CABOMETYX: Uses, Dosage & Side Effects
A multi-targeted tyrosine kinase inhibitor used in the treatment of advanced kidney cancer, liver cancer, neuroendocrine tumors, and differentiated thyroid cancer
CABOMETYX (cabozantinib) is a prescription oral cancer medicine belonging to the tyrosine kinase inhibitor (TKI) class. It works by blocking multiple receptor tyrosine kinases (RTKs) involved in tumor growth, the formation of new blood vessels that feed tumors, and the spread of cancer to other parts of the body. CABOMETYX is approved for the treatment of advanced renal cell carcinoma (kidney cancer), hepatocellular carcinoma (liver cancer) after prior sorafenib therapy, advanced neuroendocrine tumors, and locally advanced or metastatic differentiated thyroid cancer. It may be used alone or in combination with nivolumab for kidney cancer. CABOMETYX is taken once daily on an empty stomach and is available as film-coated tablets in 20 mg, 40 mg, and 60 mg strengths.
Quick Facts: CABOMETYX
Key Takeaways
- CABOMETYX is a multi-targeted tyrosine kinase inhibitor that blocks tumor growth, blood vessel formation, and cancer spread by inhibiting MET, VEGFR, AXL, and other key signaling pathways.
- It is approved for advanced kidney cancer (alone or with nivolumab), liver cancer after prior sorafenib, neuroendocrine tumors, and differentiated thyroid cancer resistant to radioactive iodine.
- Must be taken on an empty stomach — no food for 2 hours before and 1 hour after the dose. Grapefruit products must be avoided throughout treatment.
- Common side effects include diarrhea, hand-foot syndrome, fatigue, high blood pressure, decreased appetite, and nausea. Many can be managed with dose adjustments.
- Effective contraception is required during treatment and for at least 4 months after the last dose for both women and men, as CABOMETYX may harm the developing fetus.
What Is CABOMETYX and What Is It Used For?
Quick Answer: CABOMETYX (cabozantinib) is an oral cancer medication that blocks the activity of several receptor tyrosine kinases involved in tumor growth and blood vessel formation. It is used to treat advanced kidney cancer, liver cancer, neuroendocrine tumors, and differentiated thyroid cancer in adults.
CABOMETYX contains the active substance cabozantinib (S)-malate. It belongs to a class of anti-cancer drugs known as tyrosine kinase inhibitors (TKIs). These medications work by interfering with specific proteins on the surface of cancer cells and blood vessel cells that drive cancer growth and the formation of new blood vessels that supply tumors with oxygen and nutrients.
Cabozantinib targets and inhibits multiple receptor tyrosine kinases (RTKs), including MET, VEGFR-1, VEGFR-2, and VEGFR-3, AXL, RET, ROS1, TYRO3, MER, KIT, TRKB, FLT3, and TIE-2. These proteins are often present in abnormally high amounts in cancer cells. By blocking their activity, CABOMETYX can slow down or stop the growth of tumors and help cut off the blood supply that cancer cells need to survive and spread.
Approved Indications
CABOMETYX is approved for use in adults for the following conditions:
- Advanced renal cell carcinoma (kidney cancer): CABOMETYX can be used as a first-line treatment in combination with nivolumab (a checkpoint inhibitor immunotherapy) for intermediate- and poor-risk patients, or as a single agent in patients who have received prior anti-angiogenic therapy.
- Hepatocellular carcinoma (liver cancer): For patients who have previously been treated with sorafenib and whose disease has progressed despite that therapy. CABOMETYX offers an important second-line option in this difficult-to-treat cancer.
- Advanced neuroendocrine tumors (NETs): For progressive, well-differentiated neuroendocrine tumors originating from the pancreas, gastrointestinal tract, lungs, or other organs, in patients who have failed prior treatment options.
- Differentiated thyroid cancer (DTC): For locally advanced or metastatic differentiated thyroid cancer in adults who are refractory to or no longer responding to radioactive iodine (RAI) therapy and who have progressed on or after prior systemic therapy.
How CABOMETYX Works
The mechanism of action of cabozantinib is centered on blocking the activity of receptor tyrosine kinases (RTKs). These are proteins on the surface of cells that, when activated, trigger signaling pathways that promote cell growth, division, and the formation of new blood vessels (angiogenesis). In cancer, these kinases are often overactive, driving uncontrolled tumor growth.
By simultaneously inhibiting multiple RTKs, cabozantinib attacks cancer through several pathways at once. It blocks VEGF receptors to reduce blood vessel growth that feeds the tumor, inhibits MET to interfere with cancer cell growth and metastasis, and targets AXL and other kinases involved in immune evasion and drug resistance. This multi-targeted approach is thought to contribute to CABOMETYX's efficacy across several different tumor types.
When used in combination with nivolumab for advanced kidney cancer, the two drugs complement each other: CABOMETYX targets the tumor's blood supply and growth pathways while nivolumab helps the immune system recognize and attack cancer cells. Clinical trials have demonstrated that this combination can significantly improve progression-free survival and overall survival compared to sunitinib alone in previously untreated advanced renal cell carcinoma (the CheckMate 9ER trial).
What Should You Know Before Taking CABOMETYX?
Quick Answer: Before starting CABOMETYX, your doctor needs to know about all your medical conditions, especially high blood pressure, bleeding problems, liver or kidney disease, recent surgery, inflammatory bowel disease, and whether you are pregnant or planning to become pregnant. Several serious conditions require careful monitoring during treatment.
Contraindications
You should not take CABOMETYX if you are allergic (hypersensitive) to cabozantinib or any of the other ingredients in this medicine. The inactive ingredients include microcrystalline cellulose, anhydrous lactose, hydroxypropyl cellulose, croscarmellose sodium, colloidal silicon dioxide (anhydrous), and magnesium stearate. The film coating contains hypromellose, titanium dioxide (E171), triacetin, and yellow iron oxide (E172). If you have a known allergy to any of these substances, tell your doctor before starting treatment.
Warnings and Precautions
Talk to your doctor or pharmacist before taking CABOMETYX if any of the following apply to you:
- High blood pressure (hypertension): CABOMETYX commonly causes elevated blood pressure. Your blood pressure should be well controlled before starting treatment and monitored regularly throughout. Your doctor may prescribe blood pressure medication if needed.
- Aneurysm or vessel wall dissection: If you have or have had an enlargement and weakening of a blood vessel wall (aneurysm) or a tear in a blood vessel wall, this must be discussed with your doctor before starting treatment.
- Diarrhea: Tell your doctor if you currently have diarrhea, as CABOMETYX very commonly causes or worsens this symptom.
- Recent major bleeding: If you have recently had a significant bleeding episode, treatment may need to be delayed.
- Recent surgery: If you have had surgery within the past month, or if any surgery (including dental procedures) is planned, inform your doctor. CABOMETYX can impair wound healing and may need to be stopped before and after surgical procedures.
- Inflammatory bowel disease: If you have Crohn's disease, ulcerative colitis, diverticulitis, or appendicitis, there is an increased risk of gastrointestinal perforation (a hole forming in the stomach or intestine), which can be life-threatening.
- Blood clots: If you have recently had a blood clot in the leg (deep vein thrombosis), stroke, or heart attack, additional monitoring may be required.
- Thyroid problems: Tell your doctor if you notice increased tiredness, feeling cold more than usual, or changes in your voice, as these may be signs of decreased thyroid function (hypothyroidism), which is a common side effect.
- Liver or kidney disease: If you have any pre-existing liver or kidney condition, your doctor may need to adjust your dose or monitor you more closely.
Seek immediate medical attention if you experience severe abdominal pain, bloody or black stools, blood in your vomit, coughing up blood, severe headache, confusion, or loss of consciousness. These may be signs of serious complications including gastrointestinal perforation, hemorrhage, or liver problems.
Children and Adolescents
CABOMETYX is not recommended for use in children and adolescents under 18 years of age. The safety and effectiveness of this medicine in this age group have not been established.
Pregnancy and Breastfeeding
Pregnancy: You should avoid becoming pregnant while being treated with CABOMETYX. Based on its mechanism of action and animal data, cabozantinib is expected to cause harm to a developing fetus. If you or your partner could become pregnant, you must use effective contraception during treatment and for at least 4 months after the last dose. Ask your doctor about which contraceptive methods are suitable, as oral hormonal contraceptives (birth control pills) may not be effective when taken with this medicine.
Breastfeeding: Women taking CABOMETYX must not breastfeed during treatment and for at least 4 months after the last dose. Cabozantinib and/or its metabolites may be excreted in breast milk and could harm the infant.
Fertility: Talk to your doctor before starting treatment if you or your partner are considering having children in the future. There is a risk that treatment with CABOMETYX may affect fertility in both men and women.
Driving and Operating Machinery
Use caution when driving or operating machinery during treatment. CABOMETYX may cause fatigue, weakness, and dizziness, which can impair your ability to drive or use machines safely. If you experience these symptoms, do not drive or operate machinery until you feel well enough to do so safely.
Lactose and Sodium Content
CABOMETYX tablets contain lactose (a type of sugar). If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine. The tablets also contain less than 1 mmol (23 mg) of sodium per tablet, meaning they are essentially sodium-free.
How Does CABOMETYX Interact with Other Drugs?
Quick Answer: CABOMETYX interacts with many other medications because it is metabolized by the CYP3A4 enzyme. Strong CYP3A4 inhibitors (such as ketoconazole) can increase cabozantinib levels, while strong CYP3A4 inducers (such as rifampicin, phenytoin, and St. John's Wort) can decrease its effectiveness. Grapefruit products must be avoided.
Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or might take, including over-the-counter medicines and herbal products. This is important because CABOMETYX can affect how some other medicines work, and some medicines can affect how CABOMETYX works. Your doctor may need to adjust your dose.
Major Interactions
The following drug categories have clinically significant interactions with CABOMETYX and may require dose adjustments or alternative therapies:
| Drug Category | Examples | Effect | Clinical Action |
|---|---|---|---|
| Strong CYP3A4 Inhibitors | Itraconazole, ketoconazole, posaconazole, ritonavir | Increase cabozantinib blood levels | Dose reduction may be needed |
| Strong CYP3A4 Inducers | Rifampicin, phenytoin, carbamazepine, phenobarbital | Decrease cabozantinib blood levels | Dose increase may be needed |
| Herbal Products | St. John's Wort (Hypericum perforatum) | Significantly decreases cabozantinib levels | Avoid concomitant use |
| Anticoagulants | Warfarin, dabigatran etexilate | Altered anticoagulant effect; increased bleeding risk | Close monitoring of INR/coagulation |
Other Notable Interactions
In addition to the major interactions listed above, CABOMETYX may interact with several other medication classes. While these interactions are generally less severe, they still warrant discussion with your healthcare provider:
- Antibiotics: Erythromycin and clarithromycin (macrolide antibiotics) are moderate CYP3A4 inhibitors and may moderately increase cabozantinib levels.
- Antihistamines: Fexofenadine levels may be affected as cabozantinib is a substrate and modulator of drug transport proteins.
- Heart medications: Ranolazin, aliskiren, ambrisentan, digoxin, talinolol, and tolvaptan may have altered blood levels when taken with cabozantinib.
- Diabetes medications: Saxagliptin and sitagliptin levels may be affected by concurrent use.
- Gout medications: Colchicine levels may be increased, potentially leading to toxicity.
- HIV/AIDS medications: Efavirenz, ritonavir, maraviroc, and emtricitabine may interact with cabozantinib through CYP3A4 or transport protein pathways.
- Transplant rejection medications: Ciclosporin (cyclosporine) levels may be affected, requiring monitoring.
- Hormonal contraceptives: Oral birth control pills may become less effective. Use barrier methods (condoms or diaphragm) as additional contraception during treatment and for at least 4 months after.
Avoid eating or drinking products that contain grapefruit during treatment with CABOMETYX. Grapefruit inhibits the CYP3A4 enzyme responsible for metabolizing cabozantinib, which can increase the amount of the drug in your blood and raise the risk of side effects.
What Is the Correct Dosage of CABOMETYX?
Quick Answer: The standard dose of CABOMETYX is 60 mg once daily taken on an empty stomach. When given in combination with nivolumab for kidney cancer, the dose is 40 mg once daily. The tablet must be swallowed whole with a full glass of water. Do not eat for at least 2 hours before and 1 hour after taking the dose.
Always take CABOMETYX exactly as your doctor or pharmacist has told you. Do not change your dose or stop taking CABOMETYX without talking to your doctor first. If you experience serious side effects, your doctor may reduce your dose, temporarily interrupt treatment, or stop it permanently.
Adults
| Indication | Recommended Dose | Administration |
|---|---|---|
| Advanced kidney cancer (monotherapy) | 60 mg once daily | Oral, on empty stomach |
| Advanced kidney cancer (with nivolumab) | 40 mg once daily | Oral, on empty stomach |
| Hepatocellular carcinoma (liver cancer) | 60 mg once daily | Oral, on empty stomach |
| Neuroendocrine tumors | 60 mg once daily | Oral, on empty stomach |
| Differentiated thyroid cancer | 60 mg once daily | Oral, on empty stomach |
CABOMETYX must be taken on an empty stomach. Do not eat anything for at least 2 hours before taking the tablet and for 1 hour after taking it. Swallow the tablet whole with a full glass of water. Do not crush the tablets. Your doctor will determine the most appropriate dose for you and may adjust it depending on how you respond to treatment and any side effects you experience.
Dose Adjustments
Your doctor may reduce the dose from 60 mg to 40 mg or from 40 mg to 20 mg if you develop certain side effects. The available tablet strengths (20 mg, 40 mg, and 60 mg) allow for flexible dose adjustments without the need for multiple tablets. Dose reductions are a common and expected part of managing treatment with CABOMETYX and do not necessarily mean the drug is not working. The goal is to find the dose that provides the best balance between efficacy and tolerability for each individual patient.
Children
CABOMETYX is not recommended for children and adolescents under 18 years of age. There are no established dosing recommendations for this age group.
Elderly
No specific dose adjustment is required for elderly patients. However, older patients may be more susceptible to certain side effects, particularly dehydration and electrolyte imbalances. Close monitoring is advisable, and dose reductions should be implemented promptly if significant adverse effects occur.
Missed Dose
What to Do If You Miss a Dose
- If there are 12 hours or more until your next scheduled dose: Take the missed dose as soon as you remember, then take your next dose at the regular time.
- If there are fewer than 12 hours until your next dose: Skip the missed dose entirely. Take your next dose at the usual scheduled time.
- Never take a double dose to make up for a missed one.
Overdose
If you have taken more CABOMETYX than prescribed, contact your doctor immediately or go to the nearest hospital emergency department. Bring the medicine package and this information with you. There is no specific antidote for cabozantinib overdose. Treatment is supportive and symptomatic, focusing on managing any adverse effects that develop.
Stopping Treatment
Do not stop taking CABOMETYX unless your doctor tells you to. Stopping treatment prematurely could reduce the effectiveness of your cancer therapy. If you are concerned about side effects or have questions about your treatment, discuss them with your doctor before making any changes. When CABOMETYX is given in combination with nivolumab, you will receive nivolumab first (as an intravenous infusion), followed by oral CABOMETYX. Refer to the nivolumab patient information for details about that medicine.
What Are the Side Effects of CABOMETYX?
Quick Answer: Like all cancer medicines, CABOMETYX can cause side effects, though not everyone experiences them. The most common side effects include diarrhea, fatigue, nausea, decreased appetite, hand-foot syndrome (palmar-plantar erythrodysesthesia), high blood pressure, vomiting, weight loss, and constipation. Serious but less common side effects include gastrointestinal perforation, severe bleeding, and blood clots.
If you experience side effects, your doctor may reduce your dose or prescribe additional medications to help manage them. It is important to report any new or worsening symptoms to your healthcare team promptly.
