Afinitor

Package leaflet: Information for the patient

Afinitor 2.5 mg tablets, 5 mg tablets, 10 mg tablets

everolimus
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. 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. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

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 an anticancer medicine containing an active substance called 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 (known as “non-steroidal aromatase inhibitors”) are no longer able to control the disease. It is given in combination with a type of medicine called exemestane, a steroidal aromatase inhibitor, which is used for antihormonal cancer therapy.
• advanced tumours called neuroendocrine tumours originating from the stomach, intestine, lung or pancreas. It is used when the tumours are inoperable and do not overproduce specific hormones or other related natural substances.
• advanced kidney cancer (advanced renal cell carcinoma) where other treatments (known as “anti-VEGF targeted therapies”) have not been effective in stopping it.

2. What you need to know before taking Afinitor

Afinitor will only be prescribed by a doctor experienced in the treatment of cancer. Carefully follow all instructions provided by your doctor. These instructions 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 similar 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, ask your doctor for advice.

Warnings and precautions
Talk to your doctor before taking Afinitor:

• if you have liver problems or have had any illness that may have affected your liver. In such cases, your doctor may need to prescribe a different dose of Afinitor.
• if you have diabetes (high blood sugar levels). Afinitor can increase blood sugar levels and worsen diabetes mellitus. This may require treatment with insulin and/or oral antidiabetic agents. Inform your doctor if you experience excessive thirst or increased frequency of urination.
• if you need to receive a vaccine while taking Afinitor.
• if you have high cholesterol levels. Afinitor can increase cholesterol levels and/or other blood fats.
• if you have recently undergone surgery, or if you have an unhealed surgical wound. Afinitor may increase the risk of wound healing complications.
• if you have an infection. The infection may need to be treated before starting 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 the immune system. Therefore, you may be at increased risk of developing an infection during treatment with Afinitor. If you develop fever or other signs of infection, consult your doctor. Some infections may be severe and potentially fatal.
• impair kidney function. Therefore, your doctor will monitor your kidney function during treatment with Afinitor.
• cause shortness of breath, cough, and fever.
• cause mouth ulcers and the development of sores. Your doctor may need to interrupt or stop treatment with Afinitor. Treatment with mouthwash, gel, or other products may be required. Some mouthwashes and gels may worsen ulcers, so do not use any product without first consulting your doctor. Your doctor may restart Afinitor treatment at the same dose or at a lower dose.
• cause complications related to radiotherapy. Severe radiation reactions (such as shortness of breath, nausea, diarrhea, skin rash, and irritation of the mouth, gums, and throat), including fatal cases, have been observed in some patients taking everolimus concurrently with radiotherapy or shortly after radiotherapy. Additionally, in patients who previously received radiotherapy, a so-called radiation recall syndrome (including skin redness or lung inflammation at the site of prior radiotherapy) has been reported. Inform your doctor if you are planning to receive radiotherapy in the near future or have previously received radiotherapy.

Inform your doctor if you experience any of these symptoms.
You will have regular blood tests during treatment. These tests will monitor your blood cell counts (white blood cells, red blood cells, and platelets) to check whether Afinitor is having any unwanted effects on these cells. Blood tests will also monitor kidney function (creatinine levels), liver function (transaminase levels), and levels of blood sugar and cholesterol. These levels may also be affected by Afinitor.

Children and adolescents
Afinitor must not be used in children or adolescents (under 18 years of age).

Other medicines and Afinitor
Afinitor may affect the action of certain medicines. If you are taking other medicines at the same time as Afinitor, your doctor may need to adjust the dose of Afinitor or of the other medicines.
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

The following substances may increase the risk of side effects with Afinitor:

• ketoconazole, itraconazole, voriconazole, 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 conditions or high blood pressure.
• dronedarone, used to help regulate heart rhythm.
• cyclosporine, a medicine used to prevent rejection of transplanted organs.
• imatinib, used to block 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 (uses include, among others, treatment of seizures).

The following substances 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 prevent epileptic seizures.

These medicines should be avoided during treatment with Afinitor. If you are taking any of these medicines, your doctor may prescribe alternative medicines or adjust your dose of Afinitor.

Afinitor with food and drink
Avoid grapefruit and grapefruit juice while being treated with Afinitor. These can increase the amount of Afinitor in your blood, possibly to harmful levels.

