Everolimus genthon

Package leaflet: Information for the patient

Everolimus Genthon, 2.5 mg, tablets
Everolimus Genthon, 5 mg, tablets
Everolimus Genthon, 10 mg, tablets
Everolimusum
Please read this leaflet carefully before 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 further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for you personally. Do not give it to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Leaflet contents

1. What Everolimus Genthon is and what it is used for
2. What you need to know 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 down 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 prior treatment with other medicines (so-called "non-steroidal aromatase inhibitors"). This medicine is given in combination with exemestane, a steroidal aromatase inhibitor used in hormone therapy for cancer treatment.
• advanced tumours known as 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 medicines (called anti-VEGF therapies) have proven ineffective.

2. Important information before taking Everolimus Genthon

Everolimus Genthon may only be prescribed by a physician experienced in the treatment of cancers. All instructions from the physician must be followed. These may differ from the general information provided in this leaflet. For additional information about Everolimus Genthon and an explanation as to why this particular medicine was chosen, please consult your 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, consult your doctor for advice.

Warnings and precautions
Before starting treatment with Everolimus Genthon, discuss the following with your doctor:

• if the patient has liver problems or diseases that may have affected liver function. In such cases, the doctor may adjust 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 treatment with insulin and/or oral antidiabetic medicines. Inform your doctor if the patient experiences excessive thirst or increased frequency of urination.
• if the patient needs to receive vaccinations during 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 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 the disease may reactivate 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 while taking Everolimus Genthon.
• affect kidney function. Therefore, the doctor will monitor kidney function during treatment with Everolimus Genthon.
• cause shortness of breath, cough, and fever. Inform your doctor if the patient experiences these symptoms.

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 sugar 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 affect the action of 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.

Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.

The following medicines, when taken with Everolimus Genthon, may increase the risk of adverse reactions:

• 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 conditions or high blood pressure.
• 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 high blood pressure or other cardiovascular problems.

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 ), an 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 control various types of seizures.

Patients 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.

Pregnancy, breastfeeding, and effects on fertility

Pregnancy
It is not recommended to take Everolimus Genthon during pregnancy, as it may harm the unborn child. Inform your doctor if the patient is pregnant or suspects she may be pregnant. The doctor will advise whether this medicine can be taken during pregnancy. Women of childbearing potential should use highly effective methods of contraception during treatment. If, despite these precautions, the patient suspects she may have become pregnant, she should contact her doctor before taking Everolimus Genthon.

Breastfeeding
Everolimus Genthon may harm a breastfed infant. Breastfeeding must be avoided during treatment and for 2 weeks after the last dose of everolimus. Inform your doctor if the patient is breastfeeding.

Female fertility
Some patients taking Everolimus Genthon have experienced absence of menstrual periods (amenorrhea).
Everolimus Genthon may affect female fertility. Discuss with your doctor if the patient wishes to have children.

Male fertility
Everolimus Genthon may affect male fertility. Inform your doctor if the patient intends to father a child.

Driving and operating machinery
If the patient experiences unexplained fatigue (a very common side effect), particular caution should be exercised when driving or operating machinery.

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

3. How to take Everolimus Genthon

This medicine should always be taken exactly as directed by your doctor or pharmacist.
If you are unsure, 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 once daily).
If certain adverse 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 either with food or without food in a consistent manner.
Everolimus Genthon tablet(s) should be swallowed whole with a glass of water. Tablets must not be chewed or crushed.

Taking more Everolimus Genthon than recommended

• If you take more Everolimus Genthon than recommended, or if someone else accidentally takes the tablets, seek immediate medical advice from a doctor or go to a hospital. Urgent medical intervention may be necessary.
• Show the doctor the outer carton and this leaflet so that the medicine taken in excess can be identified.

Missed 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 Everolimus Genthon
Do not stop taking Everolimus Genthon without first 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 any medicine, this medicinal product can cause adverse reactions, although not everyone will experience them.
You should STOP using Everolimus Genthon and seek immediate medical help if the patient experiences any of the following symptoms of an allergic reaction:

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

Serious adverse reactions associated with 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 (signs of pneumonia)
Common (may occur in less than 1 in 10 patients)
Increased thirst, increased urination, increased appetite with weight loss, fatigue (signs 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-coloured urine (these may be signs of reactivation of hepatitis B) • Shortness of breath, difficulty breathing when lying down, swelling of feet or legs (signs of heart failure) • Swelling and/or pain in one of the legs, usually in the calf, redness or warmth of the skin in the affected area (signs of blocked blood vessel (vein) in the leg due to blood clot) • Sudden shortness of breath, chest pain or coughing up blood (potential signs of pulmonary embolism, which occurs when one or more arteries in the lungs become blocked) • Markedly reduced urine output, swelling of legs, feeling disoriented, back pain (signs of acute kidney failure) • Rash, itching, hives, difficulty breathing or swallowing, dizziness (signs 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 (signs of acute respiratory distress syndrome)
If any of the above adverse reactions occur, contact a doctor immediately, as they may lead to life-threatening consequences.
Other possible adverse reactions associated with 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) • Taste disturbance • Headache • Nosebleeds (haemorrhage) • Cough • Mouth ulcers • Stomach upset, including nausea or diarrhoea • Skin rash • Itching • Feeling weak or tired • Swelling of arms, hands, feet, ankles and other parts of the body (signs of oedema) • Weight loss
Common (may occur in less than 1 in 10 patients)
Sudden bleeding or bruising (signs of low platelet count, also known as thrombocytopenia) • Fever, sore throat, mouth ulcers due to infection (signs of low white blood cell count, leukopenia, lymphopenia and/or neutropenia) • Shortness of breath (dyspnoea) • Feeling thirsty, low urine output, dark-coloured urine, dry red skin, irritability (signs of dehydration) • Sleep problems (insomnia) • Headaches, dizziness (signs of high blood pressure, also known as hypertension) • Fever • Inflammation of the tissue lining the mouth, stomach, intestine • Dry mouth • Heartburn (dyspepsia) • Vomiting • Difficulty swallowing (dysphagia) • Abdominal pain • Acne • Rash and pain in the palms of the hands and soles of the feet (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, peeling skin, skin lesions • Nail disorders, brittle nails • Moderate hair loss • Abnormal blood test results for liver function (increased alanine aminotransferase and aspartate aminotransferase activity) • Abnormal blood test results for 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 (signs 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 • Problems with wound healing • Hot flushes • Pink or red eye (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 adverse reactions worsen, inform your doctor or pharmacist. Most adverse reactions are mild or moderate in severity and should resolve after discontinuing treatment for a few days.

Reporting of adverse reactions
If any adverse symptoms occur, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw
Tel.: +48 22 49 21 301, Fax: +48 22 49 21 309, e-mail: [email protected]
Reporting adverse reactions helps to provide more information on the safety of the medicine.
Adverse reactions can also be reported to the marketing authorisation holder.

5. How to store Everolimus Genthon

Keep this medicine out of the 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.
No special temperature storage conditions apply.
Medicines should not be disposed of via wastewater or household waste. Ask your
pharmacist how to dispose of medicines no longer required. Such measures will help
protect the environment.

6. Contents of the pack 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 components are: butylated hydroxytoluene (E321), hypromellose (E464), lactose, lactose monohydrate, 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 inscription "E9VS" engraved 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" engraved 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" engraved 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