Patient Information Leaflet

Everolimus Ethypharm 2.5 mg Tablets

Read this leaflet carefully before you start taking this medicine, as it contains important information for you.

• Keep this 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 leaflet. See section 4.

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

2. What you need to know before taking Everolimus Ethypharm

3. How to take Everolimus Ethypharm

4. Possible side effects

5. Storage of Everolimus Ethypharm

6. Contents of the pack and additional information

Everolimus Ethypharm 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 Ethypharm 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 Ethypharm 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 Ethypharm or the reason why you have been prescribed this medicine, consult your doctor.

Do not takeEverolimus Ethypharm

• 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 takeEverolimus Ethypharm:

• if you have liver problems or if you have had any disease that may have affected your liver.Your doctor may prescribe a different dose of everolimus in this case.
• if you have diabetes (high blood sugar levels).Everolimus may increase blood sugar levels and worsen diabetes mellitus.You may need 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 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 this 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 infectionwhile taking everolimus.Inform your doctor if you have a fever or other signs of infection.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 stop 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 complications from radiation therapy.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 taking everolimus shortly after receiving radiation therapy.A 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.

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 level), and blood sugar and cholesterol levels.These tests are performed because these may be affected by everolimus treatment.

Children and adolescents

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

Other medicines andEverolimus Ethypharm

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

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

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

• 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 heartbeat.
• ciclosporin, a medicine used to prevent the body from rejecting transplanted organs.

used to treat transplant rejection.

• 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 epilepsy 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 drugs used to control seizures or attacks.

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

TakingEverolimus Ethypharmwith food and drinks

Do not take grapefruit or grapefruit juice while takingEverolimus Ethypharm. It may increase the amount ofEverolimus Ethypharmin the blood, possibly to a harmful level.

Pregnancy, breastfeeding, and fertility

Pregnancy

Everolimusmay cause harm to the fetus and is not recommended for use 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 moreof this medicine.

Breastfeeding

Everolimusmay cause harm to the breastfeeding baby.Do not breastfeed during treatment and for 2 weeks after the last dose ofeverolimus. Inform your doctor if you are breastfeeding.

Female fertility

In some patients treated witheverolimusamenorrhea (absence of menstrual periods) has been observed.

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

Male fertility

Everolimusmay 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 Ethypharm contains lactose

This medicine contains lactose (milk sugar).If your doctor has told you that you have a certain sugar intolerance, consult with them 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 tablets of Everolimus Ethypharm you should take.

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

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

Take Everolimus Ethypharm 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 Ethypharm than you should

• If you have taken too much Everolimus Ethypharm, 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.

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 forgot to take Everolimus Ethypharm

If you have forgotten a dose, take the next dose at the time it is due. Do not take a double dose to compensate for the missed doses.

If you interrupt treatment with Everolimus Ethypharm

Do not stop treatment with Everolimus Ethypharm 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 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 production, increased appetite with weight loss, fatigue (signs of diabetes)
• Bleeding (hemorrhage), for example in the intestinal wall
• Significant decrease in urine production (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 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 production, 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
• Mouth ulcers
• 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)
• 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)
• Excessive thirst, decreased urine production, dark urine, dry, red, and irritated 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
• Inflammation of the mucous membranes of 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
• 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
• Proteins 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 pink eye (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 the 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(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 adverse reactions worsen, report them to your doctor and/or pharmacist. Most side effects are mild to moderate and usually disappear if treatment is interrupted 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: 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.

Do not store at a temperature above 25°C.

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 at the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medications that you no longer need. By doing so, you will help protect the environment.

Composition of Everolimus Ethypharm

• The active ingredient is everolimus.

Each Everolimus Ethypharm tablet contains 2.5 mg of everolimus.

• The other components arebutylated hydroxytoluene (E321), hypromellose, lactose monohydrate, crospovidone, lactose, and magnesium stearate.

Appearance of the product and contents of the package

Everolimus Ethypharm 2.5 mg tablets are white to off-white, oblong-shaped tablets, 9.6 x 4.5 mm. It hasthe inscription"E" on one face and "2.5" on the other.

Everolimus Ethypharm 2.5 mg is available in packages containing 30 or 90 tablets.

Only some package sizes may be marketed.

Marketing Authorization Holder

Ethypharm

194 Bureaux de la Colline – Building D

92213 Saint-Cloud cedex

France

Responsible for manufacturing

Ethypharm

Chemin de la Poudrière

76120 Grand Quevilly

France

Ethypharm

Z.I. de Saint Arnoult

28170 Châteauneuf en Thymerais

France

For more information about this medication, please contact the local representative of the marketing authorization holder:

ALTAN PHARMACEUTICALS S.A.

C/Colquide, Nº 6, Portal 2, 1st floor, Office F. Edificio Prisma

Las Rozas (Madrid)

28230 Spain

This medication is authorized in the member states of the European Economic Area withthe following names:

Last reviewed date of this leaflet 04/2023.

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