Prospect: information for the patient

CABOMETYX 20mg film-coated tablets

CABOMETYX 40mg film-coated tablets

CABOMETYX 60mg film-coated tablets

cabozantinib

Read this prospect carefully before starting to take this medicine, as it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed only for you, and you must not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, even if they are not listed in this prospect. See section 4.

What is CABOMETYX

CABOMETYX is a cancer medication that contains the active ingredient cabozantinib. It is used in adults to treat:

• advanced kidney cancer known as advanced renal cell carcinoma
• liver cancer when a specific anticancer medication (sorafenib) can no longer stop the progression of the disease.

CABOMETYX is also used to treat locally advanced or metastatic differentiated thyroid cancer, a type of cancer in the thyroid gland, in adults when treatments with radioactive iodine and anticancer medications can no longer stop the progression of the disease.

CABOMETYX can be administered in combination with nivolumab for advanced kidney cancer. It is essential to also read the prospectus for nivolumab. If you have any questions about these medications, consult with your doctor.

How does CABOMETYX work?

CABOMETYX blocks the action of proteins called tyrosine kinase receptors (RTK), which are involved in cell growth and the development of new blood vessels that supply blood to these cells. These proteins may be present in high quantities in cancer cells, and by blocking their action, this medication can slow the rate at which the tumor grows and help interrupt the blood supply that cancer needs.

Do not take CABOMETYX

• if you are allergic to cabozantinib or any of the other ingredients of this medication (listed in section 6).

Warnings and precautions

Consult your doctor or pharmacist before starting to take CABOMETYX:

• If you have high blood pressure.
• If you have or have had an aneurysm (enlargement and weakening of a blood vessel wall) or a tear in the wall of a blood vessel.
• If you have diarrhea.
• If you have had recent significant bleeding.
• If you have had surgery in the last month (or if you have any scheduled), including dental surgery.
• If you have inflammatory bowel disease (such as Crohn's disease, ulcerative colitis, diverticulitis, or appendicitis).
• If you have had recent blood clots in the leg, stroke, or heart attack.
• If you have thyroid problems. Inform your doctor if you feel more tired, feel colder than others, or if your voice becomes deeper while taking this medication.
• If you have liver or kidney disease.

Consult your doctor if you experience any of the above.

You may need treatment, or your doctor may decide to change the dose of CABOMETYX or stop treatment completely. See also section 4 “Possible side effects”.

You should also inform your dentist that you are taking this medication. It is essential for you to have good oral care during treatment.

Children and adolescents

CABOMETYX is not recommended for use in children and adolescents. The effects of this medication in individuals under 18 years old are unknown.

Other medications and CABOMETYX

Inform your doctor or pharmacist if you are taking, or have recently taken, any other medication, including those purchased without a prescription. This is because CABOMETYX may affect how other medications work. Similarly, some medications may affect how CABOMETYX works, which may require your doctor to change the dose you take. You should inform your doctor about any medication, but particularly if you are taking:

• Medications to treat fungal infections (such as itraconazole, ketoconazole, and posaconazole).
• Medications used to treat bacterial infections (antibiotics), such as erythromycin, clarithromycin, and rifampicin.
• Medications for allergies, such as fexofenadine.
• Medications to treat angina (chest pain due to inadequate blood supply to the heart), such as ranolazine.
• Medications used to treat epilepsy or seizures, such as phenytoin, carbamazepine, and phenobarbital.
• Herbal medications containing St. John's Wort (Hypericum perforatum), which is sometimes used to treat depression or related states such as anxiety.
• Anticoagulant medications such as warfarin and dabigatran etexilate.
• Medications to treat high blood pressure or other heart conditions, such as aliskiren, ambrisentan, dabigatran etexilate, digoxin, talinolol, and tolvaptan.
• Medications for diabetes, such as saxagliptin and sitagliptin.
• Medications to treat gout, such as colchicine.
• Medications used to treat HIV or AIDS, such as efavirenz, ritonavir, maraviroc, and emtricitabine.
• Medications used to prevent rejection after a transplant (ciclosporin) and treatment regimens with ciclosporin for rheumatoid arthritis and psoriasis.

CABOMETYX with food

Avoid taking products containing grapefruit juice while taking this medication, as they may increase the levels of this medication in the blood.

Pregnancy, breastfeeding, and fertility

Avoid pregnancy during treatment with CABOMETYX.If you or your partner may become pregnant, use suitable contraceptive methods during treatment and for at least four months after treatment ends. Discuss suitable contraceptive methods with your doctor while taking this medication (see also “Other medications and CABOMETYX”).

Consult your doctor if you or your partner become pregnant, or if you or your partner plan to become pregnant, during treatment with this medication.