Pregnancy, breastfeeding, and fertility
Pregnancy
Afinitor may harm the unborn baby and is not recommended during pregnancy. Inform your doctor if you are pregnant or suspect you may be pregnant. Your doctor will discuss with you whether you should take this medicine during pregnancy.
Women who could become pregnant must use highly effective contraception during treatment and for 8 weeks after stopping treatment. If, despite these precautions, you suspect you are pregnant, consult your doctor before taking any further doses of 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
Menstrual cycle disturbances (amenorrhea) have 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. Talk to your doctor if you wish to father a child.

Driving and using machines
If you feel unusually tired (tiredness is a very common side effect), take special care when driving or operating machinery.

Afinitor contains lactose
Afinitor contains lactose (milk sugar). If your doctor has diagnosed you with an intolerance to certain sugars, contact your doctor before taking this medicine.

3. How to take Afinitor

Take this medicine exactly as directed by your doctor or pharmacist. If you
have any doubts, consult your doctor or pharmacist.
The recommended dose is 10 mg, taken once daily. Your doctor will tell you how many
Afinitor tablets you should take.
If you have liver problems, your doctor may prescribe you a lower dose of Afinitor (2.5, 5, or
7.5 mg/day).
If certain side effects occur while you are taking Afinitor (see section 4), your
doctor may reduce your dose, or interrupt or permanently stop treatment.
Take Afinitor once daily, approximately at the same time each day, regularly with or without food.
Swallow the tablet(s) whole with a glass of water. Do not chew or crush the
tablets.
If you take more Afinitor than you should

• If you have taken more Afinitor than you should, or if someone else has accidentally taken your tablets, contact a doctor immediately or go to hospital. Emergency treatment may be necessary.
• Keep the packaging and this leaflet, so the doctor knows what has been taken.

If you forget to take Afinitor
If you forget to take a dose, take the next dose at the scheduled time. Do not take a
double dose to make up for the missed tablets.
If you stop taking Afinitor
Do not stop treatment with Afinitor unless your doctor tells you to.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
STOP taking Afinitor and contact your doctor immediately if you experience any of the following signs of an allergic reaction:

• Difficulty breathing or swallowing
• Swelling of the face, lips, tongue or throat
• Severe itching of the skin, with red rash or skin swellings

Serious side 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, wheezing (signs of lung inflammation, also known as pneumonitis)

Common (may affect up to 1 in 10 people)

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

Uncommon (may affect up to 1 in 100 people)

• Fever, rash, joint pain and inflammation, as well as fatigue, loss of appetite, nausea, jaundice (yellowing of the skin), pain in the upper right part of the abdomen, pale stools, dark urine (may be signs of reactivation of hepatitis B)
• Shortness of breath, breathing difficulties when lying down, swelling of the feet and legs (signs of heart failure)
• Swelling and/or pain in one of the legs, 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 blood clotting)
• Sudden onset of shortness of breath, chest pain or coughing up blood (potential signs of pulmonary embolism, a condition that occurs when one or more pulmonary arteries become blocked)
• Severe decrease in urine production, swelling of the legs, confusion, back pain (signs of sudden kidney failure)
• Skin rash, itching, hives, difficulty breathing or swallowing, dizziness (signs of severe allergic reactions, also known as hypersensitivity)

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

• Shortness of breath or rapid breathing (signs of acute respiratory distress syndrome)

If you experience any of these side effects, contact your doctor immediately, as they could be life-threatening.
Other possible side effects of Afinitor include:
Very common (may affect more than 1 in 10 people)

• High levels of sugar in the blood (hyperglycaemia)
• Loss of appetite
• Altered sense of taste (dysgeusia)
• Headache
• Nosebleeds (epistaxis)
• Cough
• Mouth ulcers
• Stomach disturbances including feeling unwell (nausea) or diarrhoea
• Skin rash
• Itching
• Tiredness or weakness
• Tiredness, shortness of breath, dizziness, pale skin, signs of low red blood cell levels (anaemia)
• Swelling of the 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)
• Shortness of breath (dyspnoea)
• Thirst, low urine output, dark urine, dry and flushed skin, irritability (signs of dehydration)
• Difficulty 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 movement, 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 lining of the mouth, stomach and intestine
• Dry mouth
• Heartburn (dyspepsia)
• Feeling unwell (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)
• Dryness, peeling and skin lesions
• Nail problems, nail breakage
• Mild hair loss
• Abnormal blood test results for liver function (increased alanine and aspartate aminotransferase)
• Abnormal blood test results for kidney function (increased creatinine)
• Swelling of the eyelids
• 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)
• Need to urinate more often during the day
• Chest pain
• Problems with wound healing
• Hot flushes
• Eye discharge with itching and redness, red eyes (conjunctivitis)

