Package Leaflet: Information for the Patient

Everolimus TAD 5 mg Tablets EFG

Everolimus TAD 10 mg Tablets EFG

Read this package leaflet carefully before you start taking this medicine because it contains important information for you.

-Keep this package leaflet, as you may need to read it again.

• If you have any questions, consult your doctor or pharmacist.

-This medicine has been prescribed for you only. Do not give it to others even if they have the same symptoms as you, as it may harm them.

-If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this package leaflet. See section 4.

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

2.What you need to know before starting to take Everolimus TAD

3.How to take Everolimus TAD

4.Possible side effects

5.Storage of Everolimus TAD

6.Contents of the pack and additional information

Everolimus TAD 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.

Everolimus TAD is used to treat adult patients with:

• advanced breast cancer with hormone receptor-positive in postmenopausal women, in whom other treatments (designated as "non-steroidal aromatase inhibitors") cannot continue to keep the disease under control. It is administered along with a type of medication called exemestane, a steroidal aromatase inhibitor, which is used for hormonal treatment of cancer.

• tumors advanced called neuroendocrine tumors that originate in thestomach, intestine, lung orpancreas. It is administered if the tumors are not operable and do not produce an excess of specific hormones or well other natural substances related.
• advanced kidney cancer (advanced renal cell carcinoma), when other treatments (designated as anti-VEGF treatment) have not helped to stop their disease.

Everolimus TAD will only be prescribed to you by a doctor with experience in cancer treatment. Follow carefully all the instructions given by your doctor. These may be different from the general information contained in this leaflet. If you have any doubts about Everolimus TAD or the reason why you have been prescribed this medicine, consult your doctor.

Do not take Everolimus TAD

• if you are allergicto everolimus, related substances such as sirolimus or temsirolimus, or to any of the other components 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 haveliver problemsor if you have had anyillnessthat may have affected your liver. In this case, your doctor may prescribe a different dose of Everolimus TAD.
• if you havediabetes(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 drugs. Inform your doctor if you notice excessive thirst or if you need to urinate more frequently.
• if you need to receive avaccinewhile taking Everolimus TAD.
• if you have ahigh cholesterol level. Everolimus TAD may increase cholesterol and/or other blood fats.
• if you have recently undergone amajor surgical operation, or if you still have anunhealed woundafter a surgical operation. Everolimus TAD may increase the risk of wound healing problems.
• if you have aninfection. You may need to treat your infection before starting treatment with Everolimus TAD.
• if you have previously hadhepatitis B, as this may reactivate during treatment with Everolimus TAD (see section 4«Adverse reactions»).
• if you have received or are about to receiveradiotherapy.

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 fatal.

-affect kidney function. Therefore, your doctor will monitor your kidney function while 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 may worsen the ulcers, so do not try any without first consulting your doctor. Your doctor may restart treatment with everolimus at the same dose or a lower dose.
• cause complications of radiotherapy. Severe complications of radiotherapy (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 radiotherapy or taking everolimus shortly after receiving radiotherapy. Radiation recall syndrome (which presents with redness of the skin or inflammation of the lungs in the area of previous radiotherapy) has also been reported in patients who had received radiotherapy in the past.

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

Inform your doctorif you experience these symptoms.

During treatment, you will have blood tests performed periodically. These tests will determine the number of cells in your blood (white blood cells, red blood cells, and platelets) to check if Everolimus TAD 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 treatment with Everolimus TAD.

Children and adolescents

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

Other medicines and Everolimus TAD

Everolimus TAD may affect how 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.

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

The following may increase the risk of adverse reactions with Everolimus TAD:

• ketoconazole,itraconazole,voriconazole, orfluconazoleand otherantifungal medicinesused to treat fungal infections.
• clarithromycin,telithromycinorerythromycin,antibioticsused to treat bacterial infections.
• ritonavirandother medicines used to treat HIV/AIDS.
• verapamilordiltiazem, used to treat heart problems or high blood pressure.
• dronedarone, a medicine used to help regulate your heart rhythm.
• ciclosporin, a medicine used to prevent your body from rejecting transplanted organs.
• imatinib, used to inhibit the growth of abnormal cells.
• angiotensin-converting enzyme (ACE) inhibitors(such asramipril) used to treat high blood pressure or other cardiovascular problems.
• nefazodone, used to treat depression.
• cannabidiol(its use includes, among others, the treatment of epilepsy seizures).

The following may reduce the effectiveness of Everolimus TAD:

• rifampicin, used to treat tuberculosis (TB).
• efavirenzornevirapine, 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,carbamazepineorphenobarbitaland otherantiepileptic medicinesused to control seizures.

You should avoid using these medicines 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 your blood, possibly to a harmful level.

Pregnancy, breastfeeding, and fertility

Pregnancy

Everolimus TAD may cause harm to the fetus and is not recommended 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 medicine during pregnancy.

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

Breastfeeding

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

Female fertility

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

Everolimus TAD may affect female fertility. Inform 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 operating machines

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

Everolimus TAD contains lactose

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

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

The recommended dose is 10 mg, once a day. Your doctor will inform you about how many Everolimus TAD tablets you should 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 adverse effects while taking Everolimus TAD (see section 4), your doctor may reduce the dose you take or interrupt treatment for a short period of time or permanently.

Take Everolimus TAD once a day, more or less at the same time, always with food or always without food.

Swallow the tablets 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 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.

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

If you forget to take Everolimus TAD

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 doses.

If you interrupt treatment with Everolimus TAD

Do not stop treatment with Everolimus TAD 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 treatment with everolimus and seek medical help 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
• Intense itching of the skin, with red rash or bumps on the skin

The serious side 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, 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 stools, dark urine (may be signs of reactivation of hepatitis B)
• Sensation of 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 in the affected skin area (signs of venous thrombosis in the legs caused by a blood clot)
• Sudden onset of breathing difficulties, 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 insufficiency)
• 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 everolimus include:

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

• High blood sugar (hyperglycemia)
• Loss of appetite
• Alteration of taste (dysgeusia)
• Headache
• Nasal bleeding (epistaxis)
• Cough
• Mouth ulcers
• Stomach discomfort, including 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)
• Excessive thirst, decreased urine output, dark urine, dry, red, and irritated skin, irritability (signs of dehydration)
• Insomnia (difficulty sleeping)
• Headache, dizziness (signs 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, leukopenia, lymphopenia, and/or neutropenia)
• Fever
• Inflammation of the mucous membranes of the mouth, stomach, and intestines
• 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
• Irregular menstrual periods
• High levels of lipids (fats) in the blood (hyperlipidemia, increased triglycerides)
• Low levels of potassium in the blood (hypokalemia)
• Low levels of phosphate in the blood (hypophosphatemia)
• Low levels of calcium 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, such as absence of periods (amenorrhea)
• Increased frequency of urination during the day
• Chest pain
• Abnormal wound healing
• Hot flashes
• Excessive tearing with itching and redness, or red eye 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 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(the frequency cannot be estimated from the available data)

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

If these adverse 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 of adverse reactions

If you experience any type of adverse reaction, consult your doctor or pharmacist, even if it is a possible adverse reaction that does not appear in this prospectus. You can also report them directly through the Spanish System of Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es. By reporting adverse reactions, 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 in the blister pack. The expiration date is the last day of the month indicated.

Store in the original packaging to protect it from light.

This medication does not require any special storage temperature.

Medications should not be disposed of through drains or in the trash. Dispose of packaging and medications you no longer need at the SIGRE collection point at the pharmacy.If in doubt, ask your pharmacist how to dispose of packaging and medications you no longer need. This will help protect the environment.

Composition of Everolimus TAD

• The active ingredient is everolimus.

Each tablet contains 5 mg or 10 mg of everolimus.

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

Appearance of the product and contents of the package

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.

Only some package sizes may be marketed.

Marketing Authorization Holder

TAD Pharma GmbH,

Heinz-Lohmann-Straße 5,

27472 Cuxhaven,

Germany

Responsible for manufacturing:

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

8501Novo mesto

Slovenia

For further information about this medicinal product, please contact the local representative of the marketing authorization holder:

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

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

Last update of the summary of product characteristics: April 2023

Further information on this medicinal product is available on the website of the Spanish Agency of Medicines and Medical Products (AEMPS)athttp://www.aemps.gob.es.