Eltrombopag Krka

Patient Information Leaflet

Eltrombopag Krka 25 mg film-coated tablets, 50 mg film-coated tablets, 75 mg film-coated tablets

eltrombopag
Generic medicine
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 others, even if they have the same symptoms as you, because it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Eltrombopag Krka is and what it is used for

Eltrombopag Krka contains the active substance eltrombopag, which belongs to a group of medicines called thrombopoietin receptor agonists. It is used to help increase the number of platelets in the blood. Platelets are blood cells that help reduce or prevent bleeding.

• Eltrombopag Krka is used to treat a blood clotting disorder called immune (primary) thrombocytopenia (ITP) in patients (over 1 year of age) who have already taken other medicines (corticosteroids or immunoglobulins) that were not effective.

ITP is caused by a low number of platelets in the blood (thrombocytopenia). People with ITP have an increased risk of bleeding. Symptoms in patients with ITP may include petechiae (small, flat, red, round spots on the skin), bruising, epistaxis (nosebleeds), bleeding gums, and difficulty controlling bleeding from cuts or injuries.

• Eltrombopag Krka may also be used to treat low platelet counts (thrombocytopenia) in patients with hepatitis C virus (HCV) if they have experienced problems due to adverse reactions during interferon therapy. Many people with hepatitis C have low platelet counts not only as a result of the disease itself but also due to certain antiviral medicines used to treat it. Taking Eltrombopag Krka may make it easier for you to complete a full course of antiviral treatment (peginterferon and ribavirin).

2. What you need to know before taking Eltrombopag Krka

Do not take Eltrombopag Krka

• if you are allergic to eltrombopag or to any of the other ingredients of this medicine (listed in section 6 under ‘What Eltrombopag Krka contains’).
• Check with your doctor if you think this applies to you.

Warnings and precautions
Talk to your doctor before taking Eltrombopag Krka:

• if you have liver problems. People who have a low platelet count and advanced chronic (long-term) liver disease are at higher risk of experiencing side effects, including liver damage and life-threatening blood clots. If your doctor believes that the benefits of taking Eltrombopag Krka outweigh the risks, you will be closely monitored during treatment.
• if you are at risk of developing blood clots in the veins or arteries, or if you know that blood clotting is common in your family. You may be at increased risk of developing blood clots if:
• you are elderly
• you have had to stay in bed for a long time
• you have cancer
• you are taking the contraceptive pill for birth control or hormone replacement therapy
• you have recently undergone surgery or suffered physical trauma
• you are very overweight (obese)
• you are a smoker
• you have advanced chronic liver disease
  If any of these apply to you, inform your doctor before starting treatment. You must not take Eltrombopag Krka unless your doctor considers that the expected benefits outweigh the risks of blood clot formation.
• if you suffer from cataracts (clouding of the eye's lens)
• if you suffer from another blood disorder such as myelodysplastic syndrome (MDS). Your doctor will perform tests to check that you do not have this blood disorder before you start taking Eltrombopag Krka. If you have MDS and take Eltrombopag Krka, your MDS may worsen. Inform your doctor if any of these conditions apply to you.

Eye examinations
Your doctor will recommend regular checks for cataracts. If you do not routinely have eye examinations, your doctor will schedule regular eye exams. You may also be monitored for any bleeding in or around the retina (the layer of light-sensitive cells at the back of the eye).
You will need regular blood tests
Before starting Eltrombopag Krka, your doctor will perform blood tests to monitor your blood cells, including platelets. These tests will be repeated at intervals while you are taking the medicine.
Liver function blood tests
Eltrombopag Krka may alter blood test results, which could indicate liver damage—an increase in certain liver enzymes, particularly bilirubin and alanine/aspartate transaminase. If you are receiving interferon-based treatments in combination with Eltrombopag Krka for low platelet count due to hepatitis C, some liver problems may worsen.
You will need blood tests to monitor liver function before starting Eltrombopag Krka and during treatment. You may need to stop taking Eltrombopag Krka if levels of these enzymes rise too much, or if physical signs of liver damage appear.

• Read the information ‘ Liver problems ’ in section 4 of this Leaflet.

Blood tests for platelet count
If you stop taking Eltrombopag Krka, your platelet count is likely to drop again within a few days. Your platelet count will be monitored, and your doctor will advise you on appropriate precautions.
A very high platelet count may increase the risk of blood clots. However, blood clots can also form when platelet counts are normal or even low. Your doctor will adjust your dose of Eltrombopag Krka to ensure that your platelet count does not rise too high.

Seek immediate medical help if you experience any of the following signs indicating a blood clot:

• swelling, pain, or tenderness in one leg
• sudden onset of shortness of breath, especially along with sharp chest pain or rapid breathing
• abdominal pain, abdominal swelling, blood in the stool

Tests to monitor bone marrow
In people who may have bone marrow problems, medicines such as Eltrombopag Krka could worsen these issues. Signs of bone marrow changes may appear as abnormalities in blood test results. Your doctor may perform tests to directly monitor your bone marrow during treatment with Eltrombopag Krka.
Tests for gastrointestinal bleeding
If you are being treated with interferon-based medicines in combination with Eltrombopag Krka, you will be monitored for any signs of bleeding in your stomach or intestines after stopping Eltrombopag Krka.
Heart monitoring
Your doctor may consider it necessary to monitor your heart during treatment with Eltrombopag Krka and may perform an electrocardiogram (ECG).
Elderly patients (65 years and over)
There is limited data on the use of Eltrombopag Krka in patients aged 65 years and older. Exercise caution when taking Eltrombopag Krka if you are aged 65 years or older.
Children and adolescents
Eltrombopag Krka is not recommended in children under 1 year of age with ITP. It is also not recommended in people under 18 years of age with low platelet count due to hepatitis C.
Other medicines and Eltrombopag Krka
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. This includes medicines taken without a prescription and vitamins.
Some common medicines interact with Eltrombopag Krka – including prescription and over-the-counter medicines and minerals. These include:

• antacid medicines used to treat indigestion, heartburn, or stomach ulcers (see also “When to take it” in section 3)
• medicines called statins, used to lower cholesterol
• some medicines used to treat HIV infection, such as lopinavir and/or ritonavir
• cyclosporine, used in transplants or immune disorders
• minerals such as iron, calcium, magnesium, aluminium, selenium, and zinc found in vitamin and mineral supplements (see also “When to take it” in section 3)
• medicines such as methotrexate and topotecan, used to treat cancer

Inform your doctor if you are taking any of these medicines. Some of them cannot be taken with Eltrombopag Krka, or you may need to adjust your dose, or the timing of administration may need to be changed. Your doctor will review all the medicines you are taking and, if necessary, suggest suitable alternatives.
There is an increased risk of bleeding if you are also taking medicines to prevent blood clots. Your doctor will discuss this with you.
If you are taking corticosteroids, danazol, and/or azathioprine, you may need to take a lower dose or stop taking them while on Eltrombopag Krka.
Eltrombopag Krka with food and drinks
Do not take Eltrombopag Krka with beverages or products derived from milk and cheese, as the calcium in dairy products affects the absorption of the medicine. For further information, see “When to take it” in section 3.
Pregnancy and breastfeeding
Do not use Eltrombopag Krka if you are pregnant unless specifically recommended by your doctor. The effect of Eltrombopag Krka during pregnancy is unknown.

• Inform your doctor if you are pregnant, think you might be pregnant, or are planning a pregnancy.
• Use a reliable method of contraception while taking Eltrombopag Krka to prevent pregnancy.
• If you become pregnant during treatment with Eltrombopag Krka, inform your doctor.

Do not breastfeed while taking Eltrombopag Krka. It is not known whether Eltrombopag Krka passes into breast milk.
If you are breastfeeding or planning to breastfeed, inform your doctor.
Driving and using machines
Eltrombopag Krka may cause dizziness and other side effects that may reduce your attention.
Do not drive or operate machinery unless you are sure you are not affected.
Eltrombopag Krka contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, i.e., essentially “sodium-free”.

3. How to take Eltrombopag Krka

Take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist. Do not change the dose or dosing schedule of Eltrombopag Krka unless your doctor or pharmacist advises you to do so. While taking Eltrombopag Krka, you will be under the care of a doctor experienced in treating your condition.

How much to take

For ITP

Adults and children (6 to 17 years of age) – the recommended starting dose for ITP is one 50 mg tablet of Eltrombopag Krka daily. If you are of East or Southeast Asian origin, you may need to start with a lower dose of 25 mg.

Children (1 to 5 years of age) – the recommended starting dose for ITP is one 25 mg tablet of Eltrombopag Krka daily.

For Hepatitis C

Adults – the recommended starting dose for hepatitis C is one 25 mg tablet of Eltrombopag Krka daily. If you are of East or Southeast Asian origin, you will start with the same 25 mg dose.

Eltrombopag Krka may take 1 to 2 weeks to take effect. Based on your response to Eltrombopag Krka, your doctor may recommend adjusting the daily dose.

How to take the tablets

Swallow the tablet whole with some water.

