EVEROLIMUS ACCORD 5 mg TABLETS

Introduction

Package Leaflet: Information for the Patient

Everolimus Accord 5 mg tablets EFG

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. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get 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 Everolimus Accord and what is it used for
2. What you need to know before you take Everolimus Accord
3. How to take Everolimus Accord
4. Possible side effects
5. Storage of Everolimus Accord
6. Contents of the pack and other information

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

Everolimus Accord 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.

Everolimus is used to treat adult patients with:

• advanced breast cancer with positive hormonal receptor 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 Everolimus Accord

Everolimus Accord will only be prescribed 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 doubts about Everolimus Accord or why you have been prescribed this medicine, ask your doctor.

Do not take Everolimus Accord

• 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

Tell your doctor before you start taking Everolimus Accord:

• 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 Everolimus Accord.
• if you have diabetes (high blood sugar). Everolimus Accord may increase blood sugar levels and worsen diabetes mellitus. This may make you need treatment with insulin and/or oral antidiabetic medicines. Tell your doctor if you notice that you are thirsty or need to urinate more often.
• if you need to be given a vaccine while taking Everolimus Accord.
• if you have high cholesterol. Everolimus Accord 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. Everolimus Accord 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 Everolimus Accord.
• if you have had hepatitis B in the past, as it may reactivate during treatment with Everolimus Accord (see section 4 'Possible side effects').
• if you have received or are about to receive radiotherapy.

Everolimus Accord may also:

• weaken your immune system. Therefore, you may be at risk of getting an infection while taking Everolimus Accord. If you have a fever or other signs of infection, consult your doctor. Some infections can be serious and have fatal consequences.
• affect kidney function. Therefore, your doctor will monitor your kidney function while you are taking Everolimus Accord.
• cause difficulty breathing, coughing, and fever.
• cause radiation therapy complications. Serious radiation therapy complications (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 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 have 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.
• cause the appearance of ulcers and sores in the mouth. Your doctor may need to interrupt or stop treatment with Everolimus Accord. You may need treatment with a mouthwash, gel, or other products. Some mouthwashes and gels can worsen ulcers, so do not try any without consulting your doctor first. Your doctor may restart treatment with Everolimus Accord at the same dose or a lower dose.

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 Everolimus Accord 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 Everolimus Accord.

Children and adolescents

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

Other medicines and Everolimus Accord

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

• 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.
• Cannabidiol (its use includes, among others, the treatment of epileptic seizures).

The following may reduce the effectiveness of Everolimus Accord:

• 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 Everolimus Accord. If you are taking any of them, your doctor may prescribe a different medicine or change your dose of Everolimus Accord.

Taking Everolimus Accord with food and drinks

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

Pregnancy, breastfeeding, and fertility

Pregnancy

Everolimus Accord 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 8 weeks after the end of treatment. If, despite these measures, you think you may be pregnant, consult your doctor beforetaking more Everolimus Accord.

Breastfeeding

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

Female fertility

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

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

Male fertility

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

Driving and using machines

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

Everolimus Accord contains lactose

If your doctor has told you that you have an intolerance to some sugars, consult them before taking this medicine.

3. How to take Everolimus Accord

Follow exactly the instructions for administration of this medicine 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 everolimus tablets to take.

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

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

Take everolimus once a day, more or less at 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 Everolimus Accord than you should

• If you have taken too much everolimus, or if someone has taken your tablets accidentally, consult your doctor or go to the hospital immediately. You may need urgent treatment.
• Take the pack and this leaflet with you to show the doctor what you have taken.

If you forget to take Everolimus Accord

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 Everolimus Accord

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

If you have any further questions on 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.

STOP treatment with everolimus 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 everolimus 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 renal 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, jaundice (yellowish skin color), 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)

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

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

Unknown

• Swelling, feeling of heaviness or tightness, pain, limited mobility of some parts of the body (this can occur in any part of the body and could indicate abnormal fluid accumulation in soft tissues due to lymphatic system obstruction, also known as lymphedema)

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

Other possible adverse effects of everolimus include:

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

• High blood sugar levels (hyperglycemia)
• Lack of appetite
• Taste alteration (dysgeusia)
• Headache
• Nosebleeds (epistaxis)
• Cough
• Mouth ulcers
• Stomach discomfort 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)

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 reddened 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 lipid levels 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 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 pancytopenia)
• Lack 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, reddened, 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 mouth and/or throat mucosa, as well as the tongue and difficulty breathing or swallowing (also known as angioedema), can be signs of an allergic reaction

Frequency Not Known(cannot be estimated from the 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 type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Everolimus Accord

• 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.
• Store in the original packaging to protect it from light.
• This medicine does not require special temperature storage conditions.

Medicines should not be disposed of via wastewater or household waste. Deposit the packaging and medicines you no longer need at the SIGRE collection point in your pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Everolimus Accord

• The active ingredient is everolimus.
• Each tablet contains 5 mg of everolimus.
• The other ingredients are butylhydroxytoluene (E321), hypromellose (E464), lactose, lactose monohydrate, crospovidone (E1202), and magnesium stearate (E470b).

Appearance of the Product and Package Contents

Everolimus Accord 5 mg tablets EFG are oval, biconvex, white to off-white tablets (approximately 13 x 6 mm) with the inscription «E9VS 5» on one side.

Everolimus Accord 5 mg tablets EFG are available in packages containing 10, 30, or 90 tablets.

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Accord Healthcare S.L.U.

Moll de Barcelona s/n.

World Trade Center. Edifici Est 6ª planta

08039 Barcelona

Spain

Manufacturer

Synthon Hispania, S.L.

C/ Castelló no1, Pol. Las Salinas, Sant Boi de Llobregat

08830 Barcelona

Spain

Or

Synthon BV

Microweg, 22

6545 CM Nijmegen

Netherlands

Date of the Last Revision of this Prospectus:June 2022

Detailed information about this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS): http://www.aemps.gob.es/