Patient Information Leaflet

Revolade 12.5 mg Film-Coated Tablets

Revolade 25 mg Film-Coated Tablets

Revolade 50 mg Film-Coated Tablets

Revolade 75 mg Film-Coated Tablets

eltrombopag

Read this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, as 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 others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

1.What Revolade is and what it is used for

2.What you need to know before you start taking Revolade

3.How to take Revolade

4.Possible side effects

5.Storage of Revolade

6.Contents of the pack and additional information

Revolade contains eltrombopag, which belongs to a group of medications called thrombopoietin receptor agonists,which is used to help increase the number of platelets in the blood. Platelets are cells present in the blood that help reduce or prevent bleeding.

• Revolade is used to treat a blood disorder called immune thrombocytopenia (primary) (PTI) in patients over 1year of age who have already taken other medications (corticosteroids or immunoglobulins) that have not worked.

PTI is caused by a low platelet count (thrombocytopenia). People with PTI have a higher risk of bleeding. Symptoms that patients with PTI may notice are petechiae (small, round, flat red spots under the skin), ecchymoses, nosebleeds, bleeding gums, and inability to control bleeding if they cut or injure themselves.

• Revolade may also be used to treat low platelet counts (thrombocytopenia) in adults with hepatitis C virus infection (HCV), in cases where they have had problems with the side effects of interferon treatment. Many people with hepatitis C have low platelet counts, not only due to the disease, but also due to antiviral treatments used to treat it. Taking Revolade may help you complete the antiviral treatment cycle (peginterferon and ribavirin).

Revolade may also be used in patients with low blood cell counts caused by severe aplastic anemia (SAA). SAA is a disease in which the bone marrow is damaged, leading to a deficiency of red blood cells (anemia), white blood cells (leukopenia), and platelets (thrombocytopenia).

Do not take Revolade

• if you are allergicto eltrombopag or any of the other ingredients of this medicine (listed in section6 under the title “Composition of Revolade”).

Consult your doctorif you think this may affect you.

Warnings and precautions

Consult your doctor before starting to take Revolade:

• if you haveliver problems. People who have a low platelet count and a chronic advanced liver disease (for a long time) have a higher risk of adverse effects, liver damage that can be fatal, and blood clots. If your doctor considers that the benefits of Revolade outweigh the risks, they will closely monitor you during treatment.
• if you havea risk of suffering a blood clotin veins or arteries, or if you know that the appearance of blood clots is a common occurrence in your family.

The risk of suffering a blood clot may be higherin the following circumstances:

• if you are elderly
• if you have been bedridden for a long time
• if you have cancer
• if you are taking the contraceptive pill or hormone replacement therapy
• if you have recently undergone surgery or have suffered physical damage
• if you are significantly overweight (obesity)
• if you are a smoker
• if you have a chronic and advanced liver disease.

If you find yourself in any of these situations,inform your doctorbefore starting treatment.You should not take Revolade unless your doctor considers that the expected benefits outweigh the risk of blood clots.

• if you havecataracts(the lens of the eye becomes cloudy).
• if you have anotherblood disorder, such as myelodysplastic syndrome (MDS). Before starting to take Revolade, your doctor will perform tests to check that you do not have this disease. If you have MDS and take Revolade, MDS may worsen.

Inform your doctorif you find yourself in any of these situations.

Eye examinations

Your doctor will recommend that you undergo a check-up to see if you have cataracts. If you do not have routine eye exams, your doctor will ask you to have them done. They should also examine your retina (the layer of light-sensitive cells at the back of the eye) to see if there is bleeding in the retina or around it.

You will need to have regular blood tests

Before starting to take Revolade, your doctor will perform a blood test to see how your blood cells, including platelets, are doing. These blood tests will be repeated frequently while you are taking the medicine.

Blood tests to check liver function

Revolade may cause abnormal results on your blood tests indicating liver damage - an increase in certain liver enzymes, especially bilirubin and alanine/aspartate transaminase. If you are taking interferon, a treatment given together with Revolade to treat low platelet counts due to hepatitis C, some liver problems may worsen.

