Everolimus 10 mg Tablets

• 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 only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

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

• if you are allergic to everolimus, to related 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.

Talk to your doctor before taking Everolimus:

• if you have any problems with your liver or if you have ever had any disease which may have affected your liver. If this is the case, your doctor may need to prescribe a different dose of Everolimus.
• if you have diabetes (high level of sugar in your blood). Everolimus may increase blood sugar levels and worsen diabetes mellitus. This may result in the need for insulin and/or oral antidiabetic agent therapy. Tell your doctor if you experience any excessive thirst or increased frequency of urination.
• if you need to receive a vaccine while taking Everolimus.
• if you have high cholesterol. Everolimus may elevate cholesterol and/or other blood fats.
• if you have had recent major surgery, or if you still have an unhealed wound following surgery. Everolimus may increase the risk of problems with wound healing.
• if you have an infection. It may be necessary to treat your infection before starting Everolimus.
• if you have previously had hepatitis B, because this may be reactivated during treatment with Everolimus (see section 4 ‘Possible side effects’).
• if you have received or are about to receive radiation therapy.

Everolimus may also:

• weaken your immune system. Therefore, you may be at risk of getting an infection while you are taking Everolimus. If you have fever or other signs of an infection, consult with your doctor. Some infections may be severe and may have fatal consequences.
• impact your kidney function. Therefore, your doctor will monitor your kidney function while you are taking Everolimus.
• cause shortness of breath, cough and fever.
• cause mouth ulcers and sores to develop. Your doctor might need to interrupt or discontinue your treatment with Everolimus. You might need treatment with a mouthwash, gel or other products. Some mouthwashes and gels can make ulcers worse, so do not try anything without checking with your doctor first. Your doctor might restart treatment with Everolimus at the same dose or at a lower dose.
• cause complications of radiation therapy. Severe complications of radiotherapy (such as shortness of breath, nausea, diarrhoea, skin rashes and soreness in mouth, gums and throat), including fatal cases, have been observed in some patients who were taking everolimus at the same time as radiation therapy or who were taking everolimus shortly after they had radiation therapy. In addition, so-called radiation recall syndrome (comprising skin redness or lung inflammation at the site of previous radiation therapy) has been reported in patients who had radiation therapy in the past.

Tell your doctor if you are planning to have radiation therapy in the near future, or if you have had radiation therapy before.

Tell your doctor if you experience these symptoms.

You will have regular blood tests during treatment. These will check the amount of blood cells (white blood cells, red blood cells and platelets) in your body to see if Everolimus is having an unwanted effect on these cells. Blood tests will also be carried out to check your kidney function (level of creatinine) and liver function (level of transaminases) and your blood sugar and cholesterol levels. This is because these can also be affected by Everolimus.

Everolimus is not to be used in children or adolescents (age below 18 years).

Everolimus may affect the way some other medicines work. If you are taking other medicines at the same time as Everolimus, your doctor may need to change the dose of Everolimus or the other medicines.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

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

• ketoconazole, itraconazole, voriconazole, or fluconazole and other antifungals used to treat fungal infections
• clarithromycin, telithromycin or erythromycin, antibiotics used to treat bacterial infections.
• ritonavir and other medicines used to treat HIV infection/AIDS
• verapamil or diltiazem, used to treat heart conditions or high blood pressure
• dronedarone, a medicine used to help regulate your heart beat
• ciclosporin, a medicine used to stop the body from rejecting organ transplants
• 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 to treat depression
• cannabidiol (uses amongst others include treatment of seizures).

The following may reduce the effectiveness of Everolimus:

• rifampicin, used to treat tuberculosis (TB)
• efavirenz or nevirapine, used to treat HIV infection/AIDS
• St. John’s wort (Hypericum perforatum), a herbal product used to treat depression and other conditions
• dexamethasone, a corticosteroid used to treat a wide variety of conditions including inflammatory or immune problems
• phenytoin, carbamazepine or phenobarbital and other anti-epileptics used to stop seizures or fits

These medicines should be avoided during your treatment with Everolimus. If you are taking any of them, your doctor may switch you to a different medicine, or may change your dose of Everolimus.

Avoid grapefruit and grapefruit juice while you are on Everolimus. It may increase the amount of Everolimus in the blood, possibly to a harmful level.

Pregnancy

Everolimus could harm your unborn baby and is not recommended during pregnancy. Tell your doctor if you are pregnant or think that you may be pregnant. Your doctor will discuss with you whether you should take this medicine during your pregnancy.

Women who could potentially become pregnant should use highly effective contraception during treatment and for up to 8 weeks after ending treatment. If, despite these measures, you think you may have become pregnant, ask your doctor for advice before taking any more Everolimus.

Breastfeeding

Everolimus could harm a breastfed baby. You should not breastfeed during treatment and for 2 weeks after the last dose of everolimus. Tell your doctor if you are breastfeeding.

Female fertility

Absence of menstrual periods (amenorrhoea) has been observed in some female patients receiving Everolimus.

Everolimus may have an impact on female fertility. Talk to your doctor if you wish to have children.

Male fertility

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

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

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

• If you have taken too much Everolimus, or if someone else accidentally takes your tablets, see a doctor or go to a hospital immediately. Urgent treatment may be necessary.
• Take the carton and this leaflet, so that the doctor knows what has been taken.

If you miss a dose, take your next dose as scheduled. Do not take a double dose to make up for the forgotten tablets.

Do not stop taking Everolimus unless your doctor tells you to.

Very common (may affect more than 1 in 10 people)

• increased temperature, chills (signs of infection)
• fever, coughing, difficulty breathing, wheezing (signs of inflammation of the lung, also known as pneumonitis)

Common (may affect up to 1 in 10 people)

• excessive thirst, high urine output, increased appetite with weight loss, tiredness (signs of diabetes)
• bleeding (haemorrhage), for example in the gut wall
• severely decreased urine output (sign of kidney failure)

Uncommon (may affect up to 1 in 100 people)

• fever, skin rash, joint pain and inflammation, as well as tiredness, loss of appetite, nausea, jaundice (yellowing of the skin), pain in the upper right abdomen, pale stools, dark urine (may be signs of hepatitis B reactivation)
• breathlessness, difficulty breathing when lying down, swelling of the feet or legs (signs of heart failure)
• swelling and/or pain in one of the legs, usually in the calf, redness or warm skin in the affected area (signs of blockade of a blood vessel (vein) in the legs caused by 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 arteries in your lungs become blocked)
• severely decreased urine output, swelling in the legs, feeling confused, pain in the back (signs of sudden kidney failure)
• rash, itching, hives
• difficulty breathing or swallowing, dizziness (signs of serious allergic reaction, also known as hypersensitivity)

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

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

If you experience any of these side effects, tell your doctor immediately as this might have life-threatening consequences.

Very common (may affect more than 1 in 10 people)

• high level of sugar in the blood (hyperglycaemia)
• loss of appetite
• disturbed taste (dysgeusia)
• headache
• nose bleeds (epistaxis)
• cough
• mouth ulcers
• upset stomach including feeling sick (nausea) or diarrhoea
• skin rash
• itching (pruritus)
• feeling weak or tired
• tiredness, breathlessness, dizziness, pale skin, signs of low level of red blood cells (anaemia)
• swelling of arms, hands, feet, ankles or other part of the body (signs of oedema)
• weight loss
• high level of lipids (fats) in the blood (hypercholesterolaemia)

Common (may affect up to 1 in 10 people)

• spontaneous bleeding or bruising (signs of low level of platelets, also known as thrombocytopenia)
• breathlessness (dyspnea)
• thirst, low urine output, dark urine, dry flushed skin, irritability (signs of dehydration)
• trouble sleeping (insomnia)
• headache, dizziness (sign of high blood pressure, also known as hypertension)
• swelling of part or all of your arm (including fingers) or leg (including toes), feeling heaviness, restricted movement, discomfort (possible symptoms of lymphoedema)
• fever, sore throat, mouth ulcers due to infections (signs of low level of white blood cells, leukopenia, lymphopenia and/or neutropenia)
• fever
• inflammation of the inner lining of the mouth, stomach, gut
• dry mouth
• heartburn (dyspepsia)
• being sick (vomiting)
• difficulty in swallowing (dysphagia)
• abdominal pain
• acne
• rash and pain on the palms of your hands or soles of your feet (hand-foot syndrome)
• reddening of the skin (erythema)
• joint pain
• pain in the mouth
• menstruation disorders such as irregular periods
• high level of lipids (fats) in the blood (hyperlipidaemia, raised triglycerides)
• low level of potassium in the blood (hypokalaemia)
• low level of phosphate in the blood (hypophosphataemia)
• low level of calcium in the blood (hypocalcaemia)
• dry skin, skin exfoliation, skin lesions
• nail disorders, breaking of your nails
• mild loss of hair
• abnormal results of liver blood tests (increased alanine and aspartate aminotransferase)
• abnormal results of renal blood tests (increased creatinine)
• swelling of the eyelid
• protein in the urine

Uncommon (may affect up to 1 in 100 people)

• weakness, spontaneous bleeding or bruising and frequent infections with signs such as fever, chills, sore throat or mouth ulcers (signs of low level of blood cells, also known as pancytopenia)
• loss of sense of taste (ageusia)
• coughing up blood (haemoptysis)
• menstruation disorders such as absence of periods (amenorrhoea)
• passing urine more often during daytime
• chest pain
• abnormal wound healing
• hot flushes
• discharge from the eye with itching and redness
• pink eye or red eye (conjunctivitis)

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

• tiredness, breathlessness, dizziness, pale skin (signs of low level of red blood cells, 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 the tongue and difficulty breathing or swallowing (also known as angioedema), may be signs of an allergic reaction

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

• reaction at the site of previous radiation therapy, e.g. skin redness or lung inflammation (so called radiation recall syndrome)
• worsening of radiation treatment side effects

If these side effects get severe please tell your doctor and/or pharmacist. Most of the side effects are mild to moderate and will generally disappear if your treatment is interrupted for a few days.

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

You can also report side effects directly via the Yellow Card Scheme website www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

The active substance is everolimus.

The other ingredients are butylhydroxytoluene (E321), hypromellose (E464), lactose, lactose monohydrate, crospovidone (E1202) and magnesium stearate (E470b).

Everolimus tablets are available in three strengths:

Everolimus 2.5 mg are white to off white oval biconvex tablets (approximately 10 x 5 mm), debossed with E9VS on one side and 2.5 on the other side.

Everolimus 5 mg are white to off white oval and biconvex tablets (approximately 13 x 6 mm), debossed with E9VS 5 on one side.

Everolimus 10 mg are white to off white oval and biconvex tablets (approximately 16 x 8 mm), debossed with E9VS 10 on one side.

Everolimus 2.5 mg tablets and Everolimus 5 mg tablets are available in packs containing 30 tablets.

Everolimus 10 mg tablets are available in packs containing 10, 30 or 90 tablets.

Not all pack sizes may be marketed.