AFINITOR 5 mg TABLETS

Introduction

Package Leaflet: Information for the Patient

Afinitor 2.5mg tablets

Afinitor 5mg tablets

Afinitor 10mg tablets

everolimus

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
  • If you have any further questions, ask your doctor or pharmacist.

• This medicine has been prescribed for you only, and you should not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Afinitor and what is it used for

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

Afinitor is used to treat adult patients with:

• advanced breast cancer with positive hormonal receptors in postmenopausal women, in whom other treatments (called "non-steroidal aromatase inhibitors") can no longer keep the disease under control. It is given together with a type of medicine called exemestane, a steroidal aromatase inhibitor, which is used for the hormonal treatment of cancer.
• advanced tumors called neuroendocrine tumors that originate in the stomach, intestine, lung, or pancreas. It is given if the tumors are not operable 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 disease.

2. What you need to know before you take Afinitor

Afinitor will only be prescribed to you by a doctor with experience in the treatment of cancer. Follow carefully all the instructions given by your doctor. They may be different from the general information contained in this leaflet. If you have any questions about Afinitor or why you have been prescribed this medicine, ask your doctor.

Do not take Afinitor

• if you are allergicto 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 you start taking Afinitor:

• if you have liver problems or if you have had any 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). Afinitor may increase blood sugar levels and worsen diabetes mellitus. This may require treatment with insulin and/or oral antidiabetic medications. Inform your doctor if you notice that you are excessively thirsty or need to urinate more frequently.
• if you need to be given a vaccine while taking Afinitor.
• if you have high cholesterol. Afinitor may increase cholesterol and/or other blood fats.
• if you have recently undergone major surgery, or if you still have an unhealed wound after surgery. 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 had hepatitis B in the past, 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 getting an infection while taking Afinitor. If you have a fever or other signs of infection, consult your doctor. Some infections can be serious and life-threatening.

• affect kidney function. Therefore, your doctor will monitor your kidney function while you are taking Afinitor.
• cause difficulty breathing, coughing, and fever.
• cause the appearance of ulcers and sores in the mouth. Your doctor may need to interrupt or stop treatment with Afinitor. You may need treatment with a mouthwash, gel, or other products. Some mouthwashes and gels can worsen ulcers, so do not try any without first consulting your doctor. Your doctor may restart treatment with Afinitor at the same dose or at a lower dose.

• cause radiation therapy complications. Serious radiation therapy complications (such as difficulty breathing, nausea, diarrhea, skin rash, and mouth, gum, and throat pain), including fatal cases, have been observed in some patients taking everolimus at the same time as receiving radiation therapy or taking everolimus shortly after receiving radiation therapy. Radiation recall syndrome (which presents with skin redness or lung inflammation at the site of previous radiation therapy) has also been reported in patients who had received radiation therapy in the past.

Tell your doctor if you are scheduled to receive radiation therapy soon, or if you have received radiation therapy in the past.

Tell your doctorif you experience these symptoms.

During treatment, you will have regular blood tests. These tests will determine the number of cells in the blood (white blood cells, red blood cells, and platelets) to check if Afinitor is having an unwanted effect on these cells. You will also have blood tests to monitor kidney function (creatinine level), liver function (transaminase level), and blood sugar and cholesterol levels. These tests are done because they may be affected by treatment with Afinitor.

Children and adolescents

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

Other medicines and Afinitor

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

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

The following may increase the risk of side 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.
• verapamil or diltiazem, used to treat heart problems or high blood pressure.
• dronedarone, a medicine used to help regulate your heart rhythm.
• 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.

The following may reduce the effectiveness of Afinitor:

• rifampicin, used to treat tuberculosis (TB).
• efavirenz or nevirapine, used to treat HIV/AIDS.
• 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 system problems.
• phenytoin, carbamazepine, or phenobarbital, and other antiepileptics used to control seizures.

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

Taking Afinitor with food and drinks

Do not take grapefruit or grapefruit juice while taking Afinitor. It may increase the amount of Afinitor in the blood, possibly to a harmful level.

Pregnancy, breastfeeding, and fertility

Pregnancy

Afinitor may harm the fetus and should not be used during pregnancy. Tell 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 up to 8 weeks after finishing treatment. If, despite these measures, you think you may be pregnant, consult your doctor beforetaking any more Afinitor.

Breastfeeding

Afinitor may harm the breastfed baby. Do not breastfeed while taking Afinitor and for 2 weeks after the last dose of Afinitor. Tell your doctor if you are breastfeeding.

Female fertility

In some patients treated with Afinitor, absence of menstrual periods (amenorrhea) has been observed.

Afinitor may have an impact on female fertility. Tell your doctor if you want to have children.

Male fertility

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

Driving and using machines

If you feel abnormally tired (fatigue is a very common side effect), be careful when driving or using machines.

Afinitor contains lactose

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

3. How to take Afinitor

Follow exactly the instructions given by your doctor or pharmacist. If you are unsure, consult your doctor or pharmacist again.

The recommended dose is 10 mg, once a day. Your doctor will tell you how many Afinitor tablets to take.

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

If you experience some side effects while taking Afinitor (see section 4), your doctor may reduce the dose you take or interrupt treatment for a short period or permanently.

Take Afinitor once a day, at about the same time, always with food or always without food.

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

If you take more Afinitor than you should

• If you have taken too much Afinitor, or if someone has taken your tablets by accident, consult your doctor or go to the hospital immediately. You may need urgent treatment.
• Take the pack and this leaflet with you so that the doctor knows what has been taken.

If you forget to take Afinitor

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

If you stop taking Afinitor

Do not stop taking Afinitor unless your doctor tells you to.

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 all people suffer from them.

DISCONTINUE treatment with Afinitor and seek immediate medical attention 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-colored rash or bumps on the skin

Severe adverse effects of Afinitor include:

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

• Increased temperature, chills (signs of infection)
• Fever, cough, difficulty breathing, wheezing (signs of lung inflammation, also known as pneumonitis)

Common(may affect up to 1 in 10 people)

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

Uncommon(may affect up to 1 in 100 people)

• Fever, skin rash, joint pain and inflammation, as well as fatigue, loss of appetite, nausea, yellowing of the skin (jaundice), pain in the upper right abdomen, pale stools, dark urine (may be signs of hepatitis B reactivation)
• Shortness of breath, difficulty breathing when lying down, swelling of the 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 legs caused by a blood clot)
• Sudden onset of breathing problems, chest pain or coughing up blood (potential signs of pulmonary embolism, a situation that occurs when one or more arteries in the lungs are blocked)
• Significant decrease in urine output, swelling in the legs, feeling of confusion, back pain (signs of sudden kidney failure)
• Rash, itching, acne, 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 fatal consequences.

Other possible adverse effects of Afinitor include:

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

• High blood sugar levels (hyperglycemia)
• Loss of appetite
• Taste disturbance (dysgeusia)
• Headache
• Nosebleeds (epistaxis)
• Cough
• Mouth ulcers
• Stomach upset including feeling of nausea or diarrhea
• Skin rash
• Itching (pruritus)
• Feeling of weakness or fatigue
• Fatigue, difficulty breathing, dizziness, pale skin, signs of low red blood cell count (anemia)
• Swelling of the arms, hands, feet, ankles, or other parts of the body (signs of edema)
• Weight loss
• High levels of lipids (fats) in the blood (hypercholesterolemia)

Common(may affect up to 1 in 10 people)

• Spontaneous bleeding or bruising (signs of low platelet count, also known as thrombocytopenia)
• Difficulty breathing (dyspnea)
• Thirst, low urine output, dark urine, dry red skin, irritability (signs of dehydration)
• Sleeping problems (insomnia)
• Headache, dizziness (sign of high blood pressure, also known as hypertension)
• Swelling of a part or all of the arm (including fingers) or leg (including toes), feeling of heaviness, limited mobility, discomfort (possible symptoms of lymphedema)
• Fever, sore throat, mouth ulcers due to infections (signs of low white blood cell count, leucopenia, lymphopenia, and/or neutropenia)
• Fever
• Inflammation of the mucous membrane inside 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 (palmar-plantar syndrome)
• Redness of the skin (erythema)
• Joint pain
• Mouth pain
• Menstrual disorders such as irregular periods
• High levels of lipids (fats) in the blood (hyperlipidemia, increased triglycerides)
• Low potassium levels in the blood (hypokalemia)
• Low phosphate levels in the blood (hypophosphatemia)
• Low calcium levels in the blood (hypocalcemia)
• Dry skin, skin peeling, skin lesions
• Nail disorders, nail rupture
• 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 signs 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 (hemoptysis)
• Menstrual disorders such as absence of periods (amenorrhea)
• Frequent urination during the day
• Chest pain
• Abnormal wound healing
• Hot flashes
• Itchy, red, and watery eyes (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 anemia called pure red cell aplasia)
• Swelling of the face, around the eyes, mouth, and inner mucous membrane of the mouth and/or throat, as well as the tongue, and difficulty breathing or swallowing (also known as angioedema), may be signs of an allergic reaction

Frequency Not Known(frequency cannot be estimated from available data)

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

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

Reporting Adverse Effects

If you experience any adverse effects, consult your doctor or pharmacist, even if they are possible adverse effects not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing 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 expiration date stated on the packaging and blister. The expiration date is 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 should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of packaging and medicines that are no longer needed. This will help protect the environment.

6. Package Contents and Additional Information

Afinitor Composition

• The active ingredient 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 ingredients are butylhydroxytoluene, magnesium stearate, lactose monohydrate, hypromellose, crospovidone type A, and anhydrous lactose.

Product Appearance and Packaging Contents

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

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

Afinitor 10 mg tablets are elongated, white to slightly yellowish in color. 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. Not all pack sizes may be marketed.

Marketing Authorization 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

Roonstrasse 25

D-90429 Nürnberg

Germany

Novartis Pharma GmbH

Sophie-Germain-Strasse 10

90443 Nürnberg

Germany

You can obtain more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet:

Other Sources of Information

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