- Gastrointestinal perforation: Severe abdominal pain, nausea, vomiting, constipation, or fever (occurs in up to 1 in 10 patients)
- Severe hemorrhage: Vomiting blood, black stools, blood in urine, coughing up blood, or severe headache (occurs in up to 1 in 10 patients)
- Liver problems: Drowsiness, confusion, or loss of consciousness (occurs in up to 1 in 10 patients)
- Swelling or shortness of breath (occurs in more than 1 in 10 patients)
- Non-healing wounds (occurs in up to 1 in 100 patients)
- PRES (posterior reversible encephalopathy syndrome): Seizures, headache, confusion, or difficulty concentrating (occurs in up to 1 in 100 patients)
- Osteonecrosis of the jaw: Mouth, tooth, or jaw pain, swelling, numbness, or loosening of teeth (occurs in up to 1 in 100 patients)
CABOMETYX Monotherapy Side Effects
Very Common
May affect more than 1 in 10 people
- Anemia (low red blood cells), low platelet count
- Hypothyroidism (underactive thyroid) — tiredness, weight gain, constipation, feeling cold, dry skin
- Decreased appetite, altered taste
- Low magnesium, potassium, or calcium in the blood
- Low blood albumin levels
- Headache, dizziness
- High blood pressure (hypertension)
- Bleeding
- Difficulty speaking, hoarseness, cough, shortness of breath
- Diarrhea, nausea, vomiting, constipation, indigestion, abdominal pain
- Stomatitis (redness, swelling, or pain in the mouth or throat)
- Rash (sometimes with blisters), itching, hand-foot syndrome (pain or redness in palms or soles), skin redness
- Pain in arms, hands, legs, or feet; joint pain
- Fatigue, weakness, mouth or GI tract inflammation, swelling of legs and arms
- Weight loss
- Abnormal liver function tests (elevated AST, ALT, alkaline phosphatase)
Common
May affect up to 1 in 10 people
- Abscess (collection of pus with swelling and inflammation)
- Dehydration
- Low phosphate and sodium in the blood; high potassium in the blood
- Elevated bilirubin (may cause jaundice — yellowing of skin or eyes)
- High or low blood sugar levels
- Peripheral neuropathy (numbness, weakness, tingling, or burning in hands and feet)
- Tinnitus (ringing in the ears)
- Blood clots in blood vessels, low blood pressure (hypotension)
- Pulmonary embolism (blood clots in the lungs), rhinitis (nasal inflammation)
- Pancreatitis, fistula (abnormal channel between body tissues), gastroesophageal reflux, hemorrhoids, dry mouth, difficulty swallowing, flatulence
- Severe skin itching, hair loss and thinning (alopecia), dry skin, acne, hair color changes, thickened skin
- Muscle spasms
- Protein in urine
- Elevated gamma-GT, creatinine, lipase, and amylase
- Elevated cholesterol or triglycerides
- Low white blood cell counts
- Pneumonia (lung infection)
Uncommon
May affect up to 1 in 100 people
- Seizures, stroke
- Severely elevated blood pressure (hypertensive crisis)
- Arterial blood clots (arterial thromboembolism)
- Decreased bile flow from the liver (cholestasis)
- Burning or painful sensation in the tongue (glossodynia)
- Heart attack (myocardial infarction)
- Arterial embolism
- Pneumothorax (collapsed lung with air trapped between lung and chest wall, often causing shortness of breath)
Not Known
Frequency cannot be estimated from available data
- Aneurysm and arterial dissection (enlargement, weakening, or tearing of blood vessel walls)
- Cutaneous vasculitis (inflammation of blood vessels in the skin)
Side Effects When Used with Nivolumab
When CABOMETYX is used in combination with nivolumab for advanced kidney cancer, additional side effects may occur due to the immune-modulating effects of nivolumab. The following side effects have been reported for the combination therapy:
Very Common (Combination Therapy)
May affect more than 1 in 10 people
- Upper respiratory tract infections
- Hypothyroidism or hyperthyroidism (underactive or overactive thyroid)
- Decreased appetite, altered taste
- Headache, dizziness
- High blood pressure, cough, shortness of breath, hoarseness
- Diarrhea, nausea, vomiting, abdominal pain, constipation, indigestion
- Stomatitis, rash, itching, hand-foot syndrome
- Joint pain, muscle spasms, muscle weakness and aching
- Protein in urine, fatigue, fever, edema (swelling)
- Abnormal liver and kidney function tests
- Anemia, low white blood cells, low platelets
- Elevated lipase and amylase; electrolyte abnormalities
- Weight loss