When to take it

Make sure that

• in the 4 hours before taking Eltrombopag Krka
• and in the 2 hours after taking Eltrombopag Krka

you do not consume any of the following:

• foods such as cheese, butter, yoghurt or ice cream
• milk or milk-based smoothies, milk-containing drinks, yoghurt or cream
• antacids, a type of medicine used for indigestion and heartburn
• certain vitamin and mineral supplements, including iron, calcium, magnesium, aluminium, selenium and zinc. If you do, the medicine will not be properly absorbed into your body.

Take Eltrombopag Krka

For 4 hours before and for 2 hours after
taking
Eltrombopag
Krka

NO dairy products,
antacids or mineral supplements

For further advice on suitable foods and drinks, please consult your doctor.

If you take more Eltrombopag Krka than you should

Contact your doctor or pharmacist immediately. If possible, show them the packaging or this leaflet. You will be monitored for any signs or symptoms of adverse effects and treated appropriately without delay.

If you forget to take Eltrombopag Krka

Take the next dose at your usual time. Do not take more than one dose of Eltrombopag Krka in a day.

If you stop taking Eltrombopag Krka

Do not stop taking Eltrombopag Krka without talking to your doctor. If your doctor advises you to stop treatment, your platelet count will be monitored weekly for four weeks. See also ‘Bleeding or bruising after stopping treatment’ in section 4.

If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Symptoms requiring attention: consult a doctor
People taking Eltrombopag Krka for ITP or low platelet count due to hepatitis C may develop signs of potentially serious side effects. It is important to inform your doctor if you experience any of these symptoms.
Increased risk of blood clots
Some people may have an increased risk of blood clots, and medicines such as Eltrombopag Krka could worsen this problem. Sudden blockage of a blood vessel by a blood clot is an uncommon side effect and may affect up to 1 in 100 people.

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

• swelling, pain, warmth, redness, or tenderness in one leg
• sudden onset of shortness of breath, especially together with sharp chest pain or rapid breathing
• abdominal pain (stomach), abdominal swelling, blood in the stool.

Liver problems
Eltrombopag Krka may cause changes detectable in blood tests, which could indicate liver damage. Liver problems (increased liver enzymes detected in blood tests) are common and may affect up to 1 in 10 people. Other liver problems are uncommon and may affect up to 1 in 100 people.
If you have any of the following signs of liver problems:

• yellowing of the skin or whites of the eyes (jaundice)
• urine that is unusually dark-colored
• Inform your doctor immediately.

Bleeding or bruising after stopping treatment
Within two weeks after stopping Eltrombopag Krka, the platelet count usually decreases to the level it was before starting Eltrombopag Krka. A lower platelet count may increase the risk of bleeding or bruising. Your doctor will monitor your platelet count for at least 4 weeks after you stop taking Eltrombopag Krka.

• Inform your doctor if you experience bleeding or bruising after stopping Eltrombopag Krka. Some people have experienced gastrointestinal bleeding after discontinuation of peginterferon, ribavirin, and Eltrombopag Krka. Symptoms include:
• dark stools (change in stool color is an uncommon side effect that may affect up to 1 in 100 people)
• blood in the stool
• vomiting blood or material resembling coffee grounds
• Inform your doctor immediately if you experience any of these symptoms.

The following side effects have been reported in association with treatment with
Eltrombopag Krka in adult patients with ITP:
Very common side effects
These may affect more than 1 in 10 people:

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

Very common side effects that may be detected by blood tests:

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

Common side effects
These may affect up to 1 in 10 people:

• muscle pain, muscle spasms
• bone pain
• heavy menstrual periods
• sore throat and pain when swallowing
• eye problems including abnormal eye tests, dry eyes, eye pain, blurred vision
• vomiting
• flu
• herpes labialis
• pneumonia
• irritation and inflammation (swelling) of the sinuses
• inflammation (swelling) and infection of the tonsils
• infections of the lungs, sinuses, nose, and throat
• inflammation of the gum tissue
• loss of appetite
• sensation of tingling, prickling, or numbness, commonly known as "pins and needles"
• decreased skin sensitivity
• feeling drowsy
• earache
• pain, swelling, and tenderness in one of the legs (usually calf), with warm skin in the affected area (signs of a blood clot in a deep vein)
• localized swelling filled with blood from a rupture in a blood vessel (haematoma)
• hot flushes
• mouth problems including dry mouth, sore mouth, sensitive tongue, bleeding gums, mouth ulcers
• runny nose
• toothache
• abdominal pain
• liver function abnormalities
• skin changes including excessive sweating, irregular itchy rash, red spots, changes in skin appearance
• hair loss
• urine that appears foamy, frothy, or fizzy (signs of protein in the urine)
• high temperature, feeling hot
• chest pain
• feeling weak
• sleep problems, depression
• migraine
• decreased vision
• sensation of spinning (dizziness)
• gas/bloating due to digestion