Regular blood tests will be performed before starting to take Revolade and while you are taking it to check your liver function. You may need to stop taking Revolade if your liver enzyme levels become too high or if you have any other signs of liver damage.

See the information “Liver problems” in section 4 of this leaflet

Blood tests to check platelet count

If you stop taking Revolade, it is likely that your platelet count will drop again within a few days. Your doctor will monitor your platelet count and advise you on the precautions you need to take.

Very high platelet counts may increase the risk of blood clots. However, blood clots can also form with normal or low platelet counts. Your doctor will adjust the dose of Revolade to ensure that your platelet count does not become too high.

Seek medical help immediatelyif you experience any of the following signs of ablood clot:

• swelling, painor sensitivityin a leg
• sudden difficulty breathing, occasionally accompanied by severe chest pain or rapid breathing
• abdominal pain(stomach), swollen abdomen, blood in the stool.

Blood tests to examine your bone marrow

In people with bone marrow disorders, medicines like Revolade can worsen the disorders. Signs of changes in the bone marrow may appear as abnormal results on your blood tests. Your doctor may also perform blood tests to directly examine your bone marrow during treatment with Revolade.

Review of gastrointestinal bleeding

If you are taking interferon, a treatment given together with Revolade, you will be monitored for any signs of bleeding in your stomach or intestines after you stop taking Revolade.

Heart monitoring

Your doctor may consider, if necessary, monitoring your heart while you are taking Revolade through an electrocardiogram.

People over 65 years old

There are few data on the use of Revolade in patients aged 65 years or older. If you are 65 years or older, you should be careful when using Revolade.

Children and adolescents

Revolade is not recommended for children under 1 year old with PTI. It is also not recommended for children under 18 years old with low platelet counts due to hepatitis C or severe aplastic anemia.

Other medicines and Revolade

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medicine. This includes medicines obtained without a prescription and vitamins.

Some common medicines may interact with Revolade(including prescription medicines, non-prescription medicines, and minerals). These include:

• anti-acid medicines to treatindigestion,heartburn, orstomach ulcers(see also section3 “When to take it”).
• statins, tolower cholesterol
• some medicines to treatHIV infection, such as lopinavir and/or ritonavir
• ciclosporin, used intransplantsor inimmune system disorders
• minerals such as iron, calcium, magnesium, aluminum, selenium, and zinc, which may be present invitamin and mineral supplements(see also section3 “When to take it”).
• medicines such as methotrexate and topotecan, used to treatcancer

Consult your doctorif you are taking any of these medicines. Some should not be taken with Revolade, you may need to adjust the dose or change the time you take them. Your doctor will review the medicines you are taking and recommend alternatives if necessary.

If you are also taking medicines to prevent blood clots, there is a higher risk of bleeding. Your doctor will discuss this with you.

If you are takingcorticosteroids, danazol,and/orazathioprinetogether with Revolade, you may need to reduce the dose or stop taking these medicines.

Taking Revolade with food and drinks

Do not take Revolade with milk or milk products, as the calcium in milk products affects the absorption of the medicine. For more information, see section3, “When to take it”.

Pregnancy and breastfeeding

Do not take Revolade if you are pregnantunless your doctor specifically recommends it. The effect of Revolade during pregnancy is unknown.

• Inform your doctorif you are pregnant, think you may be pregnant, or plan to become pregnant.
• Use a reliable method of contraceptionto prevent pregnancy while taking Revolade.
• If you become pregnant while taking Revolade, inform your doctor.

Do not breastfeed while taking Revolade. It is unknown whether Revolade passes into breast milk.

If you are breastfeeding or plan to breastfeed, inform your doctor.

Driving and operating machines

Revolade may cause dizzinessand other side effects that make you less alert.

Do not drive or operate machinesunless you are sure that Revolade does not affect you.

