Package Insert: Information for the Patient

Everolimus Stada 5 mg Tablets EFG

Everolimus Stada 10 mg Tablets EFG

Read this package insert carefully before starting to take this medication, as it contains important information for you.

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed only for you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

1. What is Everolimus Stada and how is it used

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

3. How to take Everolimus Stada

4. Possible adverse effects

5. Storage of Everolimus Stada

6. Contents of the package and additional informationadditional information

Everolimus is a cancer medication that contains the active ingredient everolimus. Everolimus reduces blood supply to the tumor and delays the growth and dissemination of cancer cells.

Everolimus 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 with a type of medication called exemestane, a steroidal aromatase inhibitor, which is used for hormonal treatment of cancer.

?advanced tumors known as neuroendocrine tumors that originate in the stomach, intestine, lung, or pancreas. It is administered if the tumors are not operable and do not produce specific hormones or other natural substances related to them.

?advanced kidney cancer (advanced renal cell carcinoma), when other treatments (designated as anti-VEGF treatment) have not helped to stop their disease.

Everolimus will only be prescribed to you by an experienced doctor in cancer treatment. Follow all the doctor's instructions carefully. They may be different from the general information contained in this prospectus. If you have any doubts about everolimus or the reason why you have been prescribed this medication, consult your doctor.

Do not take everolimus

• if you are allergicto everolimus, related substances such as sirolimus or temsirolimus, or to any of the other components of this medication (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:

• 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.
• if you have diabetes (high blood sugar levels). Everolimus 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 excessive thirst or if you need to urinate more frequently.
• if you need to be administered a vaccine while taking everolimus.
• if you have high cholesterol levels. Everolimus may increase cholesterol and/or other blood fats.
• if you have recently undergone major surgery, or if you still have an open wound after surgery. Everolimus may increase the risk of wound healing problems.
• if you have an infection. You may need to treat your infection before starting everolimus treatment.
• if you have previously had hepatitis B, as it may reactivate during everolimus treatment (see section 4 "Possible side effects").
• if you have received or are about to receive radiation therapy.

Everolimus may also:

• weaken your immune system. Therefore, you may be at risk of infection while taking everolimus. 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 you are taking everolimus.
• cause difficulty breathing, cough, and fever.
• cause the appearance of mouth ulcers and sores. Your doctor may need to interrupt or discontinue everolimus treatment. 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 consulting your doctor first. Your doctor may restart everolimus treatment at the same dose or a lower dose.
• cause radiation therapy complications. Severe radiation therapy complications (such as difficulty breathing, nausea, diarrhea, skin rash, and mouth, gum, and throat pain), including fatal cases, have been observed in some patients taking everolimus at the same time as receiving radiation therapy or who took 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 had received radiation therapy in the past.
• Inform your doctor if you are scheduled to receive radiation therapy soon, or if you have received radiation therapy previously.

Inform your doctorif you experience these symptoms.

During treatment, you will have blood tests performed periodically. These tests will determine the number of blood cells (white blood cells, red blood cells, and platelets) to check if everolimus is having an undesirable effect on these cells. You will also have blood tests to monitor kidney function (creatinine level), liver function (transaminase levels), and blood sugar and cholesterol levels. These tests are done because these may be affected by everolimus treatment.

Children and adolescents

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

Other medications and everolimus

Everolimus may affect how other medications work. If you are taking other medications at the same time as everolimus, your doctor may change the dose of everolimus or the other medications.

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

The following may increase the risk of side effects with everolimus:

• ketoconazole, itraconazole, voriconazole, or fluconazole and other antifungal medications used to treat fungal infections.
• clarithromycin, telithromycin, or erythromycin, antibiotics used to treat bacterial infections.
• ritonavir and other medications used to treat HIV/AIDS.
• verapamil or diltiazem, used to treat heart problems or high blood pressure.
• dronedarone, a medication used to help regulate your heart rhythm.
• ciclosporin, a medication used to prevent the body from rejecting transplanted organs.
• imatinib, used to inhibit the growth of abnormal cells.
• ACE inhibitors (such as ramipril) used to treat high blood pressure or other cardiovascular problems.
• nefazodone, used to treat depression.
• cannabidiol (uses include treatment of seizures).

The following may reduce the effectiveness of everolimus:

• 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 situations including inflammatory or immune problems.
• phenytoin, carbamazepine, or phenobarbital and other antiepileptic medications used to control seizures.

You should avoid using these medications during everolimus treatment. If you are taking any of them, your doctor may prescribe a different medication, or may change your everolimus dose.

Taking everolimus with food and drinks

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

Pregnancy, breastfeeding, and fertility

Pregnancy

Everolimus may cause harm to your 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 medication during pregnancy.