Common side effects that may be detected by blood tests:

• decrease in red blood cell count (anaemia)
• decrease in platelet count (thrombocytopenia)
• decrease in white blood cell count
• decrease in haemoglobin level
• increase in eosinophils
• increase in white blood cell count (leucocytosis)
• 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 levels of certain proteins

Uncommon side effects
These may affect up to 1 in 100 people:

• allergic reaction
• interruption of blood flow to part of the heart
• sudden respiratory failure, especially if accompanied by acute chest pain and/or rapid breathing, which may be a sign of a blood clot in the lungs (see 'Increased risk of blood clots' at the beginning of section 4)
• loss of function in part of the lung caused by blockage of the pulmonary artery
• possible pain, swelling, and/or redness around a vein, which could be signs of blood clot formation in a vein
• yellowing of the skin and/or abdominal pain, which could be signs of bile duct obstruction, liver injury, or liver damage due to inflammation (see 'Liver problems' at the beginning of section 4)
• drug-induced liver injury
• rapid heartbeat, irregular heartbeat, bluish skin discoloration, heart rhythm disorders (QT prolongation), which could be signs of heart and blood vessel disorders
• blood clot
• redness
• painful swelling of joints caused by uric acid (gout)
• lack of interest, mood changes, uncontrollable crying or crying at unexpected times
• balance problems, speech and nerve function issues, tremor
• painful or abnormal skin sensations
• paralysis on one side of the body
• migraine with aura
• nerve damage
• dilation or swelling of blood vessels causing headache
• eye problems including increased tear production, clouding of the eye lens (cataract), retinal bleeding, dry eyes
• problems with nose, throat, and sinuses, breathing problems during sleep
• mouth and throat blisters/sores
• loss of appetite
• digestive system problems including frequent bowel movements, food poisoning, blood in stool, vomiting with blood
• bleeding from the rectum, change in stool color, abdominal bloating, constipation
• mouth problems including dry mouth, sore mouth, painful tongue, bleeding gums, mouth discomfort
• sunburn
• feeling hot, anxiety sensation
• redness or swelling around a wound
• bleeding around a catheter (if present) in the skin
• foreign body sensation
• kidney problems including kidney inflammation, excessive urination at night, kidney failure, white blood cells in urine
• cold sweat
• general feeling of malaise
• skin infection
• skin changes including skin discoloration, peeling, redness, itching, and sweating
• muscle weakness
• cancer of the rectum and colon
  Uncommon side effects that may be detected by laboratory tests:
• changes in red blood cell shape
• presence of abnormal white blood cell development, which may indicate certain diseases
• increase in platelet count
• decrease in calcium levels
• decrease in red blood cell count (anaemia) caused by excessive destruction of red blood cells (haemolytic anaemia)
• increase in myelocytes
• increase in band neutrophils
• increase in blood urea
• increase in protein levels 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 haemoglobin level

The following side effects have been reported in association with treatment with
Eltrombopag Krka in paediatric patients (aged 1 to 17 years) with ITP:
If these side effects worsen, inform your doctor, pharmacist, or nurse.
Very common side effects
These may affect more than 1 in 10 children:

• infection of the nose, sinuses, throat, and upper airways, common cold (upper respiratory tract infection)
• diarrhoea
• abdominal pain
• cough
• high temperature
• feeling unwell (nausea)

Common side effects
These may affect up to 1 in 10 children:

• difficulty sleeping (insomnia)
• toothache
• pain in nose and throat
• itchy nose, runny or blocked nose
• sore throat, runny nose, nasal congestion, and sneezing
• mouth problems including dry mouth, sore mouth, sensitive tongue, bleeding gums, mouth ulcers

The following side effects have been reported in association with treatment with
Eltrombopag Krka in combination with peginterferon and ribavirin in patients with HCV:
Very common side effects
These may affect more than 1 in 10 people:

• headache
• loss of appetite
• cough
• feeling unwell (nausea), diarrhoea
• muscle pain, muscle weakness
• itching
• feeling tired
• fever
• unusual hair loss
• feeling weak
• flu-like illness
• swelling of hands or feet
• chills

Very common side effects that may be detected by blood tests:

• reduction in red blood cell count (anaemia).

