Everolimus synthon

Package leaflet: Information for the patient

Everolimus Genthon, 2.5 mg, tablets
Everolimus Genthon, 5 mg, tablets
Everolimus Genthon, 10 mg, tablets
Everolimus
Please read this leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you personally. Do not pass it on to others. It may harm them even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

1. What Everolimus Genthon is and what it is 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 pack and other information

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

Everolimus Genthon is an anticancer medicine containing the active substance everolimus.
Everolimus reduces blood supply to the tumour and slows the growth and spread of cancer cells.
Everolimus Genthon is used to treat adult patients with:

• advanced hormone receptor-positive breast cancer in postmenopausal women whose disease has progressed despite treatment with other medicines (so-called "non-steroidal aromatase inhibitors"). This medicine is given in combination with exemestane, a steroidal aromatase inhibitor used in hormonal anticancer therapy.
• advanced neuroendocrine tumours originating from the stomach, intestines, lungs, or pancreas. This medicine is used when tumours 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 treatments (called anti-VEGF therapy) have proven ineffective.

2. Important information before taking Everolimus Genthon

Everolimus Genthon may be prescribed only by a physician experienced in the treatment of cancer. All the physician's instructions must be followed. These may differ from the general information contained in this leaflet. If additional information about Everolimus Genthon or an explanation as to why this particular medicine was chosen is needed, the patient should contact their doctor.

When not to take Everolimus Genthon:

• if the patient is allergic to everolimus, substances similar to it such as sirolimus or temsirolimus, or any of the other ingredients of this medicine (listed in section 6).
  If an allergic reaction is suspected, the patient should consult their doctor for advice.

Warnings and precautions

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

• if the patient has liver problems or liver diseases that could affect liver function. In such a case, the doctor may adjust the dose of Everolimus Genthon.
• if the patient has diabetes (high blood sugar). Everolimus Genthon may increase blood glucose levels and worsen diabetes. This condition may require treatment with insulin and/or oral antidiabetic drugs. The patient should inform the doctor if they experience excessive thirst or increased urination.
• if the patient requires vaccinations during treatment with Everolimus Genthon.
• if the patient has elevated cholesterol levels. Everolimus Genthon may increase cholesterol and/or other blood lipid levels.
• if the patient has recently undergone major surgery or has unhealed surgical wounds. Everolimus Genthon may impair wound healing.
• if the patient has an infection. Treatment of any existing infection may be required before starting Everolimus Genthon.
• if the patient has previously had hepatitis B, as reactivation of the disease may occur during treatment with Everolimus Genthon (see section 4, "Possible side effects").

Everolimus Genthon may also:

• suppress the immune system. Therefore, the patient may be at increased risk of infections during treatment with Everolimus Genthon.
• affect kidney function. Therefore, the doctor will monitor kidney function during treatment with Everolimus Genthon.
• cause shortness of breath, cough, and fever.
• cause the development of mouth ulcers and mucosal ulcerations. The doctor may interrupt or discontinue treatment with Afinitor. The patient may require treatment with mouthwashes, gels, or other products. Some mouthwashes and gels may worsen ulcers, so the patient should not use any product without consulting their doctor. The doctor may restart treatment with Afinitor at the same or a lower dose. The patient should inform the doctor if these symptoms occur.

During treatment, the patient will undergo regular blood tests to monitor blood cell counts (white blood cells, red blood cells, and platelets) and to check whether Everolimus Genthon is having any negative effects on blood cells. Blood tests will also be performed to monitor kidney function (creatinine levels), liver function (transaminase activity), and blood glucose and cholesterol levels, as Everolimus Genthon may affect these parameters.

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 interact with other medicines. If the patient is taking other medicines concurrently with Everolimus Genthon, the doctor may adjust the dose of Everolimus Genthon or of the other medicines.

The patient should inform their doctor or pharmacist about all medicines currently used, recently used, or planned for use.

The following medicines, when taken with Everolimus Genthon, may increase the risk of side effects:

• 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 infection.
• verapamil or diltiazem, used to treat heart disease or hypertension.
• dronedarone, a medicine that helps restore normal heart rhythm.
• cyclosporine, a medicine used to prevent organ transplant rejection.
• imatinib, which inhibits the growth of abnormal cells.
• angiotensin-converting enzyme (ACE) inhibitors (such as ramipril) used to treat hypertension or other cardiovascular problems.
• nefazodone, used to treat depression.

The following medicines may reduce the effectiveness of Everolimus Genthon:

• rifampicin, used to treat tuberculosis.
• efavirenz or nevirapine, used to treat HIV/AIDS infection.
• 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 or immunological disorders.
• phenytoin, carbamazepine, or phenobarbital and other antiepileptic medicines used 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 switch to an alternative medicine or adjust the dose of Everolimus Genthon.

Taking Everolimus Synthon with food and drink
The patient should avoid eating grapefruit or drinking grapefruit juice during treatment with Everolimus Synthon.

Pregnancy, breastfeeding, and effects on fertility

Pregnancy
Everolimus Genthon should not be used during pregnancy, as it may harm the unborn child. The patient should inform the doctor if they are pregnant or suspect they may be pregnant. The doctor will advise whether the patient can take this medicine during pregnancy. Women of childbearing potential should use highly effective methods of contraception during treatment. If, despite these precautions, the patient suspects they may have become pregnant, they should contact their doctor before taking Everolimus Genthon.

Breastfeeding
Everolimus Genthon may harm a breastfed infant. Breastfeeding should be avoided during treatment and for 2 weeks after the last dose of everolimus. The patient should inform the doctor if they are breastfeeding.

Female fertility
Some female patients taking Everolimus Genthon have experienced absence of menstrual periods (amenorrhea).
Everolimus Genthon may affect female fertility. The patient should discuss with their doctor if they wish to have children.

Male fertility
Everolimus Genthon may affect male fertility. The patient should inform the doctor if they intend to father a child.

Driving and using machines
If the patient experiences unexplained fatigue (fatigue is a very common side effect), they should exercise particular caution when driving or operating machinery.

Everolimus Genthon contains lactose
If the patient has previously been diagnosed with intolerance to certain sugars, they should consult their doctor before taking this medicine.

3. How to take Everolimus Genthon

This medicine should always be taken exactly as prescribed by your doctor or pharmacist. If you are unsure, you should consult your doctor.

The recommended dose is 10 mg, taken once daily. Your doctor will determine how many tablets you should take.

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

If certain side effects occur during treatment with Everolimus Genthon (see section 4), your doctor may reduce the dose or temporarily or permanently discontinue treatment.

Everolimus Genthon should be taken once daily, at the same time each day, always taken consistently either with food or without food.

Everolimus Genthon tablets should be swallowed whole with a glass of water. Tablets must not be chewed or crushed.

Taking more than the recommended dose of Everolimus Genthon

• If you take more Everolimus Genthon than prescribed, or if someone accidentally takes the tablets, you should immediately contact a doctor or go to a hospital. Urgent medical intervention may be necessary.
• You should show the doctor the outer packaging of the medicine and this leaflet so that it can be determined which medicine has been overdosed.

Missing a dose of Everolimus Genthon
If you miss a dose, take your next scheduled dose as planned. Do not take a double dose to make up for the missed tablet.

Stopping treatment with Everolimus Genthon
Do not stop taking Everolimus Genthon without consulting your doctor.

If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicinal product may cause adverse reactions, although not everyone experiences them.

You should STOP using the medicinal product Everolimus Genthon and seek immediate medical help if the patient develops any of the following symptoms of an allergic reaction:

• Difficulty breathing or swallowing
• Swelling of the face, lips, tongue or throat
• Increasing skin itching, with red rash and appearance of lumps

Serious adverse reactions of Everolimus Genthon include:

Very common (may occur in more than 1 in 10 patients)
Increased body temperature, chills (signs of infection) • Fever, cough, difficulty breathing, wheezing (symptoms of pneumonia)

Common (may occur in less than 1 in 10 patients)
Increased thirst, passing large amounts of urine, increased appetite with weight loss, fatigue (symptoms of diabetes) • Bleeding (haemorrhage), e.g. in the intestinal wall • Markedly reduced urine output (sign of kidney failure)

Uncommon (may occur in less than 1 in 100 patients)
Fever, skin rash, joint pain and inflammation, as well as fatigue, loss of appetite, nausea, jaundice (yellowing of the skin), pain in the upper right abdomen, pale stools, dark urine (these may be symptoms of reactivation of hepatitis B) • Shortness of breath, difficulty breathing when lying down, swelling of feet or legs (symptoms of heart failure) • Swelling and/or pain in one leg, usually in the calf, with redness or warmth of the skin in the affected area (symptoms of venous thrombosis in the leg caused by blood clotting) • Sudden shortness of breath, chest pain or coughing up blood (potential symptoms of pulmonary embolism, which occurs when one or more arteries in the lungs become blocked) • Markedly reduced urine output, swelling of legs, confusion, back pain (symptoms of acute kidney failure) • Rash, itching, urticaria, difficulty breathing or swallowing, dizziness (symptoms of a serious allergic reaction, also known as hypersensitivity)

Rare (may occur in less than 1 in 1000 patients)
Shortness of breath or rapid breathing (symptoms of acute respiratory distress syndrome)

You should immediately inform your doctor if any of the above adverse reactions occur, as they may lead to life-threatening consequences.