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

Breastfeeding

Everolimus may harm your breastfeeding baby. Do not breastfeed during treatment and for the

2 weeks following the last dose of everolimus. Inform your doctor if you are breastfeeding.

Female fertility

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

Everolimus may affect female fertility. Inform your doctor if you want to have children.

Male fertility

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

Driving and operating machinery

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

This medication contains lactose

Everolimus Stada contains lactose. If your doctor has told you that you have a certain sugar intolerance, consult with them before taking this medication.

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 tablets you should 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 adverse effects while taking everolimus (see section 4), your doctor may reduce the dose you take or interrupt treatment for a short period of time or permanently.

Take everolimus 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 Stada than you should

If you have taken too much everolimus, or if someone has taken your tablets by accident, consult your doctor or pharmacist immediately, or call the Toxicological Information Service, phone: 91 562 04 20. Urgent treatment may be necessary.

Take the packaging and this leaflet so that the doctor knows what you have taken.

If you forgot to take Everolimus Stada

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 Stada

Do not interrupt treatment with everolimus 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 taking everolimus and seek medical help immediately 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

?Intense itching of the skin, with red rash or lumps 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 (yellow discoloration of the skin), right upper abdominal pain, light stools, dark urine (may be signs of reactivation of hepatitis B)

?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 heat in the skin in the affected 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, 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 have fatal consequences.

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

?Ulcers in the mouth

?Stomach discomfort, including nausea or diarrhea

?Skin rash

?Itching (pruritus)

?Feeling weak or tired

?Tiredness, difficulty breathing, dizziness, paleness of the 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)

?Bleeding or bruising (signs of low platelet count, also known as thrombocytopenia)

?Difficulty breathing (dyspnea)

?Thirst, decreased urine output, dark urine, dry, red skin, irritability (signs of dehydration)

?Insomnia

?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, leucopenia, lymphopenia, and/or neutropenia)

?Fever

?Mucosal inflammation in 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

?Changes in menstruation, 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

?Changes in nails, nail breakage

?Mild hair loss

?Abnormal liver function test results (increased alanine and aspartate aminotransferase)

?Abnormal kidney function test results (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)

?Changes in menstruation, such as absence of periods (amenorrhea)

?Increased urine output during the day

?Chest pain

?Abnormal wound healing

?Hot flashes

?Redness, itching, or discharge with a pink or red eye (conjunctivitis)

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

?Tiredness, difficulty breathing, dizziness, paleness of the 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 the mucous membrane 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(cannot be estimated from available data)

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

Reporting of side effects

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

This medication does not require any special storage temperature.Store in the original packaging to protect it from light.

Open the blister pack just before taking the tablets.

Do not use this medication if you observe that the packaging is damaged or shows signs of manipulation.

Medications should not be disposed of through drains or in the trash. Deposit the packaging and medications that you no longer need at the SIGRE collection point of the pharmacy. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. In this way, you will help protect the environment.

Composition of Everolimus Stada

?The active ingredient is everolimus.

????????Each Everolimus Stada 5 mg tablet contains 5 mg of everolimus.

Each Everolimus Stada 10 mg tablet contains 10 mg of everolimus.

?The other components are: butylated hydroxytoluene (E321), hypromellose type 2910 (E464), lactose, crospovidone type A (E1202), magnesium stearate.

Appearance of the product and contents of the package

The Everolimus Stada 5 mg tablets arewhite to off-white, oval, flat, engraved with«EVR»on one side and«5»on the other, approximately 12 mm long and 5 mm wide.

The Everolimus Stada 10 mg tablets arewhite to off-white, oval, flat, engraved with«EVR»on one side and«NAT»on the other, approximately 15 mm long and 6 mm wide.

Everolimus Stada is available in packages containing 10, 30 or 90 tablets or 10x1, 30x1, 90x1 tablets (single-dose).

Only some package sizes may be commercially available.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

STADA Laboratorios, S.L.

Frederic Mompou, 5

08960 Sant Just Desvern (Barcelona)

Spain

[email protected]

Responsible for manufacturing

STADA Arzneimittel AG

Stadastrasse 2 – 18

61118 Bad Vilbel

Germany

or

STADA Arzneimittel GmbH

Muthgasse 36/2

1190 Vienna

Austria

or

Genepharm S.A.

18th Km Marathonos Avenue

153 51 Pallini Athens

Greece

or

Pharmadox Healthcare Ltd

KW20A Kordin Industrial Park

PLA 3000 Paola

Malta

or

Pharmacare Premium Ltd

HHF003 Hal Far Industrial Estate, Birzebbugia, BBG3000,

Malta

Last review date of this leaflet:August 2022

Detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/