Common (Combination Therapy)
May affect up to 1 in 10 people
- Pneumonia (serious lung infection)
- Increased eosinophils (a type of white blood cell)
- Allergic reactions (including anaphylaxis)
- Adrenal insufficiency (decreased hormone production by adrenal glands)
- Dehydration
- Peripheral neuropathy, tinnitus
- Dry eyes, blurred vision
- Changes in heart rhythm, rapid heartbeat
- Blood clots, lung inflammation (pneumonitis), fluid around the lungs, nosebleed
- Colitis (inflammation of the colon), dry mouth, gastritis, hemorrhoids
- Hepatitis (liver inflammation)
- Dry skin, severe skin redness, hair loss, hair color changes
- Arthritis (joint inflammation)
- Kidney failure (including acute kidney injury)
- Elevated triglycerides and cholesterol
Uncommon (Combination Therapy)
May affect up to 1 in 100 people
- Infusion-related allergic reaction (to nivolumab)
- Hypophysitis (inflammation of the pituitary gland), thyroiditis (swelling of the thyroid)
- Guillain-Barré syndrome (temporary nerve inflammation causing pain, weakness, and paralysis), myasthenic syndrome
- Encephalitis (brain inflammation)
- Eye inflammation (uveitis)
- Myocarditis (heart muscle inflammation)
- Arterial embolism
- Pancreatitis, intestinal perforation, glossodynia (tongue pain)
- Psoriasis, urticaria (hives)
- Myopathy (muscle disease), osteonecrosis of the jaw, fistula
- Nephritis (kidney inflammation)
- Pneumothorax (collapsed lung)
Not Known (Combination Therapy)
Frequency cannot be estimated from available data
- Cutaneous vasculitis (inflammation of blood vessels in the skin)
- Progressive destruction and loss of intrahepatic bile ducts with jaundice
It is important to report suspected side effects after the medicine has been approved. This allows ongoing monitoring of the medicine's benefit-risk balance. You can report side effects to your national medicines regulatory authority (for example, the FDA in the United States or the EMA in Europe) or through your healthcare provider.
How Should You Store CABOMETYX?
Quick Answer: Store CABOMETYX at room temperature with no special storage requirements. Keep the tablets in the original container with the desiccants and keep out of reach of children. Do not use after the expiration date.
Keep this medicine out of the sight and reach of children. Do not use CABOMETYX after the expiration date stated on the bottle label and carton after “EXP.” The expiration date refers to the last day of the stated month.
There are no special storage conditions for CABOMETYX. Store the tablets in their original bottle. The bottle contains three desiccant canisters with silica gel and a polyester coil to prevent damage to the film-coated tablets. Keep the desiccant canisters and polyester coil in the bottle — do not swallow them.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. These measures will help protect the environment.
What Does CABOMETYX Contain?
Quick Answer: The active ingredient in CABOMETYX is cabozantinib (S)-malate. It is available as film-coated tablets in three strengths: 20 mg, 40 mg, and 60 mg. Each yellow tablet is marked with “XL” on one side and the strength number on the other.
Active Ingredient
Each tablet contains cabozantinib (S)-malate equivalent to 20 mg, 40 mg, or 60 mg of cabozantinib, depending on the tablet strength.
Inactive Ingredients
Tablet core: Microcrystalline cellulose, anhydrous lactose, hydroxypropyl cellulose, croscarmellose sodium, colloidal silicon dioxide (anhydrous), and magnesium stearate.
Film coating: Hypromellose, titanium dioxide (E171), triacetin, and yellow iron oxide (E172).
Appearance and Packaging
All CABOMETYX tablets are yellow and film-coated, marked with “XL” on one side and the strength number on the other:
- 20 mg tablets: Round, unscored, marked “XL” / “20”
- 40 mg tablets: Triangular, unscored, marked “XL” / “40”
- 60 mg tablets: Oval, unscored, marked “XL” / “60”
CABOMETYX is supplied in packs containing one plastic bottle with 30 film-coated tablets. The bottle contains three desiccant canisters with silica gel and a polyester coil to protect the tablets from damage during transport and storage.
Marketing Authorization Holder
Ipsen Pharma, 65 quai Georges Gorse, 92100 Boulogne-Billancourt, France. CABOMETYX is manufactured by Patheon France (Bourgoin-Jallieu, France) and Tjoapack Netherlands B.V. (Etten-Leur, Netherlands).
Frequently Asked Questions About CABOMETYX
CABOMETYX (cabozantinib) is used in adults to treat advanced renal cell carcinoma (kidney cancer) either alone or in combination with nivolumab, hepatocellular carcinoma (liver cancer) after prior sorafenib treatment, advanced neuroendocrine tumors (NETs) that have progressed on prior therapy, and locally advanced or metastatic differentiated thyroid cancer when radioactive iodine and other treatments are no longer effective.
Take CABOMETYX once daily on an empty stomach. You must not eat for at least 2 hours before taking the tablet and 1 hour after. Swallow the tablet whole with a full glass of water — do not crush it. The usual dose is 60 mg daily, or 40 mg daily when combined with nivolumab. Continue taking the medicine until your doctor tells you to stop.
No. Grapefruit and grapefruit juice must be avoided throughout treatment with CABOMETYX. Grapefruit inhibits the CYP3A4 enzyme that metabolizes cabozantinib, leading to higher drug levels in your blood and an increased risk of side effects. This applies to all grapefruit products, including fresh fruit, juice, and marmalade.
If you miss a dose and there are 12 hours or more until your next scheduled dose, take the missed dose as soon as you remember and then take your next dose at the usual time. If there are fewer than 12 hours until your next dose, skip the missed dose entirely and take the next one at the regular time. Never take a double dose to make up for a missed one.
CABOMETYX should not be used during pregnancy as it may harm the developing fetus. Both women and men of reproductive potential must use effective contraception during treatment and for at least 4 months after the final dose. Oral contraceptives may be less effective when taken with CABOMETYX, so barrier methods (condoms, diaphragm) should be used as well. Breastfeeding is also not recommended during treatment and for 4 months after.
CABOMETYX works by blocking the activity of several proteins called receptor tyrosine kinases (RTKs), including MET, VEGFR, and AXL. These proteins are involved in cancer cell growth, the formation of new blood vessels that feed tumors, and the spread of cancer to other parts of the body. By inhibiting these proteins simultaneously, CABOMETYX can slow down or stop tumor growth and cut off the blood supply cancer cells need to survive.
References
- European Medicines Agency (EMA). CABOMETYX — Summary of Product Characteristics. Last updated 2025. Available at: www.ema.europa.eu
- U.S. Food and Drug Administration (FDA). CABOMETYX (cabozantinib) Prescribing Information. Revised 2024. Available at: www.accessdata.fda.gov
- Choueiri TK, Powles T, Burotto M, et al. Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma (CheckMate 9ER). N Engl J Med. 2021;384(9):829-841. doi:10.1056/NEJMoa2026982
- Abou-Alfa GK, Meyer T, Cheng AL, et al. Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma (CELESTIAL). N Engl J Med. 2018;379(1):54-63. doi:10.1056/NEJMoa1717002
- National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology: Kidney Cancer. Version 4.2025. Available at: www.nccn.org
- Powles T, Albiges L, Bex A, et al. ESMO Clinical Practice Guideline update on the use of immunotherapy in early stage and advanced renal cell carcinoma. Ann Oncol. 2024;35(12):1025-1044.
- World Health Organization (WHO). WHO Model List of Essential Medicines — 23rd List (2023). Geneva: WHO; 2023.
- Brose MS, Robinson B, Sherman SI, et al. Cabozantinib for radioiodine-refractory differentiated thyroid cancer (COSMIC-311). Lancet Oncol. 2021;22(8):1126-1138. doi:10.1016/S1470-2045(21)00332-6
Editorial Team
Medical Content
Written by iMedic Medical Editorial Team — Specialists in Oncology and Clinical Pharmacology
Medical Review
Reviewed by iMedic Medical Review Board according to EMA, FDA, NCCN, and ESMO guidelines
Evidence Standard
Level 1A — Based on systematic reviews, randomized controlled trials, and international clinical practice guidelines
Independence
No commercial funding. No pharmaceutical company sponsorship. Independent medical editorial content.
Last reviewed: | Content version: 1.0 | Next scheduled review: July 2026