Everolimus Biocon

Package leaflet: Information for the patient

Everolimus Biocon 2.5 mg, 5 mg and 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 questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

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

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

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

• advanced hormone receptor-positive breast cancer in postmenopausal women in whom other treatments (referred to as “non-steroidal aromatase inhibitors”) are no longer able to control the disease. It is administered together with a type of medicine called exemestane, a steroidal aromatase inhibitor, which is used for antitumour hormonal therapy.
• advanced tumours called neuroendocrine tumours originating from the stomach, intestine, lung or pancreas. It is used when the tumours are inoperable and do not overproduce specific hormones or other related natural substances.
• advanced kidney cancer (advanced renal cell carcinoma) where other treatments (referred to as “anti-VEGF targeted therapies”) have not been effective in stopping it.

2. What you should know before taking Everolimus Biocon

Everolimus Biocon will only be prescribed by a doctor experienced in cancer treatment. Follow carefully all instructions given by your doctor. These instructions may differ from the general information contained in this leaflet. If you have any questions about Everolimus Biocon or why it has been prescribed to you, consult your doctor.

Do not take Everolimus Biocon

• if you are allergic to everolimus, to similar substances such as sirolimus or temsirolimus, or to any of the other ingredients of this medicine (listed in section 6). If you think you may be allergic, ask your doctor for advice.

Warnings and precautions
Talk to your doctor before taking Everolimus Biocon:

• if you have liver problems or have had any illness that may have affected your liver. In such cases, your doctor may need to prescribe a different dose of Everolimus Biocon.
• if you have diabetes (high blood sugar levels). Everolimus Biocon can increase blood sugar levels and worsen diabetes mellitus. This may require treatment with insulin and/or oral antidiabetic agents. Inform your doctor if you experience excessive thirst or increased frequency of urination.
• if you need to receive a vaccine while taking Everolimus Biocon.
• if you have high cholesterol levels. Everolimus Biocon can increase cholesterol levels and/or other fats in the blood.
• if you have recently undergone surgery, or if you have an unhealed surgical wound. Everolimus Biocon may increase the risk of wound-healing complications.
• if you have an infection. It may be necessary to treat the infection before starting Everolimus Biocon.
• if you have previously had hepatitis B, as it may reactivate during treatment with Everolimus Biocon (see section 4 'Possible side effects').
• if you have received or are about to receive radiotherapy.

Everolimus Biocon may also:

• weaken the immune system. Therefore, you may be at increased risk of developing an infection during treatment with Everolimus Biocon. If you develop fever or other signs of infection, consult your doctor. Some infections may be severe and potentially fatal.
• impair kidney function. Therefore, your doctor will monitor your kidney function during treatment with Everolimus Biocon.
• cause shortness of breath, cough, and fever.
• cause mouth ulcers and sores. Your doctor may need to interrupt or stop treatment with Everolimus Biocon. Treatment with a mouthwash, gel, or other products may be required. Some mouthwashes and gels may worsen ulcers, so do not use any product without first consulting your doctor. Your doctor may restart treatment with Everolimus Biocon at the same dose or at a lower dose.
• cause complications related to radiotherapy. Severe radiation reactions (such as shortness of breath, nausea, diarrhoea, skin rashes, and irritation of the mouth, gums, and throat), including fatal cases, have been observed in some patients taking everolimus concurrently with radiotherapy or shortly after radiotherapy. In addition, in patients who have previously undergone radiotherapy, a so-called radiation recall syndrome (including skin redness or lung inflammation at the site of previous radiotherapy) has been reported. Inform your doctor if you are planning to receive radiotherapy in the near future or if you have previously received radiotherapy.

Inform your doctor if you experience any of these symptoms.
You will have regular blood tests during treatment. These tests will monitor your blood cell counts (white blood cells, red blood cells, and platelets) to check whether Everolimus Biocon is having any unwanted effects on these cells. Blood tests will also be performed to monitor kidney function (creatinine levels), liver function (transaminase levels), blood glucose, and cholesterol levels. These levels may also be affected by Everolimus Biocon.