Revolade contains sodium

This medicine contains less than 1mmol of sodium (23mg) per tablet; this is, essentially “sodium-free”.

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again. Do not change the dose or treatment schedule with Revolade, unless your doctor or pharmacist advises you to do so. While taking Revolade, you will be under the supervision of a specialist doctor with experience in treating your disease.

How much to take

For PTI

Adults and children(6 to 17years old) - the usual initial dose for PTI is one50mgtablet of Revolade per day. If you are of East or Southeast Asian descent, you may need to start treatment with a lower dose, of25mg.

Children(1 to 5years old) - the usual initial dose for PTI is one25mgtablet of Revolade per day.

For Hepatitis C

Adults- the usual initial dose for hepatitis C is one25mgtablet of Revolade per day. If you are of East or Southeast Asian descent, start treatment with thesame dose of25mg.

For AAG

Adults– the usual initial dose for AAG is one50mg tablet of Revolade per day. If you are of East or Southeast Asian descent (you may need to start treatment with a lower dose of25mg.

Revolade may take 1 to 2weeks to take effect. Depending on your response to Revolade, your doctor may recommend changing your daily dose.

How to take the tablets

Swallow the tablet whole, with water

When to take it

Make sure that –

• 4hours beforetaking Revolade
• and in the2hours aftertaking Revolade

do notconsume:

• Dairy productssuch as cheese, butter, yogurt, or ice cream
• Milk or milkshakes, beverages made with milk, yogurt, or cream
• Antacids, a type of medication forindigestion and heartburn
• somevitamin and mineral supplements, including iron, calcium, magnesium, aluminum, selenium, and zinc.

If you do, your body will not absorb the medication properly.

For more information on suitable foods and beverages, consult your doctor.

If you take more Revolade than you should

Consult your doctor or pharmacist immediately. If possible, show them the packaging or this leaflet. You will be monitored for signs or symptoms of adverse effects and receive immediate treatment.

If you forget to take Revolade

Take the next dose at the usual time. Do not take more than one dose of Revolade per day.

If you interrupt treatment with Revolade

Do not stop taking Revolade without consulting your doctor first. If your doctor advises you to stop treatment, your platelet levels will be monitored every week for four weeks. See also “Bleeding or bruising after stopping treatment” in section4.

If you have any other questions about using this medication, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Signs you need to watch for: see your doctor

People taking Revolade for both PTI and low platelet counts associated with hepatitis C may experience signs related to possible severe side effects.It is important to inform your doctor if you develop symptoms.

Increased risk of thrombosis

Some people may be at a higher risk of developing a blood clot, and medicines like Revolade may make this problem worse. Sudden blockage of a blood vessel by a clot is a rare side effect that can affect up to 1 in 100 people.

Seek medical help immediately if you experience signs or symptoms of a blood clot, such as:

• Swelling, pain, heat, redness, or sensitivity in a leg
• Sudden difficulty breathing, occasionally accompanied by sharp chest pain or agitated breathing.
• Abdominal pain(stomach),enlarged abdomen, blood in your stool.

Liver problems

Revolade can cause changes that appear in blood tests, and which may be signs of liver damage. Liver problems (elevated liver enzymes in blood tests) are common and can affect up to 1 in 10 people. Other liver problems are rare and can affect up to 1 in 100 people.

If you have any of the signs of liver problems:

• Yellowing of the skin or in the white part of your eyes (jaundice)
• Dark-colored urine.

Contact your doctor immediately

Bleeding or bruising after stopping treatment

Two weeks after stopping treatment with Revolade, your platelet levels will usually return to the levels you had before starting Revolade. A decrease in platelet levels can increase the risk of bleeding or bruising. Your doctor will check your platelet levels for at least 4 weeks after stopping treatment with Revolade.

Contact your doctorif you experience bleeding or bruising after stopping Revolade.

Some peoplehavegastrointestinal bleedingafter stopping peginterferon,ribavirin, andRevolade.The symptoms include:

• Black, tarry stools (the discoloration of stools is a rare side effect that can affect up to 1 in 100 people).
• Blood in your stool
• Vomiting blood or something that looks like coffee grounds

Contact your doctor immediatelyif you experience any of these symptoms.

The following side effects have been reported in patients with PTI who have taken Revolade:

Very common side effects

Can affect more than 1 in 10 people

• Cold
• Feeling dizzy (nausea)
• Diarhea
• Cough
• Upper respiratory tract infection (infection of the nose, sinuses, throat, and airways)
• Back pain

Very common side effects that can appear in blood tests

• Elevated liver enzymes (alanine aminotransferase (ALT))

Common side effects

Can affect up to 1 in 10 people

• Muscle pain, muscle spasms, muscle weakness
• Bone pain
• Heavy menstrual bleeding
• Sore throat and difficulty swallowing
• Eye problems, including abnormal eye test results, dry eyes, eye pain, and blurred vision
• Vomiting
• Flu
• Herpes labialis
• Pneumonia
• Swelling and inflammation (hives) of the breasts
• Swelling and inflammation (hives) of the tonsils
• Infection of the lungs, sinuses, nose, and throat
• Swelling of the gums
• Loss of appetite
• Itching, tingling, or numbness
• Decreased sensitivity in the skin
• Drowsiness
• Ear pain
• Pain, swelling, and sensitivity in one leg (usually the calf) with warm skin in the affected area (signs of a blood clot in a deep vein)
• Localized swelling filled with blood from a broken blood vessel (hematoma)
• Seizures
• Mouth problems, including dry mouth or irritation, tongue sensitivity, gum bleeding, mouth ulcers
• Runny nose
• Toothache
• Abdominal pain
• Abnormal liver function
• Changes in the skin, including excessive sweating, itching, red patches, changes in skin appearance
• Hair loss
• Foamy or bubbly urine (signs of protein in the urine)
• Elevated body temperature, feeling hot
• Chest pain
• Feeling weak
• Difficulty sleeping, depression
• Migraine
• Decreased vision
• Feeling like everything is spinning (vertigo)
• Gas

Common side effects that can appear in blood tests:

• Decreased red blood cell count (anemia)
• Decreased platelet count (thrombocytopenia)
• Decreased white blood cell count
• Decreased hemoglobin levels
• Increased eosinophil count
• Increased white blood cell count (leukocytosis)
• Increased uric acid levels
• Decreased potassium levels
• Increased creatinine levels
• Increased alkaline phosphatase levels
• Increased liver enzymes (aspartate aminotransferase (AST))
• Increased bilirubin levels in the blood(a substance produced by the liver)
• Increased levels of some proteins

Rare side effects

Can affect up to 1 in 100 people:

• Allergic reaction
• Interruption of blood flow to parts of the heart

• Sudden difficulty breathing, especially when accompanied by sharp chest pain and/or agitated breathing, which could be signs of a blood clot in the lungs (see “Increased risk of thrombosis” earlier in section4)

• Partial loss of lung function caused by a blockage in the pulmonary artery
• Possible pain, swelling, and/or redness around a vein that could be signs of blood clots in a vein
• Yellow skin and/or abdominal pain that could be signs of a bile duct obstruction, liver injury, or liver damage due to inflammation (see “Liver problems” earlier in section4)
• Liver damage due to medication
• Fast heart rate, irregular heartbeat, blue discoloration of the skin, abnormal heart rhythm (prolongation of the QT interval) that could be a sign of a heart and blood vessel disorder.
• Blood clots
• Seizures
• Joint pain and swelling due to uric acid
• Lack of interest, changes in mood, difficult-to-calming crying or unexpected crying
• Problems with balance, alterations in speech and nervous function, tremors
• Pain or abnormal sensations in the skin
• Paralysis of one side of the body
• Migraine with aura
• Neuralgia
• Dilation or swelling of blood vessels that cause headache
• Eye problems, including increased tear production, clouding of the lens of the eye (cataracts), hemorrhage in the retina, dry eye
• Nose, throat, and sinus problems, breathing difficulties while sleeping
• Blistering or pain in the mouth and throat
• Loss of appetite
• Problems with the digestive system, including frequent bowel movements, food poisoning, blood in stool, vomiting of blood
• Bleeding in the rectum, changes in stool color, abdominal swelling, constipation
• Mouth problems, including dryness or irritation in the mouth, tongue pain, gum bleeding, mouth ulcers
• Sunburn
• Feeling hot, feeling anxious
• Redness or inflammation around wounds
• Bleeding around a catheter (if you have one) in the skin
• Feeling of a foreign body
• Renal problems, including inflammation of the kidneys, excessive urination at night, renal failure, white blood cells in urine
• Cold sweats
• General feeling of discomfort

• Skin infection
• Changes in the skin, including skin discoloration, peeling, redness, itching, and excessive sweating
• Muscle weakness
• Colon and rectal cancer

Rare side effects that can appear in blood tests:

• Changes in the shape of white blood cells
• Presence of immature white blood cells that may be indicative of certain diseases
• Increased platelet count
• Decreased calcium levels
• Decreased red blood cell count (anemia) due to excessive destruction of red blood cells (hemolytic anemia)
• Increased myelocyte count
• Increased neutrophil count
• Increased urea levels in the blood
• Increased protein in urine
• Increased total protein levels
• Decreased albumin levels in the blood
• Increased pH in urine
• Increased hemoglobin levels

The following side effects have been reported in children (1 to 17 years old) with PTI who have taken Revolade:

If these side effects worsen, please inform your doctor, pharmacist, or nurse.

Very common side effects

Can affect more than 1 in 10 children

• Upper respiratory tract infection (infection of the nose, sinuses, throat, and airways), cold (upper respiratory tract infection)
• Diarhea
• Abdominal pain
• Cough
• Elevated body temperature
• Feeling dizzy (nausea)

Common side effects

Can affect up to 1 in 10 children

• Difficulty sleeping (insomnia)
• Toothache
• Sore throat and nose
• Itching, runny nose, or stuffiness
• Irritation of the throat, runny nose, congestion, and sneezing
• Mouth problems, including dryness, irritation in the mouth, tongue sensitivity, gum bleeding, mouth ulcers

The following side effects have been reported in patients with hepatitis C who have taken Revolade in combination with peginterferon and ribavirin:

Very common side effects

Can affect more than 1 in 10 people:

• Headache
• Loss of appetite
• Cough
• Feeling dizzy (nausea), diarrhea
• Muscle pain, muscle weakness
• Itching
• Feeling tired
• Fever
• Hair loss
• Feeling weak
• Flu-like symptoms
• Swelling of hands or feet
• Chills

Very common side effects that can appear in blood tests:

• Decreased red blood cell count (anemia)

Common side effects

Can affect up to 1 in 10 people:

• Urinary tract infection
• Inflammation of the nasal passages, throat, and mouth, symptoms similar to the flu, dryness, irritation, or inflammation of the mouth, toothache
• Weight loss
• Sleep disorders, abnormal drowsiness, depression, anxiety
• Dizziness, attention and memory problems, changes in mood
• Decreased brain function due to liver damage
• Itching or numbness in hands and feet
• Fever, headache
• Eye problems, includingclouding of the lens of the eye (cataracts), dry eye, small yellow deposits in the retina, yellowing of the white part of the eyes
• Bleeding in the retina
• Feeling like everything is spinning
• Rapid and irregular heartbeat(palpitations),difficulty breathing
• Cough with mucus, runny nose, flu (influenza), herpes labialis, irritation of the throat and difficulty swallowing
• Abdominal problems, including difficulty swallowing, mouth pain, tongue swelling, vomiting, loss of appetite, abdominal pain, abdominal swelling, flatulence/gas, constipation, changes in bowel movements that can cause constipation, diarrhea, and/or the aforementioned symptoms, changes in stool color
• Fainting
• Skin problems, including red or purple patches due to bleeding under the skin (petechiae), rash, itching, urticaria, skin lesions
• Back pain
• Muscle pain
• Bone pain
• Weakness (asthenia)
• Swelling of the lower extremities due to fluid accumulation
• Abnormal urine color
• Interruption of blood flow to the spleen (splenic infarction)
• Runny nose

Common side effects that can appear in blood tests:

• Increased levels of some enzymes due to muscle degradation (creatinine phosphokinase)
• Iron overload in the body
• Decreased blood sugar levels (hypoglycemia)
• Increased bilirubin levels in the blood (a substance produced by the liver)
• Decreased white blood cell count

Side effects of unknown frequency

Cannot be estimated from available data

• Skin discoloration

• Skin darkening

• Medication-induced liver damage

Reporting of side effects

If you experienceany type of side effect, consult your doctor or pharmacist, even if it is apossibleside effect that does not appear in this leaflet.You can also report them directly through the national notification system included in theAppendix V.By reporting side effects, you can contribute to providing more information about the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the packaging and on the blister.

This medication does not require special storage conditions.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. In this way, you will help protect the environment.

Composition of Revolade

The active ingredient of Revolade is eltrombopag.

Coated tablets of 12.5 mg

Each coated tablet contains eltrombopag olamine equivalent to 12.5 mg of eltrombopag.

Coated tablets of 25 mg

Each coated tablet contains eltrombopag olamine equivalent to 25 mg of eltrombopag.

Coated tablets of 50 mg

Each coated tablet contains eltrombopag olamine equivalent to 50 mg of eltrombopag.

Coated tablets of 75 mg

Each coated tablet contains eltrombopag olamine equivalent to 75 mg of eltrombopag.

The other components are: hypromellose, macrogol 400, magnesium stearate, mannitol (E421), microcrystalline cellulose, povidone, sodium carboxymethylcellulose, titanium dioxide (E171).

Revolade 12.5 mg and 25 mg coated tablets also contain polysorbate 80 (E433).

Revolade 50 mg coated tablets also contain: iron oxide red (E172), iron oxide yellow (E172).

Revolade 75 mg coated tablets also contain: iron oxide red (E172), iron oxide black (E172).

Appearance of the product and contents of the pack

Revolade 12.5 mg coated tablets are white, round, biconvex, engraved with ‘GS MZ1’ and ‘12.5’ on one side.

Revolade 25 mg coated tablets are white, round, biconvex, engraved with ‘GS NX3’ and ‘25’ on one side.

Revolade 50 mg coated tablets are brown, round, biconvex, engraved with ‘GS UFU’ and ‘50’ on one side.

Revolade 75 mg coated tablets are pink, round, biconvex, engraved with ‘GS FFS’ and ‘75’ on one side.

They are supplied in aluminium blisters in a carton containing 14 or 28 coated tablets and multiple packs containing 84 coated tablets (3 packs of 28).

Only some pack sizes may be marketed.

Marketing authorisation holder

Novartis Europharm Limited

Vista Building

Elm Park, Merrion Road

Dublin 4

Ireland

Responsible for manufacturing

Lek d.d

Verovskova Ulica 57

Ljubljana 1526

Slovenia

Novartis Pharmaceutical Manufacturing LLC

Verovskova Ulica 57

Ljubljana 1000

Slovenia

Novartis Farmacéutica SA

Gran Via de les Corts Catalanes, 764

08013 Barcelona

Spain

Novartis Pharma GmbH

Roonstraße 25

D-90429 Nuremberg

Germany

Glaxo Wellcome S.A.

Avenida de Extremadura 3

09400 Aranda de Duero

Burgos

Spain

Novartis Pharma GmbH

Sophie-Germain-Strasse 10

90443 Nürnberg

Germany

For further information about this medicinal product, please contact the local representative of the marketing authorisation holder:

Last update of this leaflet:

For detailed information about this medicinal product, please visit the website of the European Medicines Agency http://www.ema.europa.eu.