Cabometyx 20 mg Film-Coated Tablets

CABOMETYX is a cancer medicine that contains the active substance cabozantinib. CABOMETYX blocks the action of proteins called receptor tyrosine kinases (RTKs), which are involved in the growth of cells and the development of new blood vessels that supply them. These proteins can be present in high amounts in cancer cells, and by blocking their action CABOMETYX can slow down the rate at which the tumour grows and help to cut off the blood supply that the cancer needs.

CABOMETYX is in adults used to treat:

• advanced stages of a type of kidney cancer called renal cell carcinoma
• liver cancer in adults who have been previously treated with a specific anticancer medicine (sorafenib).

Do not take CABOMETYX:

• If you are hypersensitive (allergic) to cabozantinib or any of the other ingredients of CABOMETYX (listed in section 6).

Warnings and precautions

Talk to your doctor or pharmacist before taking CABOMETYX if you:

• have high blood pressure
• have or have had an aneurysm (enlargement and weakening of a blood vessel wall) or a tear in a blood vessel wall
• have diarrhoea
• have a recent history of significant bleeding
• have had surgery within the last month (or if surgical procedures are planned), including dental surgery
• have inflammatory bowel disease (for example, Crohn’s disease or ulcerative colitis, diverticulitis, or appendicitis)
• have a recent history of blood clot in the leg, stroke, or heart attack
• have thyroid problems. Your thyroid function should be checked before you take CABOMETYX and regularly while you are taking it. Tell your doctor if you get tired more easily, generally feel colder than other people, or your voice deepens whilst taking this medicine. If your thyroid gland is not producing enough thyroid hormone, you may be treated with thyroid hormone replacement
• have liver or kidney disease.

Tell your doctor if any of these affect you. You may need treatment for them, or your doctor may decide to change your dose of CABOMETYX or stop treatment altogether. See also section 4 “Possible side effects”. You should also tell your dentist that you are taking CABOMETYX. It is important for you to practice good mouth care during treatment with CABOMETYX.

Children and adolescents

CABOMETYX is not recommended for children or adolescents. The effects of CABOMETYX in people younger than 18 years old are not known.

Other medicines and CABOMETYX

Always tell your health care provider if you are taking any other medicine. (This includes all complementary or traditional medicines.) Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription. This is because CABOMETYX can affect the way some other medicines work. Also, some medicines can affect the way CABOMETYX works. This could mean that your doctor needs to change the dose(s) that you take. You should tell your doctor about every medicine, but in particular if taking:

• Medicines that treat fungal infections, such as itraconazole, ketoconazole, and posaconazole.
• Medicines used to treat bacterial infections (antibiotics) such as erythromycin, clarithromycin, and rifampicin.
• Allergy medicines such as fexofenadine.
• Medicines to treat angina pectoris (chest pain owing to inadequate supply to the heart) such as ranolazine.
• Medicines used to treat epilepsy or fits such as phenytoin, carbamazepine, and phenobarbital.
• Herbal preparations containing St. John’s Wort (Hypericum perforatum), sometimes used for treating depression or depression-related conditions such as anxiety.
• Medicines used to thin the blood, such as warfarin and dabigatran etexilate.
• Medicines to treat high blood pressure or other heart conditions, such as aliskiren, ambrisentan, digoxin, talinolol, and tolvaptan.
• Medicines for diabetes, such as saxagliptin and sitagliptin.
• Medicines used to treat gout, such as colchicine.
• Medicines used to treat HIV or AIDS, such as efavirenz, ritonavir, maraviroc and emtricitabine.
• Medicines used to prevent transplant rejection (ciclosporin) and ciclosporin-based regimens in rheumatoid arthritis and psoriasis.

Oral contraceptives

If you take CABOMETYX whilst using oral contraceptives, the oral contraceptives may be ineffective. You should also use a barrier contraceptive (e.g., condom or diaphragm) whilst taking CABOMETYX and for at least 4 months after treatment has finished.

CABOMETYX with food and drink

You should not take CABOMETYX with food. You should not eat anything for at least 2 hours before taking CABOMETYX and for 1 hour after taking the medicine. Avoid consuming grapefruit-containing products for as long as you are using this medicine, as they may increase the levels of CABOMETYX in your blood.

Pregnancy, breastfeeding and fertility

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, please consult your doctor, pharmacist or other health care provider for advice before taking this medicine. Avoid becoming pregnant while being treated with CABOMETYX. If you or your partner could become pregnant, use adequate contraception during treatment and for at least 4 months after treatment has finished. Talk to your doctor about which methods of contraception are appropriate while you are taking CABOMETYX (see also under Other medicines and CABOMETYX, above).

Pregnancy: Tell your doctor if you or your partner become pregnant or plan to become pregnant while you are being treated with CABOMETYX. You should not take CABOMETYX if you are pregnant. Talk to your doctor BEFORE taking CABOMETYX if you or your partner are considering or planning to have a baby after your treatment has finished. There is a possibility your fertility could be affected by treatment with CABOMETYX.

Breast-feeding: Women taking CABOMETYX should not breast-feed during treatment and for at least 4 months after treatment has finished, as cabozantinib and/or its metabolites may be excreted in breast milk and be harmful to your child.

Do not share medicines prescribed for you with any other person. Always take CABOMETYX exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure. CABOMETYX should be taken once a day. The usual dose is 60 mg; however, your doctor will decide on the right dose for you. CABOMETYX should not be taken with food. You should not eat anything for at least 2 hours before taking CABOMETYX and for 1 hour after taking the medicine. Swallow the tablet with a full glass of water. Do not crush the tablets. Your doctor will tell you how long your treatment with CABOMETYX will last. If you have the impression that the effect of CABOMETYX is too strong or too weak, tell your doctor or pharmacist.

If you take more CABOMETYX than you should

In the event of overdosage, consult your doctor or pharmacist. If neither is available, contact the nearest hospital or poison centre.

If you forget to take CABOMETYX

If there are still 12 hours or more before your next dose is due, then take the missed dose as soon as you remember. Take the next dose at the normal time. If your next dose is due in less than 12 hours, then do not take the dose that you have missed. Take your next dose at the normal time.

If you stop taking CABOMETYX

You should continue to take this medicine until your doctor decides to stop your treatment. If you get serious side effects, your doctor may decide to change your dose or stop treatment earlier than originally planned. Your doctor will tell you if you need your dose adjusted.

CABOMETYX can have side effects. Not all side effects reported for CABOMETYX are included in this leaflet. Should your general health worsen or if you experience any untoward effects while taking CABOMETYX, please consult your health care provider for advice. If any of the following happens, stop taking CABOMETYX and tell your doctor immediately or go to the casualty department at your nearest hospital:

• swelling of the hands, feet, ankles, face, lips and mouth or throat, which may cause difficulty in swallowing or breathing,
• rash or itching,
• fainting.

These are all very serious side effects. If you have them, you may have had a serious reaction to CABOMETYX. You may need urgent medical attention or hospitalisation. Tell your doctor immediately or go to the casualty department at your nearest hospital if you notice any of the following:

• symptoms including pain in the abdomen, nausea (feeling sick), vomiting, constipation, or fever. These may be signs of a gastrointestinal perforation, a hole that develops in your stomach or intestine that could be life-threatening;
• severe or uncontrollable bleeding with symptoms such as: vomiting blood, black stools, bloody urine, headache, coughing up blood;
• a wound that does not heal;
• fits, headaches, confusion, or finding it difficult to concentrate. These may be signs of a condition called posterior reversible encephalopathy syndrome (PRES). PRES is rare (it affects less than 1 in 1000 people);
• feeling drowsy, confused or loss of consciousness. This may be due to liver problems;
• pain in the mouth, teeth and/or jaw, swelling or sores inside the mouth, numbness or a feeling of heaviness in the jaw, or loosening of a tooth. These could be signs of bone damage in the jaw (osteonecrosis).

These are all serious side effects. You may need urgent medical attention. Tell your doctor if you notice any of the following:

Very common side effects (may affect more than 1 in 10 people)

• stomach upset, including diarrhoea, nausea, vomiting, constipation, indigestion and abdominal pain,
• blisters, pain of the hands or soles of the feet, rash or redness of the skin,
• decreased appetite, weight loss, altered sense of taste,
• fatigue, weakness, headache, dizziness,
• hypertension (increase in blood pressure),
• anaemia (low levels of red blood cells),
• low level of platelets,
• redness, swelling or pain in the mouth or throat, Difficulty in speaking, hoarseness, cough,
• changes in blood tests used to monitor general health and function of your organs (including the liver, and kidney), low levels of electrolytes (like magnesium, or potassium),
• shortness of breath,
• reduced thyroid activity; symptoms can include: tiredness, weight gain, constipation, feeling cold and dry skin,
• swelling in your legs and arms,
• pain in the arms, hands, legs or feet,
• low level of albumin in blood.

Common side effects (may affect up to 1 in 10 people)

• abscess (collection of pus, with swelling and inflammation),
• dehydration,
• difficulty in swallowing,
• ringing in ears,
• blood clots in the blood vessels and lungs,
• low level of white blood cells,
• increased or decreased blood sugar level,
• decrease in levels of calcium, sodium and phosphate in the blood,
• increase in level of potassium in the blood,
• increase in the level of bilirubin in the blood (which may result in jaundice/yellow skin or eyes),
• increase in amylase levels in the blood,
• increase in lipase levels in the blood,
• increase in cholesterol or triglyceride levels in the blood,
• numbness, tingling, burning sensation or pain in the limbs,
• a painful tear or abnormal connection of the tissues in your body,
• gastro-oesophageal reflux disease (bringing up stomach acid),
• haemorrhoids (piles),
• dry mouth and pain in the mouth,
• feeling drowsy, confused or loss of consciousness due to liver problems,
• dry skin, severe itching of skin, acne,
• thickening of the skin outer layer,
• alopecia (hair loss and thinning), hair colour change,
• pain in joints, muscle spasms,
• protein in urine (seen in tests),
• a burning or stinging sensation of the tongue.

Uncommon side effects (may affect 1 in 100 people)

• fits,
• inflammation of the pancreas,
• decrease in bile flow from the liver,
• bone damage in the jaw,
• wound complications.

Not known (proportion of people affected not known)

• stroke,
• heart attack,
• an enlargement and weakening of a blood vessel wall or a tear in a blood vessel wall (aneurysms and artery dissections).

If you notice any side effects not mentioned in this leaflet, please inform your doctor or pharmacist.

Reporting of side effects

If you get side effects, talk to your doctor, pharmacist or nurse. You can also report side effects to SAHPRA via the “6.04 Adverse Drug Reaction Reporting Form”, found online under SAHPRA’s publications: https://www.sahpra.org.za/Publications/Index/8. Alternately you can contact Acino Pharma (Pty) Ltd at Email: [email protected]. By reporting side effects, you can help provide more information on the safety of CABOMETYX.

Store all medicines out of reach of children.

• Store at or below 25 °C.
• Do not use after the expiry date stated on the label / carton / bottle. Return all unused medicine to your pharmacist.
• Do not dispose of unused medicine in drains or sewerage systems (e.g. toilets).