Children and adolescents
Everolimus Biocon must not be used in children or adolescents (under 18 years of age).

Other medicines and Everolimus Biocon
Everolimus Biocon may affect the action of certain medicines. If you are taking other medicines at the same time as Everolimus Biocon, your doctor may need to adjust the dose of Everolimus Biocon or of the other medicines.
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

The following substances may increase the risk of side effects with Everolimus Biocon:

• ketoconazole, itraconazole, voriconazole, fluconazole, and other antifungal agents 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, used to help regulate heart rhythm.
• cyclosporine, a medicine used to prevent rejection of transplanted organs.
• imatinib, used to inhibit 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 in the treatment of depression.
• cannabidiol (uses include, among others, treatment of seizures).

The following substances may reduce the effectiveness of Everolimus Biocon:

• rifampicin, used to treat tuberculosis (TB).
• efavirenz or nevirapine, used to treat HIV/AIDS infection.
• St John’s wort (Hypericum perforatum), a herbal product used to treat depression and other conditions.
• dexamethasone, a corticosteroid used to treat a wide range of conditions including inflammatory or immune disorders.
• phenytoin, carbamazepine, phenobarbital, and other antiepileptic medicines used to prevent epileptic seizures.

These medicines should be avoided during treatment with Everolimus Biocon. If you are taking any of these medicines, your doctor may prescribe alternative medicines or adjust your dose of Everolimus Biocon.

Everolimus Biocon with food and drink
Avoid grapefruit and grapefruit juice while being treated with Everolimus Biocon. These may increase the amount of Everolimus Biocon in your blood, possibly to harmful levels.

Pregnancy, breast-feeding and fertility
Pregnancy
Everolimus Biocon may harm the unborn baby and is not recommended during pregnancy. Inform your doctor if you are pregnant or suspect you may be pregnant. Your doctor will discuss with you whether you should take this medicine during pregnancy.
Women who could become pregnant must use a highly effective method of contraception during treatment and for 8 weeks after the end of treatment. If, despite these precautions, you suspect you are pregnant, consult your doctor before taking any further doses of Everolimus Biocon.

Breast-feeding
Everolimus Biocon may harm the breastfed infant. You must not breast-feed during treatment and for 2 weeks after the last dose of Everolimus Biocon. Inform your doctor if you are breast-feeding.

Female fertility
Menstrual disturbances (amenorrhoea) have been observed in some patients treated with Everolimus Biocon.
Everolimus Biocon may affect female fertility. Inform your doctor if you wish to have children.

Male fertility
Everolimus Biocon may affect male fertility. Talk to your doctor if you wish to father a child.

Driving and using machines
If you feel unusually tired (fatigue is a very common side effect), take special care when driving or operating machinery.

Everolimus Biocon contains lactose
Everolimus Biocon contains lactose (milk sugar). If your doctor has diagnosed you with an intolerance to certain sugars, contact your doctor before taking this medicine.

3. How to take Everolimus Biocon

Take this medicine exactly as directed by your doctor or pharmacist. If you
have any doubts, consult your doctor or pharmacist.
The recommended dose is 10 mg taken once daily. Your doctor will tell you how many
tablets of Everolimus Biocon you should take.
If you have liver problems, your doctor may prescribe a lower dose of Everolimus Biocon (2.5, 5,
or 7.5 mg/day).
If certain adverse events occur while you are taking Everolimus Biocon (see
section 4), your doctor may reduce your dose or temporarily or permanently
discontinue treatment.
Take Everolimus Biocon once daily, approximately at the same time each day, regularly with or
without food.
Swallow the tablet(s) whole with a glass of water. Do not chew or crush the
tablets.

If you take more Everolimus Biocon than you should

• If you have taken more Everolimus Biocon than you should, or if someone else has accidentally taken your tablets, contact a doctor immediately or go to hospital. Emergency treatment may be necessary.
• Keep the packaging and this leaflet, so the doctor knows what has been taken.

If you forget to take Everolimus Biocon
If you forget to take a dose, take the next dose as scheduled. Do not take a
double dose to make up for forgotten tablets.
If you stop taking Everolimus Biocon
Do not stop treatment with Everolimus Biocon unless your doctor tells you to do so.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
STOP taking Everolimus Biocon and contact your doctor immediately if you experience any of the following signs of an allergic reaction:

• Difficulty breathing or swallowing
• Swelling of the face, lips, tongue or throat
• Severe skin itching, with red rash or skin swellings

Serious side effects of Everolimus Biocon include:
Very common (may affect more than 1 in 10 users)

• Increased body temperature, chills (signs of infection)
• Fever, cough, difficulty breathing, wheezing (signs of lung inflammation, also known as pneumonitis)

Common (may affect up to 1 in 10 users)

• Excessive thirst, increased urine production, increased appetite with weight loss, fatigue (signs of diabetes)
• Bleeding (haemorrhage), for example in the intestinal wall
• Severe decrease in urine production (signs of kidney failure)

Uncommon (may affect up to 1 in 100 users)

• Fever, 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-coloured stools, dark-coloured urine (may be signs of reactivation of hepatitis B)
• Shortness of breath, breathing difficulties when lying down, swelling of the feet and 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 blockage of a blood vessel (vein) in the leg due to blood clotting)
• Sudden onset of shortness of breath, chest pain or coughing up blood (potential signs of pulmonary embolism, a condition that occurs when one or more pulmonary arteries become blocked)
• Severe decrease in urine production, swelling of the legs, confusion, back pain (signs of sudden kidney failure)
• Skin rash, itching, hives, difficulty breathing or swallowing, dizziness (signs of severe allergic reactions, also known as hypersensitivity)

Rare (may affect up to 1 in 1,000 users)

• Shortness of breath or rapid breathing (signs of acute respiratory distress syndrome)

If you experience any of these side effects, contact your doctor immediately, as they could be life-threatening.
Other possible side effects of Everolimus Biocon include:
Very common (may affect more than 1 in 10 users)

• High levels of sugar in the blood (hyperglycaemia)
• Loss of appetite
• Altered sense of taste (dysgeusia)
• Headache
• Nosebleeds (epistaxis)
• Cough
• Mouth ulcers
• Stomach problems including feeling unwell (nausea) or diarrhoea
• Skin rash
• Itching
• Tiredness or weakness
• Tiredness, shortness of breath, dizziness, pale skin, signs of low red blood cell levels (anaemia)
• Swelling of the arms, hands, feet, ankles or other parts of the body (signs of oedema)
• Weight loss
• High levels of lipids (fats) in the blood (hypercholesterolaemia)

Common (may affect up to 1 in 10 users)

• Spontaneous bleeding or bruising (signs of low platelet levels, also known as thrombocytopenia)
• Shortness of breath (dyspnoea)
• Thirst, low urine output, dark urine, dry and flushed skin, irritability (signs of dehydration)
• Difficulty sleeping (insomnia)
• Headache, dizziness (signs of high blood pressure, also known as hypertension)
• Swelling of part or all of the arm (including fingers) or leg (including toes), feeling of heaviness, limited movement, discomfort (possible symptoms of lymphoedema)
• Fever, sore throat, mouth ulcers due to infections (signs of low white blood cell counts, leucopenia, lymphopenia and/or neutropenia)
• Fever
• Inflammation of the inner lining of the mouth, stomach and intestine
• Dry mouth
• Heartburn (dyspepsia)
• Feeling unwell (vomiting)
• Difficulty swallowing (dysphagia)
• Abdominal pain
• Acne
• Skin rash and pain on the palms of the hands or soles of the feet (hand-foot syndrome)
• Skin redness (erythema)
• Joint pain
• Mouth pain
• Menstrual disorders such as irregular cycles
• High levels of lipids (fats) in the blood (hyperlipidaemia, increased triglycerides)
• Low potassium levels in the blood (hypokalaemia)
• Low phosphate levels in the blood (hypophosphataemia)
• Low calcium levels in the blood (hypocalcaemia)
• Dryness, peeling and skin lesions
• Nail problems, nail breakage
• Mild hair loss
• Abnormal blood test results for liver function (increased alanine and aspartate aminotransferase)
• Abnormal blood test results for kidney function (increased creatinine)
• Eyelid oedema
• Protein in the urine

Uncommon (may affect up to 1 in 100 users)

• Weakness, spontaneous 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 sense of taste (ageusia)
• Coughing up blood (haemoptysis)
• Menstrual disorders such as absence of periods (amenorrhoea)
• Need to urinate more frequently during the day
• Chest pain
• Problems with wound healing
• Hot flushes
• Eye discharge with itching and redness, red eyes (conjunctivitis)

Rare (may affect up to 1 in 1,000 users)

• Tiredness, shortness of breath, dizziness, paleness (signs of low red blood cell levels in the blood, possibly due to a type of anaemia called pure red cell aplasia)
• Swelling of the face, around the eyes, mouth and inside the mouth and/or throat, as well as of the tongue, and difficulty breathing or swallowing (also known as angioedema), which may be signs of an allergic reaction

Not known (frequency cannot be estimated from the available data)

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

If these side effects worsen, inform your doctor and/or pharmacist. Most of the side effects are mild or moderate in severity and usually resolve if treatment is interrupted for a few days.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Everolimus Biocon

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the carton and blister. The expiry date refers to the last day of that month. Do not store above 25°C.
• Store in the original packaging to protect the medicine from light and moisture.
• Open the blister pack only when it is time to take the tablets.
• Do not use this medicine if the packaging is damaged or shows signs of tampering.

Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Everolimus Biocon contains

• The active substance is everolimus.
• Each tablet contains 2.5 mg everolimus.
• Each tablet contains 5 mg everolimus.
• Each tablet contains 10 mg everolimus.
• The other components are Butylated hydroxytoluene (E321), magnesium stearate (E470b), lactose monohydrate, hypromellose 2910 (E464), crospovidone (E1202), and anhydrous lactose.

Description of the appearance of Everolimus Biocon and contents of the pack
Tablets of variable colour from white to off-white, oval, flat, bevelled, approximately 10.00 mm in
length and 4.50 mm in width, with "B 2.5" engraved on one side and plain on the other.
Tablets of variable colour from white to off-white, oval, flat, bevelled, approximately 12.00 mm in
length and 5.00 mm in width, with "B 5" engraved on one side and plain on the other.
Tablets of variable colour from white to off-white, oval, flat, bevelled, approximately 16.50 mm in
length and 6.75 mm in width, with "B 10" engraved on one side and plain on the other.
A red desiccant tablet marked "DO NOT INGEST" is placed in the central round cavity. A red inscription "DESICCANT, DO NOT INGEST" is printed on each blister. This is used to protect Everolimus tablets from moisture.
The desiccant tablets that absorb moisture must not be ingested.
Everolimus Biocon 2.5 mg tablets are available in blister packs containing 30 or 90 tablets.
Everolimus Biocon 5 mg and 10 mg tablets are available in blister packs containing 10, 30 or 90 tablets.
It is possible that not all pack sizes are marketed.

Marketing Authorisation Holder
Biocon Pharma Malta I Limited
The Victoria Centre, Unit 2,
Lower Ground Floor,
Valletta Road, Mosta MST 9012, Malta

Manufacturer
Misom Labs Ltd.
Malta Life Sciences Park,
LS2.01.06,
Industrial Estate,
San Gwann, SGN 3000
Malta

This medicinal product is authorised in the Member States of the European Economic Area under the
following names: