EVEROLIMUS TAD 5 mg TABLETS

Introduction

Package Leaflet: Information for the Patient

Everolimus TAD 5 mg tablets EFG

Everolimus TAD 10 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 TAD and what is it used for
2. What you need to know before you take Everolimus TAD
3. How to take Everolimus TAD
4. Possible side effects
5. Storage of Everolimus TAD
6. Contents of the pack and other information

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

Everolimus TAD 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 TAD 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 treatment) have not helped to stop the disease.

2. What you need to know before taking Everolimus TAD

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

Do not take Everolimus TAD

• 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

Consult your doctor before starting to take Everolimus TAD:

• if you have liver problemsor if you have had any diseasethat may have affected your liver. In this case, your doctor may prescribe a different dose of Everolimus TAD.
• if you have diabetes(high blood sugar levels). Everolimus TAD 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 vaccinewhile taking Everolimus TAD.
• if you have a high cholesterol level. Everolimus TAD may increase cholesterol and/or other blood fats.
• if you have recently undergone major surgery, or if you still have an unhealed woundafter surgery. Everolimus TAD 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 TAD.
• if you have previously suffered from hepatitis B, as it may reactivate during treatment with Everolimus TAD (see section 4 "Possible side effects").
• if you have received or are about to receive radiotherapy.

Everolimus TAD may also:

• weaken your immune system. Therefore, you may be at risk of infection while taking Everolimus TAD. 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 TAD.
• 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 everolimus. 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 everolimus 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 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. The so-called 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 Everolimus TAD is having an unwanted effect on these cells. You will also have blood tests to monitor kidney function (creatinine levels), liver function (transaminase levels), and blood sugar and cholesterol levels. These tests are done because they may be affected by treatment with Everolimus TAD.

Children and adolescents

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

Other medicines and Everolimus TAD

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

• ketoconazole, itraconazole, voriconazole, or fluconazoleand other antifungal medicinesused to treat fungal infections.
• clarithromycin, telithromycin, or erythromycin, antibioticsused to treat bacterial infections.
• ritonavirand other medicines used to treat HIV/AIDS.
• verapamilor diltiazem, used to treat heart problems or high blood pressure.
• dronedarone, a medicine used to help regulate your heart rhythm.
• cyclosporin, 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 TAD:

• rifampicin, used to treat tuberculosis (TB).
• efavirenzor 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 phenobarbitaland other antiepilepticsused to control seizures.

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

Taking Everolimus TAD with food and drinks

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

Pregnancy, breastfeeding, and fertility

Pregnancy

Everolimus TAD may harm the fetus and is not recommended 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 more Everolimus TAD.

Breastfeeding

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

Female fertility

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

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

Male fertility

Everolimus TAD 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 especially careful when driving or using machines.

Everolimus TAD 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 TAD

Follow the instructions for administration of this medicine exactly as prescribed 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 TAD tablets to take.

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

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

Take Everolimus TAD 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 TAD than you should

• If you have taken too much Everolimus TAD, or if someone has taken your tablets accidentally, consult your doctor or go to the hospital immediately. Urgent treatment may be necessary.
• Take the pack and this leaflet with you so that the doctor knows what you have taken.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service (Tel. 91 562 04 20) indicating the medicine and the amount ingested.

If you forget to take Everolimus TAD

If you have missed 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 TAD

Do not stop taking Everolimus TAD 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.

DISCONTINUE treatment with everolimus and seek immediate medical help 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 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, 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 renal 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 everolimus include:

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

• High blood sugar levels (hyperglycemia)
• Lack of appetite
• Taste disturbance (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)

• 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 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 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 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)
• 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, or 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 inside 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 the available data)

• Reaction at the site of previous radiotherapy, such as skin redness or lung inflammation (called radiation recall syndrome)
• Worsening of radiotherapy 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 discontinued 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 that is not listed in this leaflet. You can also report them directly through the Spanish Medicines Monitoring System: 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 TAD

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 from light.

This medicine does not require any special storage temperature

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 TAD

• The active ingredient is everolimus.

Each tablet contains 5 mg or 10 mg of everolimus.

• The other ingredients are butylhydroxytoluene (E321), hypromellose (E464), lactose, lactose monohydrate, crospovidone (E1202), and magnesium stearate (E470b). See section 2 "Everolimus TAD contains lactose".

Appearance and Package Contents

Everolimus TAD tablets are available in two concentrations:

Everolimus TAD 5 mg are white to off-white, oval, biconvex tablets (approximately 13 x 6 mm), engraved with E9VS 5 on one side.

Everolimus TAD 10 mg are white to off-white, oval, biconvex tablets (approximately 16 x 8 mm), engraved with E9VS 10 on one side.

Everolimus TAD is available in packages containing 10, 30, or 90 tablets.

Not all pack sizes may be marketed.

Marketing Authorization Holder

TAD Pharma GmbH,

Heinz-Lohmann-Straße 5,

27472 Cuxhaven,

Germany

Manufacturer:

Synthon Hispania, S.L.,

C/ Castelló no1, Pol. Las Salinas,

Sant Boi de Llobregat, Barcelona,

Spain.

or

Synthon BV,

Microweg 22, Nijmegen,

6545 CM,

Netherlands.

or

KRKA, d.d., Novo mesto

Šmarješka cesta 6

8501 Novo mesto

Slovenia

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

KRKA Farmacéutica, S.L., C/ Anabel Segura 10, 28108 Alcobendas, Madrid, Spain

This medicine is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Date of the last revision of this leaflet: April 2023

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)