Everolimus vipharm

Package leaflet: Information for the patient

Everolimus Vipharm, 2.5 mg, tablets
Everolimus Vipharm, 5 mg, tablets
Everolimus Vipharm, 10 mg, tablets
everolimus
Please read this leaflet carefully before taking this medicine, as it contains
important information for the patient.

• 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 a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If you experience any adverse effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Leaflet contents

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

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

Everolimus Vipharm 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 Vipharm is used to treat adult patients with:

• advanced hormone receptor-positive breast cancer in postmenopausal women whose disease is no longer controlled by 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 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 renal cell carcinoma (advanced kidney cancer) when other medicines (called anti-VEGF therapies) have proven ineffective.

2. Important information before taking Everolimus Vipharm

Everolimus Vipharm 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 contained in this leaflet. For additional information about Everolimus Vipharm and an explanation as to why this particular medicine has been prescribed, please consult your doctor.

When not to take Everolimus Vipharm:

• 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).
  In case of suspected allergy, consult your doctor for advice.

Warnings and precautions
Before starting treatment with Everolimus Vipharm, discuss 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 Vipharm.
• If the patient has diabetes (high blood sugar). Everolimus Vipharm may increase blood glucose levels and worsen diabetes. This condition may require treatment with insulin and/or oral antidiabetic drugs. 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 Vipharm.
• If the patient has high cholesterol levels. Everolimus Vipharm may increase blood cholesterol and/or other blood lipids.
• If the patient has recently undergone major surgery or has unhealed surgical wounds. Everolimus Vipharm may impair wound healing.
• If the patient has an infection. Treatment with Everolimus Vipharm may require prior treatment of existing infections.
• If the patient has previously had hepatitis B, as reactivation of the disease may occur during treatment with Everolimus Vipharm (see section 4 "Possible side effects").
• If the patient has received or is scheduled to receive radiotherapy.

Everolimus Vipharm may also:

• Suppress the immune system. Therefore, the patient may be at increased risk of infections during treatment with Everolimus Vipharm. If the patient develops fever or other signs of infection, medical advice must be sought immediately. Some infections may be severe and potentially fatal.
• Affect kidney function. Therefore, the doctor will monitor kidney function during treatment with Everolimus Vipharm.
• Cause shortness of breath, cough, and fever.
• Cause development of mouth ulcers and sores. The doctor may interrupt or discontinue treatment with Everolimus Vipharm. The patient may require treatment with mouth rinses, gels, or other products. Some mouthwashes and gels may worsen ulcers; therefore, do not use any product without consulting the doctor. The doctor may restart treatment with Everolimus Vipharm at the same or a lower dose.
• Cause complications related to radiotherapy. Severe radiation reactions (such as shortness of breath, nausea, diarrhea, skin rash, and pain in the mouth, gums, and throat), including fatal cases, have been observed in some patients receiving everolimus concurrently with or shortly after radiotherapy. Additionally, cases of so-called radiation recall syndrome (including skin redness or lung inflammation at the site of prior radiotherapy) have been reported in patients previously exposed to radiotherapy.
• Inform your doctor about any planned radiotherapy in the near future or any previous radiotherapy.

Inform your doctor if the patient experiences any of 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 Vipharm is affecting 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 Vipharm may affect these parameters.

Children and adolescents
Everolimus Vipharm must not be given to children and adolescents (under 18 years of age).

Everolimus Vipharm and other medicines
Everolimus Vipharm may affect the action of other medicines. If the patient is taking other medicines concurrently with Everolimus Vipharm, the doctor may adjust the dose of Everolimus Vipharm or of the other medicines.

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

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

• Ketoconazole, itraconazole, voriconazole, fluconazole, or 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 in the treatment of 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 conditions.
• Nefazodone, used to treat depression.
• Cannabidiol (used, among others, in the treatment of epileptic seizures).

The following medicines may reduce the effectiveness of Everolimus Vipharm:

• 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.

Avoid taking these medicines during treatment with Everolimus Vipharm. If the patient is taking any of the above medicines, the doctor may switch to an alternative medicine or adjust the dose of Everolimus Vipharm.

Taking Everolimus Vipharm with food and drink
Avoid eating grapefruit or drinking grapefruit juice during treatment with Everolimus Vipharm. This may increase the amount of Everolimus Vipharm in the blood to potentially harmful levels.

Pregnancy, breastfeeding, and effects on fertility
Pregnancy
Everolimus Vipharm is not recommended 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 who could become pregnant should use highly effective contraception during treatment and for 8 weeks after treatment ends. If, despite these precautions, the patient suspects she may have become pregnant, contact the doctor before taking Everolimus Vipharm.

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

Female fertility
In some women taking everolimus, absence of menstrual periods (amenorrhea) has been observed.
Everolimus Vipharm may affect female fertility. Discuss with your doctor if the patient plans to have children.

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

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

Everolimus Vipharm contains lactose
Everolimus Vipharm contains lactose (milk sugar). If the patient has been previously diagnosed with intolerance to certain sugars, consult your doctor before taking this medicine.

3. How to take Everolimus Vipharm

This medicine should always be taken as directed by the physician. If in doubt, consult the doctor or pharmacist.
The recommended dose is 10 mg taken once daily. The physician will determine how many tablets to take.
In case of liver problems, the physician may start treatment with a lower dose of Everolimus Vipharm (2.5, 5, or 7.5 mg daily).
If certain adverse reactions occur during treatment with Everolimus Vipharm (see section 4), the physician may reduce the dose or temporarily or permanently discontinue treatment.
Everolimus Vipharm should be taken once daily at the same time each day, always taken consistently either with food or without food.
Everolimus Vipharm tablets should be swallowed whole with a glass of water. Tablets must not be chewed or crushed.

Taking more Everolimus Vipharm than prescribed

• If a higher than recommended dose of Everolimus Vipharm has been taken, or if someone accidentally ingests the tablets, seek immediate medical advice from a doctor or go to hospital. Urgent medical intervention may be necessary.
• Show the doctor the medicine carton and this leaflet so that it can be determined which medicine has been overdosed.

Missed dose of Everolimus Vipharm
If a dose of Everolimus Vipharm is missed, take the next scheduled dose as planned. Do not take a double dose to make up for the missed tablet.

Stopping Everolimus Vipharm
Do not stop taking Everolimus Vipharm without consulting your doctor.
If there are any further doubts regarding the use of this medicine, consult the doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
You should STOP using Everolimus Vipharm 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 of Everolimus Vipharm include:
Very common (may occur in more than 1 in 10 patients)

• Increased 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, passing large amounts of urine, 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 part of the abdomen, pale stools, dark-coloured 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 of the legs, usually in the calf, with redness or warmth of the skin in the affected area (symptoms of blocked blood vessel (vein) in the leg due to 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, feeling confused, back pain (symptoms of acute kidney failure)
• Rash, itching, hives, 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 the patient experiences any of the
mentioned adverse reactions, as they may lead to life-threatening consequences.
Other possible adverse reactions of Everolimus Vipharm include:
Very common (may occur in more than 1 in 10 patients)

• High blood sugar levels (hyperglycaemia)
• Loss of appetite
• Taste disturbance
• Headache
• Nosebleeds (epistaxis)
• Cough
• Mouth ulcers
• Stomach upset, including nausea and diarrhoea
• Skin rash
• Itching (pruritus)
• Feeling weak or tired
• Fatigue, shortness of breath, dizziness, pale skin (symptoms of low red blood cell count (anaemia))
• Swelling of arms, hands, feet, ankles and other body parts (symptoms of oedema)
• Weight loss
• High blood lipid (fat) levels (hypercholesterolaemia)

Common (may occur in less than 1 in 10 patients)

• Sudden bleeding or bruising (symptoms of low platelet count, also known as thrombocytopenia)
• Shortness of breath (dyspnoea)
• Feeling thirsty, low urine output, dark-coloured urine, dry red skin, irritability (symptoms of dehydration)
• Sleep problems (insomnia)
• Headaches, dizziness (symptoms of high blood pressure, also known as hypertension)
• Swelling of part or all of the hand (including fingers) or leg (including toes), feeling of heaviness, limited movement, discomfort (possible symptoms of lymphoedema)
• Fever, sore throat, mouth ulcers due to infection (symptoms of low white blood cell count, leukopenia, lymphopenia and (or) neutropenia)
• 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 blood lipid (fat) levels (hyperlipidaemia, increased triglyceride levels)
• Low blood potassium levels (hypokalaemia)
• Low blood phosphate levels (hypophosphataemia)
• Low blood calcium levels (hypocalcaemia)
• Dry skin, skin peeling, 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)
• Swelling of eyelids
• 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 count, 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
• Eye discharge accompanied by itching and redness, pink eye 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 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 and swallowing (also known as angioedema), which may be symptoms of an allergic reaction

Frequency not known (frequency cannot be determined from available data)

• Reaction at the site of previous radiotherapy, e.g. skin redness or lung inflammation (so-called radiation recall syndrome)
• Exacerbation of side effects of radiotherapy

If the above-mentioned adverse reactions worsen, 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 adverse reactions
If any adverse symptoms occur, including any adverse reactions not listed in this leaflet, inform your doctor, pharmacist or nurse. 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 49 21 301
Fax: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Everolimus Vipharm

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton or blister. The expiry date refers to the last day of the stated month.
There are no special storage temperature requirements for this medicine. Store in the original packaging to protect from light.
Open the blister pack immediately before taking the tablet.
Do not use this medicine if there are visible signs of damage or tampering.
Medicines must not be disposed of via the sewage system or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Everolimus Vipharm contains

• The active substance is everolimus. Each tablet of Everolimus Vipharm 2.5 mg contains 2.5 mg of everolimus. Each tablet of Everolimus Vipharm 5 mg contains 5 mg of everolimus. Each tablet of Everolimus Vipharm 10 mg contains 10 mg of everolimus.
• The other ingredients are: butylhydroxytoluene (E 321), hypromellose (type 2910), lactose, crospovidone (type A), magnesium stearate.

What Everolimus Vipharm looks like and contents of the pack
Everolimus Vipharm 2.5 mg tablets are white or almost white, oval, flat tablets, embossed with the
mark "EVR" on one side and "2.5" on the other.
Everolimus Vipharm 5 mg tablets are white or almost white, oval, flat tablets, embossed with the
mark "EVR" on one side and "5" on the other.
Everolimus Vipharm 10 mg tablets are white or almost white, oval, flat tablets, embossed with the
mark "EVR" on one side and "NAT" on the other.
Everolimus Vipharm 2.5 mg is available in packs containing 30 or 90 tablets.
Everolimus Vipharm 5 mg and Everolimus Vipharm 10 mg are available in packs containing 10, 30 or 90 tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder:
Vipharm S.A.
ul. A. i F. Radziwiłłów 9
05-850 Ożarów Mazowiecki
tel.: (+4822) 679 51 35
fax: (+4822) 678 92 87
e-mail: [email protected]

Manufacturer / Importer:
Genepharm S.A
18 km Marathonos Avenue
153 51 Pallini Attiki
Greece
Pharmacare Premium Ltd.
HHF003 Hal Far Industrial Estate
Birzebbugia, BBG3000
Malta
Pharmadox Healthcare Ltd.
KW20A Kordin Industrial Park
Paola, PLA 3000
Malta

This medicinal product has been authorised in the European Economic Area countries under the following names:
Hungary: Everolimus Vipharm 2.5 mg tabletta
Everolimus Vipharm 5 mg tabletta
Everolimus Vipharm 10 mg tabletta
Czech Republic: Everolimus Vipharm
Poland: Everolimus Vipharm
Slovakia: Everolimus Vipharm 2.5 mg tablety
Everolimus Vipharm 5 mg tablety
Everolimus Vipharm 10 mg tablety