Cometriq 20mg+80mg hard capsules

2. What you need to know before you take COMETRIQ

Do not take COMETRIQ

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

Warnings and precautions

Tell your doctor or pharmacist before you start taking COMETRIQ:

Tell your doctor if you are affected by any of these conditions.You may need treatment or your doctor may decide to change your dose of COMETRIQ or stop treatment altogether. See also section 4: "Possible side effects".

You should also tell your dentist that you are taking COMETRIQ. It is important that you pay special attention to your oral hygiene during treatment with COMETRIQ.

Children and adolescents

COMETRIQ is not recommended for use in children and adolescents. The effects of COMETRIQ in people under 18 years of age are not known.

Taking COMETRIQ with other medicines

Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including those obtained without a prescription. This is because COMETRIQ may affect how other medicines work. Some medicines may also affect how COMETRIQ works. This may mean that your doctor needs to change the doses of your medicines.

• Medicines for treating fungal infections (such as itraconazole, ketoconazole and posaconazole)
• Medicines used to treat bacterial infections (antibiotics) such as erythromycin, clarithromycin and rifampicin
• Medicines for allergies, such as fexofenadine
• Medicines for treating angina (chest pain due to inadequate blood supply to the heart) such as ranolazine
• Steroids used to reduce inflammation or treat various immune system diseases
• Medicines used to treat epilepsy or seizures, such as phenytoin, carbamazepine and phenobarbital
• Herbal medicines containing St. John's Wort (Hypericum perforatum), which is sometimes used to treat depression or depression-related conditions, such as anxiety
• Anticoagulant medicines such as warfarin and dabigatran etexilate
• Medicines for treating high blood pressure or other heart diseases, such as aliskiren, ambrisentan, digoxin, talinolol and tolvaptan
• Medicines for diabetes, such as saxagliptin and sitagliptin

• Medicines for treating gout, such as colchicine
• Medicines used to treat HIV or AIDS, such as ritonavir, maraviroc and emtricitabine
• Medicines used to treat viral infections, such as efavirenz
• Medicines used to prevent rejection after a transplant (ciclosporin) and treatments with ciclosporin in rheumatoid arthritis and psoriasis

Oral contraceptives

If you take COMETRIQ while using oral contraceptives, the oral contraceptive may be less effective. You should also use a barrier method (e.g. condom or diaphragm) while taking COMETRIQ and for at least 4 months after stopping treatment.

Taking COMETRIQ with food

Avoid taking products that contain grapefruit juice while taking this medicine, as they may increase the levels of COMETRIQ in your blood.

Pregnancy, breastfeeding and fertility

Pregnancy should be avoided during treatment with COMETRIQ.If you or your partner can become pregnant, you must use effective contraception during treatment and for at least 4 months after stopping treatment. Talk to your doctor about which contraceptive methods are appropriate while taking COMETRIQ. See section 2.

Tell your doctor if you or your partner become pregnant, or if you or your partner plan to become pregnant, during treatment with COMETRIQ.

Talk to your doctorbeforeyou start taking COMETRIQif you or your partner are planning to have a child after stopping treatment. There is a possibility that treatment with COMETRIQ may affect your fertility.

Women taking COMETRIQ should stop breastfeeding 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 the baby.

Driving and using machines

Be careful when driving or using machines. Bear in mind that treatment with COMETRIQ can make you feel tired or weak.

3. How to take COMETRIQ

Take this medicine exactly as your doctor or pharmacist has told you. If you are not sure, ask your doctor or pharmacist.

Keep taking this medicine until your doctor tells you to stop. If you experience serious side effects, your doctor may decide to change your dose or stop treatment earlier than planned. Your doctor will decide whether you need to have your dose adjusted, especially during the first 8 weeks of treatment with COMETRIQ.

You should take COMETRIQ once a day. Depending on the dose prescribed for you, the number of capsules you should take will be as follows:

• 140 mg (one 80 mg orange capsule and three 20 mg grey capsules)

• 100 mg (one 80 mg orange capsule and one 20 mg grey capsule)

• 60 mg (three 20 mg grey capsules)

Your doctor will decide what dose is right for you.

The capsules are presented in blister strips organised by prescribed dose. Each blister strip has enough capsules for 7 days (one week). The capsules are also presented in a 28-day pack that contains enough capsules for 28 days in 4 blister strips with 7 days' worth of capsules in each strip.

Each day, take all the capsules in one row. In section 6, later on, you will find more information about the blister strips, how many capsules you should take and the total number of capsules in each strip. To help you remember your doses, write the date you take your first dose in the space provided next to the capsules. To remove the capsules for your dose:

1. Press the tab.

1. Remove the paper from the back.

1. Push the capsule through the aluminium foil.

Do nottake COMETRIQ with food. Do not eat any food for at least 2 hours before taking COMETRIQ and for 1 hour after taking it. Swallow the capsules one at a time with water. Do not open the capsules.

If you take more COMETRIQ than you should

If you have taken more COMETRIQ than you were prescribed, talk to a doctor or go to hospital immediately with the capsules and this leaflet.

If you forget to take COMETRIQ

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

4. Possible side effects

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

Tell 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, vomiting, constipation or fever. These symptoms can be a sign of a hole in the stomach or intestine (gastrointestinal perforation) that can be life-threatening.
• Swelling, pain in hands and feet, or shortness of breath.
• A wound that does not heal.

• Vomiting blood or coughing up blood, which may be bright red or look like coffee grounds.
• Pain in the mouth, teeth and/or jaw, swelling or ulcers in the mouth, numbness or a feeling of heaviness in the jaw or movement of a tooth. These could be signs of damage to the bone in the jaw (osteonecrosis).
• Seizures, headache, confusion or difficulty concentrating. These can be signs of a condition called posterior reversible encephalopathy syndrome (PRES). PRES is rare (affects less than 1 in 100 people).
• Diarrhoea that is severe and does not seem to be getting better.

Other side effects include:

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

• Stomach problems, such as diarrhoea, nausea, vomiting, constipation, indigestion and abdominal pain
• Difficulty swallowing
• Blisters, pain in hands or soles of feet, skin rash or redness, dry skin
• Loss of appetite, weight loss, change in taste
• Fatigue, weakness, headache, dizziness

• Changes in hair colour (lightening), hair loss
• High blood pressure (hypertension)
• Redness, swelling or pain in the mouth or throat, difficulty speaking, hoarseness
• Changes in blood test results used to monitor general health and liver function, low levels of electrolytes (such as magnesium, calcium or potassium)
• Low platelet count
• Pain in joints, muscle spasms
• Inflammation of the lymph nodes
• Pain in arms, hands, legs or feet

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

• Anxiety, depression, confusion
• General pain, chest pain or muscle pain, ear pain, ringing in the ears
• Weakness or decreased sensation or tingling in the limbs
• Chills, shivering
• Dehydration
• Inflammation of the abdomen or pancreas
• Inflammation of the lips and mouth corners

• Inflammation of the hair roots, acne, blisters (on parts of the body other than hands and feet)
• Swelling of the face and other parts of the body
• Loss or change of sense of taste
• Low blood pressure (hypotension)
• Irregular heartbeat (atrial fibrillation)
• Lightening of skin colour, scaly skin, unusual paleness
• Abnormal hair growth
• Haemorrhoids
• Pneumonia (lung infection)
• Pain in the mouth, teeth and/or jaw, swelling or ulcers in the mouth, numbness or a feeling of heaviness in the jaw or movement of a tooth
• Decreased thyroid activity, whose symptoms may include, among others: tiredness, weight gain, constipation, feeling cold and dry skin

• Low white blood cell count
• Decrease in phosphate levels in the blood
• Tear, perforation or bleeding in the stomach or intestine, inflammation or tear of the anus, bleeding in the lungs or trachea (airways)
• An abnormal connection of tissue in the digestive system, whose symptoms may include severe or persistent stomach pain
• An abnormal connection of tissue in the trachea (airways), oesophagus or lungs
• Abscess (collection of pus with swelling and inflammation) in the abdominal or pelvic area, or in the gums or teeth
• Blood clots in blood vessels and lungs
• Stroke
• Fungal infections (from fungi) in the skin, mouth or genitals
• Wounds that have difficulty healing
• Presence of protein or blood in the urine, gallstones, pain when urinating
• Blurred vision

• Increased bilirubin levels in the blood (which can cause yellowing of the skin or eyes)
• Decreased protein levels in the blood (albumin)

Uncommon side effects(may affect up to 1 in 100 people):

• Inflammation of the oesophagus, whose symptoms may include, among others: chest pain, nausea, change in taste, abdominal swelling, belching and indigestion.
• Infection and inflammation of the lung, lung collapse
• Skin ulcers, cysts, red spots on the face or thighs
• Facial pain
• Changes in the results of tests that measure blood clotting or blood cell count
• Muscle coordination loss, muscle damage
• Lack of muscle coordination, loss of consciousness, speech disorders, delirium, abnormal dreams
• Chest pain due to blockage in the arteries, palpitations
• Liver damage, kidney failure
• Hearing loss
• Inflammation of the eye, cataracts
• Disruption of menstrual periods, vaginal bleeding
• A condition called posterior reversible encephalopathy syndrome (PRES), whose symptoms include, among others: seizures, headaches, confusion or difficulty concentrating

Not known(side effects with unknown frequency)

• Heart attack
• Enlargement and weakening of the wall of a blood vessel or tear in the wall of a blood vessel (aneurysms and arterial dissections)

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of COMETRIQ

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

Do not use this medicine after the expiry date which is stated on the blister strip after EXP. The expiry date refers to the last day of the month shown.

Do not store above 25°C. Store in the original package to protect from moisture.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container Contents and Additional Information

COMETRIQ Composition

The active ingredient is (S)-cabozantinib malate

The hard capsules of COMETRIQ 20 mg contain (S)-cabozantinib malate, equivalent to 20 mg of cabozantinib.

The hard capsules of COMETRIQ 80 mg contain (S)-cabozantinib malate, equivalent to 80 mg of cabozantinib.

The other components are:

• Capsule Content:microcrystalline cellulose, sodium croscarmellose, sodium starch glycolate, anhydrous colloidal silica, and stearic acid.
• Capsule Shell:gelatin and titanium dioxide (E171).
• • The 20 mg capsules also contain black iron oxide (E172).
  • The 80 mg capsules also contain red iron oxide (E172).
• Printing Ink:shellac lacquer, black iron oxide (E172), and propylene glycol.

Product Appearance and Container Contents

COMETRIQ 20 mg hard capsules are gray capsules with "XL184 20mg" printed on one side.

COMETRIQ 80 mg hard capsules are orange capsules with "XL184 80mg" printed on one side.

The hard capsules of COMETRIQ are presented in blister strips organized according to the prescribed dose. Each blister strip contains enough medication for seven days. Each row of the strip contains a daily dose.

The blister strip with a daily dose of 60 mg contains twenty-one 20 mg capsules organized into a total of seven daily doses. Each daily dose occupies a row, which contains three 20 mg capsules:

The blister strip with a daily dose of 100 mg contains seven 80 mg capsules and seven 20 mg capsules, organized into a total of seven daily doses. Each daily dose occupies a row that contains one 80 mg capsule and one 20 mg capsule.

One orange 80 mg capsule + one gray 20 mg capsule.

The blister strip with a daily dose of 140 mg contains seven 80 mg capsules and twenty-one 20 mg capsules, organized into a total of seven doses. Each daily dose occupies a row that contains one 80 mg capsule and three 20 mg capsules:

One orange 80 mg capsule + three gray 20 mg capsules.

COMETRIQ hard capsules are also presented in 28-day packs:

84 capsules (4 blister strips of 21 capsules of 20 mg) (60 mg/day dose)

56 capsules (4 blister strips of 7 capsules of 20 mg and 7 capsules of 80 mg) (100 mg/day dose)

112 capsules (4 blister strips of 21 capsules of 20 mg and 7 capsules of 80 mg) (140 mg/day dose)

Each 28-day pack contains enough medication for 28 days.

Marketing Authorization Holder

Ipsen Pharma

65 quai Georges Gorse

92100 Boulogne-Billancourt

France

Manufacturer

Catalent UK Packaging Limited

Lancaster Way

Wingates Industrial Park

Westhoughton

Bolton

Lancashire

BL5 3XX

United Kingdom

Or

Catalent Germany Schorndorf GmbH

Steinbeisstr. 1 und 2

73614 Schorndorf

Germany

You can request more information about this medication by contacting the local representative of the marketing authorization holder.

Date of Last Revision of this Leaflet:

This medicinal product has been authorized with a "conditional approval".

This type of approval means that more information is expected to be obtained about this medicinal product.

The European Medicines Agency will review the new information about this medicinal product at least once a year, and this leaflet will be updated as necessary.

Other Sources of Information

Detailed information about this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu.