Afinitor 10 mg tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Afinitor 2.5 mg tablets

Afinitor 5 mg tablets

Afinitor 10 mg tablets

everolimus

Read the entire leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.

  • If you have any questions, ask your doctor or pharmacist.

• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.

• If you experience any adverse effects, consult your doctor or pharmacist, even if these are effects not listed in this leaflet. See section 4.

Leaflet contents

1. What Afinitor is and what it is used for
2. What you need to know before taking Afinitor
3. How to take Afinitor
4. Possible side effects
5. How to store Afinitor
6. Contents of the pack and other information

1. What Afinitor is and what it is used for

Afinitor is a cancer medicine that contains the active substance everolimus. Everolimus reduces the blood supply to the tumour and slows down the growth and spread of cancer cells.

Afinitor is used to treat adult patients with:

• advanced hormone receptor-positive breast cancer in postmenopausal women, in whom other treatments (called "non-steroidal aromatase inhibitors") can no longer keep the disease under control. It is given in combination with a type of medicine called exemestane, a steroidal aromatase inhibitor, which is used for hormonal treatment of cancer.
• advanced tumours known as neuroendocrine tumours originating in the stomach, intestine, lung or pancreas. It is given when the tumours are inoperable and do not produce excess specific hormones or other related natural substances.

advanced kidney cancer (advanced renal cell carcinoma) when other treatments (called anti-VEGF therapy) have not helped to stop the progression of the disease.

2. What you need to know before taking Afinitor

Afinitor will only be prescribed by a physician experienced in the treatment of cancer. Carefully follow all instructions provided by your doctor. These may differ from the general information contained in this leaflet. If you have any questions about Afinitor or why it has been prescribed to you, consult your doctor.

Do not take Afinitor

• if you are allergic to everolimus, to related substances such as sirolimus or temsirolimus, or to any of the other ingredients of this medicine (listed in section 6).

If you think you may be allergic, consult your doctor.

Warnings and precautions

Talk to your doctor before starting Afinitor:

• if you have liver problems or have had a disease that may have affected your liver. In this case, your doctor may prescribe a different dose of Afinitor.

• if you have diabetes (high blood sugar levels). Afinitor may increase blood sugar levels and worsen diabetes mellitus. This may require treatment with insulin and/or oral antidiabetic medicines. Inform your doctor if you experience excessive thirst or need to urinate more frequently.

• if you need to receive a vaccine while taking Afinitor.

• if you have high cholesterol levels. Afinitor may increase cholesterol and/or other blood fats.

• if you have recently undergone major surgery, or if you still have an unhealed surgical wound. Afinitor may increase the risk of wound healing problems.

• if you have an infection. It may be necessary to treat your infection before starting treatment with Afinitor.

• if you have previously had hepatitis B, as it may reactivate during treatment with Afinitor (see section 4, "Possible side effects").

• if you have received or are about to receive radiotherapy. Afinitor may also:

• weaken your immune system. Therefore, you may be at risk of developing an infection while taking Afinitor. If you develop fever or other signs of infection, consult your doctor. Some infections may be severe and potentially fatal.

• affect kidney function. Therefore, your doctor will monitor your kidney function while you are taking Afinitor.

• cause difficulty breathing, cough, and fever.

• cause mouth ulcers and sores. Your doctor may need to interrupt or stop treatment with Afinitor. You may require treatment with a mouthwash, gel, or other products. Some mouthwashes and gels may worsen ulcers, so do not use any without first consulting your doctor. Your doctor may restart Afinitor at the same dose or at a lower dose.

  • cause complications related to radiotherapy. Serious complications of radiotherapy (such as difficulty breathing, nausea, diarrhea, skin rash, and pain in the mouth, gums, and throat), including fatal cases, have been observed in some patients taking everolimus at the same time as receiving radiotherapy or shortly after completing radiotherapy. The so-called radiation recall syndrome (characterized by skin redness or lung inflammation at the site of previous radiotherapy) has also been reported in patients who previously received radiotherapy.

Inform your doctor if you are scheduled to receive radiotherapy soon, or if you have previously received radiotherapy.

Tell your doctor if you experience any of these symptoms.

During treatment, you will have periodic blood tests. These tests will measure your blood cell counts (white blood cells, red blood cells, and platelets) to check whether Afinitor is having an unwanted effect on these cells. You will also have blood tests to monitor kidney function (creatinine levels), liver function (transaminase levels), and blood sugar and cholesterol levels. These tests are performed because these parameters may be affected by treatment with Afinitor.

Children and adolescents

Afinitor must not be given to children or adolescents (under 18 years of age).

Other medicines and Afinitor

Afinitor may affect how other medicines work. If you are taking other medicines at the same time as Afinitor, your doctor may adjust the dose of Afinitor or of the other medicines.

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

The following may increase the risk of adverse effects with Afinitor:

• ketoconazole, itraconazole, voriconazole, or fluconazole and other antifungal medicines used to treat fungal infections.
• clarithromycin, telithromycin, or erythromycin, antibiotics used to treat bacterial infections.
• ritonavir and other medicines used to treat HIV/AIDS infection.
• verapamil or diltiazem, used to treat heart problems or high blood pressure.
• dronedarone, a medicine used to help regulate your heartbeat.
• cyclosporine, a medicine used to prevent the body from rejecting transplanted organs.
• imatinib, used to inhibit the growth of abnormal cells.
• angiotensin-converting enzyme (ACE) inhibitors (such as ramipril) used to treat high blood pressure or other cardiovascular problems.
• nefazodone, used to treat depression.
• cannabidiol (used, among other things, for the treatment of epileptic seizures).

The following may reduce the effectiveness of Afinitor:

• rifampicin, used to treat tuberculosis (TB).
• efavirenz or nevirapine, used to treat HIV/AIDS infection.
• St John's wort (Hypericum perforatum), a herbal product used to treat depression and other conditions.
• dexamethasone, a corticosteroid used to treat a wide range of conditions including inflammatory or immune disorders.
• phenytoin, carbamazepine, or phenobarbital and other antiepileptic medicines used to control seizures.

The use of these medicines should be avoided during treatment with Afinitor. If you are taking any of them, your doctor may prescribe a different medicine, or may

adjust your dose of Afinitor.

Taking Afinitor with food and drink

Do not eat grapefruit or drink grapefruit juice while taking Afinitor. It may increase the amount of Afinitor in your blood, possibly to harmful levels.

Pregnancy, breastfeeding, and fertility

Pregnancy

Afinitor may harm the unborn baby and treatment with Afinitor is not recommended during pregnancy. Inform your doctor if you are pregnant or think you may be pregnant. Your doctor will discuss with you whether you should take this medicine during pregnancy.

Women who can become pregnant must use a highly effective method of contraception during treatment and for 8 weeks after stopping treatment. If, despite these measures, you think you may be pregnant, consult your doctor before taking any further Afinitor.

Breastfeeding

Afinitor may harm the breastfed infant. You must not breastfeed during treatment and for 2 weeks after the last dose of Afinitor. Inform your doctor if you are breastfeeding.

Female fertility

Absence of menstrual periods (amenorrhea) has been observed in some patients treated with Afinitor.

Afinitor may affect female fertility. Inform your doctor if you wish to have children.

Male fertility

Afinitor may affect male fertility. Consult your doctor if you wish to father a child.

Driving and using machines

If you feel unusually tired (fatigue is a very common side effect), take special care when driving or using machines.

Afinitor contains lactose

Afinitor contains lactose (milk sugar). If your doctor has informed you that you have an intolerance to certain sugars, consult him before taking this medicine.

3. How to take Afinitor

Follow exactly the instructions given by your doctor or pharmacist for taking this medicine. If in doubt, consult your doctor or pharmacist again.

The recommended dose is 10 mg once daily. Your doctor will inform you how many Afinitor tablets you should take.

If you have liver problems, your doctor may start treatment with a lower dose of Afinitor (2.5; 5; or 7.5 mg daily).

If you experience certain adverse effects while taking Afinitor (see section 4), your doctor may reduce your dose, temporarily interrupt treatment, or discontinue treatment altogether.

Take Afinitor once daily, at approximately the same time each day, always with food or always without food.

Swallow the tablet(s) whole with a glass of water. The tablets must not be chewed or crushed.

If you take more Afinitor than you should

• If you have taken too much Afinitor, or if someone has accidentally taken your tablets, consult your doctor or go to the hospital immediately. Urgent treatment may be necessary.
• Take the container and this leaflet with you so the doctor knows what you have taken.

If you forget to take Afinitor

If you miss a dose, take the next dose at your usual time. Do not take a double dose to make up for forgotten doses.

If you stop taking Afinitor

Do not stop treatment with Afinitor unless your doctor tells you to do so.

If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

STOP treatment with Afinitor and seek immediate medical help if you or your child experience any of the following signs of an allergic reaction:

• difficulty breathing or swallowing
• swelling of the face, lips, tongue, or throat
• severe skin itching, with red rash or lumps on the skin

Serious adverse effects of Afinitor include:

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

• Increased body temperature, chills (signs of infection)
• Fever, cough, difficulty breathing, crackling sounds in the lungs (signs of lung inflammation, also known as pneumonitis)

Common (may affect up to 1 in 10 people)

• Excessive thirst, increased urination, increased appetite with weight loss, fatigue (signs of diabetes)
• Bleeding (haemorrhage), for example in the intestinal wall
• Marked decrease in urine output (sign of kidney failure)

Uncommon (may affect up to 1 in 100 people)

• Fever, skin rash, joint pain and swelling, as well as fatigue, loss of appetite, nausea, jaundice (yellowing of the skin), pain in the upper right abdomen, pale stools, dark urine (may be signs of reactivation of hepatitis B)
• Feeling short of breath, difficulty breathing when lying down, swelling of feet or legs (signs of heart failure)
• Swelling and/or pain in one leg, usually in the calf, redness or warmth of the skin in the affected area (signs of blockage of a blood vessel (vein) in the leg caused by a blood clot)
• Sudden onset of breathing problems, chest pain, or coughing up blood (potential signs of pulmonary embolism, a condition that occurs when one or more arteries in the lungs become blocked)
• Marked decrease in urine output, swelling in the legs, confusion, back pain (signs of sudden kidney failure)
• Rash, itching, pimples, difficulty breathing or swallowing, dizziness (signs of a severe allergic reaction, also known as hypersensitivity)

Rare (may affect up to 1 in 1,000 people)

• Difficulty breathing or rapid breathing (signs of respiratory distress syndrome)

If you experience any of these adverse effects, inform your doctor immediately as they could have life-threatening consequences.

Other possible adverse effects of Afinitor include:

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

• High blood sugar level (hyperglycaemia)
• Loss of appetite
• Altered taste (dysgeusia)
• Headache
• Nosebleeds (epistaxis)
• Cough
• Mouth ulcers
• Stomach discomfort including nausea or diarrhoea
• Skin rash
• Itching (pruritus)
• Feeling weak or tired
• Fatigue, difficulty breathing, dizziness, pale skin, signs of low red blood cell count (anaemia)
• Swelling of arms, hands, feet, ankles, or other parts of the body (signs of oedema)
• Weight loss
• High levels of lipids (fats) in the blood (hypercholesterolaemia)

Common (may affect up to 1 in 10 people)

• Spontaneous bleeding or bruising (signs of low platelet count, also known as thrombocytopenia)
• Difficulty breathing (dyspnoea)
• Thirst, low urine output, dark urine, dry red skin, irritability (signs of dehydration)
• Trouble sleeping (insomnia)
• Headache, dizziness (signs of high blood pressure, also known as hypertension)
• Swelling of part or all of the arm (including fingers) or leg (including toes), feeling of heaviness, limited mobility, discomfort (possible symptoms of lymphoedema)
• Fever, sore throat, mouth ulcers due to infections (signs of low white blood cell count, leucopenia, lymphopenia and/or neutropenia)
• Fever
• Inflammation of the inner mucous lining of the mouth, stomach, intestine
• Dry mouth
• Heartburn (dyspepsia)
• Vomiting
• Difficulty swallowing (dysphagia)
• Abdominal pain
• Acne
• Rash and pain on the palms of the hands or soles of the feet (hand-foot syndrome)
• Redness of the skin (erythema)
• Joint pain
• Mouth pain
• Menstrual disorders such as irregular periods
• High levels of lipids (fats) in the blood (hyperlipidaemia, increased triglycerides)
• Low potassium levels in the blood (hypokalaemia)
• Low phosphate levels in the blood (hypophosphataemia)
• Low calcium levels in the blood (hypocalcaemia)
• Dry skin, skin peeling, skin lesions
• Nail disorders, nail breakage
• Mild hair loss
• Abnormal liver function tests (increased alanine and aspartate aminotransferase)
• Abnormal kidney function tests (increased creatinine)
• Swelling of the eyelid
• Protein in the urine

Uncommon (may affect up to 1 in 100 people)

• Weakness, spontaneous bleeding or bruising, and frequent infections with symptoms such as fever, chills, sore throat, or mouth ulcers (signs of low blood cell count, also known as pancytopenia)
• Loss of taste (ageusia)
• Coughing up blood (haemoptysis)
• Menstrual disorders such as absence of periods (amenorrhoea)
• More frequent urination during the day
• Chest pain
• Abnormal wound healing
• Hot flushes
• Watery eyes with itching and redness, pink or red eye (conjunctivitis)

Rare (may affect up to 1 in 1,000 people)

• Fatigue, difficulty breathing, dizziness, pale skin (signs of low red blood cell count, possibly due to a type of anaemia called pure red cell aplasia)
• Swelling of the face, around the eyes, mouth and inner lining of the mouth and/or throat, as well as the tongue, and difficulty breathing or swallowing (also known as angioedema), which may be signs of an allergic reaction

Frequency not known (cannot be estimated from available data)

• Reaction at the site of previous radiotherapy (e.g., skin redness or lung inflammation) (known as radiation recall syndrome)
• Worsening of adverse effects of radiotherapy

If these adverse reactions worsen, inform your doctor and/or pharmacist. Most adverse effects are mild to moderate and usually resolve if treatment is interrupted for a few days.

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system detailed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Afinitor

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the packaging and blister. The expiry date refers to the last day of the month indicated.
• Do not store above 25°C.
• Store in the original packaging to protect from light and moisture.
• Open the blister just before taking the tablets.
• Do not use this medicine if you notice that the packaging is damaged or shows signs of tampering.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Afinitor

• The active substance is everolimus.
• Each Afinitor 2.5 mg tablet contains 2.5 mg of everolimus.
• Each Afinitor 5 mg tablet contains 5 mg of everolimus.
• Each Afinitor 10 mg tablet contains 10 mg of everolimus.
• The other components are butylhydroxytoluene, magnesium stearate, monohydrate lactose, hypromellose, crospovidone type A and anhydrous lactose.

Appearance of the product and contents of the pack

Afinitor 2.5 mg tablets are elongated, white to slightly yellowish in colour. They are marked with "LCL" on one side and "NVR" on the other.

Afinitor 5 mg tablets are elongated, white to slightly yellowish in colour. They are marked with "5" on one side and "NVR" on the other.

Afinitor 10 mg tablets are elongated, white to slightly yellowish in colour. They are marked with "UHE" on one side and "NVR" on the other.

Afinitor 2.5 mg is available in blister packs containing 30 or 90 tablets.

Afinitor 5 mg and Afinitor 10 mg are available in blister packs containing 10, 30 or 90 tablets. Only certain pack sizes may be marketed.

Marketing Authorisation Holder

Novartis Europharm Limited

Vista Building

Elm Park, Merrion Road

Dublin 4

Ireland

Manufacturer

Novartis Farmacéutica SA

Gran Via de les Corts Catalanes, 764

08013 Barcelona

Spain

Novartis Pharma GmbH

Sophie-Germain-Strasse 10

90443 Nuremberg

Germany

Novartis Pharmaceuticals S.R.L.

Str. Livezeni nr. 7A

540472 Targu Mures

Romania

More information about this medicinal product is available upon request by contacting the local representative of the Marketing Authorisation Holder:

Date of the most recent review of this leaflet:

Other sources of information

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