Everolimus Sinthon

Leaflet included in the packaging: patient information

Everolimus Genthon, 2.5 mg, tablets

Everolimus Genthon, 5 mg, tablets

Everolimus Genthon, 10 mg, tablets

Everolimus

It is necessary to carefully read the contents of the leaflet before taking the medicine, as it contains important information for the patient.

• It is necessary to keep this leaflet, so that it can be re-read if necessary.
• In case of any doubts, you should consult a doctor or pharmacist.
• This medicine has been prescribed to a specific person. It should not be given to others. The medicine may harm another person, even if the symptoms of their illness are the same.
• If the patient experiences any undesirable symptoms, including any undesirable symptoms not listed in this leaflet, they should inform their doctor or pharmacist. See section 4.

Table of contents of the leaflet

• 1. What is Everolimus Genthon and what is it used for
• 2. Important information before taking Everolimus Genthon
• 3. How to take Everolimus Genthon
• 4. Possible side effects
• 5. How to store Everolimus Genthon
• 6. Contents of the packaging and other information

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

Everolimus Genthon is an anticancer medicine that contains the active substance everolimus.
Everolimus reduces blood flow to the tumor and slows down the growth and spread of cancer cells.
Everolimus Genthon is used to treat adult patients with:

• advanced breast cancer with hormonal receptor expression in postmenopausal women, in whom other medicines (so-called "non-steroidal aromatase inhibitors") have stopped controlling the disease. This medicine is given together with exemestane, a steroid aromatase inhibitor used in hormonal anticancer therapy.
• advanced neuroendocrine tumors that originate from the stomach, intestines, lungs, or pancreas. This medicine is given if the tumors are inoperable and do not secrete excessive amounts of specific hormones or other related natural substances.
• advanced kidney cancer (advanced renal cell carcinoma) when other medicines (called anti-VEGF therapy) have proven ineffective.

2. Important information before taking Everolimus Genthon

Everolimus Genthon may only be prescribed by a doctor specializing in the treatment of cancer. All the doctor's instructions must be followed. They may differ from the general information contained in this leaflet. If additional information about Everolimus Genthon and an explanation of why this medicine was chosen are needed, the patient should contact their doctor.

When not to take Everolimus Genthon:

• If the patient is allergicto everolimus, similar substances such as sirolimus or

temsirolimus, or any of the other ingredients of this medicine (listed in section 6). In case of suspected allergy, the patient should consult their doctor.

Warnings and precautions

Before starting treatment with Everolimus Genthon, the patient should discuss the following with their doctor:

• If the patient has liver problemsor diseases that may have affected liver function. In such cases, the doctor may change the dose of Everolimus Genthon.
• If the patient has diabetes(high blood sugar). Everolimus Genthon may increase blood sugar levels and worsen diabetes. This condition may require insulin and/or oral antidiabetic drugs. The patient should inform their doctor if they experience excessive thirst or frequent urination.
• If the patient needs to be vaccinatedduring treatment with Everolimus Genthon.
• If the patient has high cholesterol levels. Everolimus Genthon may increase cholesterol and/or other fats in the blood.
• If the patient has recently undergone major surgeryor has unhealed wounds, resulting from surgery. Everolimus Genthon may hinder wound healing.
• If the patient has an infection. Before starting treatment with Everolimus Genthon, it may be necessary to treat the existing infection.
• If the patient has had hepatitis B in the past, as it may reactivate during treatment with Everolimus Genthon (see section 4, "Possible side effects").

Everolimus Genthon may also:

• weaken the immune system. Therefore, the patient may be at risk of infection while taking Everolimus Genthon.
• affect kidney function. Therefore, during treatment with Everolimus Genthon, the doctor will monitor kidney function.
• cause shortness of breath, cough, and fever.
• cause the development of mouth ulcers and sores. The doctor may interrupt or discontinue treatment with Afinitor. The patient may need treatment with mouthwashes, gels, or other products. Some mouthwashes and gels may worsen ulcers, so the patient should not try anything without consulting their doctor. The doctor may restart treatment with Afinitor at the same or lower dose. The patient should inform their doctorif they experience these symptoms.

