Package Insert: Information for the Patient

Everolimus Accord 5 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 refer to 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 who may 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.

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

Do not take Everolimus Accord

• if you are allergicto everolimus, related substances such as sirolimus or temsirolimus, or 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 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 levels). Everolimus Accord 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 Accord.
• if you have high cholesterol levels. Everolimus Accord 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 Accord may increase the risk of wound healing problems.
• if you have an infection. You may need to treat your infection before starting treatment with Everolimus Accord.
• if you have previously had hepatitis B, as it may reactivate during treatment with Everolimus Accord (see section 4 "Possible side effects").
• if you have received or are about to receive radiation therapy.

Everolimus Accord may also:

• weaken your immune system. Therefore, you may be at risk of infection while taking Everolimus Accord. 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 Accord.
• cause difficulty breathing, cough, and fever.
• cause complications from radiation therapy. Severe complications from radiation therapy (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 taking everolimus shortly after receiving radiation therapy. Radiation recall syndrome (presenting 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.
• cause the appearance of mouth ulcers and sores. Your doctor may need to interrupt or discontinue treatment with Everolimus Accord. 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 treatment with Everolimus Accord at the same dose or a lower dose.

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 Accord 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 Accord.

Children and adolescents

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

Other medications and Everolimus Accord

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

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

The following may increase the risk of side effects with Everolimus Accord:

• 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 (its use includes, among others, the treatment of 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 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 treatment with Everolimus Accord. If you are taking any of them, your doctor may prescribe a different medication, or may change your dose of Everolimus Accord.

Taking Everolimus Accord with food and drinks

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

Pregnancy, breastfeeding, and fertility

Pregnancy

Everolimus Accord 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 medication 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 Accord.

Breastfeeding

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

Female fertility

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

Everolimus Accord may affect female fertility. Inform 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 operating machinery

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

Everolimus Accord contains lactose

If your doctor has told you that you have a intolerance to certain sugars, consult with them before taking this medication.

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

The recommended dose is 10 mg, once a day. Your doctor will inform you 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 Accord than you should

• If you have taken too much everolimus, or if someone has taken your tablets by accident, 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.

If you forget to take Everolimus Accord

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 Accord

Do not stop 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, pale 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 of the legs, 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)
• Onset of sudden 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)

potentially by a blood clot)

• 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)

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 may indicate an abnormal accumulation of fluid in soft tissues due to a blockage of the lymphatic system, also known as lymphedema)

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
• Ulcers in the mouth
• Stomach discomfort, including nausea or diarrhea
• Skin rash
• Itching (pruritus)
• Feeling weak or tired
• Tiredness, difficulty breathing, dizziness, pale skin, signs of low red blood cell count (anemia)

glóbulos rojos (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, and irritated skin (signs of dehydration)
• Insomnia (difficulty sleeping)
• Headache, dizziness (signs of high blood pressure, also known as hypertension)
• Swelling of one or both arms (including fingers) or legs (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 membranes of the mouth, stomach, and intestines
• Dry mouth
• Heartburn (dyspepsia)
• Vomiting
• Difficulty swallowing (dysphagia)
• Abdominal pain
• Acne
• Skin 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
• Epiphora with itching and redness, or eye redness or redness (conjunctivitis)

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

• Tiredness, 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

Frequency not known(cannot be estimated from available data)

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

If these 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 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 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 special temperature conditions for storage.

Medications should not be disposed of through drains or in the trash. Dispose of packaging and unused medications at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of unused packaging and medications. By doing so, you will help protect the environment.

Composition of Everolimus Accord

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

Appearance of the product and content of the container

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

Everolimus Accord 5 mg tablets EFG is available in containers that contain 10, 30, or 90 tablets.

Only some container sizes may be commercially marketed.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Accord Healthcare S.L.U.

Moll de Barcelona s/n.

World Trade Center. Edifici Est 6th floor

08039 Barcelona

Spain

Responsible for manufacturing

Synthon Hispania, S.L.

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

08830 Barcelona

Spain

O

Synthon BV

Microweg, 22

6545 CM Nijmegen

Netherlands

Last review date of this leaflet:June 2022

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