechanism of effect

Cabozantinib is a potent inhibitor of proinvasive receptor tyrosine kinases    (RTKs), including AXL
FLT-3
KIT
MER
MET
RET
ROS1
TIE-2
TRKB
TYRO3
VEGFR-1, -2, and -3
induces apoptosis of cancer cells and suppresses tumor growth, metastasis, and angiogenesis

Pharmacodynamic

Metabolism
Hepatic via CYP3A4
Excretion
Feces (~54%; 43% as unchanged drug); urine (~27%
Time to Peak
2
to 5 hours (Cometriq); 3 to 4 hours (Cabometyx
Half life
~55
 hours (Cometriq); ~99 hours (Cabometyx


Drug indications

Hepatocellular carcinoma, advanced (Cabometyx): Treatment of hepatocellular carcinoma (HCC) in patients who have previously been treated with sorafenib

Renal cell carcinoma, advanced (Cabometyx): Treatment of advanced renal cell carcinoma (RCC

Thyroid cancer, medullary (Cometriq): Treatment of progressive, metastatic medullary thyroid cancer (MTC

Dosage

Usual Adult Dose for Thyroid Cancer
Capsules: 140 mg orally once a day
Duration of therapy: Until patient no longer experiences clinical benefit or unacceptable toxicity occurs.
Usual Adult Dose for Renal Cell Carcinoma
Tablets: 60 mg orally once a day
Duration of therapy: Until patient no longer experiences clinical benefit or unacceptable toxicity occurs.
Usual Adult Dose for Hepatocellular Carcinoma
Tablets: 60 mg orally once a day
Duration of therapy: Until patient no longer experiences clinical benefit or unacceptable toxicity occurs.

Drug contraindications

There are no contraindications listed in the manufacturer's US labeling
Canadian labeling: Hypersensitivity to cabozantinib or any component of the formulation

Side effects

>10%
Cardiovascular: Hypertension
Central nervous system: Fatigue, mouth pain, voice disorder, headache, dizziness
Dermatologic: Palmar-plantar erythrodysesthesia, hair discoloration, skin rash, xeroderma, alopecia, erythema
Endocrine & metabolic: Increased lactate dehydrogenase, increased serum triglycerides, hypocalcemia, hypoalbuminemia, hypophosphatemia, weight loss, hyperglycemia, hypomagnesemia, hyponatremia, increased gamma-glutamyl transferase, hypokalemia, hypothyroidism
Gastrointestinal: Diarrhea, stomatitis, nausea, decreased appetite, dysgeusia ,vomiting, constipation, abdominal pain, mucositis, increased serum amylase, dysphagia, dyspepsia
Genitourinary: Proteinuria
Hematologic & oncologic: Lymphocytopenia, neutropenia , leukopenia, thrombocytopenia, anemia
Hepatic: Increased serum aspartate aminotransferase, increased serum alanine aminotransferase, increased serum alkaline phosphatase, hyperbilirubinemia
Neuromuscular & skeletal: Asthenia, arthralgia, limb pain, muscle spasm
Renal: Increased serum creatinine
Respiratory: Dyspnea, cough
1%
 to 10%
Cardiovascular: Hypotension, venous thromboembolism, syncope, pulmonary embolism, arterial thromboembolism, vascular disease
Central nervous system: Anxiety, paresthesia, peripheral sensory neuropathy, pain, peripheral neuropathy, depression, confusion
Dermatologic: Hyperkeratosis, dermal ulcer
Endocrine & metabolic: Dehydration, hyperkalemia
Gastrointestinal: Hemorrhoids, gastrointestinal hemorrhage, gastrointestinal perforation, gastrointestinal fistula
Hematologic & oncologic: Increased hemoglobin, hemorrhage
Neuromuscular & skeletal: Musculoskeletal chest pain, back pain, ostealgia, osteonecrosis of the jaw
Renal: Acute renal failure
Respiratory: Pulmonary infection
Miscellaneous: Fistula, wound healing impairment
<1%, postmarketing, and/or case reports: Cholestatic hepatitis, hypertensive crisis, nephrotic syndrome, pancreatitis, reversible posterior leukoencephalopathy syndrome, seizure

Aprepitant, Bisphosphonate Derivatives, Bosentan, Clofazimine, Conivaptan, CYP3A4 Inducers (Moderate), CYP3A4 Inducers (Strong), CYP3A4 Inhibitors (Moderate), CYP3A4 Inhibitors (Strong), Dabrafenib, Deferasirox, Duvelisib, Enzalutamide, Erdafitinib, Erdafitinib, Idelalisib,
Fosaprepitant, Fosnetupitant, Fusidic Acid (Systemic), Grapefruit Juice, Ivosidenib, Mitotane,
Larotrectinib, MiFEPRIStone, MRP2 Inhibitors, Netupitant, Palbociclib, Rifabutin, Rifapentine,
Sarilumab, Siltuximab, Simeprevir, Solriamfetol, St John's Wort, Stiripentol, Tocilizumab

Alerts

If you need surgery or dental work, stop taking cabozantinib at least 3 weeks ahead of time. After a surgery or dental procedure, you may need to wait 2 weeks before you start taking cabozantinib again. Follow your doctor's dosing instructions very carefully

Grapefruit may interact with cabozantinib and lead to unwanted side effects. Avoid the use of grapefruit products while taking cabozantinib

Gastrointestinal (GI) perforations, fistula formation, and severe hemorrhage have occurred in patients treated with cabozantinib malate. Discontinue therapy if GI perforation or fistula develop. Monitor patients for bleeding, and do not administer cabozantinib malate to patients with severe hemorrhage

Palmar-plantar erythrodysesthesia syndrome occurred in one-half of patients; grade 3 events were reported. May require treatment interruption, dosage reduction, and/or discontinuation

Severe and fatal hemorrhages have occurred with cabozantinib, including grade 3 or higher events. Discontinue cabozantinib for grade 3 or 4 hemorrhage. Do not administer to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena

Cabozantinib may increase the risk of treatment-emergent hypertension. Stage 1 and 2 hypertension were commonly seen in cabozantinib-treated patients; grade 3 and 4 hypertension has been reported. Do not initiate cabozantinib in patients with uncontrolled hypertension. Monitor blood pressure regularly; withhold cabozantinib for hypertension that is uncontrolled despite appropriate medical management. When blood pressure is controlled, resume cabozantinib at a reduced dose. Discontinue cabozantinib for severe hypertension (that cannot be controlled with antihypertensive therapy) or hypertensive crisis

Osteonecrosis of the jaw (ONJ) occurred rarely; manifestations may include 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. Oral examinations should be performed prior to and periodically throughout therapy. Patients should maintain proper oral hygiene practices. If possible, withhold therapy for at least 3 weeks prior to scheduled dental surgery or invasive dental procedures. Withhold cabozantinib until complete resolution if ONJ develops

Points of recommendation

Cabozantinib may cause a perforation (a hole or tear) or a fistula (an abnormal passageway) within your stomach or intestines. Cabozantinib can also increase your risk of serious bleeding.
Call your doctor if you have: severe stomach pain, choking or gagging when you eat or drink, unusual bleeding, bloody or tarry stools, heavy menstrual bleeding, or if you cough up blood

Tell your doctor if you have
an open wound on your skin (or a wound that is still healing-
bleeding problems (such as bloody or tarry stools, or coughing up blood or vomit that looks like coffee grounds)
high blood pressure
liver disease
a pre-existing dental problem

You may need to have a negative pregnancy test before starting this treatment.
Cabozantinib may harm an unborn baby. Use effective birth control to prevent pregnancy while you are using cabozantinib and for at least 4 months after your last dose. Tell your doctor if you think you might be pregnant

You should not breastfeed while using this medicine, and for at least 4 months after your last dose

Do not use cabozantinib tablets in place of cabozantinib capsules. Take only the pill form your doctor has prescribed. Avoid medication errors by always checking the medicine you receive at the pharmacy

Take cabozantinib on an empty stomach, at least 1 hour before or 2 hours after you eat anything

Take this medicine with a full glass of water

Do not crush, chew, or break a tablet, and do not open a capsule. Swallow the pill whole

Your blood pressure will need to be checked often


Pregnancy level

D

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

Breast feeding warning

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

Ask a Pharmacist


User's questions
    No comments yet.