Talk to your doctor BEFORE starting this medicationif you or your partner are planning or have already planned to have a child after treatment ends. There is a possibility that treatment with this medication may affect your fertility.

Women taking this medication should stop breastfeeding during treatment and for at least four months after treatment ends, as cabozantinib and/or its metabolites may be excreted in breast milk and be harmful to the infant.

If you take this medication while using oral contraceptives, oral contraceptives may be ineffective. You should also use a barrier method (e.g., condom or diaphragm) while taking this medication and for a minimum period of 4 months after treatment ends.

Driving and operating machinery

Be cautious when driving or operating machinery. Be aware that treatment with CABOMETYX may make you feel tired or weak and may affect your ability to drive and operate machinery.

CABOMETYX contains lactose

This medication contains lactose (a type of sugar).If your doctor has told you that you have an intolerance to certain sugars, consult with them before taking this medication.

CABOMETYX contains sodium

This medication contains less than 1 mmol (23 mg of sodium) per tablet; it is essentially “sodium-free”.

Follow exactly the administration instructions for this medication as indicated by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

Continue taking this medication until your doctor decides to stop treatment. If you experience severe side effects, your doctor may decide to change the dose or stop treatment earlier than planned. Your doctor will tell you if you need to adjust your dose.

You should take CABOMETYX once a day. The usual dose is 60 mg, however your doctor will decide what dose is appropriate for you.

When this medication is administered in combination with nivolumab for the treatment of advanced kidney cancer, the recommended dose of CABOMETYX is 40 mg per day.

Do nottake CABOMETYX with food.

Do noteat any food for at least two hours before and during one hour after taking this medication.

Swallow the tablet with a full glass of water. Do not crush the tablets.

If you take more CABOMETYX than you should

If you have taken more of this medication than you were told to, speak with a doctor or go to the hospital immediately with the tablets and this leaflet.

If you forget to take CABOMETYX

• If there are 12 or more hours until the next dose, take the missed dose immediately. Take the next dose at the usual time.
• If there are less than 12 hours until the next dose, do not take the missed dose. Take the next dose at the usual time.

If you interrupt treatment with CABOMETYX

Interrupting treatment may interrupt the effect of your medication. Do not stop treatment with this medication unless you have spoken with your doctor.

When this medication is administered in combination with nivolumab, nivolumab will be administered first followed by CABOMETYX.

See the nivolumab leaflet to understand how this medication is used. If you have any other questions about the use of this medication, ask your doctor.

Like all medicines, this medicine can cause side effects, although not everyone will experience them. If you experience side effects, your doctor may tell you to take CABOMETYX at a lower dose. Your doctor may also prescribe other medicines to help control side effects.

Inform your doctor immediately if you notice any of the following side effects, as you may need urgent medical treatment:

• Symptoms such as abdominal pain, nausea (discomfort), vomiting, constipation, or fever. These symptoms may be a consequence of gastrointestinal perforation, a hole in the stomach or intestine that can be life-threatening. Gastrointestinal perforation is frequent (can affect up to 1 in 10 people).
• Severe or uncontrolled bleeding with symptoms such as: blood in vomit, black stools, blood in urine, headache, coughing up blood. It is frequent (can affect up to 1 in 10 people).
• Feeling drowsy, confused, or loss of consciousness. This may be due to liver problems that are frequent (can affect up to 1 in 10 people).
• Swelling, or difficulty breathing. They are very frequent (can affect more than 1 in 10 people).
• A wound that does not heal. It is rare (can affect 1 in 100 people).
• Seizures, headache, confusion, or difficulty concentrating. These may be signs of a condition called reversible posterior encephalopathy syndrome (RPES). RPES is rare (can affect 1 in 100 people).
• Pain in the mouth, teeth, and/or jaw, inflammation, or sores in the mouth, numbness, or a feeling of heaviness in the jaw, or noticing a loose tooth. These may be symptoms of jaw bone damage (osteonecrosis).It is rare (can affect 1 in 100 people).

Other side effects that can occur with CABOMETYX alone:

Frequent side effects(can affect up to 1 in 10 people)