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

• Tiredness, shortness of breath, dizziness, paleness (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 inside the mouth and/or throat, as well as of the tongue, and difficulty breathing or swallowing (also known as angioedema), which may be signs of an allergic reaction

Not known (frequency cannot be estimated from the available data)

• Reaction at a previous radiotherapy site, e.g. skin redness or lung inflammation (so-called radiation recall syndrome)
• Increased side effects from radiation treatment

If these side effects worsen, inform your doctor and/or pharmacist. Most of the side effects are mild or moderate in intensity and usually disappear if treatment is stopped for a few days.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Afinitor

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the carton and blister. The expiry date refers to the last day of that month.
• Do not store above 25°C.
• Store in the original packaging to protect the medicine from light and moisture.
• Open the blister pack only when it is time to take the tablets.
• Do not use this medicine if the packaging is damaged or shows signs of tampering.

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

6. Package contents and other information

What Afinitor contains

• 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 butylated hydroxytoluene, magnesium stearate, monohydrate lactose, hypromellose, crospovidone type A and anhydrous lactose.

Description of the appearance of Afinitor and contents of the pack
Afinitor 2.5 mg tablets are white to yellowish, elongated tablets. They are marked with
“LCL” on one side and “NVR” on the other.
Afinitor 5 mg tablets are white to yellowish, elongated tablets. They are marked with
“5” on one side and “NVR” on the other.
Afinitor 10 mg tablets are white to yellowish, elongated tablets. 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 or strengths may be marketed in your country.

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

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Novartis Pharma N.V. SIA Novartis Baltics Lietuvos filialas
Tél/Tel: +32 2 246 16 11 Tel: +370 5 269 16 50

България Luxembourg/Luxemburg
Novartis Bulgaria EOOD Novartis Pharma N.V.
Тел.: +359 2 489 98 28 Tél/Tel: +32 2 246 16 11

Česká republika Magyarország
Novartis s.r.o. Novartis Hungária Kft
Tel: +420 225 775 111 Tel.: +36 1 457 65 00

Danmark Malta
Novartis Healthcare A/S Novartis Pharma Services Inc.
Tlf: +45 39 16 84 00 Tel: +356 2122 2872

Deutschland Nederland
Novartis Pharma GmbH Novartis Pharma B.V.
Tel: +49 911 273 0 Tel: +31 88 04 52 555

Eesti Norge
SIA Novartis Baltics Eesti filiaal Novartis Norge AS
Tel: +372 66 30 810 Tlf: +47 23 05 20 00

Ελλάδα Österreich
Novartis (Hellas) A.E.B.E. Novartis Pharma GmbH
Τηλ: +30 210 281 17 12 Tel: +43 1 86 6570

España Polska
Novartis Farmacéutica, S.A. Novartis Poland Sp. z o.o.
Tel: +34 93 306 42 00 Tel.: +48 22 375 4888

France Portugal
Novartis Pharma S.A.S. Novartis Farma - Produtos Farmacêuticos, S.A.
Tél: +33 1 55 47 66 00 Tel: +351 21 000 8600

Hrvatska România
Novartis Hrvatska d.o.o. Novartis Pharma Services Romania SRL
Tel. +385 1 6274 220 Tel: +40 21 31299 01

Ireland Slovenija
Novartis Ireland Limited Novartis Pharma Services Inc.
Tel: +353 1 260 12 55 Tel: +386 1 300 75 50

Ísland Slovenská republika
Vistor hf. Novartis Slovakia s.r.o.
Sími: +354 535 7000 Tel: +421 2 5542 5439

Italia Suomi/Finland
Novartis Farma S.p.A. Novartis Finland Oy
Tel: +39 02 96 54 1 Puh/Tel: +358 (0)10 6133 200

Κύπρος Sverige
Novartis Pharma Services Inc. Novartis Sverige AB
Τηλ: +357 22 690 690 Tel: +46 8 732 32 00

Latvija
SIA Novartis Baltics
Tel: +371 67 887 070

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu