cabozantinib (tablet)

Trade Name:

Cabometyx®

Other Names:

CABOMETYX®

Appearance:

tablet

Monograph Name:

cabozantinib

Monograph Body:

Drug Monograph

A - Drug Name

cabozantinib (tablet)

COMMON TRADE NAME(S): Cabometyx®

B - Mechanism of Action and Pharmacokinetics

Cabozantinib is an inhibitor of multiple receptor tyrosine kinases (RTKs) including AXL, FLT3, KIT, MER, MET, RET, ROS1, TIE-2, TRKB, TYRO3, and VEGF, with effects on cell proliferation and angiogenesis.

Absorption

Effects with food

Co-administration with a high-fat meal increased peak concentrations by 41% and AUC by 57%, relative to fasted conditions.

Peak plasma levels

3 to 4 hours

Time to reach steady state

15 Days

Distribution

PPB	≥99.7% to plasma proteins

Metabolism

Active metabolites

Yes

Inactive metabolites

Yes

Elimination

Half-life

~ 99 hours

Feces

54%

Urine

27%

C - Indications and Status

Health Canada Approvals:

Renal cell carcinoma (RCC)
Hepatocellular carcinoma (HCC)
Differentiated thyroid carcinoma (DTC)

Refer to the product monograph for a full list of approved indications.

D - Adverse Effects

Emetogenic Potential:

Moderate – Consider prophylaxis daily

The following table lists adverse effects that occurred in ≥10% of patients with advanced renal cell carcinoma receiving cabozantinib, where incidences were higher compared to everolimus in a phase III trial. Severe adverse events from other studies or post-marketing may also be included. Adverse effects marked with “^” were observed in combination treatment with nivolumab.

ORGAN SITE	SIDE EFFECT* (%)	ONSET**
Cardiovascular	Arterial thromboembolism (1%)	E
	Artery aneurysm (rare)	E D L
	Artery dissection (rare)	E D L
	Hypertension (39%) (16% severe; including hypertensive crisis)	E
	PR interval prolonged ,bradycardia (rare)	E
	QT interval prolonged (rare)	E
	Venous thromboembolism (9%)	E D
Dermatological	Hand-foot syndrome (42%) (8% severe)	E
	Rash (23%) (including dry skin)	E
Gastrointestinal	Abdominal pain (23%)	E
	Anorexia, weight loss (46%)	E
	Constipation (25%)	E
	Diarrhea (74%) (11% severe)	E
	Dyspepsia (12%)	E
	Gastrointestinal fistula (2%) (may be severe)	E
	GI perforation (1%)	E
	Mucositis (22%)	E
	Nausea, vomiting (50%) (4% severe)	E
General	Fatigue (56%) (9% severe)	E
	Wound complication (<2%) (may be severe)	E
Hematological	Anemia (17%)	E
	Hemorrhage (3%) (severe)	E
	Thrombocytopenia (11%) (HCC study)	E
Hepatobiliary	Cholestasis (<2%)	E
	Hepatic encephalopathy (4%)	E
	Hepatotoxicity (rare)	E
	↑ LFTs (26%) (3% severe)	E
	Other - vanishing bile duct syndrome (rare) (with prior or concurrent immune checkpoint inhibitor exposure)	E D
	Pancreatitis (<2%)	E
Metabolic / Endocrine	Abnormal electrolyte(s) (23%) (↓ PO4, Mg, Ca, Na, K)	E
	Adrenal insufficiency (5%) ^	E D
	Hyperthyroidism (10%) ^	E
	Hypothyroidism (21%)	E
Musculoskeletal	Musculoskeletal pain (14%) (including muscle spasms)	E
	Osteonecrosis of jaw (<2%)	D
Nervous System	Dizziness (11%)	E
	Dysgeusia (24%)	E
	Headache (11%)	E
	Posterior reversible encephalopathy syndrome (PRES) (<2%)	E
	Seizure (<2%)	E
Renal	Proteinuria (12%)	E
Respiratory	Cough, dyspnea (19%)	E
	Dysphonia (20%)	E
	Pleural effusion (may be severe)	E

* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare" may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal reports.

** I = immediate (onset in hours to days) E = early (days to weeks)
D = delayed (weeks to months) L = late (months to years)

The most common side effects for cabozantinib include diarrhea, fatigue, nausea, vomiting, anorexia, weight loss, hypertension, hand-foot syndrome (HFS), ↑ LFTs, constipation, dysgeusia and abdominal pain.

Most side effects can occur early in the course of treatment, physicians should evaluate the patient closely during the first eight weeks of treatment to determine if dose modifications are warranted. Some side effects with early onset include hypocalcemia, hypokalemia, thrombocytopenia, hypertension, HFS, proteinuria, and GI events.

Cabozantinib is associated with an increased risk of arterial or venous thrombotic events, including fatal cases. In the HCC study, portal vein thrombosis was observed. Patients with a history of portal vein invasion appear to be at higher risk.

Serious GI perforations and fistulas, sometimes fatal, have been observed with cabozantinib. Persistent or recurring diarrhea while on treatment may be a risk factor for the development of anal fistula.

Severe cases of artery dissection (with or without hypertension) and artery aneurysm (including rupture) have been reported in patients using VEGFR TKIs.

Severe hemorrhage, including fatal events have occurred with cabozantinib. Risk factors in advanced HCC may include tumour invasion of major blood vessels, underlying liver cirrhosis resulting in esophageal varices, portal hypertension, and thrombocytopenia.

Osteonecrosis of the jaw (ONJ) occurred rarely with cabozantinib. Patients should maintain proper oral hygiene practices. If possible, withhold therapy for at least 28 days prior to scheduled invasive dental procedures.

Posterior reversible leukoencephalopathy syndrome (PRES) has been rarely observed in the thyroid cancer pivotal trial. This syndrome should be considered in any patient presenting with multiple symptoms, including seizures, headache, visual disturbances, confusion or altered mental function.