During treatment, the patient will undergo regular blood tests to monitor the number of blood cells (white blood cells, red blood cells, and platelets) and to check if Everolimus Genthon has a negative effect on blood cells. Blood tests will also be performed to monitor kidney function (creatinine levels), liver function (transaminase activity), as well as blood sugar and cholesterol levels, as Everolimus Genthon may affect them.

Children and adolescents

Everolimus Genthon is not given to children and adolescents (under 18 years of age).

Everolimus Genthon and other medicines

Everolimus Genthon may affect the action of other medicines. If the patient is taking other medicines at the same time as Everolimus Genthon, the doctor may change the dose of Everolimus Genthon or other medicines.
The patient should tell their doctor or pharmacistabout all the medicines they are currently taking or have recently taken, as well as any medicines they plan to take.
The following medicines taken with Everolimus Genthon may increase the risk of side effects:

• Ketoconazole, itraconazole, voriconazoleor fluconazole, other antifungal medicinesused to treat fungal infections.
• Clarithromycin, telithromycinor erythromycin, antibioticsused to treat bacterial infections.
• Ritonavirand other medicines used to treat HIV/AIDS.
• Verapamilor diltiazemused to treat heart diseases or high blood pressure.
• Dronedarone, a medicine that helps restore a regular heart rhythm.
• Cyclosporine, a medicine used to prevent transplant rejection by the body.
• Imatinib, which inhibits 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

The following medicines may reduce the effectiveness of Everolimus Genthon:

• Rifampicinused to treat tuberculosis.
• Efavirenzor nevirapine, used to treat HIV/AIDS.
• St. John's Wort(Hypericum perforatum), a herbal product used to treat depression and other disorders.
• Dexamethasone, a corticosteroid used to treat various diseases, including inflammatory conditions or immune disorders.
• Phenytoin, carbamazepineor phenobarbitaland other antiepileptic medicinesused to prevent various types of seizures.

The patient should avoid taking these medicines during treatment with Everolimus Genthon. If the patient is taking any of the above medicines, the doctor may replace them with another medicine or change the dose of Everolimus Genthon.

Taking Everolimus Genthon with food and drink

The patient should avoid eating grapefruits and drinking grapefruit juice during treatment with Everolimus Synthon.

Pregnancy, breastfeeding, and fertility

Pregnancy
It is not recommended to take Everolimus Genthon during pregnancy, as it may harm the unborn child. The patient should inform their doctor if they are pregnant or think they may be pregnant. The doctor will inform the patient whether they can take this medicine during pregnancy.
Women who may become pregnant during treatment should use highly effective contraceptive methods. If, despite these measures, the patient suspects they may have become pregnant, they should contact their doctor beforetaking Everolimus Genthon.
Breastfeeding
Everolimus Genthon may harm the breastfed child. The patient should not breastfeed during treatment and for 2 weeks after the last dose of everolimus. The patient should inform their doctor if they are breastfeeding.
Female fertility
In some patients taking Everolimus Genthon, menstrual irregularities have been observed (amenorrhea).
Everolimus Genthon may affect female fertility. The patient should discuss this with their doctor if they want to have children.
Male fertility
Everolimus Genthon may affect male fertility. The patient should tell their doctor if they want to become a father.

Driving and using machines

If the patient experiences fatigue of unknown cause (fatigue is a very common side effect), they should be particularly careful when driving vehicles and operating machines.

Everolimus Genthon contains lactose

If the patient has been diagnosed with intolerance to some sugars, they should contact their doctor before taking the medicine.

3. How to take Everolimus Genthon

This medicine should always be taken exactly as prescribed by the doctor or pharmacist. In case of doubts, the patient should consult their doctor.
The recommended dose is 10 mg, taken once a day. The doctor will determine how many tablets to take.
In case of liver problems, the doctor may start treatment with a lower dose of Everolimus Genthon (2.5, 5, or 7.5 mg per day).
In case of certain side effects during treatment with Everolimus Genthon (see section 4), the doctor may reduce the dose or interrupt treatment, temporarily or permanently.
Everolimus Genthon should be taken once a day, at the same time of day, always in the same way, with or without food.
The tablet(s) of Everolimus Genthon should be swallowed whole, with a glass of water. The tablets should not be chewed or crushed.

Taking a higher dose of Everolimus Genthon than recommended

• In case of taking a higher dose of Everolimus Genthon than recommended or if another person accidentally takes the tablets, the patient should immediately consult their doctor or go to the hospital. Emergency medical attention may be necessary.
• The patient should show their doctor the carton of the medicine and this leaflet, so that it can be determined which medicine was overdosed.

Missing a dose of Everolimus Genthon

In case of missing a dose, the patient should take the next planned dose. They should not take a double dose to make up for the missed tablet.

Stopping treatment with Everolimus Genthon

The patient should not stop taking Everolimus Genthon without their doctor's advice.
In case of any further doubts related to the use of this medicine, the patient should consult their doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The patient should STOPtaking Everolimus Genthon and seek medical help immediately if they experience any of the following symptoms of an allergic reaction:

• Difficulty breathing or swallowing
• Swelling of the face, lips, tongue, or throat
• Increasing redness of the skin, with a rash and bumps

The following are serious side effects of Everolimus Genthon:

Very common(may affect more than 1 in 10 patients)
Increased temperature, chills (infection symptoms) •Fever, cough, difficulty breathing, wheezing (pneumonia symptoms)
Common(may affect up to 1 in 10 patients)
Increased thirst, frequent urination, increased appetite with weight loss, fatigue (diabetes symptoms) •Bleeding (e.g., in the intestinal wall) •Severe reduction in the amount of urine excreted (kidney failure symptom)
Uncommon(may affect up to 1 in 100 patients)
Fever, rash, joint pain, as well as fatigue, loss of appetite, nausea, jaundice (yellowing of the skin), pain in the upper right abdomen, pale stools, dark urine color (may be symptoms of hepatitis B reactivation) •Shortness of breath, difficulty breathing when lying down, swelling of the feet or ankles (heart failure symptoms) •Swelling and/or pain in one leg, usually in the calf, with redness or warmth of the skin in the affected area (symptoms of deep vein thrombosis)
Rare(may affect up to 1 in 1000 patients)
Shortness of breath, cough, fever (symptoms of pulmonary embolism, which occurs when one or more pulmonary arteries become blocked)

The patient should immediately inform their doctor if they experience any of the above side effects, as they may be life-threatening.

Other possible side effects of Everolimus Genthon include:

Very common(may affect more than 1 in 10 patients)
Fatigue, shortness of breath, dizziness, paleness, symptoms of low red blood cell count (anemia) •High blood sugar levels (hyperglycemia) •Loss of appetite •High levels of lipids (fats) in the blood (hypercholesterolemia) •Taste disorders •Headache •Nosebleeds (nosebleeds) •Cough •Mouth sores •Stomach upset, including nausea (nausea) or diarrhea •Skin rash •Itching (pruritus) •Feeling of weakness or fatigue •Swelling of the arms, hands, feet, ankles, and other parts of the body (edema symptoms) •Weight loss
Common(may affect up to 1 in 10 patients)
Appearance of sudden bleeding or bruising (symptoms of low platelet count, also known as thrombocytopenia) •Fever, sore throat, mouth sores caused by infection (symptoms of low white blood cell count, leukopenia, lymphopenia, and/or neutropenia) •Shortness of breath (dyspnea) •Feeling of thirst, low urine output, dark urine color, dry reddened skin, irritability (symptoms of dehydration) •Sleep disorders (insomnia) •Headaches, dizziness (symptoms of high blood pressure, also known as hypertension) •Fever •Inflammation of the tissue lining the mouth, stomach, or intestines •Dry mouth •Heartburn (indigestion) •Vomiting •Difficulty swallowing (dysphagia) •Abdominal pain •Flatulence •Skin rash and pain in the hands and feet (hand-foot syndrome) •Redness of the skin (flushing) •Joint pain

• Pain in the mouth •Menstrual disorders, such as irregular menstrual bleeding •High levels of lipids (fats) in the blood (hyperlipidemia, increased triglyceride levels) •Low potassium levels in the blood (hypokalemia) •Low phosphate levels in the blood (hypophosphatemia)
• Low calcium levels in the blood (hypocalcemia) •Dry skin, peeling skin, skin conditions •Nail disorders, brittle nails •Moderate hair loss •Abnormal liver function test results (elevated alanine aminotransferase and aspartate aminotransferase activity) •Abnormal kidney function test results (elevated creatinine levels) •Eye discharge, accompanied by itching, redness, and swelling •Presence of protein in the urine

Uncommon(may affect up to 1 in 100 patients)
Weakness, unexpected bleeding or bruising, and frequent infections, with symptoms such as fever, chills, sore throat, or mouth sores (symptoms of low blood cell count, also known as pancytopenia) •Loss of taste (ageusia) •Coughing up blood (hemoptysis) •Menstrual disorders, such as amenorrhea •Frequent urination during the day •Chest pain •Wound healing problems •Hot flashes •Eye inflammation (conjunctivitis)

If the above side effects worsen, the patient should inform their doctor or pharmacist. Most side effects are mild or moderate and should resolve after discontinuing treatment for a few days.

Reporting side effects

If the patient experiences any side effects, including those not listed in the leaflet, they should inform their doctor or pharmacist. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw
Phone: +48 22 49 21 301, Fax: +48 22 49 21 309, e-mail: ndl@urpl.gov.pl
Reporting side effects helps to gather more information on the safety of the medicine.
Side effects can also be reported to the marketing authorization holder.

5. How to store Everolimus Genthon

The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after {Expiry date (EXP)}. The expiry date refers to the last day of the month stated.
Store in the original packaging to protect from light
There are no special instructions for storing the medicine at a certain temperature.
Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Everolimus Genthon contains

• The active substance of the medicine is everolimus. One tablet of Everolimus Genthon contains 2.5 mg, 5 mg, or 10 mg of everolimus
• The other ingredients are: butylhydroxytoluene (E321), hypromellose (E464), lactose, lactose monohydrate, crospovidone (E1202), magnesium stearate (E470b)

What Everolimus Genthon looks like and what the pack contains

Everolimus Genthon tablets are available in three strengths:
Everolimus Genthon 2.5 mg are white or almost white, oval, biconvex tablets (approximately 10 mm x 5 mm) with the inscription E9VS on one side and 2.5 on the other side.
Everolimus Genthon 5 mg are white or almost white, oval, biconvex tablets (approximately 13 mm x 6 mm) with the inscription E9VS 5 on one side.
Everolimus Genthon 10 mg are white or almost white, oval, biconvex tablets (approximately 16 mm x 8 mm) with the inscription E9VS 10 on one side.
Everolimus Genthon 2.5 mg is available in packs containing 30 or 90 tablets.
Everolimus Genthon 5 mg and Everolimus Genthon 10 mg are available in packs containing 10, 30, or 90 tablets.
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder
Genthon BV
Microweg 22
6545 CM Nijmegen
Netherlands
Manufacturer/Importer
Synthon BV
Microweg 22
6545 CM Nijmegen
Netherlands
Synthon Hispania, S.L.
C/Castellón n°1
Pol. Las Salinas
Sant Boi de Llobregat
08830 Barcelona
Spain

Date of last revision of the leaflet: 23.08.2019