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

You should carefully read the contents of the leaflet before taking the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• In case of any doubts, you should consult a doctor or pharmacist.
• This medicine has been prescribed to you by a doctor for a specific person. Do not pass it on 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 who specializes in the treatment of cancer. You should follow all the doctor's recommendations. They may differ from the general information contained in this leaflet. If you need additional information about Everolimus Genthon and an explanation of why this medicine was chosen, you should contact your 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, you should consult a doctor.

Warnings and precautions

Before starting treatment with Everolimus Genthon, you should discuss the following with your doctor:

• If the patient has liver problemsor diseases that may have affected liver function. In such a case, 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 the administration of insulin and/or oral antidiabetic drugs. You should inform your doctor if you 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 levels and/or other fats in the blood.
• If the patient has recently undergone major surgeryor has unhealed woundsresulting 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 cure the existing infection.
• If the patient has had hepatitis B in the past, as it may lead to the reactivation of the disease 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 ulcers. 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 you should not try anything without consulting a doctor. The doctor may restart treatment with Afinitor at the same or lower dose. You should inform your doctorif you 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 should not be 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.
You should tell your doctor or pharmacistabout all the medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans 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 disease 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.

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

Taking Everolimus Genthon with food and drink

You should avoid eating grapefruits and drinking grapefruit juice during treatment with Everolimus Genthon.

Pregnancy, breastfeeding, and fertility

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

Driving and using machines

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

Everolimus Genthon contains lactose

If you have been diagnosed with intolerance to some sugars, you should contact your doctor before taking the medicine.

3. How to take Everolimus Genthon

This medicine should always be taken exactly as prescribed by your doctor or pharmacist. In case of doubts, you should consult your 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 of the medicine or interrupt treatment, for a short time 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, you should immediately consult a doctor or go to the hospital. Emergency medical attention may be necessary.
• You should show the doctor the carton of the medicine and this leaflet, so that they can determine which medicine has been overdosed.

Missing a dose of Everolimus Genthon

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

Stopping treatment with Everolimus Genthon

You should not stop taking Everolimus Genthon without consulting your doctor.
In case of any further doubts related to the use of this medicine, you should consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
You should STOPtaking Everolimus Genthon and seek medical help immediately if you 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 people)
High temperature, chills (infection symptoms) • Fever, cough, difficulty breathing, wheezing (pneumonia symptoms)
Common(may affect up to 1 in 10 people)
Increased thirst, frequent urination, increased appetite with weight loss, fatigue (diabetes symptoms) • Bleeding (e.g., gastrointestinal bleeding) • Severe reduction in urine output (kidney failure symptom)

You should immediately inform your doctor if you 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 people)
Fatigue, shortness of breath, dizziness, paleness (anemia symptoms) • High blood sugar levels (hyperglycemia) • Loss of appetite • High levels of lipids (fats) in the blood (hypercholesterolemia) • Taste disorders • Headache • Nosebleeds (epistaxis) • Cough • Mouth ulcers • Gastrointestinal disorders, including nausea (nausea) or diarrhea • Skin rash • Itching (pruritus) • Feeling of weakness or fatigue • Swelling of arms, hands, feet, ankles, and other parts of the body (edema symptoms) • Weight loss •
Common(may affect up to 1 in 10 people)
Appearance of sudden bleeding or bruising (thrombocytopenia symptoms) • Fever, sore throat, mouth ulcers caused by infection (leukopenia, lymphopenia, and/or neutropenia symptoms) • Shortness of breath (dyspnea) •
Thirst, low urine output, dark urine, dry reddened skin, irritability (dehydration symptoms) • Sleep disorders (insomnia) • Headache, dizziness (high blood pressure symptoms) • Fever • Inflammation of the lining of the mouth, stomach, or intestines • Dry mouth • Heartburn (dyspepsia) • Vomiting • Difficulty swallowing (dysphagia) • Abdominal pain • Flatulence • Hand-foot syndrome (palmar-plantar erythrodysesthesia) • Redness of the skin (erythema) • Joint pain

• Mouth pain • 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, skin peeling, skin lesions • Nail disorders, nail fragility • 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 • Protein in the urine

Uncommon(may affect up to 1 in 100 people)
Weakness, unexpected bleeding or bruising, and frequent infections, with symptoms such as fever, chills, sore throat, or mouth ulcers (pancytopenia symptoms) • 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)
Rare(may affect up to 1 in 1,000 people)
Fatigue, shortness of breath, dizziness, paleness (anemia symptoms, possibly due to pure red cell aplasia) • Swelling of the face, around the eyes, mouth, inside the mouth, and/or throat, as well as difficulty breathing and swallowing (angioedema, also known as hypersensitivity)

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

Reporting side effects

If you experience any side effects, including any side effects not listed in this leaflet, you should inform your doctor or pharmacist. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Urząd Rejestracji Produktów Leczniczych, Wyrobów Medycznych i Produktów Biobójczych, Al. Jerozolimskie 181C, 02-222 Warsaw
Phone: +48 22 49 21 301, Fax: +48 22 49 21 309, e-mail: ndl@urpl.gov.pl
Thanks to the reporting of side effects, more information can be collected 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 "EXP". The expiry date refers to the last day of the month.
Store in the original packaging to protect from light.
There are no special storage temperature requirements for the medicine.
Medicines should not be disposed of via wastewater or household waste. You should ask your 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 does Everolimus Genthon contain?

• 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 does Everolimus Genthon look like and what does the packaging contain?

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 packaging containing 30 or 90 tablets.
Everolimus Genthon 5 mg and Everolimus Genthon 10 mg are available in packaging 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