• Anemia (low levels of red blood cells that transport oxygen), low levels of platelets (cells that help blood to clot)
• Reduced thyroid activity, symptoms may include: fatigue, weight gain, constipation, feeling cold, and dry skin
• Decreased appetite, weight loss, altered sense of taste
• Decreased levels of magnesium or potassium in the blood
• Decreased levels of albumin protein in the blood (which transports substances such as hormones, medicines, and enzymes throughout the body)
• Headache, dizziness
• High blood pressure (hypertension)
• Bleeding
• Difficulty speaking, hoarseness (dysphonia), cough, and difficulty breathing
• Gastrointestinal disorders, such as diarrhea, nausea, vomiting, constipation, indigestion, and abdominal pain
• Oral inflammation, hives, or pain in the mouth or throat (stomatitis)
• Skin rash, sometimes with blisters, itching, pain in the hands or feet, or intense skin itching
• Pain in the arms, hands, legs, or feet
• Feeling tired or weak, inflammation of the oral and gastrointestinal mucosa, inflammation of the arms and legs
• Weight loss
• Anomalies in liver function tests (increased levels of liver enzymes aspartate aminotransferase, alanine aminotransferase)
• Anomalies in kidney function tests (increased levels of creatinine in the blood)
• Increased levels of lipase and amylase enzymes
• Increased levels of cholesterol or triglycerides in the blood
• Pulmonary infection (pneumonia)

Frequent side effects(can affect up to 1 in 10 people)

• Abscess (accumulation of pus with swelling and inflammation)
• Low levels of white blood cells (important for fighting infection)
• Dehydration
• Decreased levels of phosphate, sodium, and calcium in the blood
• Increased levels of potassium in the blood
• Increased levels of bilirubin waste product in the blood (which can cause jaundice/yellowing of the eyes or skin)
• Increased or decreased levels of blood sugar
• Inflammation of the nerves (causing numbness, weakness, tingling, or burning in the arms and legs)
• Tinnitus (ringing in the ears)
• Clots in the veins
• Clots in the lungs
• Inflammation of the pancreas, painful or abnormal connection of body tissues (fistula), gastroesophageal reflux disease (acid reflux from the stomach), hemorrhoids (piles), dry mouth, and difficulty swallowing
• Intense skin itching, alopecia (hair loss and finer hair), dry skin, acne, change in hair color, thickening of the outer skin layer, skin redness
• Muscle spasms, joint pain,
• Protein in the urine (detected in tests)
• Abnormal liver function tests (increased levels of liver enzymes alkaline phosphatase and gamma-glutamyl transferase in the blood)
• Abnormal kidney function tests (increased levels of creatinine in the blood)
• Increased levels of lipase and amylase enzymes
• Increased levels of cholesterol or triglycerides in the blood
• Pulmonary infection (pneumonia)

Rare side effects(can affect up to 1 in 100 people)

• Seizures, strokeElevated blood pressure
• Clots in the arteries
• Decreased bile flow from the liver
• Sensation of pain or burning in the tongue (glossodynia)
• Heart attack
• Clot/embolus that traveled through your arteries and got stuck
• Pulmonary collapse with air leaking into the space between the lung and the chest wall, which often causes difficulty breathing (pneumothorax)

Unknown frequency (proportion of affected people unknown)

• Increased and weakened blood vessel wall or blood vessel wall tear (aneurysms and arterial dissections)
• Inflammation of blood vessels in the skin (cutaneous vasculitis)

The following side effects have been reportedwith CABOMETYX in combination with nivolumab:

Frequent side effects(can affect more than 1 in 10 people)

• Upper respiratory tract infections
• Reduced thyroid activity; symptoms may include fatigue, weight gain, constipation, feeling cold, and dry skin
• Increased thyroid activity; symptoms may include rapid heart rate, sweating, and weight loss
• Decreased appetite, altered sense of taste
• Headache, dizziness
• High blood pressure (hypertension)
• Difficulty speaking, hoarseness (dysphonia), cough, and difficulty breathing
• Gastrointestinal disorders, including diarrhea, nausea, vomiting, indigestion, abdominal pain, and constipation
• Oral inflammation, hives, or pain in the mouth or throat (stomatitis)
• Skin rash, sometimes with blisters, itching, pain in the hands or feet, or intense skin itching
• Joint pain (arthritis), muscle spasms, weakness, and painful muscles
• Protein in the urine (detected in tests)
• Feeling tired or weak, fever, and edema (swelling)
• Abnormal liver function tests (increased levels of liver enzymes aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase in the blood, elevated bilirubin waste product levels)
• Abnormal kidney function tests (increased levels of creatinine in the blood)
• Increased or decreased levels of blood sugar
• Anemia (low levels of red blood cells that transport oxygen), low levels of white blood cells (important for fighting infection), low levels of platelets (cells that help blood to clot)
• Increased levels of lipase and amylase enzymes
• Decreased levels of phosphate
• Increased or decreased levels of potassium
• Decreased or increased levels of calcium, magnesium, or sodium in the blood
• Weight loss

Frequent side effects(can affect up to 1 in 10 people)

• Severe pulmonary infection (pneumonia)
• Increased eosinophils (a type of white blood cell)
• Allergic reaction (including anaphylactic reaction)
• Decreased secretion of hormones produced by the adrenal glands (glands located above the kidneys)
• Dehydration
• Inflammation of the nerves (causing numbness, weakness, tingling, or burning in the arms and legs)
• Tinnitus (ringing in the ears)
• Dry eyes and blurred vision
• Changes in heart rhythm or frequency, rapid heart rate
• Clots in blood vessels
• Inflammation of the lungs (pneumonitis, characterized by cough and difficulty breathing), clots in the lung, fluid around the lungs
• Nasal bleeding
• Inflammation of the colon (colitis), dry mouth, pain in the mouth, inflammation of the stomach (gastritis), and hemorrhoids (piles)
• Inflammation of the liver (hepatitis)
• Dry skin and skin redness
• Alopecia (hair loss and finer hair), change in hair color
• Inflammation of the joints (arthritis)
• Renal insufficiency (including sudden loss of kidney function)

• Pain, chest pain
• Increased levels of triglycerides in the blood
• Increased levels of cholesterol in the blood

Rare side effects(can affect 1 in 100 people)

• Allergic reactions related to nivolumab infusion
• Inflammation of the pituitary gland located at the base of the brain (hypophysitis), inflammation of the thyroid gland (thyroiditis)
• A temporary inflammation of the nerves that causes pain, weakness, and paralysis in the limbs (Guillain-Barré syndrome); muscle weakness and fatigue without atrophy (myasthenic syndrome)
• Inflammation of the brain
• Inflammation of the eye (causing pain and redness)
• Inflammation of the heart muscle
• Clot/embolus that traveled through your arteries and got stuck
• Inflammation of the pancreas (pancreatitis), intestinal perforation, pain or burning sensation in the tongue (glossodynia)
• Skin disease with thickened, red skin areas, often with silver scales (psoriasis)
• Urticaria (hives)

• Muscle weakness not caused by exercise (myopathy), jaw bone damage, painful or abnormal connection of body tissues (fistula)

• Inflammation of the kidney
• Pulmonary collapse with air leaking into the space between the lung and the chest wall, which often causes difficulty breathing (pneumothorax)

Unknown frequency (proportion of affected people unknown)

• Inflammation of blood vessels in the skin (cutaneous vasculitis)
• Progressive destruction and loss of intrahepatic bile ducts and jaundice

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:https://www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the blister pack and the label of the bottle and box after CAD. The expiration date is the last day of the month indicated.

This medication does not require special storage conditions.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. By doing so, you will help protect the environment.

CABOMETYX Composition

The active ingredient is (S)-malate of cabozantinib.

CABOMETYX 20mg film-coated tablets: each tablet contains (S)-malate of cabozantinib, equivalent to 20mg of cabozantinib.

CABOMETYX 40mg film-coated tablets: each tablet contains (S)-malate of cabozantinib, equivalent to 40mg of cabozantinib.

CABOMETYX 60mg film-coated tablets: each tablet contains (S)-malate of cabozantinib, equivalent to 60mg of cabozantinib.

The other components are:

• Tablet core:microcrystalline cellulose, anhydrous lactose, hydroxypropyl cellulose, sodium croscarmellose, colloidal anhydrous silica, magnesium stearate. (see section 2 for lactose content)
• Film coating:hypromellose 2910, titanium dioxide (E171), triacetin, iron oxide yellow (E172)

Appearance of CABOMETYX and packaging

The CABOMETYX 20mg film-coated tablets are yellow, round, and have no score, with the inscription «XL» on one side and «20» on the other.

The CABOMETYX 40mg film-coated tablets are yellow, triangular, and have no score, with the inscription «XL» on one side and «40» on the other.

The CABOMETYX 60mg film-coated tablets are yellow, oval, and have no score, with the inscription «XL» on one side and «60» on the other.

CABOMETYX is available in packs containing a plastic bottle with 30film-coated tablets.

The bottle contains three desiccant gel containers and a polyester plug to prevent damage to the film-coated tablets.Keep these desiccant containers and the polyester plug in the bottle and do not swallow them.

Marketing Authorization Holder

Ipsen Pharma

65 quai Georges Gorse

92100 Boulogne-Billancourt

France

Responsible Person

Patheon France

40 Boulevard de Champaret

38300 Bourgoin Jallieu, France

Tjoapack Netherlands B.V.

Nieuwe Donk 9

4879 AC Etten-Leur

Netherlands

Rottendorf Pharma GmbH

Ostenfelderstrasse 51 – 61

D-59320 Ennigerloh

Germany

For more information about this medicine, please contact the local representative of the marketing authorization holder.

Last update of this leaflet: October 2023

Other sources of information

Further information on this medicine is available on the website of the European Medicines Agency:http://www.ema.europa.eu.