REVOLADE 25 mg FILM-COATED TABLETS

2. What you need to know before you take Revolade

Do not take Revolade

• to eltrombopag or any of the other ingredients of this medicine (listed in section 6 under the heading “Composition of Revolade”).

Consult your doctorif you think this may affect you.

Warnings and precautions

Consult your doctor before starting to take Revolade:

• . People who have a low platelet count and advanced chronic liver disease are at higher risk of side effects, liver damage that can be fatal, and blood clots. If your doctor considers that the benefit of Revolade outweighs the risks, you will be closely monitored during treatment.
• in your veins or arteries, or if you know that blood clots are common in your family.

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

If you are in any of these situations, tell your doctorbefore starting treatment. You should not take Revolade unless your doctor considers that the expected benefit outweighs the risk of having blood clots.

• (the lens of the eye becomes cloudy).
• , 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.

Tell your doctorif you are in any of these situations.

Eye examinations

Your doctor will recommend that you have an eye examination to check for cataracts. If you do not have regular eye examinations, your doctor will ask you to have one. They will also examine your retina (the light-sensitive layer at the back of the eye) to see if there is any bleeding in the retina or around it.

You will need to have regular blood tests

Before you start taking Revolade, your doctor will perform a blood test to check your blood cells, including platelets. These tests will be repeated frequently while you are taking the medicine.

Blood tests to check liver function

Revolade may cause changes in your liver function tests, including increased levels of certain liver enzymes, especially bilirubin and alanine/aspartate transaminase. If you are taking interferon, the basic treatment along with Revolade to treat low platelet counts due to hepatitis C, some liver problems may worsen.

You will have blood tests before starting to take Revolade and frequently while taking it to check your liver function. You may need to stop taking Revolade if the levels of these markers increase too much or if you have any other signs of liver damage.

Read the information on “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 decrease again within a few days. Your platelet count will be monitored, and your doctor will advise you on what precautions to take.

Very high platelet counts may increase the risk of blood clots. However, blood clots can also form with normal or even 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 have any of these signs of a blood clot:

• swelling, painor tenderness in one leg
• sudden difficulty breathing, exceptionally accompanied by sharp chest pain or rapid breathing
• abdominal pain(stomach), enlarged abdomen, blood in the stool.

Tests to examine your bone marrow

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

Review of gastrointestinal bleeding

If you are taking interferon, the basic treatment along with Revolade, you will be monitored for any signs of bleeding in your stomach or intestine after you stop taking Revolade.

Heart monitoring

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

Elderly (65 years and over)

There is limited data on the use of Revolade in patients aged 65 years or over. If you are 65 or over, you should be cautious when using Revolade.

Children and adolescents

Revolade is not recommended for use in children under 1 year of age with ITP. It is also not recommended for use in children under 18 years of age with low platelet counts due to hepatitis C or severe aplastic anemia.

Other medicines and Revolade

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. This includes medicines obtained without a prescription and vitamins.

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

• antacids for indigestion, heartburn, or stomach ulcers(see also section 3 “When to take it”).
• statins to lower cholesterol
• certain medicines to treat HIV infection, such as lopinavir and/or ritonavir
• cyclosporin, used in transplantsor immune system diseases
• minerals such as iron, calcium, magnesium, aluminum, selenium, and zinc, which may be present in vitamin and mineral supplements(see also section 3 “When to take it”).
• medicines such as methotrexate and topotecan, used to treat cancer

Consult your doctorif you are taking any of these medicines. Some should not be taken with Revolade; the dose may need to be adjusted, or you may need to change the times when 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 taking corticosteroids, danazol,and/or azathioprinewith Revolade, you may need to reduce the dose or stop treatment with these medicines.

Taking Revolade with food and drinks

Do not take Revolade with dairy products or drinks, as the calcium in these products affects the absorption of the medicine. For more information, see section 3, “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 not known.

• Tell your doctor if you are pregnant,think you may be pregnant, or plan to become pregnant.
• Use a reliable contraceptive methodto prevent pregnancy while taking Revolade.
• If you become pregnant during treatmentwith Revolade, tell your doctor.