Wound complications have been reported in 2% of RCC patients treated with cabozantinib after VEGF-targeted therapy. Treatment should be held for at least 28 days prior to scheduled surgery, with resumption of therapy dependent on judgment of adequate wound healing post-surgery.

Primary and secondary adrenal insufficiency have been reported in cabozantinib combination treatment with nivolumab. Majority of patients received hormone replacement therapy, including systemic corticosteroids and adrenal insufficiency resolving in approximately 1/4 of patients.

Higher incidences of severe LFT elevations were observed with cabozantinib and nivolumab relative to cabozantinib monotherapy. Some cases occurred after treatment discontinuation.

Hypocalcemia has been observed at a higher frequency and/or increased severity in patients with thyroid cancer compared to patients with other cancers.

E - Dosing

Refer to protocol by which the patient is being treated.

Screen for hepatitis B virus in all cancer patients starting systemic treatment. Refer to the hepatitis B virus screening and management guideline.

Cabozantinib tablets and capsules are not interchangeable.

Adults:

Prior to initiating cabozantinib therapy:

Blood pressure should be well-controlled.
Hypokalemia, hypomagnesemia, and hypocalcemia should be corrected.
Optimal control of thyroid function is recommended.
An oral examination is recommended.

Hold treatment for at least 28 days prior to scheduled surgery, including dental surgery; resume based on clinical judgment of adequate wound healing.

Monotherapy:

Oral: 60 mg Daily

In combination with nivolumab:

Oral: 40 mg Daily

Refer to the CABO+NIVL regimen monograph for details.

Refer to Interactions section for dosing when co-administered with strong CYP3A4 inducers or inhibitors.

Dosage with Toxicity:

Dose Levels

Monotherapy Dose Levels:

Dose Level	Cabozantinib (Tablet) Dose (mg/day)
0	60
-1	40
-2^*	20
-3	Discontinue

*If previously receiving lowest dose, restart at the same dose if tolerated. Otherwise, discontinue.

Dose Levels in Combination with Nivolumab:

Dose Level	Cabozantinib (Tablet) Dose
0	40 mg daily
-1	20 mg daily
-2^*	20 mg every other day
-3	Discontinue

*If previously receiving lowest dose, restart at the same dose if tolerated. Otherwise, discontinue.

Dosage with Toxicity:

Toxicity	Severity	Action for Cabozantinib
Hand-foot syndrome	Intolerable Grade 2 or Grade 3	Hold**; restart at 1 dose level ↓
Diarrhea	Intolerable Grade 2 OR Grade 3-4 diarrhea that cannot be managed with standard antidiarrheals	Hold**; restart at 1 dose level ↓^
Hypertension	Intolerable Grade 2 OR Grade 3	Hold**, restart at 1 dose level ↓
Hypertension	Grade 4 (including hypertensive crisis) OR Severe uncontrolled hypertension despite optimal therapy	Discontinue
Proteinuria	Grade 2 or 3	Hold**, restart at 1 dose level ↓
Proteinuria	Grade 4 (including nephrotic syndrome)	Discontinue
Osteonecrosis of the jaw	Any	Hold until complete resolution. Restart at 1 dose level ↓
Unmanageable fistula or GI perforation	Any	Discontinue
Severe hemorrhage
Arterial or venous thromboembolic event that requires medical intervention (e.g., MI, cerebral infarction)
Torsade de pointes or polymorphic ventricular tachycardia or signs/symptoms of serious arrhythmia
Posterior reversible leukoencephalopathy syndrome
Wound healing complications requiring medical intervention
Other related hematologic/ non-hematologic/ organ toxicity	Intolerable grade 2 and cannot be adequately managed	Hold**; restart at 1 dose level ↓^{^}
Other related hematologic/ non-hematologic/ organ toxicity	≥ Grade 3	Hold**; restart at 1 dose level ↓^{^}

**Restart if toxicity resolved to ≤ grade 1 or baseline. Discontinue if toxicity does not resolve after 6 weeks.

^{^}Or consider discontinuing for persistent or recurrent significant GI toxicity.

Hepatic Toxicity During Treatment

Refer to the product monographs for details during combination treatment with nivolumab (RCC).

Suggested Dose Modifications for Hepatic Toxicity During Monotherapy*:

Baseline

During treatment

Action

AST, ALT, and bilirubin ≤ 3 x ULN

and

AST or ALT > 5 x ULN OR bilirubin > 3 x ULN

Consider hold, then

Reduce dose when resolved, OR
Discontinue if no recovery

Any

and

Drug-induced liver injury (AST or ALT > 3 ULN AND bilirubin > 2 x ULN in absence of another likely cause)

Discontinue

*adapted from Abou-Alfa et al, and Choueiri et al.

Dosage with Hepatic Impairment:

Starting Dose:

Liver Impairment	Monotherapy (Tablet) Starting Dose (mg/day)	Starting Dose in Combination with Nivolumab
Mild	No dosage adjustment required. Monitor patient closely.	Not been studied; no dosing recommendation can be provided.
Moderate	40 mg. Monitor patient closely.	Not been studied; no dosing recommendation can be provided.
Severe	Not recommended (has not been studied)	Not recommended (has not been studied)

Note: The HCC clinical trial (Abou-Alfa et al) included patients with Child-Pugh class A, with AST or ALT < 5 x ULN at baseline.

Dosage with Renal Impairment:

Renal Impairment	Cabozantinib (Tablet) Dose (mg/day)
Mild or moderate (eGFR ≥ 30mL/min)	No dosage adjustment required. Use with caution.
Severe (eGFR < 29 mL/min)	Not recommended (has not been studied)

Dosage in the elderly:

No dosage adjustment is required. There were no overall differences in safety or efficacy between patients aged 65 or older and younger patients.

Dosage based on ethnicity:

There were no overall differences in pharmacokinetics based on race.

Children:

The safety and efficacy has not been established in the pediatric population.

F - Administration Guidelines

Tablets should be administered on an empty stomach, at least 1 hour before or at least 2 hours after food.
Tablets should be swallowed whole, not chewed or crushed.
In combination treatment, administer nivolumab first during the day, then cabozantinib on an empty stomach, preferably in the evening.
Avoid grapefruit, starfruit, Seville oranges, their juices or products during treatment.
If a dose is missed, it should not be taken within 12 hours of the next dose.

Cabozantinib should be stored between 15^oC to 25^oC.

G - Special Precautions

Contraindications:

Patients who have a hypersensitivity to this drug or to any components of the formulation.

Other Warnings/Precautions:

Patients with a history of severe bleeding should be evaluated carefully before starting treatment. Do not give cabozantinib to patients with or at risk for severe hemorrhage or a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.
Patients were excluded from clinical studies if they had conditions such as cardiac impairment, untreated or incompletely treated varices with bleeding or high risk for bleeding (in HCC study)
Use cabozantinib with caution in patients at risk for, or who have a history of:
- Venous and/or arterial thromboembolism
- Hypertension
- Inflammatory bowel disease, tumour infiltration in the GI tract, or complications from prior GI surgery (particularly when associated with delayed or incomplete healing)
- Severe bleeding
- Low heart rate at baseline (< 60 beats per minute)
- Syncope/arrhythmia, QT prolongation, sick sinus syndrome, sinoatrial block, atrioventricular (AV) block, ischemic heart disease, or congestive heart failure
- Wound complications
Tablets contain lactose; carefully consider use in patients with hereditary galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption.
Use caution when driving or operating machinery as cabozantinib may cause fatigue, dizziness and weakness.

Other Drug Properties:

Carcinogenicity: Unknown

Pregnancy and Lactation:

Genotoxicity: No
Clastogenicity: No
Teratogenicity: Documented in animals
Embryotoxicity: Documented in animals
Pregnancy:
- Cabozantinib is not recommended for use in pregnancy. Adequate contraception should be used by patients and their partners during treatment, and for at least 4 months after the last dose.
- The effect of cabozantinib on oral contraceptives has not been studied; an additional contraceptive method (e.g. barrier) is recommended.
Excretion into breast milk: Unknown
Breastfeeding:
Breastfeeding is not recommended during treatment and for at least 4 months after the last dose.
Fertility effects: Probable

Documented in animals.

H - Interactions

Cabozantinib is a substrate of CYP3A4 and a moderate inhibitor of the multidrug efflux pump P-glycoprotein (P-gp).

In vitro, cabozantinib is a competitive inhibitor of CYP3A4 and a mixed inhibitor of CYP2D6.

No dose adjustment required for cabozantinib when it is used with gastric pH modifying agents (e.g. PPIs, H2 RAs, antacids).

The effect of cabozantinib on oral contraceptives has not been studied; an additional contraceptive method (e.g. barrier) is recommended.

AGENT	EFFECT	MECHANISM	MANAGEMENT
CYP3A4 inhibitors (i.e. ketoconazole, clarithromycin, ritonavir, fruit or juice from grapefruit, Seville oranges or starfruit)	↑ cabozantinib exposure (co-administration with ketoconazole increased AUC by 38%)	↓ metabolism and ↓ clearance of cabozantinib	Consider alternatives to strong inhibitors. If concurrent use with a strong inhibitor cannot be avoided, reduce cabozantinib dose by 20 mg. 2 to 3 days after discontinuation of the strong inhibitor, resume cabozantinib at previous dose.
CYP3A4 inducers (i.e. phenytoin, rifampin, dexamethasone, carbamazepine, phenobarbital, St. John’s Wort, etc)	↓ cabozantinib exposure (co-administration with rifampicin decreased AUC by 77%)	↑ metabolism and ↑ clearance of cabozantinib	Avoid chronic co-administration with strong inducers. If concurrent use cannot be avoided, increase cabozantinib dose by 20 mg as tolerated. 2 to 3 days after discontinuation of the strong inducers, resume cabozantinib at previous dose. Do not exceed a daily dose of 80 mg.
MRP2 Inhibitors (i.e. cyclosporine, reserpine, estradiol-17β-glucuronide, etc)	↑ cabozantinib concentration and/or toxicity in vitro	Cabozantinib is a substrate of MRP2	Caution; monitor therapy
P-glycoprotein substrates (i.e. verapamil, digoxin, morphine, ondansetron)	↑ substrate concentration and/or toxicity	Cabozantinib is a P-gp inhibitor	Caution; monitor therapy
Drugs that may prolong QT (i.e. amiodarone, procainamide, sotalol, venlafaxine, amitriptyline, sunitinib, methadone, chloroquine, clarithromycin, haloperidol, fluconazole, moxifloxacin, domperidone, ondansetron, etc)	↑ risk of life-threatening arrhythmias	Additive	Avoid co-administration to the extent possible.
Drugs that decrease heart rate and/or prolong PR Interval (i.e. antiarrhythmics, beta antagonists, non-dihydropyridine Ca channel blockers, digitalis glycosides, cholinesterase inhibitors, sphingosine-1 phosphate receptor modulators, HIV protease inhibitors, alpha2-adrenoceptor agonists, etc)	↑ risk of bradycardia and PR Interval	Additive	Avoid co-administration to the extent possible.
Drugs that disrupt electrolyte levels (i.e. loop/thiazide diuretics, laxatives, amphotericin B, high dose corticosteroids)	↑ risk of life-threatening arrhythmias		Caution; monitor therapy
Drugs with high protein binding (e.g. warfarin)	Possible ↑ effects of displaced drugs	Cabozantinib protein binding may displace other protein-bound drugs	Caution; monitor therapy (e.g. INR)
Bisphosphonates	↑ risk of ONJ	Additive	Caution

I - Recommended Clinical Monitoring

Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.

Refer to the hepatitis B virus screening and management guideline for monitoring during and after treatment.

Recommended Clinical Monitoring

Monitor Type	Monitor Frequency
ECG, heart rate and blood pressure	Baseline and as clinically indicated
Electrolytes, including calcium, potassium and magnesium	Baseline and as clinically indicated (more frequent monitoring may be required in patients at risk of serious arrhythmias or hypocalcemia)
Liver function tests	Baseline and as clinically indicated (more frequently when used in combination with nivolumab)
Renal function tests	Baseline and as clinically indicated
Thyroid function tests	Baseline and as clinically indicated
Clinical toxicity assessment for GI effects (including perforations, fistulas), bleeding, skin effects including hand-foot syndrome, respiratory and neurologic effects, thromboembolism, proteinuria, pancreatitis, osteonecrosis of the jaw and wound healing complications	At each visit

Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version

Suggested Clinical Monitoring

Monitor Type	Monitor Frequency
INR for patients receiving warfarin	Baseline and as clinically indicated

J - Supplementary Public Funding

Exceptional Access Program (EAP Website)

cabozantinib - For the treatment of advanced renal cell carcinoma (RCC), based on criteria
cabozantinib - For the treatment of unresectable, advanced hepatocellular carcinoma (HCC), based on criteria
cabozantinib - For the treatment of adult patients with locally advanced or metastatic differentiated thyroid carcinoma that has progressed following prior VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible
cabozantinib – For the first-line treatment of adult patients with advanced or metastatic renal cell carcinoma, in combination with nivolumab, based on criteria

K - References

Abou-Alfa GK, Meyer T, Cheng AL. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Engl J Med 2018;379:54-63.

Choueiri TK, Escudier B, Powles T, et al. Cabozantinib versus everolimus in advanced renal-cell carcinoma. N Engl J Med 2015;373:1814-23.

Choueiri TK, Escudier B, Powels T, et al. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomized, open-label, phase 3 trial. Lancet Oncol 2016;17(7):917-927.

Choueiri TK, Halabi S, Sanford BL, et al. Cabozantinib versus sunitinib as initial targeted therapy for patients with metastatic renal cell carcinoma of poor or intermediate risk: the Alliance A031203 CABOSUN trial. J Clin Oncol 2017 Feb 20;35(6):591-7.

Choueiri TK, Powles T, Burotto M, et al. Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med 2021 Mar 4;384(9):829-41.

EPAR - Product Information: Cabometyx™ (cabozantinib tablets). Ipsen Pharma, September 2023.

Prescribing Information: Cabometyx ® Exelixis, Inc. Alameda, CA 94502. September 2021.

Product Monograph: Cabometyx ™ (cabozantinib tablets). Ipsen Biopharmaceuticals Canada Inc., September 2024.

Product Monograph Update: Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKIs). Health Canada InfoWatch, June 2020.

December 2024 Updated Indications, Adverse effects, Dosing, Dosage with toxicity, and Monitoring sections

L - Disclaimer

Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.

Info Sheet Name:

cabozantinib (patient)

Info Sheet Introduction:

For treating certain types of kidney, liver or thyroid cancers

Info Sheet Date: Thursday, May 15, 2025 Info Sheet body:

cabozantinib (tablet)

Pronunciation:

ka boe ZAN ti nib

Other Name(s):

CABOMETYX®

Appearance:

tablet

This handout gives general information about this cancer medication.

You will learn:

who to contact for help
what the medication is
how it is given
what to expect while on medication

This handout was created by Ontario Health (Cancer Care Ontario) together with patients and their caregivers who have also gone through cancer treatment. It is meant to help support you through your cancer treatment and answer some of your questions.

This information does not replace the advice of your health care team. Always talk to your health care team about your treatment.

Who do I contact if I have questions or need help?

My cancer health care provider is: _____________________________________________

During the day I should contact: _______________________________________________

Evenings, weekends and holidays: _____________________________________________

This page gives general information about this cancer medication.

You will learn:

who to contact for help
what the medication is
how it is given
what to expect while on this medication

This information was created by Ontario Health (Cancer Care Ontario) together with patients and their caregivers who have also gone through cancer treatment. It is meant to help support you through your cancer treatment and answer some of your questions.

This information does not replace the advice of your health care team. Always talk to your health care team about your treatment.

What is this treatment for?

For treating certain types of kidney, liver or thyroid cancers

What should I do before I start this treatment?

Tell your health care team if you have or had significant medical condition(s), espeically if you have / had:
- high blood pressure
- heart problems (including irregular heartbeat)
- thyroid, liver or kidney problems
- diarrhea or inflammatory bowel disease (for example Crohn’s disease or ulcerative colitis, diverticulitis, or appendicitis)
- any bleeding problems, blood clots, or problems with wound healing
- any allergies
Tell your health care team if you have had any recent surgery or plan to have any surgery, including dental surgery.
Cabozantinib tablets contains a small amount of lactose. If you cannot have lactose, talk to your healthcare team.

Remember To:

Tell your health care team about all of the other medications you are taking.
Keep taking other medications that have been prescribed for you, unless you have been told not to by your health care team.

You will have a blood test to check for hepatitis B before starting treatment. See the Hepatitis B and Cancer Medications pamphlet for more information.

How is this treatment given?

This medication is usually taken once a day by mouth on an empty stomach, at least 1 hour before or at least 2 hours after food.
Do not crush or chew the tablets.
Do not eat or drink grapefruit, starfruit, Seville oranges or their juices (or products that contain these) while taking this drug. They may increase the amount of drug in your blood and increase side effects.
If you miss a dose and your next dose is in:
- less than 12 hours, take your next dose at its scheduled time. Do not make up the missed dose.
- 12 hours or more, take the missed dose as soon as you remember. Take your next dose at the normal time.
Do not take 2 doses at the same time or extra doses.
If you vomit (throw up) after taking your medication, talk to your health care team about what to do.
If you take too much of your medication by accident, or if you think a child or a pet may have swallowed your medication, you must call the Ontario Poison Control Center right away at: 1-800-268-9017.

Other medications you may be given with this treatment

To Prevent or Treat Nausea and Vomiting

You may be given medications to prevent or stop nausea (feeling like throwing up) and vomiting (throwing up) before they start. These are called anti-nausea medications.

Medications to prevent nausea and vomiting before they start include ondansetron (Zofran®), granisetron (Kytril®), aprepitant (Emend®), or others.

If you already have nausea and/or vomiting, some anti-nausea medications can stop them from getting worse. You may be given these medications to have at home in case you start to feel nausea or if you vomit.

Medications to stop nausea and vomiting include prochlorperazine (Stemetil®), metoclopramide (Maxeran®), or others.

To Treat Diarrhea

Diarrhea is when you have loose bowel movements (watery poo) or you need to go poo (have bowel movements) more often than usual. Diarrhea may start a few days after your treatment.

You may be given a medication called loperamide (Imodium®) to help treat your diarrhea. Take this medication only if you need it. Keep your loperamide with you all the time. When diarrhea starts, take the loperamide right away.

If you start to have diarrhea:

Take 2 tablets (4mg) of loperamide right away.
Take 1 tablet (2mg) after each episode of diarrhea up to a maximum of 8 tablets (16 mg) per day.

DO this while on treatment

DO check with your health care team before getting any vaccinations, surgery, dental work or other medical procedures. Your health care team may ask you to stop cabozantinib treatment for 28 days or more before any scheduled surgery. While taking cabozantinib, wounds may take longer to heal than normal or may not fully heal.

DO NOT do this while on treatment

Stop Icon

DO NOT smoke or drink alcohol while on treatment without talking to your health care team first. Smoking and drinking can make side effects worse and make your treatment not work as well.
DO NOT eat or drink grapefruit, starfruit, Seville oranges or their juices (or products that contain these) while taking this drug. They may increase the amount of drug in your blood and increase side effects.
DO NOT start any complementary or alternative therapies, such as acupuncture or homeopathic medications, without checking with your health care team.
DO NOT take any other medications, such as vitamins, over-the-counter (non-prescription) drugs, or natural health products without checking with your health care team.
DO NOT drive, operate machinery or do any tasks that need you to be alert if you feel drowsy or dizzy.

DO this while on treatment

Check Mark Icon

DO check with your health care team before getting any vaccinations, surgery, dental work or other medical procedures. Your health care team may ask you to stop cabozantinib treatment for 28 days or more before any scheduled surgery. While taking cabozantinib, wounds may take longer to heal than normal or may not fully heal.

DO NOT do this while on treatment

Stop Icon

DO NOT smoke or drink alcohol while on treatment without talking to your health care team first. Smoking and drinking can make side effects worse and make your treatment not work as well.
DO NOT eat or drink grapefruit, starfruit, Seville oranges or their juices (or products that contain these) while taking this drug. They may increase the amount of drug in your blood and increase side effects.
DO NOT start any complementary or alternative therapies, such as acupuncture or homeopathic medications, without checking with your health care team.
DO NOT take any other medications, such as vitamins, over-the-counter (non-prescription) drugs, or natural health products without checking with your health care team.
DO NOT drive, operate machinery or do any tasks that need you to be alert if you feel drowsy or dizzy.

Will this treatment interact with other medications or natural health products?

Yes, this medication can interact with other medications, vitamins, foods and natural health products. Interactions can make this medication not work as well or cause severe side effects.

Tell your health care team about all of your:

prescription and over-the-counter (non-prescription) medications and all other drugs, such as cannabis/marijuana (medical or recreational)
natural health products such as vitamins, herbal teas, homeopathic medicines, and other supplements

Check with your health care team before starting or stopping any of them.

Talk to your health care team BEFORE taking or using these :

Anti-inflammatory medications such as ibuprofen (Advil^® or Motrin^®), naproxen (Aleve^®) or Aspirin^®.
Over-the-counter products such as dimenhydrinate (Gravol^®)
Natural health products such as St. John’s Wort
Supplements such as vitamin C
Grapefruit juice
Alcoholic drinks
Tobacco
All other drugs, such as marijuana or cannabis (medical or recreational)

What to do if you feel unwell, have pain, a headache or a fever

Always check your temperature to see if you have a fever before taking any medications for fever or pain (such as acetaminophen (Tylenol^®) or ibuprofen (Advil^®)).
- Fever can be a sign of infection that may need treatment right away.
- If you take these medications before you check for fever, they may lower your temperature and you may not know you have an infection.

How to check for fever:

Keep a digital (electronic) thermometer at home and take your temperature if you feel hot or unwell (for example, chills, headache, mild pain).

You have a fever if your temperature taken in your mouth (oral temperature) is:
- 38.3°C (100.9°F) or higher at any time
OR
- 38.0°C (100.4°F) or higher for at least one hour.

If you do have a fever:

Try to contact your health care team. If you are not able to talk to them for advice, you MUST get emergency medical help right away.
Ask your health care team for the Fever pamphlet for more information.

If you do not have a fever but have mild symptoms such as headache or mild pain:

Ask your health care team about the right medication for you. Acetaminophen (Tylenol^®) is a safe choice for most people.

Talk to your health care team before you start taking ibuprofen (Advil^®, Motrin^®), naproxen (Aleve^®) or ASA (Aspirin^®), as they may increase your chance of bleeding or interact with your cancer treatment.

Talk to your health care team if you already take low dose aspirin for a medical condition (such as a heart problem). It may still be safe to take.

How will this treatment affect sex, pregnancy and breastfeeding?

Talk to your health care team about:

How this medication may affect your sexual health.
How this medication may affect your ability to have a baby, if this applies to you.

This medication may harm an unborn baby. Tell your health care team if you or your partner are pregnant, become pregnant during treatment, or are breastfeeding.

If there is any chance of pregnancy happening, you and your partner together must use 2 effective forms of birth control at the same time until at least 4 months after your last dose. Talk to your health care team about which birth control options are best for you.
Do not breastfeed while on this medication and until at least 4 months after your last treatment dose.

How to safely store and handle this medication

Keep this medication in the original packaging at room temperature in a dry place, away from heat and light. Keep out of sight and reach of children and pets.

Do not throw out any unused medications at home. Bring them to your pharmacy to be thrown away safely.

How to safely touch oral anti-cancer medication

If you are a patient:

Wash your hands before and after touching your oral anti-cancer medication.
Swallow each pill whole. Do not crush or chew your pills.

If you are a caregiver:

Wear nitrile or latex gloves when touching tablets, capsules or liquids.
Wash your hands before putting on your gloves and after taking them off, even if your skin did not touch the oral anti-cancer medication.
Throw out your gloves after each use. Do not re-use gloves.
Do not touch oral anti-cancer medications if you are pregnant or breastfeeding.

What to do if anti-cancer medication gets on your skin or in your eyes

If medication gets on your skin:

Wash your skin with a lot of soap and water.
If your skin gets red or irritated, talk to your health care team.

If medication gets in your eyes:

Rinse your eyes with running water right away. Keep water flowing over your open eyes for at least 15 minutes.

What are the side effects of this treatment?

The following table lists side effects that you may have when getting cabozantinib. The table is set up to list the most common side effects first and the least common last. It is unlikely that you will have all of the side effects listed and you may have some that are not listed.

Read over the side effect table so that you know what to look for and when to get help. Keep this paper during your treatment so that you can refer to it if you need to.

Very Common Side Effects (50 or more out of 100 people)
Side effects and what to do	When to contact health care team
Diarrhea (May be severe) What to look for? Loose, watery, unformed stool (poo) that may happen days to weeks after you get your treatment. What to do? If you have diarrhea: Take anti-diarrhea medication if your health care team prescribed it or told you to take it. Do not eat foods or drinks with artificial sweetener (like chewing gum or ‘diet’ drinks), coffee and alcohol, until your diarrhea has stopped. Eat many small meals and snacks instead of 2 or 3 large meals. Drink at least 6 to 8 cups of liquids each day, unless your health care team has told you to drink more or less. Talk to your health care team if you can’t drink 6 to 8 cups of liquids each day when you have diarrhea. You may need to drink special liquids with salt and sugar, called Oral Rehydration Therapy. Talk to your health care team if your diarrhea does not improve after 24 hours of taking diarrhea medication or if you have diarrhea more than 7 times in one day. Ask your health care team for the Diarrhea pamphlet for more information.	Talk to your health care team if no improvement after 24 hours of taking diarrhea medication or if severe (more than 7 times in one day).
Fatigue What to look for? Feeling of tiredness or low energy that lasts a long time and does not go away with rest or sleep. What to do? Be active. Aim to get 30 minutes of moderate exercise (you are able to talk comfortably while exercising) on most days. Check with your health care team before starting any new exercise. Pace yourself, do not rush. Put off less important activities. Rest when you need to. Ask family or friends to help you with things like housework, shopping, and child or pet care. Eat well and drink at least 6 to 8 glasses of water or other liquids every day (unless your health care team has told you to drink more or less). Avoid driving or using machinery if you are feeling tired. Ask your health care team for the Fatigue pamphlet for more information.	Talk to your health care team if it does not improve or if it is severe.
Nausea and vomiting (Generally mild) What to look for? Nausea is feeling like you need to throw up. You may also feel light-headed. You may feel nausea within hours to days after your treatment. What to do? To help prevent nausea: It is easier to prevent nausea than to treat it once it happens. If you were given anti-nausea medication(s), take them as prescribed, even if you do not feel like throwing up. Drink clear liquids and have small meals. Get fresh air and rest. Do not eat spicy, fried foods or foods with a strong smell. Limit caffeine (like coffee, tea) and avoid alcohol. If you have nausea or vomiting: Take your rescue (as-needed) anti-nausea medication(s) as prescribed. Ask your health care team for the Nausea & Vomiting pamphlet for more information. Talk to your health care team if: nausea lasts more than 48 hours vomiting lasts more than 24 hours or if it is severe	Talk to your healthcare team if nausea lasts more than 48 hours or vomiting lasts more than 24 hours or if it is severe.

Common Side Effects (25 to 49 out of 100 people)
Side effects and what to do	When to contact health care team
Low appetite, weight loss What to look for? Loss of interest in food or not feeling hungry. Weight loss. What to do? Try to eat your favourite foods. Eat small meals throughout the day. You may need to take meal supplements to help keep your weight up. Talk to your health care team if you have no appetite. Ask your health care team for the Loss of Appetite pamphlet for more information.	Talk to your health care team if it does not improve or if it is severe.
Rash on your hands and feet (hand-foot syndrome) What to look for? Tingling or swelling of the skin on the palms of your hands and the bottoms of your feet. This can become painful, red and numb. In worse cases your skin may start to peel and you can get blisters or sores. This may happen days or weeks after you start treatment. Less commonly, you may have a rash, or dry skin that is not related to hand-foot syndrome: You may have cracked, rough, flaking or peeling areas of the skin. Your skin may look red and feel warm, like a sunburn. Your skin may have bumps, itch, burn, sting or feel very tender when touched. What to do? To help prevent Hand-foot syndrome: Do not do activities that cause rubbing or pressure on your skin, like heavy-duty washing, gripping tools, typing, playing musical instruments, and driving. Moisturize your hands and feet often, especially in the skin folds. Wear loose, comfortable footwear and clothes. Rest and try to keep off your feet. Do not let your hands and feet get too hot. Ask your health care team for the Hand-foot syndrome pamphlet for more information. To prevent and treat dry skin: Use fragrance-free skin moisturizer. Protect your skin from the sun and the cold. Use sunscreen with UVA and UVB protection and a SPF of at least 30. Avoid perfumed products and lotions that contain alcohol. Drink 6 to 8 cups of non-alcoholic, non-caffeinated liquids each day, unless your health care team has told you to drink more or less.	Talk to your health care team if it does not improve or if it is severe.
High blood pressure (May be severe) What to look for? There are usually no signs of high blood pressure. Rarely, you may have headaches, shortness of breath or nosebleeds. What to do? Check your blood pressure regularly. Your doctor may prescribe medication to treat high blood pressure. If you have a severe headache get emergency help right away as it may be a sign your blood pressure is too high.	Talk to your health care team if it does not improve or if it is severe.
Liver problems (May be severe) Your health care team may check your liver function with a blood test. Liver changes do not usually cause any symptoms. What to look for? Rarely, you may develop yellowish skin or eyes, unusually dark pee or pain on the right side of your belly. This may be severe. What to do? If you have any symptoms of liver problems, get emergency medical help right away.	Get emergency medical help right away.
Constipation What to look for? Having bowel movements (going poo) less often than normal. Small hard stools (poo) that look like pellets. The need to push hard and strain to have any stool (poo) come out. Stomach ache or cramps. A bloated belly, feeling of fullness, or discomfort. Leaking of watery stools (poo). Lots of gas or burping. Nausea or vomiting. What to do? To help prevent constipation: Try to eat more fiber rich foods like fruits with skin, leafy greens and whole grains. Drink at least 6 to 8 cups of liquids each day unless your health care team has told you to drink more or less. Be Active. Exercise can help to keep you regular. If you take opioid pain medication, ask your health care team if eating more fibre is right for you. To help treat constipation: If you have not had a bowel movement in 2 to 3 days you may need to take a laxative (medication to help you poo) to help you have regular bowel movements. Ask your health care team what to do. Ask your health care team for the Constipation Pamphlet for more information.	Talk to your health care team if it does not improve or if it is severe.

Less Common Side Effects (10 to 24 out of 100 people)
Side effects and what to do	When to contact health care team
Taste changes What to look for? Food and drinks may taste different than usual. What to do? Eat foods that are easy to chew, such as scrambled eggs, pasta, soups, cooked vegetables. Taste foods at different temperatures, since the flavour may change. Try different forms of foods, like fresh, frozen or canned. Experiment with non-spicy foods, spices and seasonings.	Talk to your health care team if it does not improve or if it is severe.
Too much or too little salt in your body What to look for? Muscle spasms, cramping, weakness, twitching, or convulsions. Irregular heartbeat, confusion or blood pressure changes. What to do? Get emergency medical help right away for severe symptoms.	Get emergency medical help right away for severe symptoms.
Mouth sores What to look for? Round, painful, white or gray sores inside your mouth that can occur on the tongue, lips, gums, or inside your cheeks. In more severe cases they may make it hard to swallow, eat or brush your teeth. They may last for 3 days or longer. What to do? To help prevent mouth sores: Take care of your mouth by gently brushing and flossing regularly. Rinse your mouth often with a homemade mouthwash. To make a homemade mouthwash, mix 1 teaspoonful of baking soda and 1 teaspoonful of salt in 4 cups (1L) of water. Do not use store-bought mouthwashes, especially those with alcohol, because they may irritate your mouth. If you have mouth sores: Avoid hot, spicy, acidic, hard or crunchy foods. Your doctor may prescribe a special mouthwash to relieve mouth sores and prevent infection. Talk to your health care team as soon as you notice mouth or lip sores or if it hurts to eat, drink or swallow. Ask your health care team for the Oral Care (Mouth Care) pamphlet for more information.	Talk to your health care team as soon as you notice mouth or lip sores or if it hurts to eat, drink or swallow.
Changes in thyroid activity Thyroid changes may happen weeks to months after you receive your treatment. Your health care team may check your thyroid activity regularly with a blood test. What to look for? Unusual weight gain A lack of energy or feeling tired Getting cold easily Dry skin, nails or hair that breaks easily Constipation (having bowel movements (poo) less often than normal) What to do? Your health care team may give you prescription medication to treat underactive thyroid. If you have weight changes along with any of the other symptoms listed, talk to your health care team as soon as possible.	Contact your health care team as soon as possible (office hours).
Speech problems (hoarseness) What to look for? Your voice may become hoarse or raspy. What to do? Talk to your health care team if it does not improve or if it is severe.	Talk to your health care team if it does not improve or if it is severe.
Cough and feeling short of breath What to look for? You may have a cough and feel short of breath. Symptoms that commonly occur with a cough are: wheezing or a whistling breathing runny nose sore throat heartburn weight loss fever and chills Rarely this may be severe with chest pain, trouble breathing or coughing up blood. What to do? Check your temperature to see if you have a fever. Read the above section "What should I do if I feel unwell, have pain, a headache or a fever?". If you have a fever, try to talk to your health care team. If you are not able to talk to them for advice, you MUST get emergency medical help right away. If you have a severe cough with chest pain, trouble breathing or you are coughing up blood, get medical help right away.	Talk to your health care team. If you are not able to talk to your health care team for advice, and you have a fever or severe symptoms, you MUST get emergency medical help right away.
Anemia (low red blood cells) What to look for? You may feel more tired or weaker than normal. Pale skin and cold hands and feet. You may feel short of breath, dizzy or lightheaded. This may occur in days to weeks after your treatment starts. What to do? If your health care team has told you that you have anemia (low red blood cells): Rest often and eat well. Light exercise, such as walking may help. You may need medication or a blood transfusion. If it is very bad, your doctor may need to make changes to your treatment regimen.	Talk to your health care team if it does not improve or if it is severe.
Headache; mild joint, muscle pain or cramps What to look for? Mild headache New pain in your muscles or joints, muscle cramps, or feeling achy. What to do? Take pain medication (acetaminophen or opioids such as codeine, morphine, hydromorphone, oxycodone) as prescribed. Read the above section: "What should I do if I feel unwell, have pain, a headache or a fever?" before taking acetaminophen (Tylenol®), ibuprofen (Advil®, Motrin®), naproxen (Aleve®) or Aspirin. These medications may hide an infection that needs treatment or they may increase your risk of bleeding. Rest often and try light exercise (such as walking) as it may help. Ask your health care team for the Pain pamphlet for more information.	Talk to your health care team if it does not improve or if it is severe.
Heartburn; stomach upset; bloating What to look for? Pain or burning in the middle or top part of your chest. It may get worse when you are lying down or bending over or when you swallow. A bitter or acidic taste in your mouth. What to do? Drink clear liquids and eat small meals. Do not eat acidic, fatty or spicy foods. Limit caffeine (like coffee, tea) and avoid alcohol. Avoid smoking or being around tobacco. Sit up or stand after eating. Do not lie down. Raise the head of your bed six to eight inches. You may need to use extra pillows to do this.	Talk to your health care team if it does not improve or if it is severe.
Proteins in Urine (pee) Your health care team may do urine tests to check for proteins in your pee. What to look for? Swelling in your face, legs, or belly. Recent weight gain that is not normal for you. Foamy, frothy, or bubbly-looking pee. What to do? Talk to your health care team if it does not improve or if it is severe.	Talk to your health care team if it does not improve or if it is severe.
Dizziness What to look for? You may feel light-headed and like you might faint (pass out). What to do? Lay down right away so you do not fall. Slowly get up and start moving once you feel better. Do not drive a motor vehicle or use machinery if you feel dizzy.	Talk to your health care team if it does not improve or if it is severe.
Bleeding; Low platelets in the blood When platelets are low, you are at risk for bleeding and bruising. Ask your health care team for the Low Platelet Count pamphlet for more information. What to look for? Watch for signs of bleeding: bleeding from your gums unusual or heavy nosebleeds bruising easily or more than normal black coloured stools (poo) or blood in your stools (poo) coughing up red or brown coloured mucus dizziness, constant headache or changes in your vision heavy vaginal bleeding red or pink coloured urine (pee) What to do? If your health care team has told you that you have low platelets: Tell your pharmacist that your platelet count may be low before taking any prescriptions or over-the-counter medication. Check with your healthcare team before you go to the dentist. Take care of your mouth and use a soft toothbrush. Try to prevent cuts and bruises. Ask your health care team what activities are safe for you. Your treatment may have to be delayed if you have low platelets. Your health care team may recommend blood transfusion. If you have signs of bleeding: If you have a small bleed, clean the area with soap and water or a saline (saltwater) rinse. Apply pressure for at least 10 minutes. If you have bleeding that does not stop or is severe (very heavy), you must get emergency medical help right away.	Talk to your health care team if you have any signs of bleeding. If you have bleeding that doesn’t stop or is severe, you MUST get emergency medical help right away.

Other rare, but serious side effects are possible with this treatment.

If you have any of the following, talk to your cancer health care team or get emergency medical help right away:

pain, swelling and hardening of the vein in an arm or leg
weakness on one side of your body
sudden severe pain in your chest or upper back, that moves up your neck or down your back, when you didn’t hurt yourself
irregular heartbeat
wounds that do not heal well
severe belly pain
unexpected changes in your bowel movements (poo) or digestion, trouble swallowing
unusual pulsating or throbbing feeling in your chest or belly
yellowing of your skin or eyes
teeth, mouth or jaw pain and swelling, poor healing of mouth sores, unusual discharge from gums, loosening of teeth and the feeling of numbness or heaviness in the jaw
fainting (passing out), severe headache, seizures, confusion, mood or personality changes, changes in your vision.

For more information on how to manage your symptoms ask your health care provider, or visit: https://www.cancercareontario.ca/symptoms.

Notes

December 2024 Updated drug information sheet

The information set out in the medication information sheets, regimen information sheets, and symptom management information (for patients) contained in the Drug Formulary (the "Formulary") is intended to be used by health professionals and patients for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or side effects of a certain drug, nor should it be used to indicate that use of a particular drug is safe, appropriate or effective for a given condition.

A patient should always consult a healthcare provider if he/she has any questions regarding the information set out in the Formulary. The information in the Formulary is not intended to act as or replace medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.

Info Sheet (English):

cabozantinib patient.pdf Info Sheet (French):

cabozantinib pour le patient.pdf Monograph:

cabozantinib.pdf Funding Program: Exceptional Access Program Funding Instance:

cabozantinib - For the treatment of advanced renal cell carcinoma (RCC), based on criteria
cabozantinib - For the treatment of unresectable, advanced hepatocellular carcinoma (HCC), based on criteria
cabozantinib - For the treatment of adult patients with locally advanced or metastatic differentiated thyroid carcinoma that has progressed following prior VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible
cabozantinib – For the first-line treatment of adult patients with advanced or metastatic renal cell carcinoma, in combination with nivolumab, based on criteria

Phonetic Spelling:

ka boe ZAN ti nib

Cancer Type: Endocrine Thyroid Gastrointestinal Hepatobiliary / Liver / Bile Duct Genitourinary Renal cell / Kidney Type of Content: Drug Monograph Status: Null Info Sheet Status: Null Global Date: Wednesday, December 4, 2024 Universal Date: 2025-05-15 00:00:00 AddThis: Title URL: cabozantinibtablet Drug Display Status: Active Revision Summary:
Patient Info Sheet FR: Updated/Revised information sheet (Fiche d’information mise à jour/révisée)