Common side effects
These may affect up to 1 in 10 people:

• urinary tract infections
• inflammation of the nose, throat, and mouth, flu-like symptoms, dry mouth, sore or inflamed mouth, toothache
• weight loss
• sleep disorders, abnormal drowsiness, depression, anxiety
• dizziness, concentration and memory problems, mood changes
• decreased brain function following liver damage
• tingling or numbness in hands or feet
• fever, headache
• eye problems including clouding of the eye lens (cataract), dry eyes, small yellow deposits in the retina, yellowing of the whites of the eyes
• retinal bleeding
• sensation of spinning (dizziness)
• fast or irregular heartbeat (palpitations), shortness of breath
• productive cough, runny nose, flu, herpes labialis, sore throat, and discomfort when swallowing
• digestive system problems, including vomiting, stomach ache, indigestion, constipation, stomach bloating, taste disturbances, haemorrhoids, stomach pain/discomfort, dilated blood vessels and bleeding in the oesophagus
• toothache
• liver problems, including liver tumour, yellowing of the whites of the eyes or skin (jaundice), drug-induced liver damage (see 'Liver problems' at the beginning of section 4)
• skin changes including rash, dry skin, eczema, skin redness, itching, excessive sweating, unusual skin growths, hair loss
• joint pain, back pain, bone pain, limb pain (in arms, legs, hands, or feet), muscle spasms
• irritability, general feeling of malaise, skin reaction such as redness, swelling, and pain at injection site, chest pain and discomfort, fluid accumulation in the body or extremities causing swelling
• infection of the nose, sinuses, throat, and upper airways, common cold (upper respiratory tract infection), inflammation of the mucosa lining the bronchi
• depression, anxiety, sleep disorders, nervousness

Common side effects that may be detected by blood tests:

• increased blood sugar (glucose)
• reduction in white blood cell count
• reduction in neutrophil count
• reduction in albumin in blood
• reduction in haemoglobin level
• increase in bilirubin (a substance produced by the liver)
• changes in enzymes controlling blood clotting

Uncommon side effects
These may affect up to 1 in 100 people:

• pain during urination
• heart rhythm disorders (QT interval prolongation)
• stomach flu (gastroenteritis), sore throat
• blisters/sores in the mouth, stomach inflammation
• skin changes including color changes, peeling, redness, itching, lesions, and night sweats
• blood clots in a liver vein (possible liver and/or digestive system damage)
• abnormal blood clotting in small blood vessels with kidney failure
• skin rash, bruising at injection site, chest discomfort
• decrease in red blood cell count (anaemia) caused by excessive destruction of red blood cells (haemolytic anaemia)
• confusion, agitation
• liver failure

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.
Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Eltrombopag Krka

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 after
Exp./EXP. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of medicines via waste water. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Eltrombopag Krka contains
Eltrombopag Krka 25 mg film-coated tablets
Each film-coated tablet contains eltrombopag olamine equivalent to 25 mg of eltrombopag.
Eltrombopag Krka 50 mg film-coated tablets
Each film-coated tablet contains eltrombopag olamine equivalent to 50 mg of eltrombopag.
Eltrombopag Krka 75 mg film-coated tablets
Each film-coated tablet contains eltrombopag olamine equivalent to 75 mg of eltrombopag.

The other components are:
tablet core: magnesium stearate, mannitol, microcrystalline cellulose, povidone,
sodium carboxymethyl starch (type A), hydroxypropylcellulose.
coating: hypromellose, macrogol, talc, titanium dioxide (E171), red iron oxide (E172)
(only for 50 mg and 75 mg), yellow iron oxide (E172) (only for 50 mg), and indigo carmine
(E132) (only for 50 mg and 75 mg). See section 2 “Eltrombopag Krka contains sodium”.

Description of the appearance and contents of the pack
Eltrombopag Krka 25 mg film-coated tablets are white, round, biconvex, film-coated tablets with "25" printed on one side.
Eltrombopag Krka 50 mg film-coated tablets are brown, round, biconvex, film-coated tablets with "50" printed on one side.
Eltrombopag Krka 75 mg film-coated tablets are pink, round, film-coated tablets with "75" printed on one side.

Eltrombopag Krka is available in boxes containing 14, 28, 56 or 84 film-coated tablets, or multiple packs containing 84 tablets (3 packs of 28) film-coated tablets, in blisters.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Manufacturer
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
Elpen Pharmaceutical Co. Inc, 95 Marathonos Ave., Pikermi, Attiki, 19009, Greece
TAD Pharma GmbH, Heinz-Lohmann-Strasse 5, Cuxhaven, Germany

Local representative for Italy:
KRKA Farmaceutici Milano S.r.l. – Italy

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