Do not breastfeed while taking Revolade. It is not known if Revolade passes into breast milk.

If you are breastfeedingor plan to breastfeed, tell your doctor.

Driving and using machines

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

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

Revolade contains sodium

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

3. How to take Revolade

Follow the instructions for taking this medicine exactly as your doctor has told you. If you are unsure, 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 ITP

Adults and children(6 to 17 years) - the usual starting dose for ITP is one 50mgRevolade tablet per day. If you are of East or Southeast Asian descent, you may need to start treatment with a lower dose of 25mg.

Children(1 to 5 years) - the usual starting dose for ITP is one 25mgRevolade tablet per day.

For Hepatitis C

Adults- the usual starting dose for hepatitis C is one 25mgRevolade tablet per day. If you are of East or Southeast Asian descent, start treatment with the same dose of 25mg.

For SAA

Adults– the usual starting dose for SAA is one 50mgRevolade tablet per day. If you are of East or Southeast Asian descent, you may need to start treatment with a lower dose of 25mg.

Revolade may take 1 to 2 weeks to work. 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 –

• in the 4 hours beforetaking Revolade
• and in the 2 hours aftertaking Revolade

do notconsume any of the following:

• dairy productssuch as cheese, butter, yogurt, or ice cream
• milk or milkshakes, milk-based drinks, yogurt, or cream
• antacids, a type of medicine for indigestion and heartburn
• certain vitamin and mineral supplements, including iron, calcium, magnesium, aluminum, selenium, and zinc.

If you do, your body may not absorb the medicine properly.

For more information on what foods and drinks are suitable, consult your doctor.

If you take more Revolade than you should

Consult your doctor or pharmacist immediately. If possible, show them the pack or this leaflet. You will be monitored for signs or symptoms of side effects and given the necessary treatment immediately.

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 stop taking Revolade

Do not stop taking Revolade without consulting your doctor first. If your doctor advises you to stop treatment, your platelet count will be monitored every week for four weeks. See also “Bleeding or bruising after stopping treatment” in section 4.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Symptoms to which you need to pay attention: consult your doctor

People taking Revolade for both ITP and low platelet counts associated with hepatitis C may exhibit signs related to potential serious adverse effects. It is essential that you inform your doctor if you develop symptoms.

Increased Risk of Thrombosis

Some people may have a higher risk of having a thrombus, and medications like Revolade can worsen this problem. The sudden blockage of a blood vessel by a thrombus is a rare adverse effect that can affect up to 1 in 100 people.

Seek medical help immediately if you experience signs or symptoms of thrombosis, such as:

• swelling, pain, heat, redness, orsensitivity in one leg
• sudden difficulty breathing, exceptionally accompanied by acute 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, which can be signs of liver damage. Liver problems (increased liver enzymes in blood tests) are frequent 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 signs of liver problems:

• yellowish coloron the skin or in the white area of the eyes (jaundice)
• dark-colored urinethat is unusual.

contact your doctor immediately

Bleeding or Hematoma after Treatment Interruption

Two weeks after interrupting treatment with Revolade, your platelet levels will normally drop to levels similar to those before starting Revolade. A decrease in platelet levels can increase the risk of bleeding or hematoma. Your doctor will check your platelet levels for at least 4 weeks after interrupting treatment with Revolade.

Contact your doctorif you experience bleeding or hematoma when stopping Revolade.

Some people have bleeding in thedigestive systemafter stopping peginterferon, ribavirin, and Revolade. Symptoms include:

• black, tar-like stools (stool discoloration is a rare adverse effect that can affect up to 1 in 100 people).
• blood in the stool
• vomiting blood or something that looks like coffee grounds

Contact your doctor immediatelyif you experience any of these symptoms.

The following adverse effects have been reported in relation to treatment with Revolade in adult patients with ITP

Very Common Adverse Effects

Can affect more than 1 in 10people

• cold
• feeling of dizziness (nausea)
• diarrhea
• cough
• infection of the nose, nasal sinuses, throat, and respiratory tract (upper respiratory tract infection)
• back pain

Very Common Adverse Effects that can appear in Blood Tests:

• increase in liver enzymes (alanine aminotransferase (ALT))

Common Adverse Effects

Can affect up to 1 in 10people

• muscle pain, muscle spasm, muscle weakness
• bone pain
• heavy menstruation
• irritation of the throat and discomfort when swallowing
• eye problems including abnormal eye tests, dry eye, eye pain, and blurred vision
• vomiting
• flu
• cold sore
• pneumonia
• irritation and inflammation (swelling) of the breasts
• inflammation (swelling) and infection in the tonsils
• infection of the lungs, sinuses, nose, and throat
• inflammation of the gums
• loss of appetite
• feeling of tingling, itching, or numbness
• decreased sensitivity in the skin
• drowsiness
• ear pain
• pain, swelling, and sensitivity in one leg (usually the calf) with hot 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)
• hot flashes
• alterations in the mouth including dryness or irritation in the mouth, sensitivity in the tongue, bleeding gums, mouth sores
• runny nose
• toothache
• abdominal pain
• abnormal liver function
• skin changes including excessive sweating, itchy rash, red spots, changes in skin appearance
• hair loss
• foamy or bubbly urine (signs of protein in the urine)
• high temperature, feeling of heat
• chest pain
• feeling of weakness
• sleep problems, depression
• migraine
• decreased vision
• feeling that everything is spinning (vertigo)
• gas

Common Adverse Effects that can appear in Blood Tests:

• decrease in the number of red blood cells (anemia)
• decrease in the number of platelets (thrombocytopenia)
• decrease in the number of white blood cells
• decrease in hemoglobin levels
• increase in the number of eosinophils
• increase in the number of white blood cells (leukocytosis)
• increase in uric acid levels
• decrease in potassium levels
• increase in creatinine levels
• increase in alkaline phosphatase levels
• increase in liver enzymes (aspartate aminotransferase (AST))
• increase in blood bilirubin (a substance produced by the liver)
• increase in some protein levels

Uncommon Adverse Effects

Can affect up to 1 in 100people:

• allergic reaction
• interruption of blood supply to parts of the heart

• sudden difficulty breathing, especially when accompanied by acute chest pain and/or agitated breathing, which could be signs of a pulmonary thrombus (see “Increased Risk of Thrombosis” above in section 4)

• 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 thrombosis in a vein
• yellowish skin and/or abdominal pain that could be signs of a bile duct obstruction, liver injury, liver damage due to inflammation (see “Liver Problems” above in section 4)
• liver damage due to medication
• rapid or irregular heartbeat, discoloration of the skin, alterations in heart rhythm (prolongation of the QT interval) that could be a sign of a heart and blood vessel disorder.
• blood clots
• hot flashes
• joint pain and swelling due to uric acid (gout)
• lack of interest, mood changes, uncontrolled crying or that occurs unexpectedly
• balance problems, speech and nervous system alterations, tremors
• pain or abnormal sensations in the skin
• paralysis of one side of the body
• migraine with aura
• nerve pain
• dilation or swelling of blood vessels that cause headache
• eye problems, including increased tearing, clouding of the eye lens (cataracts), retinal hemorrhage, dry eye
• nose, throat, and sinus problems, breathing problems when sleeping
• blisters/pain in mouth and throat
• loss of appetite
• digestive system problems, including frequent bowel movements, food poisoning, blood in stool, vomiting blood
• rectal bleeding, changes in stool color, abdominal swelling, constipation
• alterations in the mouth, including dryness or irritation in the mouth, tongue pain, gum bleeding, mouth sores
• 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
• kidney problems, including kidney inflammation, frequent urination (increased need to urinate) at night, kidney failure, white blood cells in urine
• cold sweat
• feeling of general discomfort

• skin infection
• skin changes, including skin discoloration, peeling, redness, itching, and sweating
• muscle weakness
• rectal and colon cancer

Uncommon Adverse Effects that can appear in Blood Tests:

• changes in the shape of white blood cells
• presence of immature white blood cells that can be indicative of certain diseases
• increase in platelet count
• decrease in calcium levels
• decrease in the number of red blood cells (anemia) caused by excessive destruction of red blood cells (hemolytic anemia)
• increase in the number of myelocytes
• increase in neutrophils
• increase in blood urea
• increase in protein in urine
• increase in albumin levels in blood
• increase in total protein levels
• decrease in albumin levels in blood
• increase in urine pH
• increase in hemoglobin levels

The following adverse effects have been reported in relation to treatment with Revolade in children (from 1 to 17 years) with ITP

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

Very Common Adverse Effects

Can affect more than 1 in 10children

• infection of the nose, nasal sinuses, throat, and upper respiratory tract, cold (upper respiratory tract infection)
• diarrhea
• abdominal pain
• cough
• high temperature
• feeling of dizziness (nausea)

Common Adverse Effects

Can affect up to 1 in 10children

• difficulty sleeping (insomnia)
• toothache
• sore throat and nose
• itching, runny nose, or stuffiness
• irritation of the throat, runny nose, nasal congestion, and sneezing
• alterations in the mouth, including dryness, irritation in the mouth, sensitivity in the tongue, gum bleeding, mouth sores

The following adverse effects have been reported in relation to treatment with Revolade in combination with peginterferon and ribavirin in patients with HCV

Very Common Adverse Effects

Can affect more than 1 in 10people:

• headache
• loss of appetite
• cough
• feeling dizzy (nausea), diarrhea
• muscle pain, muscle weakness
• itching
• feeling tired
• fever
• hair loss
• feeling weak
• discomfort similar to that produced by the flu
• swelling of hands or feet
• chills

Very Common Adverse Effects that can appear in Blood Tests:

• decrease in the number of red blood cells (anemia)

Common Adverse Effects

Can affect up to 1 in 10people:

• urinary tract infection
• inflammation of the nasal passages, throat, and mouth, flu-like symptoms, dryness, irritation, or inflammation of the mouth, toothache
• weight loss
• sleep disorders, abnormal drowsiness, depression, anxiety
• dizziness, attention and memory problems, mood changes
• decrease in brain function due to liver damage
• tingling or numbness in hands and feet
• fever, headache
• eye problems, including clouding of the eye lens (cataracts), dry eye, small yellow deposits in the retina, yellowish color in the white area of the eyes
• retinal bleeding
• feeling that everything is spinning
• rapid or irregular heartbeat (palpitations), difficulty breathing
• cough with phlegm, runny nose, flu (influenza), cold sore, throat irritation, and discomfort when swallowing
• digestive system alterations, including vomiting, stomach pain, indigestion, constipation, bloating, gas, changes in taste, hemorrhoids (piles), abdominal pain/discomfort, stomach swelling, alterations in intestinal motility that can cause constipation, bloating, diarrhea, and/or the aforementioned symptoms, changes in stool color
• toothache
• liver problems, including liver tumor, yellowing of the white area of the eyes or skin (jaundice), liver damage due to medication (see “Liver Problems” above in section 4)
• skin changes, including rash, dry skin, eczema, skin redness, itching, excessive sweating, unusual skin growth, hair loss
• joint pain, back pain, bone pain, pain in the limbs (arms, legs, hands, and feet), muscle spasms
• irritability, feeling of general discomfort, skin reactions such as redness or swelling and pain at the injection site, chest pain, and discomfort, fluid retention in the body or limbs that causes swelling

• infection of the nose, nasal sinuses, throat, and respiratory tract, cold (upper respiratory tract infection), inflammation of the mucous membrane that lines the bronchi

• depression, anxiety, sleep problems, nervousness

Common Adverse Effects that can appear in Blood Tests:

• increase in blood sugar (glucose)
• decrease in the number of white blood cells
• decrease in the number of neutrophils
• decrease in blood albumin
• decrease in hemoglobin levels
• increase in blood bilirubin (a substance produced by the liver)
• changes in the enzymes that control blood clotting

Uncommon Adverse Effects

Can affect up to 1 in 100people:

• pain when urinating
• alterations in heart rhythm (prolongation of the QT interval)

• stomach flu (gastroenteritis), sore throat
• blisters/pain in the mouth, stomach inflammation
• skin changes, including changes in color, peeling, skin redness, itching, and sweating at night

• blood clots in the liver veins (possible liver damage and/or digestive system damage)
• poor blood clotting in small blood vessels with kidney failure
• itching and bruising at the injection site, chest discomfort
• decrease in the number of red blood cells (anemia) caused by massive destruction of red blood cells (hemolytic anemia)

• confusion, agitation
• liver failure

The following adverse effects have been observed in relation to treatment with Revolade in patients with severe aplastic anemia (SAA)

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

Very Common Adverse Effects

Can affect more than 1 in 10people:

• cough
• headache
• pain in the mouth and throat
• diarrhea
• dizziness, nausea
• joint pain (arthralgia)
• pain in the limbs (arms, legs, hands, and feet)
• dizziness
• feeling very tired
• fever
• chills
• eye itching
• blisters in the mouth
• gum bleeding
• abdominal pain
• muscle spasms

Very Common Adverse Effects that can appear in a Blood Test

• abnormal changes in bone marrow cells
• increase in liver enzymes (aspartate aminotransferase (AST))

Common Adverse Effects

Can affect up to 1 in 10people:

• anxiety
• depression
• feeling cold
• feeling of general discomfort
• eye problems, including vision problems, clouding of the eye lens (cataracts), spots or deposits in the eye (vitreous floaters), dry eye, eye itching, yellowish color in the white area of the eyes or skin
• nosebleeds
• digestive problems, including difficulty swallowing, mouth pain, tongue swelling, vomiting, loss of appetite, stomach pain/discomfort, stomach swelling, gas, changes in bowel movements, constipation, changes in intestinal motility that can cause constipation, bloating, diarrhea, and/or the aforementioned symptoms, changes in stool color
• passing out
• skin problems, including red or purple spots due to bleeding under the skin (petechiae), rash, itching, hives, skin lesions
• back pain
• muscle pain
• bone pain
• weakness (asthenia)
• swelling of the lower limbs due to fluid accumulation
• abnormal urine color
• interruption of blood flow to the spleen (splenic infarction)
• runny nose

Common Adverse Effects that can appear in a Blood Test

• increase in some enzymes due to muscle breakdown (creatine phosphokinase)
• iron accumulation in the body (iron overload)
• decrease in blood sugar levels (hypoglycemia)
• increase in blood bilirubin (a substance produced by the liver)
• decrease in the number of white blood cells

Adverse Effects of Unknown Frequency

Cannot be estimated from the available data

• skin discoloration

• skin darkening

• liver damage due to medication

5. Storage of Revolade

Keep this medication out of sight and reach of children.

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

This medication does not require special storage conditions.

Medicines should not be thrown away in drains or in the trash. Ask your pharmacist how to dispose of packaging and medicines that are no longer needed. This will help protect the environment.

6. Package contents and additional information

Composition of Revolade

The active ingredient of Revolade is eltrombopag.

12.5 mg film-coated tablets

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

25 mg film-coated tablets

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

50 mg film-coated tablets

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

75 mg film-coated tablets

Each film-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 carboxymethyl starch, titanium dioxide (E171).

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

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

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

Appearance and packaging of the product

Revolade 12.5 mg film-coated tablets are white, round, biconvex, engraved with 'GS MZ1' and '12.5' on one side.

Revolade 25 mg film-coated tablets are white, round, biconvex, engraved with 'GS NX3' and '25' on one side.

Revolade 50 mg film-coated tablets are brown, round, biconvex, engraved with 'GS UFU' and '50' on one side.

Revolade 75 mg film-coated tablets are pink, round, biconvex, engraved with 'GS FFS' and '75' on one side.

They are supplied in aluminum blisters in a box containing 14 or 28 film-coated tablets and multiple packages containing 84 film-coated tablets (3 packages of 28).

Only some pack sizes may be marketed.

Marketing authorization holder

Novartis Europharm Limited

Vista Building

Elm Park, Merrion Road

Dublin 4

Ireland

Manufacturer

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

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

Date of last revision of this prospectus:

Detailed information on this medication is available on the European Medicines Agency website http://www.ema.europa.eu.