Other possible adverse reactions of Everolimus Genthon include:

Very common (may occur in more than 1 in 10 patients)
Fatigue, shortness of breath, dizziness, pale skin, symptoms of low red blood cell count (anaemia) • High blood sugar levels (hyperglycaemia) • Loss of appetite • High levels of lipids (fats) in the blood (hypercholesterolaemia) • Altered taste • Headache • Nosebleeds (haemorrhage) • Cough • Mouth ulcers • Gastrointestinal disturbances, including nausea or diarrhoea • Skin rash • Itching (pruritus) • Feeling weak or tired • Swelling of arms, hands, feet, ankles and other parts of the body (symptoms of oedema) • Weight loss

Common (may occur in less than 1 in 10 patients)
Sudden bleeding or bruising (symptoms of low platelet count, also known as thrombocytopenia) • Fever, sore throat, mouth ulcers due to infection (symptoms of low white blood cell count, leukopenia, lymphopenia and/or neutropenia) • Shortness of breath (dyspnoea) • Feeling thirsty, low urine output, dark urine, dry red skin, irritability (symptoms of dehydration) • Sleep problems (insomnia) • Headaches, dizziness (symptoms of high blood pressure, also known as hypertension) • Fever • Inflammation of tissues lining the mouth, stomach, intestine • Dry mouth • Heartburn (dyspepsia) • Vomiting • Difficulty swallowing (dysphagia) • Abdominal pain • Acne • Rash and pain in palms and soles (hand-foot syndrome) • Skin redness (erythema) • Joint pain

• Mouth pain • Menstrual disorders, such as irregular menstrual bleeding • High levels of lipids (fats) in the blood (hyperlipidaemia, increased triglyceride levels) • Low potassium levels in the blood (hypokalaemia) • Low phosphate levels in the blood (hypophosphataemia) • Low calcium levels in the blood (hypocalcaemia) • Dry skin, skin peeling, skin lesions • Nail disorders, brittle nails • Moderate hair loss • Abnormal blood test results indicating liver function (increased alanine aminotransferase and aspartate aminotransferase activity) • Abnormal blood test results indicating kidney function (increased creatinine levels) • Eye discharge accompanied by itching, redness and swelling • Presence of protein in urine

Uncommon (may occur in less than 1 in 100 patients)
Weakness, unexpected bleeding or bruising, and frequent infections with symptoms such as fever, chills, sore throat or mouth ulcers (symptoms of low blood cell counts, also known as pancytopenia) • Loss of taste (ageusia) • Coughing up blood (haemoptysis) • Menstrual disorders, such as absence of menstruation • More frequent urination during the day • Chest pain • Wound healing problems • Hot flushes • Eye irritation or redness (conjunctivitis)

Rare (may occur in less than 1 in 1000 patients)
Fatigue, shortness of breath, dizziness, pale skin (symptoms of low red blood cell count, possibly due to a type of anaemia called pure red cell aplasia) • Swelling of the face, around the eyes, lips, inside the mouth and/or throat, as well as the tongue, and difficulty breathing or swallowing (also known as angioedema), which may be symptoms of an allergic reaction

If the above-mentioned adverse reactions worsen, you should inform your doctor or pharmacist. Most adverse reactions are mild or moderate in severity and should resolve within a few days after stopping treatment.

Reporting of adverse reactions

If any adverse effects occur, including any not listed in this leaflet, you should inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw
Tel.: +48 22 4921301, Fax: +48 22 4921309, e-mail: [email protected]

By reporting adverse reactions, more information on the safety of the medicine can be collected.

Adverse reactions can also be reported to the responsible entity.

5. How to store Everolimus Genthon

Keep this medicine 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 stated month.
Store in the original packaging to protect from light.
There are no special requirements for storage temperature.
Medicines must not be disposed of via wastewater or household waste. Ask your
pharmacist how to dispose of medicines no longer required. This will help protect
the environment.

6. Contents of the package and other information

What Everolimus Genthon contains

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

What Everolimus Genthon looks like and contents of the pack
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 imprint "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 imprint "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 imprint "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 Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Genthon BV
Microweg 22
6545 CM Nijmegen
The Netherlands

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