Everolimus accord

Package leaflet: Information for the patient

Everolimus Accord, 2.5 mg, tablets
Everolimus Accord, 5 mg, tablets
Everolimus Accord, 10 mg, tablets
Everolimus
Please read this leaflet carefully before 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 further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm them, even if their symptoms are the same.
• If you experience any side effects, including any not listed in this leaflet, please tell your doctor or pharmacist. See section 4.

Contents of the leaflet

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

1. What Everolimus Accord is and what it is used for

Everolimus Accord is an anticancer medicine containing the active substance everolimus.
Everolimus reduces blood supply to the tumour and slows down the growth and spread of
cancer cells.
Everolimus Accord is used to treat adult patients with:

• advanced hormone receptor-positive breast cancer in postmenopausal women whose disease has progressed despite treatment with other medicines (known as "non-steroidal aromatase inhibitors"). This medicine is given together with exemestane, a steroid aromatase inhibitor used in hormone therapy for cancer treatment.
• advanced tumours known as neuroendocrine tumours originating in the stomach, intestines, lungs or pancreas. This medicine is used when tumours are inoperable and do not secrete excessive amounts of specific hormones or other related natural substances.
• advanced kidney cancer (advanced renal cell carcinoma) when other medicines (called anti-VEGF therapy) have not been effective.

2. Important information before taking Everolimus Accord

Everolimus Accord may only be prescribed by a physician experienced in the treatment of
cancer. All instructions from the physician must be followed. These may differ from the general
information contained in this leaflet. If additional information about Everolimus
Accord or an explanation as to why this particular medicine was chosen is needed, please contact your physician.
When not to take Everolimus Accord:

• if the patient is allergic to everolimus, substances similar to it such as sirolimus or temsirolimus, or any of the other ingredients of this medicine (listed in section 6). If an allergic reaction is suspected, consult your doctor for advice.

Warnings and precautions
Before starting treatment with Everolimus Accord, discuss the following with your doctor:

• if the patient has liver problems or diseases that may have affected liver function. In such cases, the doctor may adjust the dose of Everolimus Accord.
• if the patient has diabetes (high blood sugar). Everolimus Accord may increase blood glucose levels and worsen diabetes. This condition may require treatment with insulin and/or oral antidiabetic drugs. Inform your doctor if the patient experiences excessive thirst or increased frequency of urination.
• if the patient requires vaccinations during treatment with Everolimus Accord.
• if the patient has elevated cholesterol levels. Everolimus Accord may increase blood cholesterol and/or other blood lipids.
• if the patient has recently undergone major surgery or has unhealed surgical wounds. Everolimus Accord may impair wound healing.
• if the patient has an infection. Existing infections may need to be treated before starting Everolimus Accord.
• if the patient has previously had hepatitis B, as reactivation of the disease may occur during treatment with Everolimus Accord (see section 4 "Possible side effects").
• if the patient has received or is due to receive radiotherapy.

Everolimus Accord may also:

• suppress the immune system. Therefore, the patient may be at increased risk of infection while taking Everolimus Accord. If the patient develops fever or other signs of infection, consult a doctor immediately. Some infections may be severe and potentially fatal.
• affect kidney function. Therefore, the doctor will monitor kidney function during treatment with Everolimus Accord.
• cause shortness of breath, cough, and fever.
• cause development of mouth ulcers and sores. The doctor may interrupt or discontinue treatment with Everolimus Accord. The patient may require treatment with mouthwashes, gels, or other products. Some mouthwashes and gels may worsen ulcers, so nothing should be used without consulting the doctor. The doctor may restart treatment with Everolimus Accord at the same or a lower dose.
• cause radiation therapy complications. Severe radiation-related reactions (such as shortness of breath, nausea, diarrhea, skin rash, and pain in the mouth, gums, and throat), including fatal cases, have been observed in some patients receiving everolimus concurrently with or shortly after radiotherapy. Additionally, in patients who previously underwent 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 about any planned radiotherapy in the near future or any previous radiotherapy.

Inform your doctor if the patient experiences any of these symptoms.
During treatment, the patient will undergo regular blood tests to monitor blood cell counts (white blood cells, red blood cells, and platelets) and to check whether Everolimus
Accord is adversely affecting blood cells. Blood tests will also be performed to monitor kidney function (creatinine levels), liver function (transaminase activity), and blood glucose and cholesterol levels, as Everolimus Accord may affect these parameters.
Children and adolescents
Everolimus Accord should not be given to children and adolescents (under 18 years of age).
Everolimus Accord and other medicines
Everolimus Accord may affect the action of other medicines. If the patient is taking other medicines
concurrently with Everolimus Accord, the doctor may adjust the dose of Everolimus Accord or
other medicines.
Tell your doctor or pharmacist about all medicines currently taken, recently taken, or planned to be taken.
The following medicines, when taken with Everolimus Accord, may increase the risk of
adverse effects:

• 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 conditions or hypertension.
• dronedarone, a medicine that helps restore normal heart rhythm.
• cyclosporine, a medicine used to prevent organ transplant rejection.
• imatinib, which inhibits the growth of abnormal cells.
• angiotensin-converting enzyme (ACE) inhibitors (such as ramipril) used to treat hypertension or other cardiovascular problems.
• nefazodone, used to treat depression.
• Cannabidiol (used, among others, in the treatment of epileptic seizures)

The following medicines may reduce the effectiveness of Everolimus Accord:

• rifampicin, used to treat tuberculosis.
• efavirenz or nevirapine, used to treat HIV/AIDS infection.
• St. John’s wort ( Hypericum perforatum ), an herbal product used to treat depression and other disorders.
• dexamethasone, a corticosteroid used to treat various diseases, including inflammatory or immunological disorders.
• phenytoin, carbamazepine, or phenobarbital and other antiepileptic medicines used to prevent various types of seizures.

Concomitant use of these medicines during treatment with Everolimus Accord should be avoided. If
the patient is taking any of the above medicines, the doctor may switch to an alternative medicine or
adjust the dose of Everolimus Accord.
Taking Everolimus Accord with food and drink
Avoid eating grapefruit and drinking grapefruit juice during treatment with
Everolimus Accord. This may increase the amount of Everolimus Accord in the blood, potentially to
harmful levels.
Pregnancy, breastfeeding, and effects on fertility
Pregnancy
Everolimus Accord is not recommended during pregnancy, as it may harm the unborn child. Inform your doctor if the patient is pregnant or suspects she may be pregnant. The doctor will advise whether this medicine can be taken during pregnancy.
Women of childbearing potential should use highly effective contraception during treatment and for 8 weeks after treatment ends. If, despite these precautions, the patient suspects she may have become pregnant, contact the doctor before taking Everolimus Accord.
Breastfeeding
Everolimus Accord may harm a breastfed infant. Breastfeeding should be avoided during treatment and for 2 weeks after the last dose of everolimus. Inform your doctor if the patient is breastfeeding.
Female fertility
In some patients taking Everolimus Accord, absence of menstrual periods (amenorrhea) has been observed.
Everolimus Accord may affect female fertility. Discuss with your doctor if the patient wishes to have children.
Male fertility
Everolimus Accord may affect male fertility. Inform your doctor if the patient intends to father a child.
Driving and operating machinery
If the patient experiences unexplained fatigue (fatigue is a very common side effect), exercise particular caution when driving or operating machinery.
Everolimus Accord contains lactose
Everolimus Accord contains lactose (milk sugar). If the patient has previously been diagnosed with intolerance to certain sugars, the patient should consult their doctor before taking this medicine.

3. How to take Everolimus Accord

This medicine should always be taken exactly as prescribed by your doctor. If in doubt,
consult your doctor or pharmacist.
The recommended dose is 10 mg taken once daily. Your doctor will determine how many tablets you should take.
If you have liver problems, your doctor may start treatment with a lower dose of
Everolimus Accord (2.5, 5, or 7.5 mg daily).
If certain adverse effects occur during treatment with Everolimus Accord (see section 4), your doctor may reduce the dose or discontinue treatment temporarily or permanently.
Everolimus Accord should be taken once daily, at the same time each day, and always taken with food or always taken without food (consistently either way).
Everolimus Accord tablet(s) should be swallowed whole with a glass of water. Tablets must not be chewed or crushed.

Taking more Everolimus Accord than prescribed

• If you take more Everolimus Accord than prescribed, or if someone else accidentally takes the tablets, seek immediate medical advice from a doctor or go to a hospital. Urgent medical intervention may be necessary.
• Show the doctor the outer carton and this leaflet so that the medicine taken can be identified.

Missing a dose of Everolimus Accord
If you miss a dose, take your next scheduled dose as planned. Do not take a double dose to make up for the missed tablet.

Stopping Everolimus Accord
Do not stop taking Everolimus Accord without first consulting your doctor.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everyone will experience them.
You should STOP using the medicinal product Everolimus Accord and seek medical help immediately if the patient experiences any of the following symptoms of an allergic reaction:

• Difficulty breathing or swallowing
• Swelling of the face, lips, tongue, or throat
• Worsening skin itching, with red rash and appearance of lumps

Serious adverse reactions associated with Everolimus Accord include:
Very common (may occur in more than 1 in 10 patients)

• Increased body temperature, chills (signs of infection)
• Fever, cough, difficulty breathing, wheezing (signs of pneumonia)

Common (may occur in less than 1 in 10 patients)

• Increased thirst, passing large amounts of urine, increased appetite with weight loss, fatigue (symptoms of diabetes)
• Bleeding (haemorrhage), e.g. in the intestinal wall
• Significantly reduced urine output (sign of kidney failure)

Uncommon (may occur in less than 1 in 100 patients)

• Fever, skin 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-coloured urine (these may be symptoms of reactivation of hepatitis B)
• Shortness of breath, difficulty breathing when lying down, swelling of feet or legs (symptoms 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 (symptoms of blocked blood vessel (vein) in the legs due to blood clotting)
• Sudden shortness of breath, chest pain or coughing up blood (potential symptoms of pulmonary embolism, which occurs when one or more arteries in the lungs become blocked)
• Significantly reduced urine output, swelling of legs, feeling disoriented, back pain (symptoms of acute kidney failure)
• Rash, itching, urticaria
• Difficulty breathing or swallowing, dizziness (symptoms of severe allergic reaction, also known as hypersensitivity)

Rare (may occur in less than 1 in 1000 patients)

• Breathlessness or rapid breathing (symptoms of acute respiratory distress syndrome)

If any of the adverse reactions listed above occur, contact a doctor immediately,
as they may lead to life-threatening consequences.
Other possible adverse reactions associated with Everolimus Accord include:
Very common (may occur in more than 1 in 10 patients)

• Fatigue, breathlessness, dizziness, pale skin, symptoms of low red blood cell count (anaemia)
• High blood sugar levels (hyperglycaemia)
• Loss of appetite
• Taste disturbances
• Headache
• Nosebleeds (epistaxis)
• Cough
• Mouth ulcers
• Stomach upset, including nausea, diarrhoea
• Skin rash
• Itching (pruritus)
• Feeling weak or tired
• Swelling of arms, hands, feet, ankles, and other parts of the body (symptoms of oedema)
• Weight loss
• High levels of lipids (fats) in the blood (hypercholesterolaemia)

Common (may occur in less than 1 in 10 patients)

• Sudden bleeding or bruising (symptoms of low platelet count, also known as thrombocytopenia), fever, sore throat, mouth ulcers due to infection (symptoms of low white blood cell count, leukopenia, lymphopenia and/or neutropenia)
• Breathlessness (dyspnoea)
• Feeling thirsty, low urine output, dark-coloured urine, dry red skin, irritability (symptoms of dehydration)
• Sleep problems (insomnia)
• Headaches, dizziness (symptoms of high blood pressure, also known as hypertension)
• Swelling of part or all of the hand (including fingers) or leg (including toes), feeling of heaviness, limited movement, discomfort (possible symptoms of lymphoedema)
• Inflammation of the tissue lining the mouth, stomach, intestine
• Dry mouth
• Heartburn (dyspepsia)
• Vomiting
• Difficulty swallowing (dysphagia)
• Abdominal pain
• Acne
• Rash and pain in the palms of the hands and soles of the feet (hand-foot syndrome)
• Skin redness (erythema)
• Joint pain
• Mouth pain
• Menstrual disorders, such as irregular menstrual bleeding
• High levels of lipids (fats) in the blood (hyperlipidaemia, increased triglyceride levels)
• 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, brittle nails
• Moderate hair loss
• Abnormal blood test results for liver function (increased alanine aminotransferase and aspartate aminotransferase activity)
• Abnormal blood test results for kidney function (increased creatinine levels)
• Swelling of eyelids
• Presence of protein in urine

Uncommon (may occur in less than 1 in 100 patients)

• Weakness, unexpected bleeding or bruising, and frequent infections with symptoms such as fever, chills, sore throat, or mouth ulcers (symptoms of low blood cell count, also known as pancytopenia)
• Loss of taste (ageusia)
• Coughing up blood (haemoptysis)
• Menstrual disorders, such as absence of menstruation
• More frequent urination during the day
• Chest pain
• Problems with wound healing
• Hot flushes
• Eye discharge accompanied by itching, redness, pinkish discoloration or redness of the eye (conjunctivitis)

Rare (may occur in less than 1 in 1000 patients)

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

Frequency not known (cannot be estimated from the available data)

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

If the adverse reactions listed above worsen, inform your doctor or pharmacist. Most adverse reactions are mild or moderate in severity and should resolve after interrupting treatment for a few days.
Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: 22 49-21-301, fax: 22 49-21-309,
website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder.
By reporting adverse reactions, additional information on the safety of the medicine can be collected.

5. How to store Everolimus Accord

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton or blister pack.
The expiry date refers to the last day of the stated month.
Store in the original packaging to protect from light.
There are no special temperature storage requirements for this medicine.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Everolimus Accord contains
The active substance is everolimus.
Each Everolimus Accord tablet contains 2.5 mg, 5 mg or 10 mg of everolimus.
The other ingredients are: butylhydroxytoluene (E321), hypromellose (2910) (3 mPa·s), lactose,
lactose monohydrate, crospovidone (type A) and magnesium stearate.

What Everolimus Accord looks like and contents of the pack
Everolimus Accord 2.5 mg are white or almost white, oval, biconvex tablets (approximately 10 x 5 mm in size), embossed with the code E9VS on one side and 2.5 on the other side.
Everolimus Accord 5 mg are white or almost white, oval, biconvex tablets (approximately 13 x 6 mm in size), embossed with the code E9VS 5 on one side.
Everolimus Accord 10 mg are white or almost white, oval, biconvex tablets (approximately 16 x 8 mm in size), embossed with the code E9VS 10 on one side.

Pack sizes:
Everolimus Accord 2.5 mg – OPA/Al/PVC/Al blisters containing 30 or 90 tablets.
Everolimus Accord 5 mg and 10 mg – OPA/Al/PVC/Al blisters containing 10, 30 or 90 tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Accord Healthcare Polska Sp. z o.o.
ul. Taśmowa 7
02-677 Warsaw
Tel: +48 22 577 28 00

Manufacturer/Importer
Synthon Hispania, S.L.
C/ Castelló no1, Pol. Las Salinas, Sant Boi de Llobregat
Barcelona, 08830
Spain

This medicinal product is authorised for marketing in the European Economic Area member states under the following names: