Prospect: information for the patient

Afinitor 2.5mg tablets

Afinitor 5mg tablets

Afinitor 10mg tablets

everolimus

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 should not give it to other people even if they have the same symptoms as you, as it may harm them.

-If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this prospect. See section4.

1.What is Afinitor and what it is used for

2.What you need to know before starting to take Afinitor

3.How to take Afinitor

4.Possible adverse effects

5.Storage of Afinitor

6.Contents of the package and additional information

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

Afinitor is used to treat adult patients with:

• advanced breast cancer with hormone receptor-positive status in postmenopausal women, in whom other treatments (designated as «non-steroidal aromatase inhibitors») cannot continue to keep the disease under control. It is administered in conjunction with a type of medication called exemestane, a steroidal aromatase inhibitor, which is used for hormonal treatment of cancer.
• advanced tumors known as neuroendocrine tumors that originate in the stomach, intestine, lung, or pancreas. It is administered if the tumors are not operable and do not produce specific excess hormones or other natural substances related to them.
• advanced kidney cancer (advanced renal cell carcinoma), when other treatments (designated as anti-VEGF treatment) have not helped to stop their disease.

Afinitor should only be prescribed by an experienced doctor in cancer treatment. Follow the doctor's instructions carefully. They may be different from the general information contained in this prospectus. If you have any doubts about Afinitor or the reason why you have been prescribed this medication, consult your doctor.

Do not take Afinitor

• if you are allergicto everolimus, related substances such as sirolimus or temsirolimus, or any of the other components of this medication (listed in section6).

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

Warnings and precautions

Consult your doctor before starting to take 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 levels). 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 excessive thirst or if you 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 open wound after surgery. Afinitor may increase the risk of wound healing problems.
• if you have an infection. You may need to treat your infection before starting Afinitor treatment.
• if you have previously had hepatitis B, as it may reactivate during Afinitor treatment (see section4«Adverse reactions»).
• if you have received or are about to receive radiation therapy.

Afinitor may also:

-weaken your immune system. Therefore, you may be at risk of infection while taking Afinitor. If you have a fever or other signs of infection, consult your doctor. Some infections can be serious and fatal.

-affect kidney function. Therefore, your doctor will monitor your kidney function while taking Afinitor.

-cause difficulty breathing, cough, and fever.

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

• cause radiation therapy complications. Severe 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 (presenting 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.

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

Inform your doctorif you experience these symptoms.

During treatment, you will have blood tests performed periodically. These tests will determine the number of blood cells (white blood cells, red blood cells, and platelets) to check if Afinitor is having an undesirable 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 these may be affected by Afinitor treatment.

Children and adolescents

Afinitor should not be administered to children or adolescents (under 18years).

Other medications and Afinitor

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

Inform your doctor or pharmacistif you are using, have used recentlyor may need to use any other medication.

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

• ketoconazole, itraconazole, voriconazole, or fluconazole and other antifungal medications used to treat fungal infections.
• clarithromycin, telithromycin, or erythromycin, antibiotics used to treat bacterial infections.
• ritonavir and other medications used to treat HIV/AIDS.
• verapamil or diltiazem, used to treat heart problems or high blood pressure.
• dronedarone, a medication used to help regulate your heart rhythm.
• ciclosporin, a medication 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 situations including inflammatory or immune problems.
• phenytoin, carbamazepine, or phenobarbital and other antiepileptic medications used to control seizures.

You should avoid using these medications during Afinitor treatment. If you are taking any of them, your doctor may prescribe a different medication, or may change your Afinitor dose.

Afinitor with food and drinks

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

Pregnancy, breastfeeding, and fertility

Pregnancy

Afinitor may cause harm to the fetus and is not recommended for use 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 medication during pregnancy.

Women who may become pregnant should use a highly effective contraceptive method during treatment and for 8weeks after completing treatment. If, despite these measures, you think you may be pregnant, consult your doctorbeforetaking more Afinitor.

Breastfeeding

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

Female fertility

Some patients treated with Afinitor have experienced amenorrhea (absence of menstrual periods).

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

Male fertility

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

Driving and operating machinery

If you feel abnormally tired (fatigue is a very common adverse effect), be extra careful when driving or operating machinery.

Afinitor contains lactose

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

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

The recommended dose is 10mg, once a day. 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 7.5mg per day).

If you experience some side effects while taking Afinitor (see section4), your doctor may reduce the dose you take or interrupt treatment for a short period of time or permanently.

Take Afinitor once a day, at the same time, either with food or 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 mistake, consult your doctor or go to the hospital immediately. Urgent treatment may be necessary.
• Bring the packaging and this leaflet so that the doctor knows what you have taken.

If you forget to take Afinitor

If you have forgotten a dose, take the next dose at the time it is due. Do not take a double dose to make up for the missed dose.

If you interrupt treatment with Afinitor

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

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

STOP taking Afinitor and seek medical help immediately 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
• Intense itching of the skin, with red rash or lumps on the skin

The serious side 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, increased 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 renal insufficiency)

Uncommon(may affect up to 1 in 100 people)

• Fever, skin rash, joint pain and inflammation, as well as fatigue, loss of appetite, nausea, jaundice (yellowing of the skin), right upper abdominal pain, light-colored stools, dark urine (may be signs of reactivation of hepatitis B)
• 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 heat in the affected skin area (signs of venous thrombosis 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, confusion, back pain (signs of sudden renal insufficiency)
• Skin rash, itching, acne, difficulty breathing or swallowing, dizziness (signs of 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 side effects, report them to your doctor immediately as they may be fatal.

Other possible side effects of Afinitor include:

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

• High blood sugar (hyperglycemia)
• Loss of appetite
• Altered taste (dysgeusia)
• Headache
• Nasal bleeding (epistaxis)
• Cough
• Mouth ulcers
• Stomach discomfort, including nausea or diarrhea
• Skin rash
• Itching (pruritus)
• Feeling weak or tired
• 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)

• Bleeding or bruising (signs of low platelet count, also known as thrombocytopenia)
• Difficulty breathing (dyspnea)
• Thirst, decreased urine output, dark urine, dry, red skin, irritability (signs of dehydration)
• Insomnia
• Headache, dizziness (signs of high blood pressure, also known as hypertension)
• Swelling of a limb or the entire 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 membranes of the mouth, stomach, intestine
• Dry mouth
• Heartburn (dyspepsia)
• Vomiting
• Difficulty swallowing (dysphagia)
• Abdominal pain
• Acne
• Skin 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
• Irregular menstrual 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 changes, 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 signs such as fever, chills, sore throat, or mouth ulcers (signs of low blood cell count, also known as pancitopenia)
• Loss of taste (ageusia)
• Coughing up blood (hemoptysis)
• Irregular menstrual periods (amenorrhea)
• Increased frequency of urination during the day
• Chest pain
• Abnormal wound healing
• Epiphora with itching and redness, or eye redness or redness (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 the mucous membranes 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

Unknown frequency(cannot be estimated from available data)

• Reaction at the site where you received previous radiation therapy (for example, skin redness or lung inflammation) (known as radiation recall syndrome)
• Worsening of radiation therapy side effects

If these reactions worsen, report them to your doctor and/or pharmacist. Most side effects are mild to moderate and usually disappear if treatment is stopped for a few days.

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 thenational notification system included in theAppendixV. 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 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 it from light and moisture.
• Open the blister just before taking the tablets.
• Do not use this medication if you observe that the packaging is damaged or shows signs of manipulation.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. This will help protect the environment.

Composition of Afinitor

• 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 components are butylhydroxytoluene, magnesium stearate, lactose monohydrate, hypromellose, crospovidone type A, and anhydrous lactose.

Appearance of the product and contents of the package

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

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

Afinitor 10 mg tablets are elongated, white to slightly yellowish in color. They have the inscription "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 some package sizes may be marketed.

Marketing Authorization Holder

Novartis Europharm Limited

Vista Building

Elm Park, Merrion Road

Dublin 4

Ireland

Responsible Person

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

For more information about this medication, please contact the local representative of the marketing authorization holder:

Last revision date of this leaflet:

Other sources of information

The detailed information about this medication is available on the website of the European Medicines Agency:http://www.ema.europa.eu