Revolade

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 

 



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1. NAME OF THE MEDICINAL PRODUCT 
 

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 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

Revolade 12.5 mg film-coated tablets 

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

 

Revolade 25 mg film-coated tablets 

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

 

Revolade 50 mg film-coated tablets 

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

 

Revolade 75 mg film-coated tablets 

Each film-coated tablet contains eltrombopag olamine equivalent to 75 mg eltrombopag. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Film-coated tablet. 

 

Revolade 12.5 mg film-coated tablets 

White, round, biconvex film-coated tablet (approximately 7.9 mm in diameter) debossed with ‘GS 

MZ1’ and ‘12.5’ on one side. 

 

Revolade 25 mg film-coated tablets 

White, round, biconvex film-coated tablet (approximately 10.3 mm in diameter) debossed with ‘GS 

NX3’ and ‘25’ on one side. 

 

Revolade 50 mg film-coated tablets 

Brown, round, biconvex film-coated tablet (approximately 10.3 mm in diameter) debossed with ‘GS 

UFU’ and ‘50’ on one side. 

 

Revolade 75 mg film-coated tablets 

Pink, round, biconvex film-coated tablet (approximately 10.3 mm in diameter) debossed with ‘GS 

FFS’ and ‘75’ on one side. 

 

 

  



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4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Revolade is indicated for the treatment of patients aged 1 year and above with primary immune 

thrombocytopenia (ITP) lasting 6 months or longer from diagnosis and who are refractory to other 

treatments (e.g. corticosteroids, immunoglobulins) (see sections 4.2 and 5.1). 

 

Revolade is indicated in adult patients with chronic hepatitis C virus (HCV) infection for the treatment 

of thrombocytopenia, where the degree of thrombocytopenia is the main factor preventing the 

initiation or limiting the ability to maintain optimal interferon-based therapy (see sections 4.4 and 5.1). 

 

Revolade is indicated in adult patients with acquired severe aplastic anaemia (SAA) who were either 

refractory to prior immunosuppressive therapy or heavily pretreated and are unsuitable for 

haematopoietic stem cell transplantation (see section 5.1). 

 

4.2 Posology and method of administration 

 

Eltrombopag treatment should be initiated by and remain under the supervision of a physician who is 

experienced in the treatment of haematological diseases or the management of chronic hepatitis C and 

its complications. 

 

Posology 

 

Eltrombopag dosing requirements must be individualised based on the patient’s platelet counts. The 

objective of treatment with eltrombopag should not be to normalise platelet counts. 

 

The powder for oral suspension may lead to higher eltrombopag exposure than the tablet formulation 

(see section 5.2). When switching between the tablet and powder for oral suspension formulations, 

platelet counts should be monitored weekly for 2 weeks. 

 

Immune (primary) thrombocytopenia 

 

The lowest dose of eltrombopag to achieve and maintain a platelet count ≥50,000/µl should be used. 

Dose adjustments are based upon the platelet count response. Eltrombopag must not be used to 

normalise platelet counts. In clinical studies, platelet counts generally increased within 1 to 2 weeks 

after starting eltrombopag and decreased within 1 to 2 weeks after discontinuation. 

 

Adults and paediatric population aged 6 to 17 years 

The recommended starting dose of eltrombopag is 50 mg once daily. For patients of Asian ancestry 

(such as Chinese, Japanese, Taiwanese, Korean or Thai), eltrombopag should be initiated at a reduced 

dose of 25 mg once daily (see section 5.2). 

 

Paediatric population aged 1 to 5 years 

The recommended starting dose of eltrombopag is 25 mg once daily. 

 

  



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Monitoring and dose adjustment 

After initiating eltrombopag, the dose must be adjusted to achieve and maintain a platelet count 

≥50,000/µl as necessary to reduce the risk for bleeding. A daily dose of 75 mg must not be exceeded. 

 

Clinical haematology and liver tests should be monitored regularly throughout therapy with 

eltrombopag and the dose regimen of eltrombopag modified based on platelet counts as outlined in 

Table 1. During therapy with eltrombopag full blood counts (FBCs), including platelet count and 

peripheral blood smears, should be assessed weekly until a stable platelet count (≥50,000/µl for at 

least 4 weeks) has been achieved. FBCs including platelet counts and peripheral blood smears should 

be obtained monthly thereafter. 

 

Table 1 Dose adjustments of eltrombopag in ITP patients 

 

Platelet count Dose adjustment or response 

<50,000/µl following at least 

2 weeks of therapy 

Increase daily dose by 25 mg to a maximum of 75 mg/day*. 

50,000/µl to 150,000/µl Use lowest dose of eltrombopag and/or concomitant ITP 

treatment to maintain platelet counts that avoid or reduce 

bleeding. 

>150,000/µl to 250,000/µl Decrease the daily dose by 25 mg. Wait 2 weeks to assess the 

effects of this and any subsequent dose adjustments♦. 

>250,000/µl Stop eltrombopag; increase the frequency of platelet monitoring 

to twice weekly. 

 

Once the platelet count is ≤ 100,000/µl, reinitiate therapy at a 

daily dose reduced by 25 mg. 

* For patients taking 25 mg eltrombopag once every other day, increase dose to 25 mg once daily. 

♦ For patients taking 25 mg eltrombopag once daily, consideration should be given to dosing at 

12.5 mg once daily or alternatively a dose of 25 mg once every other day. 

 

Eltrombopag can be administered in addition to other ITP medicinal products. The dose regimen of 

concomitant ITP medicinal products should be modified, as medically appropriate, to avoid excessive 

increases in platelet counts during therapy with eltrombopag. 

 

It is necessary to wait for at least 2 weeks to see the effect of any dose adjustment on the patient’s 

platelet response prior to considering another dose adjustment. 

 

The standard eltrombopag dose adjustment, either decrease or increase, would be 25 mg once daily. 

 

Discontinuation 

Treatment with eltrombopag should be discontinued if the platelet count does not increase to a level 

sufficient to avoid clinically important bleeding after 4 weeks of eltrombopag therapy at 75 mg once 

daily. 

 

Patients should be clinically evaluated periodically and continuation of treatment should be decided on 

an individual basis by the treating physician. In non-splenectomised patients this should include 

evaluation relative to splenectomy. The reoccurrence of thrombocytopenia is possible upon 

discontinuation of treatment (see section 4.4). 

 

Chronic hepatitis C (HCV) associated thrombocytopenia 

 

When eltrombopag is given in combination with antivirals reference should be made to the full 

summary of product characteristics of the respective coadministered medicinal products for 

comprehensive details of relevant safety information or contraindications. 

 

In clinical studies, platelet counts generally began to increase within 1 week of starting eltrombopag. 

The aim of treatment with eltrombopag should be to achieve the minimum level of platelet counts 



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needed to initiate antiviral therapy, in adherence to clinical practice recommendations. During antiviral 

therapy, the aim of treatment should be to keep platelet counts at a level that prevents the risk of 

bleeding complications, normally around 50,000-75,000/µl. Platelet counts >75,000/µl should be 

avoided. The lowest dose of eltrombopag needed to achieve the targets should be used. Dose 

adjustments are based upon the platelet count response. 

 

Initial dose regimen 

Eltrombopag should be initiated at a dose of 25 mg once daily. No dosage adjustment is necessary for 

HCV patients of East Asian ancestry or patients with mild hepatic impairment (see section 5.2). 

 

Monitoring and dose adjustment 

The dose of eltrombopag should be adjusted in 25 mg increments every 2 weeks as necessary to 

achieve the target platelet count required to initiate antiviral therapy. Platelet counts should be 

monitored every week prior to starting antiviral therapy. On initiation of antiviral therapy the platelet 

count may fall, so immediate eltrombopag dose adjustments should be avoided (see Table 2). 

 

During antiviral therapy, the dose of eltrombopag should be adjusted as necessary to avoid dose 

reductions of peginterferon due to decreasing platelet counts that may put patients at risk of bleeding 

(see Table 2). Platelet counts should be monitored weekly during antiviral therapy until a stable 

platelet count is achieved, normally around 50,000-75,000/µl. FBCs including platelet counts and 

peripheral blood smears should be obtained monthly thereafter. Dose reductions on the daily dose by 

25 mg should be considered if platelet counts exceed the required target. It is recommended to wait for 

2 weeks to assess the effects of this and any subsequent dose adjustments. 

 

A dose of 100 mg eltrombopag once daily must not be exceeded. 

 

Table 2 Dose adjustments of eltrombopag in HCV patients during antiviral therapy 

 

Platelet count Dose adjustment or response 

<50,000/µl following at least 

2 weeks of therapy 

Increase daily dose by 25 mg to a maximum of 100 mg/day. 

≥50,000/µl to ≤100,000/µl Use lowest dose of eltrombopag as necessary to avoid dose 

reductions of peginterferon. 

>100,000/µl to ≤150,000/µl Decrease the daily dose by 25 mg. Wait 2 weeks to assess the 

effects of this and any subsequent dose adjustments♦. 

>150,000/µl Stop eltrombopag; increase the frequency of platelet monitoring to 

twice weekly. 

 

Once the platelet count is ≤100,000/µl, reinitiate therapy at a daily 

dose reduced by 25 mg*. 

* For patients taking 25 mg eltrombopag once daily, consideration should be given to reinitiating 

dosing at 25 mg every other day. 
♦ On initiation of antiviral therapy the platelet count may fall, so immediate eltrombopag dose 

reductions should be avoided. 

 

Discontinuation 

If after 2 weeks of eltrombopag therapy at 100 mg the required platelet level to initiate antiviral 

therapy is not achieved, eltrombopag should be discontinued. 

 

Eltrombopag treatment should be terminated when antiviral therapy is discontinued unless otherwise 

justified. Excessive platelet count responses or important liver test abnormalities also necessitate 

discontinuation. 

 

  



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Severe aplastic anaemia 

 

Initial dose regimen 

Eltrombopag should be initiated at a dose of 50 mg once daily. For patients of Asian ancestry, 

eltrombopag should be initiated at a reduced dose of 25 mg once daily (see section 5.2). The treatment 

should not be initiated when the patients has existing cytogenetic abnormalities of chromosome 7. 

 

Monitoring and dose adjustment 

Haematological response requires dose titration, generally up to 150 mg, and may take up to 16 weeks 

after starting eltrombopag (see section 5.1). The dose of eltrombopag should be adjusted in 50 mg 

increments every 2 weeks as necessary to achieve the target platelet count ≥50,000/µl. For patients 

taking 25 mg once daily, the dose should be increased to 50 mg daily before increasing the dose 

amount by 50 mg. A dose of 150 mg daily must not be exceeded. Clinical haematology and liver tests 

should be monitored regularly throughout therapy with eltrombopag and the dosage regimen of 

eltrombopag modified based on platelet counts as outlined in Table 3. 

 

Table 3 Dose adjustments of eltrombopag in patients with severe aplastic anaemia 

 

Platelet count Dose adjustment or response 

<50,000/µl following at least 

2 weeks of therapy 

Increase daily dose by 50 mg to a maximum of 150 mg/day. 

 

For patients taking 25 mg once daily, increase the dose to 

50 mg daily before increasing the dose amount by 50 mg. 

50,000/µl to 150,000/µl Use lowest dose of eltrombopag to maintain platelet counts. 

>150,000/µl to 250,000/µl Decrease the daily dose by 50 mg. Wait 2 weeks to assess the 

effects of this and any subsequent dose adjustments. 

>250,000/µl Stop eltrombopag; for at least one week. 

 

Once the platelet count is ≤100,000/µl, reinitiate therapy at a 

daily dose reduced by 50 mg. 

 

Tapering for tri-lineage (white blood cells, red blood cells, and platelets) responders 

For patients who achieve tri-lineage response, including transfusion independence, lasting at least 

8 weeks: the dose of eltrombopag may be reduced by 50%. 

 

If counts remain stable after 8 weeks at the reduced dose, then eltrombopag must be discontinued and 

blood counts monitored. If platelet counts drop to <30,000/µl, haemoglobin drops to < 9 g/dl or 

absolute neutrophil count (ANC) <0.5 x 109/l, eltrombopag may be reinitiated at the previous effective 

dose. 

 

Discontinuation 

If no haematological response has occurred after 16 weeks of therapy with eltrombopag, therapy 

should be discontinued. If new cytogenetic abnormalities are detected, it must be evaluated whether 

continuation of eltrombopag is appropriate (see sections 4.4 and 4.8). Excessive platelet count 

responses (as outlined in Table 3) or important liver test abnormalities also necessitate discontinuation 

of eltrombopag (see section 4.8). 

 

Special populations 

 

Renal impairment 

No dose adjustment is necessary in patients with renal impairment. Patients with impaired renal 

function should use eltrombopag with caution and close monitoring, for example by testing serum 

creatinine and/or performing urine analysis (see section 5.2). 

 

  



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Hepatic impairment 

Eltrombopag should not be used in ITP patients with hepatic impairment (Child-Pugh score ≥5) unless 

the expected benefit outweighs the identified risk of portal venous thrombosis (see section 4.4). 

 

If the use of eltrombopag is deemed necessary for ITP patients with hepatic impairment the starting 

dose must be 25 mg once daily. After initiating the dose of eltrombopag in patients with hepatic 

impairment an interval of 3 weeks should be observed before increasing the dose. 

 

No dose adjustment is required for thrombocytopenic patients with chronic HCV and mild hepatic 

impairment (Child-Pugh score ≤6). Chronic HCV patients and severe aplastic anaemia patients with 

hepatic impairment should initiate eltrombopag at a dose of 25 mg once daily (see section 5.2). After 

initiating the dose of eltrombopag in patients with hepatic impairment an interval of 2 weeks should be 

observed before increasing the dose. 

 

There is an increased risk for adverse events, including hepatic decompensation and thromboembolic 

events, in thrombocytopenic patients with advanced chronic liver disease treated with eltrombopag, 

either in preparation for invasive procedure or in HCV patients undergoing antiviral therapy (see 

sections 4.4 and 4.8). 

 

Elderly 

There are limited data on the use of eltrombopag in ITP patients aged 65 years and older and no 

clinical experience in ITP patients aged over 85 years. In the clinical studies of eltrombopag, overall 

no clinically significant differences in safety of eltrombopag were observed between patients aged at 

least 65 years and younger patients. Other reported clinical experience has not identified differences in 

responses between the elderly and younger patients, but greater sensitivity of some older individuals 

cannot be ruled out (see section 5.2). 

 

There are limited data on the use of eltrombopag in HCV and SAA patients aged over 75 years. 

Caution should be exercised in these patients (see section 4.4). 

 

Asian patients 

For patients of Asian ancestry (such as Chinese, Japanese, Taiwanese, Korean or Thai), including 

those with hepatic impairment, eltrombopag should be initiated at a dose of 25 mg once daily (see 

section 5.2). 

 

Patient platelet count should continue to be monitored and the standard criteria for further dose 

modification followed. 

 

Paediatric population 

Revolade is not recommended for use in children under the age of one year with ITP due to 

insufficient data on safety and efficacy. The safety and efficacy of eltrombopag has not been 

established in children and adolescents (<18 years) with chronic HCV related thrombocytopenia or 

SAA. No data are available. 

 

Method of administration 

 

Oral use. 

The tablets should be taken at least two hours before or four hours after any products such as antacids, 

dairy products (or other calcium containing food products), or mineral supplements containing 

polyvalent cations (e.g. iron, calcium, magnesium, aluminium, selenium and zinc) (see sections 4.5 

and 5.2). 

 

  



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4.3 Contraindications 
 

Hypersensitivity to eltrombopag or to any of the excipients listed in section 6.1. 

 

4.4 Special warnings and precautions for use 

 

There is an increased risk for adverse reactions, including potentially fatal hepatic decompensation and 

thromboembolic events, in thrombocytopenic HCV patients with advanced chronic liver disease, as 

defined by low albumin levels ≤35 g/l or model for end stage liver disease (MELD) score ≥10, when 

treated with eltrombopag in combination with interferon-based therapy. In addition, the benefits of 

treatment in terms of the proportion achieving sustained virological response (SVR) compared with 

placebo were modest in these patients (especially for those with baseline albumin ≤35g/l) compared 

with the group overall. Treatment with eltrombopag in these patients should be initiated only by 

physicians experienced in the management of advanced HCV, and only when the risks of 

thrombocytopenia or withholding antiviral therapy necessitate intervention. If treatment is considered 

clinically indicated, close monitoring of these patients is required. 

 

Combination with direct-acting antiviral agents 

 

Safety and efficacy have not been established in combination with direct-acting antiviral agents 

approved for treatment of chronic hepatitis C infection. 

 

Risk of hepatotoxicity 

 

Eltrombopag administration can cause abnormal liver function and severe hepatotoxicity, which might 

be life-threatening (see section 4.8). 

 

Serum alanine aminotransferase (ALT), aspartate aminotrasferase (AST) and bilirubin should be 

measured prior to initiation of eltrombopag, every 2 weeks during the dose adjustment phase and 

monthly following establishment of a stable dose. Eltrombopag inhibits UGT1A1 and OATP1B1, 

which may lead to indirect hyperbilirubinaemia. If bilirubin is elevated fractionation should be 

performed. Abnormal serum liver tests should be evaluated with repeat testing within 3 to 5 days. If 

the abnormalities are confirmed, serum liver tests should be monitored until the abnormalities resolve, 

stabilise, or return to baseline levels. Eltrombopag should be discontinued if ALT levels increase 

(3 times the upper limit of normal [x ULN] in patients with normal liver function, or ≥3 x baseline or 

>5 x ULN, whichever is the lower, in patients with pre-treatment elevations in transaminases) and are: 

 progressive, or 

 persistent for ≥4 weeks, or 

 accompanied by increased direct bilirubin, or 

 accompanied by clinical symptoms of liver injury or evidence for hepatic decompensation. 
 

Caution is required when administering eltrombopag to patients with hepatic disease. In ITP and SAA 

patients a lower starting dose of eltrombopag should be used. Close monitoring is required when 

administering to patients with hepatic impairment (see section 4.2). 

 

Hepatic decompensation (use with interferon) 

 

Hepatic decompensation in patients with chronic hepatitis C: Monitoring is required in patients with 

low albumin levels (≤35 g/l) or with MELD score ≥10 at baseline. 

 

Chronic HCV patients with cirrhosis may be at risk of hepatic decompensation when receiving alfa 

interferon therapy. In 2 controlled clinical studies in thrombocytopenic patients with HCV, hepatic 

decompensation (ascites, hepatic encephalopathy, variceal haemorrhage, spontaneous bacterial 

peritonitis) occurred more frequently in the eltrombopag arm (11%) than in the placebo arm (6%). In 

patients with low albumin levels (≤ 35 g/l) or with a MELD score ≥10 at baseline, there was a 3-fold 

greater risk of hepatic decompensation and an increase in the risk of a fatal adverse event compared to 

those with less advanced liver disease. In addition, the benefits of treatment in terms of the proportion 



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achieving SVR compared with placebo were modest in these patients (especially for those with 

baseline albumin ≤35 g/l) compared with the group overall. Eltrombopag should only be administered 

to such patients after careful consideration of the expected benefits in comparison with the risks. 

Patients with these characteristics should be closely monitored for signs and symptoms of hepatic 

decompensation. The respective interferon summary of product characteristics should be referenced 

for discontinuation criteria. Eltrombopag should be terminated if antiviral therapy is discontinued for 

hepatic decompensation. 

 

Thrombotic/thromboembolic complications 

 

In controlled studies in thrombocytopenic patients with HCV receiving interferon-based therapy 

(n=1,439), 38 out of 955 patients (4%) treated with eltrombopag and 6 out of 484 patients (1%) in the 

placebo group experienced thromboembolic events (TEEs). Reported thrombotic/thromboembolic 

complications included both venous and arterial events. The majority of TEEs were non-serious and 

resolved by the end of the study. Portal vein thrombosis was the most common TEE in both treatment 

groups (2% in patients treated with eltrombopag versus <1% for placebo). No specific temporal 

relationship between start of treatment and event of TEE were observed. Patients with low albumin 

levels (≤35 g/l) or MELD ≥10 had a 2-fold greater risk of TEEs than those with higher albumin levels; 

those aged ≥60 years had a 2-fold greater risk of TEEs compared to younger patients. Eltrombopag 

should only be administered to such patients after careful consideration of the expected benefits in 

comparison with the risks. Patients should be closely monitored for signs and symptoms of TEE. 

 

The risk of TEEs has been found to be increased in patients with chronic liver disease (CLD) treated 

with 75 mg eltrombopag once daily for 2 weeks in preparation for invasive procedures. Six of 143 

(4%) adult patients with CLD receiving eltrombopag experienced TEEs (all of the portal venous 

system) and 2 of 145 (1%) patients in the placebo group experienced TEEs (one in the portal venous 

system and one myocardial infarction). Five of the 6 patients treated with eltrombopag experienced the 

thrombotic complication at a platelet count >200,000/µl and within 30 days of the last dose of 

eltrombopag. Eltrombopag is not indicated for the treatment of thrombocytopenia in patients with 

chronic liver disease in preparation for invasive procedures. 

 

In eltrombopag clinical studies in ITP thromboembolic events were observed at low and normal 

platelet counts. Caution should be used when administering eltrombopag to patients with known risk 

factors for thromboembolism including but not limited to inherited (e.g. Factor V Leiden) or acquired 

risk factors (e.g. ATIII deficiency, antiphospholipid syndrome), advanced age, patients with prolonged 

periods of immobilisation, malignancies, contraceptives and hormone replacement therapy, 

surgery/trauma, obesity and smoking. Platelet counts should be closely monitored and consideration 

given to reducing the dose or discontinuing eltrombopag treatment if the platelet count exceeds the 

target levels (see section 4.2). The risk-benefit balance should be considered in patients at risk of TEEs 

of any aetiology. 

 

No case of TEE was identified from a clinical study in refractory SAA, however the risk of these 

events cannot be excluded in this patient population due to the limited number of exposed patients. As 

the highest authorised dose is indicated for patients with SAA (150 mg/day) and due to the nature of 

the reaction, TEEs might be expected in this patient population. 

 

Eltrombopag should not be used in ITP patients with hepatic impairment (Child-Pugh score ≥5) unless 

the expected benefit outweighs the identified risk of portal venous thrombosis. When treatment is 

considered appropriate, caution is required when administering eltrombopag to patients with hepatic 

impairment (see sections 4.2 and 4.8). 

 

  



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Bleeding following discontinuation of eltrombopag 

 

Thrombocytopenia is likely to reoccur in ITP patients upon discontinuation of treatment with 

eltrombopag. Following discontinuation of eltrombopag, platelet counts return to baseline levels 

within 2 weeks in the majority of patients, which increases the bleeding risk and in some cases may 

lead to bleeding. This risk is increased if eltrombopag treatment is discontinued in the presence of 

anticoagulants or anti-platelet agents. It is recommended that, if treatment with eltrombopag is 

discontinued, ITP treatment be restarted according to current treatment guidelines. Additional medical 

management may include cessation of anticoagulant and/or anti-platelet therapy, reversal of 

anticoagulation, or platelet support. Platelet counts must be monitored weekly for 4 weeks following 

discontinuation of eltrombopag. 

 

In HCV clinical studies, a higher incidence of gastrointestinal bleeding, including serious and fatal 

cases, was reported following discontinuation of peginterferon, ribavirin, and eltrombopag. Following 

discontinuation of therapy, patients should be monitored for any signs or symptoms of gastrointestinal 

bleeding. 

 

Bone marrow reticulin formation and risk of bone marrow fibrosis 

 

Eltrombopag may increase the risk for development or progression of reticulin fibres within the bone 

marrow. The relevance of this finding, as with other thrombopoietin receptor (TPO-R) agonists, has 

not been established yet. 

 

Prior to initiation of eltrombopag, the peripheral blood smear should be examined closely to establish 

a baseline level of cellular morphologic abnormalities. Following identification of a stable dose of 

eltrombopag, full blood count (FBC) with white blood cell count (WBC) differential should be 

performed monthly. If immature or dysplastic cells are observed, peripheral blood smears should be 

examined for new or worsening morphological abnormalities (e.g. teardrop and nucleated red blood 

cells, immature white blood cells) or cytopenia(s). If the patient develops new or worsening 

morphological abnormalities or cytopenia(s), treatment with eltrombopag should be discontinued and 

a bone marrow biopsy considered, including staining for fibrosis. 

 

Progression of existing myelodysplastic syndrome (MDS) 

 

There is a theoretical concern that TPO-R agonists may stimulate the progression of existing 

haematological malignancies such as MDS. TPO-R agonists are growth factors that lead to 

thrombopoietic progenitor cell expansion, differentiation and platelet production. The TPO-R is 

predominantly expressed on the surface of cells of the myeloid lineage. For TPO-R agonists there is a 

concern that they may stimulate the progression of existing haematopoietic malignancies such as 

MDS. 

 

In clinical studies with a TPO-R agonist in patients with MDS, cases of transient increases in blast cell 

counts were observed and cases of MDS disease progression to acute myeloid leukaemia (AML) were 

reported. 

 

The diagnosis of ITP or SAA in adults and elderly patients should be confirmed by the exclusion of 

other clinical entities presenting with thrombocytopenia, in particular the diagnosis of MDS must be 

excluded. Consideration should be given to performing a bone marrow aspirate and biopsy over the 

course of the disease and treatment, particularly in patients over 60 years of age, those with systemic 

symptoms, or abnormal signs such as increased peripheral blast cells. 

 

The effectiveness and safety of Revolade have not been established for the treatment of 

thrombocytopenia due to MDS. Revolade should not be used outside of clinical studies for the 

treatment of thrombocytopenia due to MDS. 

 



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Cytogenetic abnormalities and progression to MDS/AML in patients with SAA 

 

Cytogenetic abnormalities are known to occur in SAA patients. It is not known whether eltrombopag 

increases the risk of cytogenetic abnormalities in patients with SAA. In the phase II refractory SAA 

clinical study with eltrombopag with a starting dose of 50 mg/day (escalated every 2 weeks to a 

maximum of 150 mg/day) (ELT112523), the incidence of new cytogenetic abnormalities was 

observed in 17.1% of adult patients [7/41 (where 4 of them had changes in chromosome 7)]. The 

median time on study to a cytogenetic abnormality was 2.9 months. 
 

In the phase II refractory SAA clinical study with eltrombopag at a dose of 150 mg/day (with ethnic or 

age related modifications as indicated) (ELT116826), the incidence of new cytogenetic abnormalities 

was observed in 22.6% of adult patients [7/31 (where 3 of them had changes in chromosome 7)]. All 

7 patients had normal cytogenetics at baseline. Six patients had cytogenetic abnormality at Month 3 of 

eltrombopag therapy and one patient had cytogenetic abnormality at Month 6. 
 

In clinical studies with eltrombopag in SAA, 4% of patients (5/133) were diagnosed with MDS. The 

median time to diagnosis was 3 months from the start of eltrombopag treatment. 

 

For SAA patients refractory to or heavily pretreated with prior immunosuppressive therapy, bone 

marrow examination with aspirations for cytogenetics is recommended prior to initiation of 

eltrombopag, at 3 months of treatment and 6 months thereafter. If new cytogenetic abnormalities are 

detected, it must be evaluated whether continuation of eltrombopag is appropriate. 

 

Ocular changes 

 

Cataracts were observed in toxicology studies of eltrombopag in rodents (see section 5.3). In 

controlled studies in thrombocytopenic patients with HCV receiving interferon therapy (n=1,439), 

progression of pre-existing baseline cataract(s) or incident cataracts was reported in 8% of the 

eltrombopag group and 5% of the placebo group. Retinal haemorrhages, mostly Grade 1 or 2, have 

been reported in HCV patients receiving interferon, ribavirin and eltrombopag (2% of the eltrombopag 

group and 2% of the placebo group. Haemorrhages occurred on the surface of the retina (preretinal), 

under the retina (subretinal), or within the retinal tissue. Routine ophthalmologic monitoring of 

patients is recommended. 

 

QT/QTc prolongation 

 

A QTc study in healthy volunteers dosed 150 mg eltrombopag per day did not show a clinically 

significant effect on cardiac repolarisation. QTc interval prolongation has been reported in clinical 

studies of patients with ITP and thrombocytopenic patients with HCV. The clinical significance of 

these QTc prolongation events is unknown. 

 

Loss of response to eltrombopag 

 

A loss of response or failure to maintain a platelet response with eltrombopag treatment within the 

recommended dosing range should prompt a search for causative factors, including an increased bone 

marrow reticulin. 

 

Paediatric population 

 

The above warnings and precautions for ITP also apply to the paediatric population. 

 

Interference with laboratory tests 

 

Eltrombopag is highly coloured and so has the potential to interfere with some laboratory tests. Serum 

discolouration and interference with total bilirubin and creatinine testing have been reported in 

patients taking Revolade. If the laboratory results and clinical observations are inconsistent, re-testing 

using another method may help in determining the validity of the result. 



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4.5 Interaction with other medicinal products and other forms of interaction 
 

Effects of eltrombopag on other medicinal products 

 

HMG CoA reductase inhibitors 

 

Administration of eltrombopag 75 mg once daily for 5 days with a single 10 mg dose of the OATP1B1 

and BCRP substrate rosuvastatin to 39 healthy adult subjects increased plasma rosuvastatin Cmax 103% 

(90% confidence interval [CI]: 82%, 126%) and AUC0- 55% (90% CI: 42%, 69%). Interactions are 

also expected with other HMG-CoA reductase inhibitors, including atorvastatin, fluvastatin, lovastatin, 

pravastatin and simvastatin. When co-administered with eltrombopag, a reduced dose of statins should 

be considered and careful monitoring for statin adverse reactions should be undertaken (see 

section 5.2). 

 

OATP1B1 and BCRP substrates 

 

Concomitant administration of eltrombopag and OATP1B1 (e.g. methotrexate) and BCRP (e.g. 

topotecan and methotrexate) substrates should be undertaken with caution (see section 5.2). 

 

Cytochrome P450 substrates 

 

In studies utilising human liver microsomes, eltrombopag (up to 100 M) showed no in vitro 

inhibition of the CYP450 enzymes 1A2, 2A6, 2C19, 2D6, 2E1, 3A4/5, and 4A9/11 and was an 

inhibitor of CYP2C8 and CYP2C9 as measured using paclitaxel and diclofenac as the probe 

substrates. Administration of eltrombopag 75 mg once daily for 7 days to 24 healthy male subjects did 

not inhibit or induce the metabolism of probe substrates for 1A2 (caffeine), 2C19 (omeprazole), 2C9 

(flurbiprofen), or 3A4 (midazolam) in humans. No clinically significant interactions are expected 

when eltrombopag and CYP450 substrates are co-administered (see section 5.2). 

 

HCV protease inhibitors 

 

Dose adjustment is not required when eltrombopag is co-administered with either telaprevir or 

boceprevir. Co-administration of a single dose of eltrombopag 200 mg with telaprevir 750 mg every 

8 hours did not alter plasma telaprevir exposure. 

 

Co-administration of a single dose of eltrombopag 200 mg with boceprevir 800 mg every 8 hours did 

not alter plasma boceprevir AUC(0-), but increased Cmax by 20%, and decreased Cmin by 32%. The 

clinical relevance of the decrease in Cmin has not been established, increased clinical and laboratory 

monitoring for HCV suppression is recommended. 

 

Effects of other medicinal products on eltrombopag 

 

Ciclosporin 

 
A decrease in eltrombopag exposure was observed with co-administration of 200 mg and 600 mg 

ciclosporin (a BCRP inhibitor). The co-administration of 200 mg ciclosporin decreased the Cmax and 

the AUCinf of eltrombopag by 25% and 18%, respectively. The co-administration of 600 mg 

ciclosporin decreased the Cmax and the AUCinf of eltrombopag by 39% and 24%, respectively. 

Eltrombopag dose adjustment is permitted during the course of the treatment based on the patient’s 

platelet count (see section 4.2). Platelet count should be monitored at least weekly for 2 to 3 weeks 

when eltrombopag is co-administered with ciclosporin. Eltrombopag dose may need to be increased 

based on these platelet counts. 

 

  



13 

Polyvalent cations (chelation) 

 

Eltrombopag chelates with polyvalent cations such as iron, calcium, magnesium, aluminium, selenium 

and zinc. Administration of a single dose of eltrombopag 75 mg with a polyvalent cation-containing 

antacid (1524 mg aluminium hydroxide and 1425 mg magnesium carbonate) decreased plasma 

eltrombopag AUC0- by 70% (90% CI: 64%, 76%) and Cmax by 70% (90% CI: 62%, 76%). 

Eltrombopag should be taken at least two hours before or four hours after any products such as 

antacids, dairy products or mineral supplements containing polyvalent cations to avoid significant 

reduction in eltrombopag absorption due to chelation (see sections 4.2 and 5.2). 

 

Lopinavir/ritonavir 

 

Co-administration of eltrombopag with lopinavir/ritonavir may cause a decrease in the concentration 

of eltrombopag. A study in 40 healthy volunteers showed that the co-administration of a single 100 mg 

dose of eltrombopag with repeat dose lopinavir/ritonavir 400/100 mg twice daily resulted in a 

reduction in eltrombopag plasma AUCinf by 17% (90% CI: 6.6%, 26.6%). Therefore, caution should 

be used when co-administration of eltrombopag with lopinavir/ritonavir takes place. Platelet count 

should be closely monitored in order to ensure appropriate medical management of the dose of 

eltrombopag when lopinavir/ritonavir therapy is initiated or discontinued. 

 

CYP1A2 and CYP2C8 inhibitors and inducers 

 

Eltrombopag is metabolised through multiple pathways including CYP1A2, CYP2C8, UGT1A1, and 

UGT1A3 (see section 5.2). Medicinal products that inhibit or induce a single enzyme are unlikely to 

significantly affect plasma eltrombopag concentrations, whereas medicinal products that inhibit or 

induce multiple enzymes have the potential to increase (e.g. fluvoxamine) or decrease (e.g. rifampicin) 

eltrombopag concentrations. 

 

HCV protease inhibitors 

 

Results of a drug-drug pharmacokinetic (PK) interaction study show that co-administration of repeat 

doses of boceprevir 800 mg every 8 hours or telaprevir 750 mg every 8 hours with a single dose of 

eltrombopag 200 mg did not alter plasma eltrombopag exposure to a clinically significant extent. 

 

Medicinal products for treatment of ITP 

 

Medicinal products used in the treatment of ITP in combination with eltrombopag in clinical studies 

included corticosteroids, danazol, and/or azathioprine, intravenous immunoglobulin (IVIG), and 

anti-D immunoglobulin. Platelet counts should be monitored when combining eltrombopag with other 

medicinal products for the treatment of ITP in order to avoid platelet counts outside of the 

recommended range (see section 4.2). 

 

Food interaction 

 

The administration of eltrombopag tablet or powder for oral suspension formulations with a high-

calcium meal (e.g. a meal that included dairy products) significantly reduced plasma eltrombopag 

AUC0-∞ and Cmax. In contrast, the administration of eltrombopag 2 hours before or 4 hours after a high-

calcium meal or with low-calcium food [<50 mg calcium] did not alter plasma eltrombopag exposure 

to a clinically significant extent (see section 4.2). 

 

Administration of a single 50 mg dose of eltrombopag in tablet form with a standard high-calorie, 

high-fat breakfast that included dairy products reduced plasma eltrombopag mean AUC0-∞ by 59% and 

mean Cmax by 65%. 

 

  



14 

Administration of a single 25 mg dose of eltrombopag as powder for oral suspension with a high-

calcium, moderate-fat and moderate-calorie meal reduced plasma eltrombopag mean AUC0-∞ by 75% 

and mean Cmax by 79%. This decrease of exposure was attenuated when a single 25 mg dose of 

eltrombopag powder for oral suspension was administered 2 hours before a high-calcium meal (mean 

AUC0-∞ was decreased by 20% and mean Cmax by 14%). 

 

Food low in calcium (<50 mg calcium), including fruit, lean ham, beef and unfortified (no added 

calcium, magnesium or iron) fruit juice, unfortified soya milk and unfortified grain, did not 

significantly impact plasma eltrombopag exposure, regardless of calorie and fat content (see 

sections 4.2 and 4.5). 

 

4.6 Fertility, pregnancy and lactation 
 

Pregnancy 

 

There are no or limited amount of data from the use of eltrombopag in pregnant women. Studies in 

animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. 

 

Revolade is not recommended during pregnancy. 

 

Women of childbearing potential / Contraception in males and females 

 

Revolade is not recommended in women of childbearing potential not using contraception. 

 

Breast-feeding 

 

It is not known whether eltrombopag/metabolites are excreted in human milk. Studies in animals have 

shown that eltrombopag is likely secreted into milk (see section 5.3); therefore a risk to the suckling 

child cannot be excluded. A decision must be made whether to discontinue breast-feeding or to 

continue/abstain from Revolade therapy, taking into account the benefit of breast-feeding for the child 

and the benefit of therapy for the woman. 

 

Fertility 

 

Fertility was not affected in male or female rats at exposures that were comparable to those in humans. 

However a risk for humans cannot be ruled out (see section 5.3). 

 

4.7 Effects on ability to drive and use machines 
 

Eltrombopag has negligible influence on the ability to drive and use machines. The clinical status of 

the patient and the adverse reaction profile of eltrombopag, including dizziness and lack of alertness, 

should be borne in mind when considering the patient’s ability to perform tasks that require 

judgement, motor and cognitive skills. 

 

  



15 

4.8 Undesirable effects 

 

Summary of the safety profile 

 

Immune thrombocytopenia in adult and paediatric patients 

 

The safety of Revolade was assessed using the pooled double-blind, placebo-controlled studies 

TRA100773A and B, TRA102537 (RAISE) and TRA113765, in which 403 patients were exposed to 

Revolade and 179 to placebo, in addition to data from the completed open-label studies TRA108057, 

TRA105325 (EXTEND) and TRA112940. Patients received study medication for up to 8 years (in 

EXTEND). The most important serious adverse reactions were hepatotoxicity and 

thrombotic/thromboembolic events. The most common adverse reactions occurring in at least 10% of 

patients included nausea, diarrhoea and increased alanine aminotransferase. 

 

The safety of Revolade in paediatric patients (aged 1 to 17 years) with previously treated ITP has been 

demonstrated in two studies. PETIT2 (TRA115450) was a 2-part, double-blind and open-label, 

randomised, placebo-controlled study. Patients were randomised 2:1 and received Revolade (n=63) or 

placebo (n=29) for up to 13 weeks in the randomised period of the study. PETIT (TRA108062) was a 

3-part, staggered-cohort, open-label and double-blind, randomised, placebo-controlled study. Patients 

were randomised 2:1 and received Revolade (n=44) or placebo (n=21), for up to 7 weeks. The profile 

of adverse reactions was comparable to that seen in adults with some additional adverse reactions, 

marked ♦ in the table below. The most common adverse reactions in paediatric ITP patients 1 year and 

older (≥3% and greater than placebo) were upper respiratory tract infection, nasopharyngitis, cough, 

pyrexia, abdominal pain, oropharyngeal pain, toothache and rhinorrhoea. 

 

Thrombocytopenia with HCV infection in adult patients 

 

ENABLE 1 (TPL103922 n=716) and ENABLE 2 (TPL108390 n=805) were randomised, 

double-blind, placebo-controlled, multicentre studies to assess the efficacy and safety of Revolade in 

thrombocytopenic patients with HCV infection who were otherwise eligible to initiate antiviral 

therapy. In the HCV studies the safety population consisted of all randomised patients who received 

double-blind study medicinal product during Part 2 of ENABLE 1 (Revolade treatment n=450, 

placebo treatment n=232) and ENABLE 2 (Revolade treatment n=506, placebo treatment n=253). 

Patients are analysed according to the treatment received (total safety double-blind population, 

Revolade n=955 and placebo n=484). The most important serious adverse reactions identified were 

hepatotoxicity and thrombotic/thromboembolic events. The most common adverse reactions occurring 

in at least 10% of patients included headache, anaemia, decreased appetite, cough, nausea, diarrhoea, 

hyperbilirubinaemia, alopecia, pruritus, myalgia, pyrexia, fatigue, influenza-like illness, asthenia, 

chills and oedema. 

 

Severe aplastic anaemia in adult patients 

 

The safety of eltrombopag in severe aplastic anaemia was assessed in a single-arm, open-label study 

(N=43) in which 11 patients (26%) were treated for >6 months and 7 patients (21%) were treated for 

>1 year. The most important serious adverse reactions were febrile neutropenia and sepsis/infection. 

The most common adverse reactions occurring in at least 10% of patients included headache, 

dizziness, cough, oropharyngeal pain, nausea, diarrhoea, abdominal pain, transaminases increased, 

arthralgia, pain in extremity, fatigue and pyrexia. 

 

  



16 

List of adverse reactions 

 

The adverse reactions in the adult ITP studies (N=763), paediatric ITP studies (N=171), the HCV 

studies (N=1,520), the SAA studies (N=43) and post-marketing reports are listed below by MedDRA 

system organ class and by frequency. Within each system organ class, the adverse drug reactions are 

ranked by frequency, with the most frequent reactions first. The corresponding frequency category for 

each adverse drug reaction is based on the following convention (CIOMS III): very common (≥1/10); 

common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); not known 

(cannot be estimated from the available data). 

 

ITP study population 

 

System organ class Frequency Adverse reaction 

Infections and infestations Very 

common 

Nasopharyngitis♦, upper respiratory tract infection♦ 

Common Pharyngitis, influenza, oral herpes, pneumonia, sinusitis, tonsillitis, 

respiratory tract infection, gingivitis 

Uncommon Skin infection 

Neoplasms benign, 

malignant and unspecified 

(incl cysts and polyps) 

Uncommon Rectosigmoid cancer 

Blood and lymphatic system 

disorders 

Common Anaemia, eosinophilia, leukocytosis, thrombocytopenia, 

haemoglobin decreased, white blood cell count decreased 

Uncommon Anisocytosis, haemolytic anaemia, myelocytosis, band neutrophil 

count increased, myelocyte present, platelet count increased, 

haemoglobin increased 

Immune system disorders Uncommon Hypersensitivity 

Metabolism and nutrition 

disorders 

Common Hypokalaemia, decreased appetite, blood uric acid increased 

Uncommon Anorexia, gout, hypocalcaemia 

Psychiatric disorders Common Sleep disorder, depression 

Uncommon Apathy, mood altered, tearfulness 

Nervous system disorders Common Paraesthesia, hypoaesthesia, somnolence, migraine 

Uncommon Tremor, balance disorder, dysaesthesia, hemiparesis, migraine with 

aura, neuropathy peripheral, peripheral sensory neuropathy, speech 

disorder, toxic neuropathy, vascular headache 

Eye disorders Common Dry eye, vision blurred, eye pain, visual acuity reduced 

Uncommon Lenticular opacities, astigmatism, cataract cortical, lacrimation 

increased, retinal haemorrhage, retinal pigment epitheliopathy, 

visual impairment, visual acuity tests abnormal, blepharitis, 

keratoconjunctivitis sicca 

Ear and labyrinth disorders Common Ear pain, vertigo 

Cardiac disorders Uncommon Tachycardia, acute myocardial infarction, cardiovascular disorder, 

cyanosis, sinus tachycardia, electrocardiogram QT prolonged 



17 

Vascular disorders Common Deep vein thrombosis, haematoma, hot flush 

Uncommon Embolism, thrombophlebitis superficial, flushing 

Respiratory, thoracic and 

mediastinal disorders 

Very 

common 

Cough♦ 

Common Oropharyngeal pain, rhinorrhoea♦ 

Uncommon Pulmonary embolism, pulmonary infarction, nasal discomfort, 

oropharyngeal blistering, sinus disorder, sleep apnoea syndrome 

Gastrointestinal disorders Very 

common 

Nausea, diarrhoea♦ 

Common Mouth ulceration, toothache♦, vomiting, abdominal pain*, mouth 

haemorrhage, flatulence 

* Very common in paediatric ITP 

Uncommon Dry mouth, glossodynia, abdominal tenderness, faeces discoloured, 

food poisoning, frequent bowel movements, haematemesis, oral 

discomfort 

Hepatobiliary disorders Very 

common 

Alanine aminotransferase increased† 

Common Aspartate aminotransferase increased†, hyperbilirubinaemia, hepatic 

function abnormal 

Uncommon Cholestasis, hepatic lesion, hepatitis, drug-induced liver injury 

Skin and subcutaneous tissue 

disorders 

Common Rash, alopecia, hyperhidrosis, pruritus generalised, petechiae 

Uncommon Urticaria, dermatosis, cold sweat, erythema, melanosis, 

pigmentation disorder, skin discolouration, skin exfoliation 

Musculoskeletal and 

connective tissue disorders 

Common Myalgia, muscle spasm, musculoskeletal pain, bone pain, back pain 

Uncommon Muscular weakness 

Renal and urinary disorders Common Proteinuria, blood creatinine increased, thrombotic microangiopathy 

with renal failure‡ 

Uncommon Renal failure, leukocyturia, lupus nephritis, nocturia, blood urea 

increased, urine protein/creatinine ratio increased 

Reproductive system and 

breast disorders 

Common Menorrhagia 

General disorders and 

administration site 

conditions 

Common Pyrexia*, chest pain, asthenia 

*Very common in paediatric ITP 

Uncommon Feeling hot, vessel puncture site haemorrhage, feeling jittery, 

inflammation of wound, malaise, sensation of foreign body 

Investigations Common Blood alkaline phosphatase increased 

Uncommon Blood albumin increased, protein total increased, blood albumin 

decreased, pH urine increased 

Injury, poisoning and 

procedural complications 

Uncommon Sunburn 

♦ Additional adverse reactions observed in paediatric studies (aged 1to 17 years). 
† Increase of alanine aminotransferase and aspartate aminotransferase may occur simultaneously, 

although at a lower frequency. 
‡ Grouped term with preferred terms acute kidney injury and renal failure 

 

HCV study population (in combination with anti-viral interferon and ribavirin therapy) 

 

System organ class Frequency Adverse reaction 

Infections and infestations Common Urinary tract infection, upper respiratory tract infection, 

bronchitis, nasopharyngitis, influenza, oral herpes 

Uncommon Gastroenteritis, pharyngitis 

Neoplasms benign, malignant 

and unspecified (incl cysts and 

polyps) 

Common Hepatic neoplasm malignant 



18 

Blood and lymphatic system 

disorders 

Very 

common 

Anaemia 

Common Lymphopenia 

Uncommon Haemolytic anaemia 

Metabolism and nutrition 

disorders 

Very 

common 

Decreased appetite 

Common Hyperglycaemia, abnormal loss of weight 

Psychiatric disorders Common Depression, anxiety, sleep disorder 

Uncommon Confusional state, agitation 

Nervous system disorders Very 

common 

Headache 

Common Dizziness, disturbance in attention, dysgeusia, hepatic 

encephalopathy, lethargy, memory impairment, paraesthesia 

Eye disorders Common Cataract, retinal exudates, dry eye, ocular icterus, retinal 

haemorrhage 

Ear and labyrinth disorders Common Vertigo 

Cardiac disorders Common Palpitations 

Respiratory, thoracic and 

mediastinal disorders 

Very 

common 

Cough 

Common Dyspnoea, oropharyngeal pain, dyspnoea exertional, productive 

cough 

Gastrointestinal disorders Very 

common 

Nausea, diarrhoea 

Common Vomiting, ascites, abdominal pain, abdominal pain upper, 

dyspepsia, dry mouth, constipation, abdominal distension, 

toothache, stomatitis, gastrooesophagal reflux disease, 

haemorrhoids, abdominal discomfort, varices oesophageal 

Uncomon Oesophageal varices haemorrhage, gastritis, aphthous stomatitis 

Hepatobiliary disorders Common Hyperbilirubinaemia, jaundice, drug-induced liver injury 

Uncommon Portal vein thrombosis, hepatic failure 

Skin and subcutaneous tissue 

disorders 

Very 

common 

Pruritus 

Common Rash, dry skin, eczema, rash pruritic, erythema, hyperhidrosis, 

pruritus generalised, alopecia 

Uncommon Skin lesion, skin discolouration, skin hyperpigmentation, night 

sweats 

Musculoskeletal and 

connective tissue disorder 

Very 

common 

Myalgia 

Common Arthralgia, muscle spasms, back pain, pain in extremity, 

musculoskeletal pain, bone pain 

Renal and urinary disorders Uncommon Thrombotic microangiopathy with acute renal failure†, dysuria  

General disorders and 

administration site conditions 

Very 

common 

Pyrexia, fatigue, influenza-like illness, asthenia, chills 

Common Irritability, pain, malaise, injection site reaction, non-cardiac chest 

pain, oedema, oedema peripheral 

Uncommon Injection site pruritus, injection site rash, chest discomfort 

Investigations Common Blood bilirubin increased, weight decreased, white blood cell 

count decreased, haemoglobin decreased, neutrophil count 

decreased, international normalised ratio increased, activated 

partial thromboplastin time prolonged, blood glucose increased, 

blood albumin decreased 

Uncommon Electrocardiogram QT prolonged 
† Grouped term with preferred terms oliguria, renal failure and renal impairment 

 



19 

SAA study population 

 

System organ class Frequency Adverse reaction 

Blood and lymphatic system 

disorders 

Common Neutropenia, splenic infarction 

Metabolism and nutrition 

disorders 

Common Iron overload, decreased appetite, hypoglycaemia, increased 

appetite 

Psychiatric disorders Common Anxiety, depression 

Nervous system disorders Very 

common 

Headache, dizziness 

Common Syncope 

Eye disorders Common Dry eye, cataract, ocular icterus, vision blurred, visual 

impairment, vitreous floaters 

Respiratory, thoracic and 

mediastinal disorders 

Very 

common 

Cough, oropharyngeal pain, rhinorrhoea 

Common Epistaxis 

Gastrointestinal disorders Very 

common 

Diarrhoea, nausea, gingival bleeding, abdominal pain 

Common Oral mucosal blistering, oral pain, vomiting, abdominal 

discomfort, constipation, abdominal distension, dysphagia, faeces 

discoloured, swollen tongue, gastrointestinal motility disorder, 

flatulence 

Hepatobiliary disorders Very 

common 

Transaminases increased 

Common Blood bilirubin increased (hyperbilirubinemia), jaundice 

Not known Drug-induced liver injury* 

* Cases of drug-induced liver injury have been reported in 

patients with ITP and HCV 

Skin and subcutaneous tissue 

disorders 

Common Petechiae, rash, pruritus, urticaria, skin lesion, rash macular 

Not known Skin discolouration, skin hyperpigmentation 

Musculosketal and connective 

tissue disorders 

Very 

common 

Arthralgia, pain in extremity, muscle spasms 

Common Back pain, myalgia, bone pain 

Renal and urinary disorders Common Chromaturia 

General disorders and 

administration site conditions 

Very 

common 

Fatigue, pyrexia, chills 

Common Asthenia, oedema peripheral, malaise 

Investigations Common Blood creatine phosphokinase increased 

 

Description of selected adverse reactions 

 

Thrombotic/thromboembolic events (TEEs) 

 

In 3 controlled and 2 uncontrolled clinical studies among adult ITP patients receiving eltrombopag 

(n=446), 17 patients experienced a total of 19 TEEs, which included (in descending order of 

occurrence) deep vein thrombosis (n=6), pulmonary embolism (n=6), acute myocardial infarction 

(n=2), cerebral infarction (n=2), embolism (n=1) (see section 4.4). 

 

In a placebo-controlled study (n=288, Safety population), following 2 weeks’ treatment in preparation 

for invasive procedures, 6 of 143 (4%) adult patients with chronic liver disease receiving eltrombopag 

experienced 7 TEEs of the portal venous system and 2 of 145 (1%) patients in the placebo group 

experienced 3 TEEs. Five of the 6 patients treated with eltrombopag experienced the TEE at a platelet 

count >200,000/µl 

 

No specific risk factors were identified in those patients who experienced a TEE with the exception of 

platelet counts ≥200,000/µl (see section 4.4). 



20 

 

In controlled studies in thrombocytopenic patients with HCV (n=1,439), 38 out of 955 patients (4%) 

treated with eltrombopag experienced a TEE and 6 out of 484 patients (1%) in the placebo group 

experienced TEEs. Portal vein thrombosis was the most common TEE in both treatment groups (2% in 

patients treated with eltrombopag versus < 1% for placebo) (see section 4.4). Patients with low 

albumin levels (≤ 35 g/l) or MELD ≥10 had a 2-fold greater risk of TEEs than those with higher 

albumin levels; those aged ≥60 years had a 2-fold greater risk of TEEs compared to younger patients. 

 

Hepatic decompensation (use with interferon) 

 

Chronic HCV patients with cirrhosis may be at risk of hepatic decompensation when receiving alfa 

interferon therapy. In 2 controlled clinical studies in thrombocytopenic patients with HCV, hepatic 

decompensation (ascites, hepatic encephalopathy, variceal haemorrhage, spontaneous bacterial 

peritonitis) was reported more frequently in the eltrombopag arm (11%) than in the placebo arm (6%). 

In patients with low albumin levels (≤35 g/l) or MELD score ≥10 at baseline, there was a 3-fold 

greater risk of hepatic decompensation and an increase in the risk of a fatal adverse event compared to 

those with less advanced liver disease. Eltrombopag should only be administered to such patients after 

careful consideration of the expected benefits in comparison with the risks. Patients with these 

characteristics should be closely monitored for signs and symptoms of hepatic decompensation (see 

section 4.4). 

 

Hepatotoxixity 

 

In the controlled clinical studies in chronic ITP with eltrombopag, increases in serum ALT, AST and 

bilirubin were observed (see section 4.4). 

 

These findings were mostly mild (Grade 1-2), reversible and not accompanied by clinically significant 

symptoms that would indicate an impaired liver function. Across the 3 placebo-controlled studies in 

adults with chronic ITP, 1 patient in the placebo group and 1 patient in the eltrombopag group 

experienced a Grade 4 liver test abnormality. In two placebo-controlled studies in paediatric patients 

(aged 1 to 17 years) with chronic ITP, ALT 3 x ULN was reported in 4.7% and 0% of the 

eltrombopag and placebo groups, respectively. 

 

In 2 controlled clinical studies in patients with HCV, ALT or AST 3 x ULN was reported in 34% and 

38% of the eltrombopag and placebo groups, respectively. Most patients receiving eltrombopag in 

combination with peginterferon / ribavirin therapy will experience indirect hyperbilirubinaemia. 

Overall, total bilirubin ≥1.5 x ULN was reported in 76% and 50% of the eltrombopag and placebo 

groups, respectively. 

 

In the single-arm phase II monotherapy refractory SAA study, concurrent ALT or AST >3 x ULN 

with total (indirect) bilirubin >1.5 x ULN were reported in 5% of patients. Total bilirubin >1.5 x ULN 

occurred in 14% of patients. 

 

Thrombocytopenia following discontinuation of treatment 

 

In the 3 controlled clinical ITP studies, transient decreases in platelet counts to levels lower than 

baseline were observed following discontinuation of treatment in 8% and 8% of the eltrombopag and 

placebo groups, respectively (see section 4.4). 

 

Increased bone marrow reticulin 

 

Across the programme, no patients had evidence of clinically relevant bone marrow abnormalities or 

clinical findings that would indicate bone marrow dysfunction. In a small number of ITP patients, 

eltrombopag treatment was discontinued due to bone marrow reticulin (see section 4.4). 

 



21 

Cytogenetic abnormalities 

 

In the phase II refractory SAA clinical study with eltrombopag with a starting dose of 50 mg/day 

(escalated every 2 weeks to a maximum of 150 mg/day) (ELT112523), the incidence of new 

cytogenetic abnormalities was observed in 17.1% of adult patients [7/41 (where 4 of them had changes 

in chromosome 7)]. The median time on study to a cytogenetic abnormality was 2.9 months. 

 

In the phase II refractory SAA clinical study with eltrombopag at a dose of 150 mg/day (with ethnic or 

age related modifications as indicated) (ELT116826), the incidence of new cytogenetic abnormalities 

was observed in 22.6% of adult patients [7/31 (where 3 of them had changes in chromosome 7)]. All 

7 patients had normal cytogenetics at baseline. Six patients had cytogenetic abnormality at Month 3 of 

eltrombopag therapy and one patient had cytogenetic abnormality at Month 6. 

 

Haematologic malignancies 

 

In the single-arm, open-label study in SAA, three (7%) patients were diagnosed with MDS following 

treatment with eltrombopag, in the two ongoing studies (ELT116826 and ELT116643), 1/28 (4%) and 

1/62 (2%) patient has been diagnosed with MDS or AML in each study. 

 

Reporting of suspected adverse reactions 

 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the national reporting system 

listed in Appendix V. 

 

4.9 Overdose 
 

In the event of overdose, platelet counts may increase excessively and result in 

thrombotic/thromboembolic complications. In case of an overdose, consideration should be given to 

oral administration of a metal cation-containing preparation, such as calcium, aluminium, or 

magnesium preparations to chelate eltrombopag and thus limit absorption. Platelet counts should be 

closely monitored. Treatment with eltrombopag should be reinitiated in accordance with dosing and 

administration recommendations (see section 4.2). 

 

In the clinical studies there was one report of overdose where the patient ingested 5000 mg of 

eltrombopag. Reported adverse reactions included mild rash, transient bradycardia, ALT and AST 

elevation, and fatigue. Liver enzymes measured between Days 2 and 18 after ingestion peaked at a 

1.6-fold ULN in AST, a 3.9-fold ULN in ALT, and a 2.4-fold ULN in total bilirubin, The platelet 

counts were 672,000/µl on Day 18 after ingestion and the maximum platelet count was 929,000/µl. All 

events were resolved without sequelae following treatment. 

 

Because eltrombopag is not significantly renally excreted and is highly bound to plasma proteins, 

haemodialysis would not be expected to be an effective method to enhance the elimination of 

eltrombopag. 

 

 

  



22 

5. PHARMACOLOGICAL PROPERTIES 
 

5.1 Pharmacodynamic properties 
 

Pharmacotherapeutic group: Antihemorrhagics, other systemic hemostatics. ATC code: B02BX 05. 

 

Mechanism of action 

 

TPO is the main cytokine involved in regulation of megakaryopoiesis and platelet production, and is 

the endogenous ligand for the TPO-R. Eltrombopag interacts with the transmembrane domain of the 

human TPO-R and initiates signalling cascades similar but not identical to that of endogenous 

thrombopoietin (TPO), inducing proliferation and differentiation from bone marrow progenitor cells. 

 

Clinical efficacy and safety 

 

Immune (primary) thrombocytopenia (ITP) studies 

 

Two phase III, randomised, double-blind, placebo-controlled studies RAISE (TRA102537) and 

TRA100773B and two open-label studies REPEAT (TRA108057) and EXTEND (TRA105325) 

evaluated the safety and efficacy of eltrombopag in adult patients with previously treated ITP. Overall, 

eltrombopag was administered to 277 ITP patients for at least 6 months and 202 patients for at least 

1 year. 

 

Double-blind placebo-controlled studies 

RAISE: 197 ITP patients were randomised 2:1, eltrombopag (n=135) to placebo (n=62), and 

randomisation was stratified based upon splenectomy status, use of ITP medicinal products at baseline 

and baseline platelet count. The dose of eltrombopag was adjusted during the 6-month treatment 

period based on individual platelet counts. All patients initiated treatment with eltrombopag 50 mg. 

From Day 29 to the end of treatment, 15 to 28% of eltrombopag-treated patients were maintained on 

≤25 mg and 29 to 53% received 75 mg. 

 

In addition, patients could taper off concomitant ITP medicinal products and receive rescue treatments 

as dictated by local standard of care. More than half of all patients in each treatment group had ≥3 

prior ITP therapies and 36% had a prior splenectomy. 

 

Median platelet counts at baseline were 16,000/l for both treatment groups and in the eltrombopag 

group were maintained above 50,000/µl at all on-therapy visits starting at Day 15; in contrast, median 

platelet counts in the placebo group remained <30,000/µl throughout the study. 

 

Platelet count response between 50,000-400,000/l in the absence of rescue treatment was achieved by 

significantly more patients in the eltrombopag treated group during the 6 month treatment period, 

p <0.001. Fifty-four percent of the eltrombopag-treated patients and 13% of placebo-treated patients 

achieved this level of response after 6 weeks of treatment. A similar platelet response was maintained 

throughout the study, with 52% and 16% of patients responding at the end of the 6-month treatment 

period. 

 



23 

Table 4 Secondary efficacy results from RAISE 

 

 

Eltrombopag 

N=135 

Placebo 

N=62 

Key secondary endpoints 

Number of cumulative weeks with platelet counts 

50,000-400,000/µl, Mean (SD) 
11.3 (9.46) 2.4 (5.95) 

Patients with ≥75% of assessments in the target range (50,000 to 

400,000/l), n (%) 

p-value a 

51 (38) 4 (7) 

<0.001 

Patients with bleeding (WHO Grades 1-4) at any time during 

6 months, n (%) 

 p-value a 

106 (79) 56 (93) 

0.012 

Patients with bleeding (WHO Grades 2-4) at any time during 

6 months, n (%) 

 p-value a 

44 (33) 32 (53) 

0.002 

Requiring rescue therapy, n (%) 

 p-value a 

24 (18) 25 (40) 

0.001 

Patients receiving ITP therapy at baseline (n) 63 31 

Patients who attempted to reduce or discontinue baseline 

therapy, n (%)b 

 p-value a 

37 (59) 10 (32) 

0.016 

a Logistic regression model adjusted for randomisation stratification variables 

b 21 out of 63 (33%) patients treated with eltrombopag who were taking an ITP medicinal product 

at baseline permanently discontinued all baseline ITP medicinal products. 

 

At baseline, more than 70% of ITP patients in each treatment group reported any bleeding (WHO 

Grades 1-4) and more than 20% reported clinically significant bleeding (WHO Grades 2-4), 

respectively. The proportion of eltrombopag-treated patients with any bleeding (Grades 1-4) and 

clinically significant bleeding (Grades 2-4) was reduced from baseline by approximately 50% from 

Day 15 to the end of treatment throughout the 6-month treatment period. 

 

TRA100773B: The primary efficacy endpoint was the proportion of responders, defined as ITP 

patients who had an increase in platelet counts to 50,000/l at Day 43 from a baseline of <30,000/l; 

patients who withdrew prematurely due to a platelet count 200,000/l were considered responders, 

those that discontinued for any other reason were considered non-responders irrespective of platelet 

count. A total of 114 patients with previously treated ITP were randomised 2:1 eltrombopag (n=76) to 

placebo (n=38). 

 

Table 5 Efficacy results from TRA100773B 

 

 

Eltrombopag 

N=74 

Placebo 

N=38 

Key primary endpoints 

Eligible for efficacy analysis, n 73 37 

Patients with platelet count 50,000/l after up to 42 days 

of dosing (compared to a baseline count of <30,000/l), n 

(%) 

 

p-valuea 

43 (59) 6 (16) 

<0.001 

Key secondary endpoints 

Patients with a Day 43 bleeding assessment, n 51 30 

Bleeding (WHO Grades 1-4) n (%) 

 

p-valuea 

20 (39) 18 (60) 

0.029 

a Logistic regression model adjusted for randomisation stratification variables 



24 

 

In both RAISE and TRA100773B the response to eltrombopag relative to placebo was similar 

irrespective of ITP medicinal product use, splenectomy status and baseline platelet count (≤15,000/µl, 

>15,000/µl) at randomisation. 

 

In RAISE and TRA100773B studies, in the subgroup of ITP patients with baseline platelet count 

≤15,000/μl the median platelet counts did not reach the target level (>50,000/l), although in both 

studies 43% of these patients treated with eltrombopag responded after 6 weeks of treatment. In 

addition, in the RAISE study, 42% of patients with baseline platelet count ≤15,000/μl treated with 

eltrombopag responded at the end of the 6 month treatment period. Forty-two to 60% of the 

eltrombopag-treated patients in the RAISE study were receiving 75 mg from Day 29 to the end of 

treatment. 

 

An open-label, repeat-dose study (3 cycles of 6 weeks of treatment, followed by 4 weeks off 

treatment) showed that episodic use with multiple courses of eltrombopag has demonstrated no loss of 

response. 

 

Eltrombopag was administered to 302 ITP patients in the open-label extension study EXTEND 

(TRA105325), 218 patients completed 1 year, 180 completed 2 years, 107 completed 3 years, 75 

completed 4 years, 34 completed 5 years and 18 completed 6 years. The median baseline platelet count 

was 19,000/l prior to eltrombopag administration. Median platelet counts at 1, 2, 3, 4, 5, 6 and 

7 years on study were 85,000/l, 85,000/l, 105,000/l, 64,000/l, 75,000/l, 119,000/l and 

76,000/l, respectively. 

 

Clinical studies comparing eltrombopag to other treatment options (e.g. splenectomy) have not been 

conducted. The long-term safety of eltrombopag should be considered prior to starting therapy. 

 

Paediatric population (aged 1 to 17 years) 

The safety and efficacy of eltrombopag in paediatric patients have been investigated in two studies. 

 

TRA115450 (PETIT2): The primary endpoint was a sustained response, defined as the proportion of 

patients receiving eltrombopag, compared to placebo, achieving platelet counts ≥50,000/µl for at least 

6 out of 8 weeks (in the absence of rescue therapy), between weeks 5 to 12 during the double-blind 

randomised period. Patients were diagnosed with chronic ITP for at least 1 year and were refractory or 

relapsed to at least one prior ITP therapy or unable to continue other ITP treatments for a medical 

reason and had platelet count <30,000/µl. Ninety-two patients were randomised by three age cohort 

strata (2:1) to eltrombopag (n=63) or placebo (n=29). The dose of eltrombopag could be adjusted 

based on individual platelet counts. 

 

Overall, a significantly greater proportion of eltrombopag patients (40%) compared with placebo 

patients (3%) achieved the primary endpoint (Odds Ratio: 18.0 [95% CI: 2.3, 140.9] p <0.001) which 

was similar across the three age cohorts (Table 6). 

 

Table 6 Sustained platelet response rates by age cohort in paediatric patients with chronic 

ITP 

 

 Eltrombopag 

n/N (%) 

[95% CI] 

Placebo 

n/N (%) 

[95% CI] 

Cohort 1 (12 to 17 years) 

 

Cohort 2 (6 to 11 years) 

 

Cohort 3 (1 to 5 years) 

9/23 (39%) 

[20%, 61%] 

11/26 (42%) 

[23%, 63%] 

5/14 (36%) 

[13%, 65%] 

1/10 (10%) 

[0%, 45%] 

0/13 (0%) 

[N/A] 

0/6 (0%) 

[N/A] 

 



25 

Statistically fewer eltrombopag patients required rescue treatment during the randomised period 

compared to placebo patients (19% [12/63] vs. 24% [7/29], p=0.032). 

 

At baseline, 71% of patients in the eltrombopag group and 69% in the placebo group reported any 

bleeding (WHO Grades 1-4). At Week 12, the proportion of eltrombopag patients reporting any 

bleeding was decreased to half of baseline (36%). In comparison, at Week 12, 55% of placebo patients 

reported any bleeding. 

 

Patients were permitted to reduce or discontinue baseline ITP therapy only during the open-label phase 

of the study and 53% (8/15) of patients were able to reduce (n=1) or discontinue (n=7) baseline ITP 

therapy, mainly corticosteroids, without needing rescue therapy. 

 

TRA108062 (PETIT): The primary endpoint was the proportion of patients achieving platelet counts 

≥50,000/µl at least once between weeks 1 and 6 of the randomised period. Patients were diagnosed 

with ITP for at least 6 months and were refractory or relapsed to at least one prior ITP therapy with a 

platelet count <30,000/µl (n=67). During the randomised period of the study, patients were 

randomised by three age cohort strata (2:1) to eltrombopag (n=45) or placebo (n=22). The dose of 

eltrombopag could be adjusted based on individual platelet counts. 

 

Overall, a significantly greater proportion of eltrombopag patients (62%) compared with placebo 

patients (32%) met the primary endpoint (Odds Ratio: 4.3 [95% CI: 1.4, 13.3] p=0.011). 

 

Sustained response was seen in 50% of the initial responders during 20 out of 24 weeks in the 

PETIT 2 study and 15 out of 24 weeks in the PETIT study. 

 

Chronic hepatitis C associated thrombocytopenia studies 

 

The efficacy and safety of eltrombopag for the treatment of thrombocytopenia in patients with HCV 

infection were evaluated in two randomised, double-blind, placebo-controlled studies. ENABLE 1 

utilised peginterferon alfa-2a plus ribavirin for antiviral treatment and ENABLE 2 utilised 

peginterferon alfa-2b plus ribavirin. Patients did not receive direct acting antiviral agents. In both 

studies, patients with a platelet count of <75,000/µl were enrolled and stratified by platelet count 

(<50,000/µl and ≥50,000/µl to <75,000/µl), screening HCV RNA (<800,000 IU/ml and 

≥800,000 IU/ml), and HCV genotype (genotype 2/3, and genotype 1/4/6). 

 

Baseline disease characteristics were similar in both studies and were consistent with compensated 

cirrhotic HCV patient population. The majority of patients were HCV genotype 1 (64%) and had 

bridging fibrosis/cirrhosis. Thirty-one percent of patients had been treated with prior HCV therapies, 

primarily pegylated interferon plus ribavirin. The median baseline platelet count was 59,500/µl in both 

treatment groups: 0.8%, 28% and 72% of the patients recruited had platelet counts <20,000/µl, 

<50.000/µl and ≥50,000/µl respectively. 

 

The studies consisted of two phases – a pre-antiviral treatment phase and an antiviral treatment phase. 

In the pre-antiviral treatment phase, patients received open-label eltrombopag to increase the platelet 

count to ≥90,000/µl for ENABLE 1 and ≥100,000/µl for ENABLE 2. The median time to achieve the 

target platelet count ≥90,000/µl (ENABLE 1) or ≥100,000/µl (ENABLE 2) was 2 weeks. 

 

The primary efficacy endpoint for both studies was sustained virologic response (SVR), defined as the 

percentage of patients with no detectable HCV-RNA at 24 weeks after completion of the planned 

treatment period. 

 

  



26 

In both HCV studies, a significantly greater proportion of patients treated with eltrombopag (n=201, 

21%) achieved SVR compared to those treated with placebo (n=65, 13%) (see Table 7). The 

improvement in the proportion of patients who achieved SVR was consistent across all subgroups in 

the randomisation strata (baseline platelet counts (<50,000 vs. >50,000), viral load (<800,000 IU/ml 

vs. ≥800,000 IU/ml) and genotype (2/3 vs. 1/4/6)). 

 

Table 7 Virologic response in HCV patients in ENABLE 1 and ENABLE 2 

 

 Pooled data ENABLE 1a ENABLE 2b 

Patients achieving 

target platelet counts 

and initiating antiviral 

therapy c 

 

1,439/1,520 (95%) 

 

680/715 (95%) 

 

759/805 (94%) 

 Eltrombopag Placebo Eltrombopag Placebo Eltrombopag Placebo 

Total number of 

patients entering 

antiviral treatment 

phase 

n=956 n=485 n=450 n=232 n=506 n=253 

 % patients achieving virologic response 

Overall SVR d  21 13 23 14 19 13 

HCV RNA Genotype       

Genotype 2/3 35 25 35 24 34 25 

Genotype 1/4/6e 15 8 18 10 13 7 

Albumin levels f    

≤ 35g/l 11 8 

> 35g/l 25 16 

MELD scoref   

≥ 10  18 10 

< 10 23 17 

a Eltrombopag given in combination with peginterferon alfa-2a (180 μg once weekly for 

48 weeks for genotypes 1/4/6; 24 weeks for genotype 2/3) plus ribavirin (800 to 1200 mg daily 

in 2 divided doses orally) 

b Eltrombopag given in combination with peginterferon alfa-2b (1.5 μg/kg once weekly for 

48 weeks for genotype 1/4/6; 24 weeks for genotype 2/3) plus ribavirin (800 to 1400 mg orally 

in 2 divided doses) 

c Target platelet count was 90,000/µl for ENABLE 1 and 100,000/µl for ENABLE 2. For 

ENABLE 1, 682 patients were randomised to the antiviral treatment phase; however 2 patients 

then withdrew consent prior to receiving antiviral therapy 

d p-value <0.05 for eltrombopag versus placebo 

e 64% patients participating in ENABLE 1 and ENABLE 2 were genotype 1 

f Post-hoc analyses 

 

Other secondary findings of the studies included the following: significantly fewer patients treated 

with eltrombopag prematurely discontinued antiviral therapy compared to placebo (45% vs. 60%, 

p=<0.0001). A greater proportion of patients on eltrombopag did not require any antiviral dose 

reduction as compared to placebo (45% vs. 27%). Eltrombopag treatment delayed and reduced the 

number of peginterferon dose reductions. 

 

  



27 

Severe aplastic anaemia 

 

Eltrombopag was studied in a single-arm, single-centre open-label study in 43 patients with severe 

aplastic anaemia with refractory thrombocytopenia following at least one prior immunosuppressive 

therapy (IST) and who had a platelet count ≤30,000/µl. 

 

The majority of patients, 33 (77%), were considered to have ‘primary refractory disease’, defined as 

having no prior adequate response to IST in any lineage. The remaining 10 patients had insufficient 

platelet response to prior therapies. All 10 had received at least 2 prior IST regimens and 50% had 

received at least 3 prior IST regimens. Patients with diagnosis of Fanconi anaemia, infection not 

responding to appropriate therapy, PNH clone size in neutrophils of ≥50%, where excluded from 

participation. 

 

At baseline the median platelet count was 20,000/µl, haemoglobin was 8.4 g/dl, ANC was 0.58 x 109/l 

and absolute reticulocyte count was 24.3 x 109/l. Eighty-six percent of patients were RBC transfusion 

dependent, and 91% were platelet transfusion dependent. The majority of patients (84%) had received 

at least 2 prior immunosuppressive therapies. Three patients had cytogenetic abnormalities at baseline. 

 

The primary endpoint was haematological response assessed after 12 weeks of eltrombopag treatment. 

Haematological response was defined as meeting one or more of the following criteria: 1) platelet 

count increases to 20,000/µl above baseline or stable platelet counts with transfusion independence for 

a minimum of 8 weeks; 2) haemoglobin increase by >1.5g/dl, or a reduction in ≥4 units of red blood 

cell (RBC) transfusions for 8 consecutive weeks; 3) absolute neutrophil count (ANC) increase of 

100% or an ANC increase >0.5 x 109/l. 

 

The haematological response rate was 40% (17/43 patients; 95% CI 25, 56), the majority were 

unilineage responses (13/17, 76%) whilst there were 3 bilineage and 1 trilineage responses at week 12. 

Eltrombopag was discontinued after 16 weeks if no haematological response or transfusion 

independence was observed. Patients who responded continued therapy in an extension phase of the 

study. A total of 14 patients entered the extension phase of the trial. Nine of these patients achieved a 

multi-lineage response, 4 of the 9 remain on treatment and 5 tapered off treatment with eltrombopag 

and maintained the response (median follow up: 20.6 months, range: 5.7 to 22.5 months). The 

remaining 5 patients discontinued treatment, three due to relapse at the month 3 extension visit. 

 

During treatment with eltrombopag 59% (23/39) became platelet transfusion independent (28 days 

without platelet transfusion) and 27% (10/37) became RBC transfusion independent (56 days without 

RBC transfusion). The longest platelet transfusion-free period for non-responders was 27 days 

(median). The longest platelet transfusion-free period for responders was 287 days (median). The 

longest RBC transfusion-free period for non-responders was 29 days (median). The longest RBC 

transfusion-free period for responders was 266 days (median). 

 

Over 50% of responders who were transfusion-dependent at baseline, had >80% reduction in both 

platelet and RBC transfusion requirements compared to baseline. 

 

Preliminary results from a supportive study (Study ELT116826), an ongoing non-randomised, 

phase II, single-arm, open-label study in refractory SAA patients, showed consistent results. Data are 

limited to 21 out of the planned 60 patients with haematological responses reported by 52% of patients 

at 6 months. Multilineage responses were reported by 45% of patients. 

 

  



28 

5.2 Pharmacokinetic properties 
 

Pharmacokinetics 

 

The plasma eltrombopag concentration-time data collected in 88 patients with ITP in studies 

TRA100773A and TRA100773B were combined with data from 111 healthy adult subjects in a 

population PK analysis. Plasma eltrombopag AUC(0-) and Cmax estimates for ITP patients are 

presented (Table 8). 

 

Table 8 Geometric mean (95% confidence intervals) of steady-state plasma eltrombopag 

pharmacokinetic parameters in adults with ITP 

 

Eltrombopag dose, once 

daily 

N AUC(0-)a, g.h/ml Cmaxa, g/ml 

30 mg 28 47 (39, 58) 3.78 (3.18, 4.49) 

50 mg 34 108 (88, 134) 8.01 (6.73, 9.53) 

75 mg 26 168 (143, 198) 12.7 (11.0, 14.5) 

a AUC(0-) and Cmax based on population PK post-hoc estimates. 

 

Plasma eltrombopag concentration-time data collected in 590 patients with HCV enrolled in phase III 

studies TPL103922/ENABLE 1 and TPL108390/ENABLE 2 were combined with data from patients 

with HCV enrolled in the phase II study TPL102357 and healthy adult patients in a population PK 

analysis. Plasma eltrombopag Cmax and AUC(0-) estimates for patients with HCV enrolled in the 

phase III studies are presented for each dose studied in Table 9. 
 

Table 9 Geometric mean (95% CI) steady-state plasma eltrombopag pharmacokinetic 

parameters in patients with chronic HCV 

 

Eltrombopag dose 

(once daily) 

N AUC(0-) 

(g.h/ml) 

Cmax 

(g/ml) 

25 mg 330 118 

(109, 128) 

6.40 

(5.97, 6.86) 

50 mg 119 166 

(143, 192) 

9.08 

(7.96, 10.35) 

75 mg 45 301 

(250, 363) 

16.71 

(14.26, 19.58) 

100 mg 96 354 

(304, 411) 

19.19 

(16.81, 21.91) 

Data presented as geometric mean (95% CI). 

AUC (0-) and Cmax based on population PK post-hoc estimates at the highest dose in the data for each 

patient. 

 

Absorption and bioavailability 

 

Eltrombopag is absorbed with a peak concentration occurring 2 to 6 hours after oral administration. 

Administration of eltrombopag concomitantly with antacids and other products containing polyvalent 

cations such as dairy products and mineral supplements significantly reduces eltrombopag exposure 

(see section 4.2). In a relative bioavailability study in adults, the eltrombopag powder for oral 

suspension delivered 22% higher plasma AUC(0-) than the film-coated tablet formulation. The 

absolute oral bioavailability of eltrombopag after administration to humans has not been established. 

Based on urinary excretion and metabolites eliminated in faeces, the oral absorption of drug-related 

material following administration of a single 75 mg eltrombopag solution dose was estimated to be at 

least 52%. 

 



29 

Distribution 

 

Eltrombopag is highly bound to human plasma proteins (>99.9%), predominantly to albumin. 

Eltrombopag is a substrate for BCRP, but is not a substrate for P-glycoprotein or OATP1B1. 

 

Biotransformation 

 

Eltrombopag is primarily metabolised through cleavage, oxidation and conjugation with glucuronic 

acid, glutathione, or cysteine. In a human radiolabel study, eltrombopag accounted for approximately 

64% of plasma radiocarbon AUC0-. Minor metabolites due to glucuronidation and oxidation were 

also detected. In vitro studies suggest that CYP1A2 and CYP2C8 are responsible for oxidative 

metabolism of eltrombopag. Uridine diphosphoglucuronyl transferase UGT1A1 and UGT1A3 are 

responsible for glucuronidation, and bacteria in the lower gastrointestinal tract may be responsible for 

the cleavage pathway. 

 

Elimination 

 

Absorbed eltrombopag is extensively metabolised. The predominant route of eltrombopag excretion is 

via faeces (59%) with 31% of the dose found in the urine as metabolites. Unchanged parent compound 

(eltrombopag) is not detected in urine. Unchanged eltrombopag excreted in faeces accounts for 

approximately 20% of the dose. The plasma elimination half-life of eltrombopag is approximately 

21-32 hours. 

 

Pharmacokinetic interactions 

 

Based on a human study with radiolabelled eltrombopag, glucuronidation plays a minor role in the 

metabolism of eltrombopag. Human liver microsome studies identified UGT1A1 and UGT1A3 as the 

enzymes responsible for eltrombopag glucuronidation. Eltrombopag was an inhibitor of a number of 

UGT enzymes in vitro. Clinically significant drug interactions involving glucuronidation are not 

anticipated due to limited contribution of individual UGT enzymes in the glucuronidation of 

eltrombopag. 

 

Approximately 21% of an eltrombopag dose could undergo oxidative metabolism. Human liver 

microsome studies identified CYP1A2 and CYP2C8 as the enzymes responsible for eltrombopag 

oxidation. Eltrombopag does not inhibit or induce CYP enzymes based on in vitro and in vivo data 

(see section 4.5). 

 

In vitro studies demonstrate that eltrombopag is an inhibitor of the OATP1B1 transporter and an 

inhibitor of the BCRP transporter and eltrombopag increased exposure of the OATP1B1 and BCRP 

substrate rosuvastatin in a clinical drug interaction study (see section 4.5). In clinical studies with 

eltrombopag, a dose reduction of statins by 50% was recommended. 

 

Eltrombopag chelates with polyvalent cations such as iron, calcium, magnesium, aluminium, selenium 

and zinc (see sections 4.2 and 4.5). 

 

In vitro studies demonstrated that eltrombopag is not a substrate for the organic anion transporter 

polypeptide, OATP1B1, but is an inhibitor of this transporter (IC50 value of 2.7 μM (1.2 μg/ml). In 

vitro studies also demonstrated that eltrombopag is a breast cancer resistance protein (BCRP) substrate 

and inhibitor (IC50 value of 2.7 μM (1.2 μg/ml). 

 

  



30 

Special patient populations 

 

Renal impairment 

 

The pharmacokinetics of eltrombopag have been studied after administration of eltrombopag to adult 

patients with renal impairment. Following administration of a single 50 mg dose, the AUC0- of 

eltrombopag was 32% to 36% lower in patients with mild to moderate renal impairment, and 60% 

lower in patients with severe renal impairment compared with healthy volunteers. There was 

substantial variability and significant overlap in exposures between patients with renal impairment and 

healthy volunteers. Unbound eltrombopag (active) concentrations for this highly protein-bound 

medicinal product were not measured. Patients with impaired renal function should use eltrombopag 

with caution and close monitoring, for example by testing serum creatinine and/or urine analysis (see 

section 4.2). The efficacy and safety of eltrombopag have not been established in patients with both 

moderate to severe renal impairment and hepatic impairment. 

 

Hepatic impairment 

 

The pharmacokinetics of eltrombopag have been studied after administration of eltrombopag to adult 

patients with hepatic impairment. Following the administration of a single 50 mg dose, the AUC0- of 

eltrombopag was 41% higher in patients with mild hepatic impairment and 80% to 93% higher in 

patients with moderate to severe hepatic impairment compared with healthy volunteers. There was 

substantial variability and significant overlap in exposures between patients with hepatic impairment 

and healthy volunteers. Unbound eltrombopag (active) concentrations for this highly protein-bound 

medicinal product were not measured. 

 

The influence of hepatic impairment on the pharmacokinetics of eltrombopag following repeat 

administration was evaluated using a population pharmacokinetic analysis in 28 healthy adults and 

714 patients with hepatic impairment (673 patients with HCV and 41 patients with chronic liver 

disease of other aetiology). Of the 714 patients, 642 were with mild hepatic impairment, 67 with 

moderate hepatic impairment, and 2 with severe hepatic impairment. Compared to healthy volunteers, 

patients with mild hepatic impairment had approximately 111% (95% CI: 45% to 283%) higher 

plasma eltrombopag AUC(0-) values and patients with moderate hepatic impairment had 

approximately 183% (95% CI: 90% to 459%) higher plasma eltrombopag AUC(0-) values. 

 

Therefore, eltrombopag should not be used in ITP patients with hepatic impairment (Child-Pugh score 

≥5) unless the expected benefit outweighs the identified risk of portal venous thrombosis (see 

sections 4.2 and 4.4). For patients with HCV initiate eltrombopag at a dose of 25 mg once daily (see 

section 4.2). 

 

Race 

 

The influence of Asian ethnicity (such as Japanese, Chinese, Taiwanese and Korean) on the 

pharmacokinetics of eltrombopag was evaluated using a population pharmacokinetic analysis in 111 

healthy adults (31 Asians) and 88 patients with ITP (18 Asians). Based on estimates from the 

population pharmacokinetic analysis, Asian ITP patients had approximately 49% higher plasma 

eltrombopag AUC(0-) values as compared to non-Asian patients who were predominantly Caucasian 

(see section 4.2). 

 

The influence of Asian ethnicity (such as Chinese, Japanese, Taiwanese, Korean, and Thai) on the 

pharmacokinetics of eltrombopag was evaluated using a population pharmacokinetic analysis in 

635 patients with HCV (145 Asians and 69 South Asians). Based on estimates from the population 

pharmacokinetic analysis, Asian patients had approximately 55% higher plasma eltrombopag AUC(0-) 

values as compared to patients of other races who were predominantly Caucasian (see section 4.2). 

 

  



31 

Gender 

 

The influence of gender on the pharmacokinetics of eltrombopag was evaluated using a population 

pharmacokinetic analysis in 111 healthy adults (14 females) and 88 patients with ITP (57 females). 

Based on estimates from the population pharmacokinetic analysis, female ITP patients had 

approximately 23% higher plasma eltrombopag AUC(0-) as compared to male patients, without 

adjustment for body weight differences. 

 

The influence of gender on eltrombopag pharmacokinetics was evaluated using population 

pharmacokinetics analysis in 635 patients with HCV (260 females). Based on model estimate, female 

HCV patient had approximately 41% higher plasma eltrombopag AUC(0-) as compared to male 

patients. 

 

Age 

 

The influence of age on eltrombopag pharmacokinetics was evaluated using population 

pharmacokinetics analysis in 28 healthy subjects, 673 patients with HCV, and 41 patients with chronic 

liver disease of other aetiology ranging from 19 to 74 years old. There are no PK data on the use of 

eltrombopag in patients ≥75 years. Based on model estimate, elderly (≥65 years) patients had 

approximately 41% higher plasma eltrombopag AUC(0-) as compared to younger patients (see 

section 4.2). 

 

Paediatric population (aged 1 to 17 years) 

 

The pharmacokinetics of eltrombopag have been evaluated in 168 paediatric ITP patients dosed once 

daily in two studies, TRA108062/PETIT and TRA115450/PETIT-2. Plasma eltrombopag apparent 

clearance following oral administration (CL/F) increased with increasing body weight. The effects of 

race and sex on plasma eltrombopag CL/F estimates were consistent between paediatric and adult 

patients. Asian paediatric ITP patients had approximately 43% higher plasma eltrombopag AUC(0-) 

values as compared to non-Asian patients. Female paediatric ITP patients had approximately 25% 

higher plasma eltrombopag AUC(0-) values as compared to male patients. 

 

The pharmacokinetic parameters of eltrombopag in paediatric patients with ITP are shown in 

Table 10. 

 

Table 10 Geometric mean (95% CI) steady-state plasma eltrombopag pharmacokinetic 

parameters in paediatric patients with ITP (50 mg once daily dosing regimen) 

 

Age Cmax 
(µg/ml) 

AUC(0-) 
(µg.hr/ml) 

12 to 17 years (n=62) 6.80 

(6.17, 7.50) 

103 

(91.1, 116) 

6 to 11 years (n=68) 10.3 

(9.42, 11.2) 

153 

(137, 170) 

1 to 5 years (n=38) 11.6 

(10.4, 12.9) 

162 

(139, 187) 

Data presented as geometric mean (95%CI). AUC(0-) and Cmax based on population PK post-hoc 

estimates 

 

  



32 

5.3 Preclinical safety data 
 

Safety pharmacology and repeat-dose toxicity 

 

Eltrombopag does not stimulate platelet production in mice, rats or dogs because of unique TPO 

receptor specificity. Therefore, data from these animals do not fully model potential adverse effects 

related to the pharmacology of eltrombopag in humans, including the reproduction and carcinogenicity 

studies. 

 

Treatment-related cataracts were detected in rodents and were dose and time-dependent. At ≥6 times 

the human clinical exposure in adult ITP patients at 75 mg/day and 3 times the human clinical 

exposure in adult HCV patients at 100 mg/day, based on AUC, cataracts were observed in mice after 

6 weeks and rats after 28 weeks of dosing. At 4 times the human clinical exposure in ITP patients at 

75 mg/day and 2 times the human exposure in HCV patients at 100 mg/day, based on AUC, cataracts 

were observed in mice after 13 weeks and in rats after 39 weeks of dosing. At non-tolerated doses in 

pre-weaning juvenile rats dosed from Days 4-32 (approximately equating to a 2-year-old human at the 

end of the dosing period), ocular opacities were observed (histology not performed) at 9 times the 

maximum human clinical exposure in paediatric ITP patients at 75 mg/day, based on AUC. However, 

cataracts were not observed in juvenile rats given tolerated doses at 5 times the human clinical 

exposure in paediatric ITP patients, based on AUC. Cataracts have not been observed in adult dogs 

after 52 weeks of dosing at 2 times the human clinical exposure in adult or paediatric ITP patients at 

75 mg/day and equivalent to the human clinical exposure in HCV patients at 100 mg/day, based on 

AUC). 

 

Renal tubular toxicity was observed in studies of up to 14 days duration in mice and rats at exposures 

that were generally associated with morbidity and mortality. Tubular toxicity was also observed in a 

2-year oral carcinogenicity study in mice at doses of 25, 75 and 150 mg/kg/day. Effects were less 

severe at lower doses and were characterised by a spectrum of regenerative changes. The exposure at 

the lowest dose was 1.2 or 0.8 times the human clinical exposure based on AUC in adult or paediatric 

ITP patients at 75 mg/day and 0.6 times the human clinical exposure in HCV patients at 100 mg/day, 

based on AUC. Renal effects were not observed in rats after 28 weeks or in dogs after 52 weeks at 

exposures 4 and 2 times the human clinical exposure in adult ITP patients and 3 and 2 times the 

human clinical exposure in paediatric ITP patients at 75 mg/day and 2 times and equivalent to the 

human clinical exposure in HCV patients at 100 mg/day, based on AUC. 

 

Hepatocyte degeneration and/or necrosis, often accompanied by increased serum liver enzymes, was 

observed in mice, rats and dogs at doses that were associated with morbidity and mortality or were 

poorly tolerated. No hepatic effects were observed after chronic dosing in rats (28 weeks) and in dogs 

(52 weeks) at 4 or 2 times the human clinical exposure in adult ITP patients and 3 or 2 times the 

human clinical exposure in paediatric ITP patients at 75 mg/day and 2 times or equivalent to the 

human clinical exposure in HCV patients at 100 mg/day, based on AUC. 

 

At poorly tolerated doses in rats and dogs (>10 or 7 times the human clinical exposure in adult or 

paediatric ITP patients at 75 mg/day and>4 times the human clinical exposure in HCV patients at 

100 mg/day, based on AUC), decreased reticulocyte counts and regenerative bone marrow erythroid 

hyperplasia (rats only) were observed in short-term studies. There were no effects of note on red cell 

mass or reticulocyte counts after dosing for up to 28 weeks in rats, 52 weeks in dogs and 2 years in 

mice or rats at maximally tolerated doses which were 2 to 4 times human clinical exposure in adult or 

paediatric ITP patients at 75 mg/day and ≤2 times the human clinical exposure in HCV patients at 

100 mg/day, based on AUC. 

 

Endosteal hyperostosis was observed in a 28-week toxicity study in rats at a non-tolerated dose of 

60 mg/kg/day (6 times or 4 times the human clinical exposure in adult or paediatric ITP patients at 

75 mg/day and 3 times the human clinical exposure in HCV patients at 100 mg/day, based on AUC). 

There were no bone changes observed in mice or rats after lifetime exposure (2 years) at 4 times or 

2 times the human clinical exposure in adult or paediatric ITP patients at 75 mg/day and 2 times the 

human clinical exposure in HCV patients at 100 mg/day, based on AUC. 



33 

 

Carcinogenicity and mutagenicity 

 

Eltrombopag was not carcinogenic in mice at doses up to 75 mg/kg/day or in rats at doses up to 

40 mg/kg/day (exposures up to 4 or 2 times the human clinical exposure in adult or paediatric ITP 

patients at 75 mg/day and 2 times the human clinical exposure in HCV patients at 100 mg/day, based 

on AUC). Eltrombopag was not mutagenic or clastogenic in a bacterial mutation assay or in two in 

vivo assays in rats (micronucleus and unscheduled DNA synthesis, 10 times or 8 times the human 

clinical exposure in adult or paediatric ITP patients at 75 mg/day and 7 times the human clinical 

exposure in HCV patients at 100 mg/day, based on Cmax). In the in vitro mouse lymphoma assay, 

eltrombopag was marginally positive (<3-fold increase in mutation frequency). These in vitro and in 

vivo findings suggest that eltrombopag does not pose a genotoxic risk to humans. 

 

Reproductive toxicity 

 

Eltrombopag did not affect female fertility, early embryonic development or embryofoetal 

development in rats at doses up to 20 mg/kg/day (2 times the human clinical exposure in adult or 

adolescent (12-17 years old) ITP patients at 75 mg/day and equivalent to the human clinical exposure 

in HCV patients at 100 mg/day, based on AUC). Also there was no effect on embryofoetal 

development in rabbits at doses up to 150 mg/kg/day, the highest dose tested (0.3 to 0.5 times the 

human clinical exposure in ITP patients at 75 mg/day and HCV patients at 100 mg/day, based on 

AUC). However, at a maternally toxic dose of 60 mg/kg/day (6 times the human clinical exposure in 

ITP patients at 75 mg/day and 3 times the human clinical exposure in HCV patients at 100 mg/day, 

based on AUC) in rats, eltrombopag treatment was associated with embryo lethality (increased pre- 

and post-implantation loss), reduced foetal body weight and gravid uterine weight in the female 

fertility study and a low incidence of cervical ribs and reduced foetal body weight in the embryofoetal 

development study. Eltrombopag should be used during pregnancy only if the expected benefit 

justifies the potential risk to the foetus (see section 4.6). Eltrombopag did not affect male fertility in 

rats at doses up to 40 mg/kg/day, the highest dose tested (3 times the human clinical exposure in ITP 

patients at 75 mg/day and 2 times the human clinical exposure in HCV patients at 100 mg/day, based 

on AUC). In the pre- and post-natal development study in rats, there were no undesirable effects on 

pregnancy, parturition or lactation of F0 female rats at maternally non-toxic doses (10 and 

20 mg/kg/day) and no effects on the growth, development, neurobehavioural or reproductive function 

of the offspring (F1). Eltrombopag was detected in the plasma of all F1 rat pups for the entire 22 hour 

sampling period following administration of medicinal product to the F0 dams, suggesting that rat pup 

exposure to eltrombopag was likely via lactation. 

 

Phototoxicity 

 

In vitro studies with eltrombopag suggest a potential phototoxicity risk; however, in rodents there was 

no evidence of cutaneous phototoxicity (10 or 7 times the human clinical exposure in adult or 

paediatric ITP patients at 75 mg/day and 5 times the human clinical exposure in HCV patients at 

100 mg/day, based on AUC) or ocular phototoxicity (4 times the human clinical exposure in adult or 

paediatric ITP patients at 75 mg/day and 3 times the human clinical exposure in HCV patients at 

100 mg/day, based on AUC). Furthermore, a clinical pharmacology study in 36 subjects showed no 

evidence that photosensitivity was increased following administration of eltrombopag 75 mg. This was 

measured by delayed phototoxic index. Nevertheless, a potential risk of photoallergy cannot be ruled 

out since no specific preclinical study could be performed. 

 

Juvenile animal studies 

 

At non-tolerated doses in pre-weaning rats, ocular opacities were observed. At tolerated doses, no 

ocular opacities were observed (see above subsection ‘Safety pharmacology and repeat-dose toxicity’). 

In conclusion, taking into account the exposure margins based on AUC, a risk of eltrombopag-related 

cataracts in paediatric patients cannot be excluded. There are no findings in juvenile rats to suggest a 

greater risk of toxicity with eltrombopag treatment in paediatric vs. adult ITP patients. 

 



34 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Revolade 12.5 mg film-coated tablets 

Tablet core 

Magnesium stearate 

Mannitol (E421) 

Microcrystalline cellulose 

Povidone 

Sodium starch glycolate 

 

Tablet coating 

Hypromellose (E464) 

Macrogol 400 (E1521) 

Polysorbate 80 (E433) 

Titanium dioxide (E171) 

 

Revolade 25 mg film-coated tablets 

Tablet core 

Magnesium stearate 

Mannitol (E421) 

Microcrystalline cellulose 

Povidone 

Sodium starch glycolate 

 

Tablet coating 

Hypromellose (E464) 

Macrogol 400 (E1521) 

Polysorbate 80 (E433) 

Titanium dioxide (E171) 

 

Revolade 50 mg film-coated tablets 

Tablet core 

Magnesium stearate 

Mannitol (E421) 

Microcrystalline cellulose 

Povidone 

Sodium starch glycolate 

 

Tablet coating 

Hypromellose (E464) 

Iron oxide red (E172) 

Iron oxide yellow (E172) 

Macrogol 400 (E1521) 

Titanium dioxide (E171) 

 

  



35 

Revolade 75 mg film-coated tablets 

Tablet core 

Magnesium stearate 

Mannitol (E421) 

Microcrystalline cellulose 

Povidone 

Sodium starch glycolate 

 

Tablet coating 

Hypromellose (E464) 

Iron oxide red (E172) 

Iron oxide black (E172) 

Macrogol 400 (E1521) 

Titanium dioxide (E171) 

 

6.2 Incompatibilities 
 

Not applicable. 

 

6.3 Shelf life 
 

4 years. 

 

6.4 Special precautions for storage 
 

This medicinal product does not require any special storage conditions. 

 

6.5 Nature and contents of container 

 

Film-coated tablets 

Aluminum blisters (PA/Alu/PVC/Alu) in a carton containing 14 or 28 film-coated tablets and 

multipacks containing 84 (3 packs of 28) film-coated tablets. 

 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal 
 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

  



36 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

Revolade 12.5 mg film-coated tablets 

EU/1/10/612/010 

EU/1/10/612/011 

EU/1/10/612/012 

 

Revolade 25 mg film-coated tablets 

EU/1/10/612/001 

EU/1/10/612/002 

EU/1/10/612/003 

 

Revolade 50 mg film-coated tablets 

EU/1/10/612/004 

EU/1/10/612/005 

EU/1/10/612/006 

 

Revolade 75 mg film-coated tablets 

EU/1/10/612/007 

EU/1/10/612/008 

EU/1/10/612/009 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 11 March 2010 

Date of latest renewal: 15 January 2015 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu/. 



37 

1. NAME OF THE MEDICINAL PRODUCT 
 

Revolade 25 mg powder for oral suspension 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

Each sachet contains eltrombopag olamine equivalent to 25 mg of eltrombopag. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Powder for oral suspension 

 

Reddish-brown to yellow powder. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Revolade is indicated for the treatment of patients aged 1 year and above with primary immune 

thrombocytopenia (ITP) lasting 6 months or longer from diagnosis and who are refractory to other 

treatments (e.g. corticosteroids, immunoglobulins) (see sections 4.2 and 5.1). 

 

Revolade is indicated in adult patients with chronic hepatitis C virus (HCV) infection for the treatment 

of thrombocytopenia, where the degree of thrombocytopenia is the main factor preventing the 

initiation or limiting the ability to maintain optimal interferon-based therapy (see sections 4.4 and 5.1). 

 

Revolade is indicated in adult patients with acquired severe aplastic anaemia (SAA) who were either 

refractory to prior immunosuppressive therapy or heavily pretreated and are unsuitable for 

haematopoietic stem cell transplantation (see section 5.1). 

 

4.2 Posology and method of administration 

 

Eltrombopag treatment should be initiated by and remain under the supervision of a physician who is 

experienced in the treatment of haematological diseases or the management of chronic hepatitis C and 

its complications. 

 

Posology 

 

Eltrombopag dosing requirements must be individualised based on the patient’s platelet counts. The 

objective of treatment with eltrombopag should not be to normalise platelet counts. 

 

The powder for oral suspension may lead to higher eltrombopag exposure than the tablet formulation 

(see section 5.2). When switching between the tablet and powder for oral suspension formulations, 

platelet counts should be monitored weekly for 2 weeks. 

 

Immune (primary) thrombocytopenia 

 

The lowest dose of eltrombopag to achieve and maintain a platelet count ≥50,000/µl should be used. 

Dose adjustments are based upon the platelet count response. Eltrombopag must not be used to 

normalise platelet counts. In clinical studies, platelet counts generally increased within 1 to 2 weeks 

after starting eltrombopag and decreased within 1 to 2 weeks after discontinuation. 

 



38 

Adults and paediatric population aged 6 to 17 years 

The recommended starting dose of eltrombopag is 50 mg once daily. For patients of Asian ancestry 

(such as Chinese, Japanese, Taiwanese, Korean or Thai), eltrombopag should be initiated at a reduced 

dose of 25 mg once daily (see section 5.2). 

 

Paediatric population aged 1 to 5 years 

The recommended starting dose of eltrombopag is 25 mg once daily. 

 

Monitoring and dose adjustment 

After initiating eltrombopag, the dose must be adjusted to achieve and maintain a platelet count 

≥50,000/µl as necessary to reduce the risk for bleeding. A daily dose of 75 mg must not be exceeded. 

 

Clinical haematology and liver tests should be monitored regularly throughout therapy with 

eltrombopag and the dose regimen of eltrombopag modified based on platelet counts as outlined in 

Table 1. During therapy with eltrombopag full blood counts (FBCs), including platelet count and 

peripheral blood smears, should be assessed weekly until a stable platelet count (≥50,000/µl for at 

least 4 weeks) has been achieved. FBCs including platelet counts and peripheral blood smears should 

be obtained monthly thereafter. 

 

Table 1 Dose adjustments of eltrombopag in ITP patients 

 

Platelet count Dose adjustment or response 

<50,000/µl following at least 

2 weeks of therapy 

Increase daily dose by 25 mg to a maximum of 75 mg/day*. 

50,000/µl to 150,000/µl Use lowest dose of eltrombopag and/or concomitant ITP 

treatment to maintain platelet counts that avoid or reduce 

bleeding. 

>150,000/µl to 250,000/µl Decrease the daily dose by 25 mg. Wait 2 weeks to assess the 

effects of this and any subsequent dose adjustments♦. 

>250,000/µl Stop eltrombopag; increase the frequency of platelet monitoring 

to twice weekly. 

 

Once the platelet count is ≤100,000/µl, reinitiate therapy at a 

daily dose reduced by 25 mg. 

* For patients taking 25 mg eltrombopag once every other day, increase dose to 25 mg once daily. 

♦ For patients taking 25 mg eltrombopag once daily, consideration should be given to dosing at 

12.5 mg once daily or alternatively a dose of 25 mg once every other day. 

 

Eltrombopag can be administered in addition to other ITP medicinal products. The dose regimen of 

concomitant ITP medicinal products should be modified, as medically appropriate, to avoid excessive 

increases in platelet counts during therapy with eltrombopag. 

 

It is necessary to wait for at least 2 weeks to see the effect of any dose adjustment on the patient’s 

platelet response prior to considering another dose adjustment. 

 

The standard eltrombopag dose adjustment, either decrease or increase, would be 25 mg once daily. 

 

Discontinuation 

Treatment with eltrombopag should be discontinued if the platelet count does not increase to a level 

sufficient to avoid clinically important bleeding after 4 weeks of eltrombopag therapy at 75 mg once 

daily. 

 

Patients should be clinically evaluated periodically and continuation of treatment should be decided on 

an individual basis by the treating physician. In non-splenectomised patients this should include 

evaluation relative to splenectomy. The reoccurrence of thrombocytopenia is possible upon 

discontinuation of treatment (see section 4.4). 

 



39 

Chronic hepatitis C (HCV) associated thrombocytopenia 

 

When eltrombopag is given in combination with antivirals reference should be made to the full 

summary of product characteristics of the respective coadministered medicinal products for 

comprehensive details of relevant safety information or contraindications. 

 

In clinical studies, platelet counts generally began to increase within 1 week of starting eltrombopag. 

The aim of treatment with eltrombopag should be to achieve the minimum level of platelet counts 

needed to initiate antiviral therapy, in adherence to clinical practice recommendations. During antiviral 

therapy, the aim of treatment should be to keep platelet counts at a level that prevents the risk of 

bleeding complications, normally around 50,000-75,000/µl. Platelet counts >75,000/µl should be 

avoided. The lowest dose of eltrombopag needed to achieve the targets should be used. Dose 

adjustments are based upon the platelet count response. 

 

Initial dose regimen 

Eltrombopag should be initiated at a dose of 25 mg once daily. No dosage adjustment is necessary for 

HCV patients of Asian ancestry or patients with mild hepatic impairment (see section 5.2). 

 

Monitoring and dose adjustment 

The dose of eltrombopag should be adjusted in 25 mg increments every 2 weeks as necessary to 

achieve the target platelet count required to initiate antiviral therapy. Platelet counts should be 

monitored every week prior to starting antiviral therapy. On initiation of antiviral therapy the platelet 

count may fall, so immediate eltrombopag dose adjustments should be avoided (see Table 2). 

 

During antiviral therapy, the dose of eltrombopag should be adjusted as necessary to avoid dose 

reductions of peginterferon due to decreasing platelet counts that may put patients at risk of bleeding 

(see Table 2). Platelet counts should be monitored weekly during antiviral therapy until a stable 

platelet count is achieved, normally around 50,000-75,000/µl. FBCs including platelet counts and 

peripheral blood smears should be obtained monthly thereafter. Dose reductions on the daily dose by 

25 mg should be considered if platelet counts exceed the required target. It is recommended to wait for 

2 weeks to assess the effects of this and any subsequent dose adjustments. 

 

A dose of 100 mg eltrombopag once daily must not be exceeded. 

 

Table 2 Dose adjustments of eltrombopag in HCV patients during antiviral therapy 

 

Platelet count Dose adjustment or response 

<50,000/µl following at least 

2 weeks of therapy 

Increase daily dose by 25 mg to a maximum of 100 mg/day. 

≥50,000/µl to ≤100,000/µl Use lowest dose of eltrombopag as necessary to avoid dose 

reductions of peginterferon. 

>100,000/µl to ≤150,000/µl Decrease the daily dose by 25 mg. Wait 2 weeks to assess the 

effects of this and any subsequent dose adjustments♦. 

>150,000/µl Stop eltrombopag; increase the frequency of platelet monitoring to 

twice weekly. 

 

Once the platelet count is ≤100,000/µl, reinitiate therapy at a daily 

dose reduced by 25 mg*. 

* For patients taking 25 mg eltrombopag once daily, consideration should be given to reinitiating 

dosing at 25 mg every other day. 
♦ On initiation of antiviral therapy the platelet count may fall, so immediate eltrombopag dose 

reductions should be avoided. 

 

  



40 

Discontinuation 

If after 2 weeks of eltrombopag therapy at 100 mg the required platelet level to initiate antiviral 

therapy is not achieved, eltrombopag should be discontinued. 

 

Eltrombopag treatment should be terminated when antiviral therapy is discontinued unless otherwise 

justified. Excessive platelet count responses or important liver test abnormalities also necessitate 

discontinuation. 

 

Severe aplastic anaemia 

 

Initial dose regimen 

Eltrombopag should be initiated at a dose of 50 mg once daily. For patients of Asian ancestry, 

eltrombopag should be initiated at a reduced dose of 25 mg once daily (see section 5.2). The treatment 

should not be initiated when the patients has existing cytogenetic abnormalities of chromosome 7. 

 

Monitoring and dose adjustment 

Haematological response requires dose titration, generally up to 150 mg, and may take up to 16 weeks 

after starting eltrombopag (see section 5.1). The dose of eltrombopag should be adjusted in 50 mg 

increments every 2 weeks as necessary to achieve the target platelet count ≥50,000/µl. For patients 

taking 25 mg once daily, the dose should be increased to 50 mg daily before increasing the dose 

amount by 50 mg. A dose of 150 mg daily must not be exceeded. Clinical haematology and liver tests 

should be monitored regularly throughout therapy with eltrombopag and the dosage regimen of 

eltrombopag modified based on platelet counts as outlined in Table 3. 

 

Table 3 Dose adjustments of eltrombopag in patients with severe aplastic anaemia 

 

Platelet count Dose adjustment or response 

<50,000/µl following at least 

2 weeks of therapy 

Increase daily dose by 50 mg to a maximum of 150 mg/day. 

 

For patients taking 25 mg once daily, increase the dose to 

50 mg daily before increasing the dose amount by 50 mg. 

50,000/µl to 150,000/µl Use lowest dose of eltrombopag to maintain platelet counts. 

>150,000/µl to 250,000/µl Decrease the daily dose by 50 mg. Wait 2 weeks to assess the 

effects of this and any subsequent dose adjustments. 

>250,000/µl Stop eltrombopag; for at least one week. 

 

Once the platelet count is ≤100,000/µl, reinitiate therapy at a 

daily dose reduced by 50 mg. 

 

Tapering for tri-lineage (white blood cells, red blood cells, and platelets) responders 

For patients who achieve tri-lineage response, including transfusion independence, lasting at least 

8 weeks: the dose of eltrombopag may be reduced by 50%. 

 

If counts remain stable after 8 weeks at the reduced dose, then eltrombopag must be discontinued and 

blood counts monitored. If platelet counts drop to <30,000/µl, haemoglobin drops to <9 g/dl or 

absolute neutrophil count (ANC) to <0.5 x 109/l, eltrombopag may be reinitiated at the previous 

effective dose. 

 

Discontinuation 

If no haematological response has occurred after 16 weeks of therapy with eltrombopag, therapy 

should be discontinued. If new cytogenetic abnormalities are detected, it must be evaluated whether 

continuation of eltrombopag is appropriate (see sections 4.4 and 4.8). Excessive platelet count 

responses (as outlined in Table 3) or important liver test abnormalities also necessitate discontinuation 

of eltrombopag (see section 4.8). 

 



41 

Special populations 

 

Renal impairment 

No dose adjustment is necessary in patients with renal impairment. Patients with impaired renal 

function should use eltrombopag with caution and close monitoring, for example by testing serum 

creatinine and/or performing urine analysis (see section 5.2). 

 

Hepatic impairment 

Eltrombopag should not be used in ITP patients with hepatic impairment (Child-Pugh score ≥5) unless 

the expected benefit outweighs the identified risk of portal venous thrombosis (see section 4.4). 

 

If the use of eltrombopag is deemed necessary for ITP patients with hepatic impairment the starting 

dose must be 25 mg once daily. After initiating the dose of eltrombopag in patients with hepatic 

impairment an interval of 3 weeks should be observed before increasing the dose. 

 

No dose adjustment is required for thrombocytopenic patients with chronic HCV and mild hepatic 

impairment (Child-Pugh score ≤6). Chronic HCV patients and severe aplastic anaemia patients with 

hepatic impairment should initiate eltrombopag at a dose of 25 mg once daily (see section 5.2). After 

initiating the dose of eltrombopag in patients with hepatic impairment an interval of 2 weeks should be 

observed before increasing the dose. 

 

There is an increased risk for adverse events, including hepatic decompensation and thromboembolic 

events, in thrombocytopenic patients with advanced chronic liver disease treated with eltrombopag, 

either in preparation for invasive procedure or in HCV patients undergoing antiviral therapy (see 

sections 4.4 and 4.8). 

 

Elderly 

There are limited data on the use of eltrombopag in ITP patients aged 65 years and older and no 

clinical experience in ITP patients aged over 85 years. In the clinical studies of eltrombopag, overall 

no clinically significant differences in safety of eltrombopag were observed between patients aged at 

least 65 years and younger patients. Other reported clinical experience has not identified differences in 

responses between the elderly and younger patients, but greater sensitivity of some older individuals 

cannot be ruled out (see section 5.2). 

 

There are limited data on the use of eltrombopag in HCV and SAA patients aged over 75 years. 

Caution should be exercised in these patients (see section 4.4). 

 

Asian patients 

For patients of Asian ancestry (such as Chinese, Japanese, Taiwanese, Korean or Thai), including 

those with hepatic impairment, eltrombopag should be initiated at a dose of 25 mg once daily (see 

section 5.2). 

 

Patient platelet count should continue to be monitored and the standard criteria for further dose 

modification followed. 

 

Paediatric population 

Revolade is not recommended for use in children under the age of one year with ITP due to 

insufficient data on safety and efficacy. The safety and efficacy of eltrombopag has not been 

established in children and adolescents (<18 years) with chronic HCV related thrombocytopenia or 

SAA. No data are available. 

 

  



42 

Method of administration (see section 6.6) 

 

Oral use. 

The suspension should be taken at least two hours before or four hours after any products such as 

antacids, dairy products (or other calcium containing food products), or mineral supplements 

containing polyvalent cations (e.g. iron, calcium, magnesium, aluminium, selenium and zinc) (see 

sections 4.5 and 5.2). 

 

4.3 Contraindications 
 

Hypersensitivity to eltrombopag or to any of the excipients listed in section 6.1. 

 

4.4 Special warnings and precautions for use 

 

There is an increased risk for adverse reactions, including potentially fatal hepatic decompensation and 

thromboembolic events, in thrombocytopenic HCV patients with advanced chronic liver disease, as 

defined by low albumin levels ≤35 g/l or model for end stage liver disease (MELD) score ≥10, when 

treated with eltrombopag in combination with interferon-based therapy. In addition, the benefits of 

treatment in terms of the proportion achieving sustained virological response (SVR) compared with 

placebo were modest in these patients (especially for those with baseline albumin ≤35 g/l) compared 

with the group overall. Treatment with eltrombopag in these patients should be initiated only by 

physicians experienced in the management of advanced HCV, and only when the risks of 

thrombocytopenia or withholding antiviral therapy necessitate intervention. If treatment is considered 

clinically indicated, close monitoring of these patients is required. 

 

Combination with direct-acting antiviral agents 

 

Safety and efficacy have not been established in combination with direct-acting antiviral agents 

approved for treatment of chronic hepatitis C infection. 

 

Risk of hepatotoxicity 

 

Eltrombopag administration can cause abnormal liver function and severe hepatotoxicity, which might 

be life-threatening (see section 4.8). 

 

Serum alanine aminotransferase (ALT), aspartate aminotrasferase (AST) and bilirubin should be 

measured prior to initiation of eltrombopag, every 2 weeks during the dose adjustment phase and 

monthly following establishment of a stable dose. Eltrombopag inhibits UGT1A1 and OATP1B1, 

which may lead to indirect hyperbilirubinaemia. If bilirubin is elevated fractionation should be 

performed. Abnormal serum liver tests should be evaluated with repeat testing within 3 to 5 days. If 

the abnormalities are confirmed, serum liver tests should be monitored until the abnormalities resolve, 

stabilise, or return to baseline levels. Eltrombopag should be discontinued if ALT levels increase 

(3 times the upper limit of normal [x ULN] in patients with normal liver function, or ≥3 x baseline or 

>5 x ULN, whichever is the lower, in patients with pre-treatment elevations in transaminases) and are: 

 progressive, or 

 persistent for ≥4 weeks, or 

 accompanied by increased direct bilirubin, or 

 accompanied by clinical symptoms of liver injury or evidence for hepatic decompensation. 
 

Caution is required when administering eltrombopag to patients with hepatic disease. In ITP and SAA 

patients a lower starting dose of eltrombopag should be used. Close monitoring is required when 

administering to patients with hepatic impairment (see section 4.2). 

 

  



43 

Hepatic decompensation (use with interferon) 

 

Hepatic decompensation in patients with chronic hepatitis C: Monitoring is required in patients with 

low albumin levels (≤35 g/l) or with MELD score ≥10 at baseline. 

 

Chronic HCV patients with cirrhosis may be at risk of hepatic decompensation when receiving alfa 

interferon therapy. In 2 controlled clinical studies in thrombocytopenic patients with HCV, hepatic 

decompensation (ascites, hepatic encephalopathy, variceal haemorrhage, spontaneous bacterial 

peritonitis) occurred more frequently in the eltrombopag arm (11%) than in the placebo arm (6%). In 

patients with low albumin levels (≤35 g/l) or with a MELD score ≥10 at baseline, there was a 3-fold 

greater risk of hepatic decompensation and an increase in the risk of a fatal adverse event compared to 

those with less advanced liver disease. In addition, the benefits of treatment in terms of the proportion 

achieving SVR compared with placebo were modest in these patients (especially for those with 

baseline albumin ≤35 g/l) compared with the group overall. Eltrombopag should only be administered 

to such patients after careful consideration of the expected benefits in comparison with the risks. 

Patients with these characteristics should be closely monitored for signs and symptoms of hepatic 

decompensation. The respective interferon summary of product characteristics should be referenced 

for discontinuation criteria. Eltrombopag should be terminated if antiviral therapy is discontinued for 

hepatic decompensation. 

 

Thrombotic/thromboembolic complications 

 

In controlled studies in thrombocytopenic patients with HCV receiving interferon-based therapy 

(n=1,439), 38 out of 955 patients (4%) treated with eltrombopag and 6 out of 484 patients (1%) in the 

placebo group experienced thromboembolic events (TEEs). Reported thrombotic/thromboembolic 

complications included both venous and arterial events. The majority of TEEs were non-serious and 

resolved by the end of the study. Portal vein thrombosis was the most common TEE in both treatment 

groups (2% in patients treated with eltrombopag versus <1% for placebo). No specific temporal 

relationship between start of treatment and event of TEE were observed. Patients with low albumin 

levels (≤35 g/l) or MELD ≥10 had a 2-fold greater risk of TEEs than those with higher albumin levels; 

those aged ≥60 years had a 2-fold greater risk of TEEs compared to younger patients. Eltrombopag 

should only be administered to such patients after careful consideration of the expected benefits in 

comparison with the risks. Patients should be closely monitored for signs and symptoms of TEE. 

 

The risk of TEEs has been found to be increased in patients with chronic liver disease (CLD) treated 

with 75 mg eltrombopag once daily for 2 weeks in preparation for invasive procedures. Six of 143 

(4%) adult patients with CLD receiving eltrombopag experienced TEEs (all of the portal venous 

system) and 2 of 145 (1%) patients in the placebo group experienced TEEs (one in the portal venous 

system and one myocardial infarction). Five of the 6 patients treated with eltrombopag experienced the 

thrombotic complication at a platelet count >200,000/µl and within 30 days of the last dose of 

eltrombopag. Eltrombopag is not indicated for the treatment of thrombocytopenia in patients with 

chronic liver disease in preparation for invasive procedures. 

 

In eltrombopag clinical studies in ITP thromboembolic events were observed at low and normal 

platelet counts. Caution should be used when administering eltrombopag to patients with known risk 

factors for thromboembolism including but not limited to inherited (e.g. Factor V Leiden) or acquired 

risk factors (e.g. ATIII deficiency, antiphospholipid syndrome), advanced age, patients with prolonged 

periods of immobilisation, malignancies, contraceptives and hormone replacement therapy, 

surgery/trauma, obesity and smoking. Platelet counts should be closely monitored and consideration 

given to reducing the dose or discontinuing eltrombopag treatment if the platelet count exceeds the 

target levels (see section 4.2). The risk-benefit balance should be considered in patients at risk of TEEs 

of any aetiology. 

 

No case of TEE was identified from a clinical study in refractory SAA, however the risk of these 

events cannot be excluded in this patient population due to the limited number of exposed patients. As 

the highest authorised dose is indicated for patients with SAA (150 mg/day) and due to the nature of 

the reaction, TEEs might be expected in this patient population. 



44 

 

Eltrombopag should not be used in ITP patients with hepatic impairment (Child-Pugh score ≥5) unless 

the expected benefit outweighs the identified risk of portal venous thrombosis. When treatment is 

considered appropriate, caution is required when administering eltrombopag to patients with hepatic 

impairment (see sections 4.2 and 4.8). 

 

Bleeding following discontinuation of eltrombopag 

 

Thrombocytopenia is likely to reoccur in ITP patients upon discontinuation of treatment with 

eltrombopag. Following discontinuation of eltrombopag, platelet counts return to baseline levels 

within 2 weeks in the majority of patients, which increases the bleeding risk and in some cases may 

lead to bleeding. This risk is increased if eltrombopag treatment is discontinued in the presence of 

anticoagulants or anti-platelet agents. It is recommended that, if treatment with eltrombopag is 

discontinued, ITP treatment be restarted according to current treatment guidelines. Additional medical 

management may include cessation of anticoagulant and/or anti-platelet therapy, reversal of 

anticoagulation, or platelet support. Platelet counts must be monitored weekly for 4 weeks following 

discontinuation of eltrombopag. 

 

In HCV clinical studies, a higher incidence of gastrointestinal bleeding, including serious and fatal 

cases, was reported following discontinuation of peginterferon, ribavirin, and eltrombopag. Following 

discontinuation of therapy, patients should be monitored for any signs or symptoms of gastrointestinal 

bleeding. 

 

Bone marrow reticulin formation and risk of bone marrow fibrosis 

 

Eltrombopag may increase the risk for development or progression of reticulin fibres within the bone 

marrow. The relevance of this finding, as with other thrombopoietin receptor (TPO-R) agonists, has 

not been established yet. 

 

Prior to initiation of eltrombopag, the peripheral blood smear should be examined closely to establish 

a baseline level of cellular morphologic abnormalities. Following identification of a stable dose of 

eltrombopag, full blood count (FBC) with white blood cell count (WBC) differential should be 

performed monthly. If immature or dysplastic cells are observed, peripheral blood smears should be 

examined for new or worsening morphological abnormalities (e.g. teardrop and nucleated red blood 

cells, immature white blood cells) or cytopenia(s). If the patient develops new or worsening 

morphological abnormalities or cytopenia(s), treatment with eltrombopag should be discontinued and 

a bone marrow biopsy considered, including staining for fibrosis. 

 

Progression of existing myelodysplastic syndrome (MDS) 

 

There is a theoretical concern that TPO-R agonists may stimulate the progression of existing 

haematological malignancies such as MDS. TPO-R agonists are growth factors that lead to 

thrombopoietic progenitor cell expansion, differentiation and platelet production. The TPO-R is 

predominantly expressed on the surface of cells of the myeloid lineage. For TPO-R agonists there is a 

concern that they may stimulate the progression of existing haematopoietic malignancies such as 

MDS. 

 

In clinical studies with a TPO-R agonist in patients with MDS, cases of transient increases in blast cell 

counts were observed and cases of MDS disease progression to acute myeloid leukaemia (AML) were 

reported. 

 

The diagnosis of ITP or SAA in adults and elderly patients should be confirmed by the exclusion of 

other clinical entities presenting with thrombocytopenia, in particular the diagnosis of MDS must be 

excluded. Consideration should be given to performing a bone marrow aspirate and biopsy over the 

course of the disease and treatment, particularly in patients over 60 years of age, those with systemic 

symptoms, or abnormal signs such as increased peripheral blast cells. 

 



45 

The effectiveness and safety of Revolade have not been established for the treatment of 

thrombocytopenia due to MDS. Revolade should not be used outside of clinical studies for the 

treatment of thrombocytopenia due to MDS. 

 

Cytogenetic abnormalities and progression to MDS/AML in patients with SAA 

 

Cytogenetic abnormalities are known to occur in SAA patients. It is not known whether eltrombopag 

increases the risk of cytogenetic abnormalities in patients with SAA. In the phase II refractory SAA 

clinical study with eltrombopag with a starting dose of 50 mg/day (escalated every 2 weeks to a 

maximum of 150 mg/day) (ELT112523), the incidence of new cytogenetic abnormalities was 

observed in 17.1% of patients [7/41 (where 4 of them had changes in chromosome 7)]. The median 

time on study to a cytogenetic abnormality was 2.9 months. 

 

In the phase II refractory SAA clinical study with eltrombopag at a dose of 150 mg/day (with ethnic or 

age related modifications as indicated) (ELT116826), the incidence of new cytogenetic abnormalities 

was observed in 22.6% of adult patients [7/31 (where 3 of them had changes in chromosome 7)]. All 

7 patients had normal cytogenetics at baseline. Six patients had cytogenetic abnormality at Month 3 of 

eltrombopag therapy and one patient had cytogenetic abnormality at Month 6. 
 

In clinical studies with eltrombopag in SAA, 4% of patients (5/133) were diagnosed with MDS. The 

median time to diagnosis was 3 months from the start of eltrombopag treatment. 

 

For SAA patients refractory to or heavily pretreated with prior immunosuppressive therapy, bone 

marrow examination with aspirations for cytogenetics is recommended prior to initiation of 

eltrombopag, at 3 months of treatment and 6 months thereafter. If new cytogenetic abnormalities are 

detected, it must be evaluated whether continuation of eltrombopag is appropriate. 

 

Ocular changes 

 

Cataracts were observed in toxicology studies of eltrombopag in rodents (see section 5.3). In 

controlled studies in thrombocytopenic patients with HCV receiving interferon therapy (n=1,439), 

progression of pre-existing baseline cataract(s) or incident cataracts was reported in 8% of the 

eltrombopag group and 5% of the placebo group. Retinal haemorrhages, mostly Grade 1 or 2, have 

been reported in HCV patients receiving interferon, ribavirin and eltrombopag (2% of the eltrombopag 

group and 2% of the placebo group. Haemorrhages occurred on the surface of the retina (preretinal), 

under the retina (subretinal), or within the retinal tissue. Routine ophthalmologic monitoring of 

patients is recommended. 

 

QT/QTc prolongation 

 

A QTc study in healthy volunteers dosed 150 mg eltrombopag per day did not show a clinically 

significant effect on cardiac repolarisation. QTc interval prolongation has been reported in clinical 

studies of patients with ITP and thrombocytopenic patients with HCV. The clinical significance of 

these QTc prolongation events is unknown. 

 

Loss of response to eltrombopag 

 

A loss of response or failure to maintain a platelet response with eltrombopag treatment within the 

recommended dosing range should prompt a search for causative factors, including an increased bone 

marrow reticulin. 

 

  



46 

Paediatric population 

 

The above warnings and precautions for ITP also apply to the paediatric population. 

 

Interference with laboratory tests 

 

Eltrombopag is highly coloured and so has the potential to interfere with some laboratory tests. Serum 

discolouration and interference with total bilirubin and creatinine testing have been reported in 

patients taking Revolade. If the laboratory results and clinical observations are inconsistent, re-testing 

using another method may help in determining the validity of the result. 

 

4.5 Interaction with other medicinal products and other forms of interaction 
 

Effects of eltrombopag on other medicinal products 

 

HMG CoA reductase inhibitors 

 

Administration of eltrombopag 75 mg once daily for 5 days with a single 10 mg dose of the OATP1B1 

and BCRP substrate rosuvastatin to 39 healthy adult subjects increased plasma rosuvastatin Cmax 103% 

(90% confidence interval [CI]: 82%, 126%) and AUC0- 55% (90% CI: 42%, 69%). Interactions are 

also expected with other HMG-CoA reductase inhibitors, including atorvastatin, fluvastatin, lovastatin, 

pravastatin and simvastatin. When co-administered with eltrombopag, a reduced dose of statins should 

be considered and careful monitoring for statin adverse reactions should be undertaken (see 

section 5.2). 

 

OATP1B1 and BCRP substrates 

 

Concomitant administration of eltrombopag and OATP1B1 (e.g. methotrexate) and BCRP (e.g. 

topotecan and methotrexate) substrates should be undertaken with caution (see section 5.2). 

 

Cytochrome P450 substrates 

 

In studies utilising human liver microsomes, eltrombopag (up to 100 M) showed no in vitro 

inhibition of the CYP450 enzymes 1A2, 2A6, 2C19, 2D6, 2E1, 3A4/5, and 4A9/11 and was an 

inhibitor of CYP2C8 and CYP2C9 as measured using paclitaxel and diclofenac as the probe 

substrates. Administration of eltrombopag 75 mg once daily for 7 days to 24 healthy male subjects did 

not inhibit or induce the metabolism of probe substrates for 1A2 (caffeine), 2C19 (omeprazole), 2C9 

(flurbiprofen), or 3A4 (midazolam) in humans. No clinically significant interactions are expected 

when eltrombopag and CYP450 substrates are co-administered (see section 5.2). 

 

HCV protease inhibitors 

 

Dose adjustment is not required when eltrombopag is co-administered with either telaprevir or 

boceprevir. Co-administration of a single dose of eltrombopag 200 mg with telaprevir 750 mg every 

8 hours did not alter plasma telaprevir exposure. 

 

Co-administration of a single dose of eltrombopag 200 mg with boceprevir 800 mg every 8 hours did 

not alter plasma boceprevir AUC(0-), but increased Cmax by 20%, and decreased Cmin by 32%. The 

clinical relevance of the decrease in Cmin has not been established, increased clinical and laboratory 

monitoring for HCV suppression is recommended. 

 

  



47 

Effects of other medicinal products on eltrombopag 

 

Ciclosporin 

 
A decrease in eltrombopag exposure was observed with co-administration of 200 mg and 600 mg 

ciclosporin (a BCRP inhibitor). The co-administration of 200 mg ciclosporin decreased the Cmax and 

the AUCinf of eltrombopag by 25% and 18%, respectively. The co-administration of 600 mg 

ciclosporin decreased the Cmax and the AUCinf of eltrombopag by 39% and 24%, respectively. 

Eltrombopag dose adjustment is permitted during the course of the treatment based on the patient’s 

platelet count (see section 4.2). Platelet count should be monitored at least weekly for 2 to 3 weeks 

when eltrombopag is co-administered with ciclosporin. Eltrombopag dose may need to be increased 

based on these platelet counts. 

 

Polyvalent cations (chelation) 

 

Eltrombopag chelates with polyvalent cations such as iron, calcium, magnesium, aluminium, selenium 

and zinc. Administration of a single dose of eltrombopag 75 mg with a polyvalent cation-containing 

antacid (1524 mg aluminium hydroxide and 1425 mg magnesium carbonate) decreased plasma 

eltrombopag AUC0- by 70% (90% CI: 64%, 76%) and Cmax by 70% (90% CI: 62%, 76%). 

Eltrombopag should be taken at least two hours before or four hours after any products such as 

antacids, dairy products or mineral supplements containing polyvalent cations to avoid significant 

reduction in eltrombopag absorption due to chelation (see sections 4.2 and 5.2). 

 

Lopinavir/ritonavir 

 

Co-administration of eltrombopag with lopinavir/ritonavir may cause a decrease in the concentration 

of eltrombopag. A study in 40 healthy volunteers showed that the co-administration of a single 100 mg 

dose of eltrombopag with repeat dose lopinavir/ritonavir 400/100 mg twice daily resulted in a 

reduction in eltrombopag plasma AUCinf by 17% (90% CI: 6.6%, 26.6%). Therefore, caution should 

be used when co-administration of eltrombopag with lopinavir/ritonavir takes place. Platelet count 

should be closely monitored in order to ensure appropriate medical management of the dose of 

eltrombopag when lopinavir/ritonavir therapy is initiated or discontinued. 

 

CYP1A2 and CYP2C8 inhibitors and inducers 

 

Eltrombopag is metabolised through multiple pathways including CYP1A2, CYP2C8, UGT1A1, and 

UGT1A3 (see section 5.2). Medicinal products that inhibit or induce a single enzyme are unlikely to 

significantly affect plasma eltrombopag concentrations, whereas medicinal products that inhibit or 

induce multiple enzymes have the potential to increase (e.g. fluvoxamine) or decrease (e.g. rifampicin) 

eltrombopag concentrations. 

 

HCV protease inhibitors 

 

Results of a drug-drug pharmacokinetic (PK) interaction study show that co-administration of repeat 

doses of boceprevir 800 mg every 8 hours or telaprevir 750 mg every 8 hours with a single dose of 

eltrombopag 200 mg did not alter plasma eltrombopag exposure to a clinically significant extent. 

 

Medicinal products for treatment of ITP 

 

Medicinal products used in the treatment of ITP in combination with eltrombopag in clinical studies 

included corticosteroids, danazol, and/or azathioprine, intravenous immunoglobulin (IVIG), and 

anti-D immunoglobulin. Platelet counts should be monitored when combining eltrombopag with other 

medicinal products for the treatment of ITP in order to avoid platelet counts outside of the 

recommended range (see section 4.2). 

 



48 

Food interaction 

 

The administration of eltrombopag tablet or powder for oral suspension formulations with a high-

calcium meal (e.g. a meal that included dairy products) significantly reduced plasma eltrombopag 

AUC0-∞ and Cmax. In contrast, the administration of eltrombopag 2 hours before or 4 hours after a high-

calcium meal or with low-calcium food [<50 mg calcium] did not alter plasma eltrombopag exposure 

to a clinically significant extent (see section 4.2). 

 

Administration of a single 50 mg dose of eltrombopag in tablet form with a standard high-calorie, 

high-fat breakfast that included dairy products reduced plasma eltrombopag mean AUC0-∞ by 59% and 

mean Cmax by 65%. 

 

Administration of a single 25 mg dose of eltrombopag as powder for oral suspension with a high-

calcium, moderate-fat and moderate-calorie meal reduced plasma eltrombopag mean AUC0-∞ by 75% 

and mean Cmax by 79%. This decrease of exposure was attenuated when a single 25 mg dose of 

eltrombopag powder for oral suspension was administered 2 hours before a high-calcium meal (mean 

AUC0-∞ was decreased by 20% and mean Cmax by 14%). 

 

Food low in calcium (<50 mg calcium), including fruit, lean ham, beef and unfortified (no added 

calcium, magnesium or iron) fruit juice, unfortified soya milk and unfortified grain, did not 

significantly impact plasma eltrombopag exposure, regardless of calorie and fat content (see 

sections 4.2 and 4.5). 

 

4.6 Fertility, pregnancy and lactation 
 

Pregnancy 

 

There are no or limited amount of data from the use of eltrombopag in pregnant women. Studies in 

animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. 

 

Revolade is not recommended during pregnancy. 

 

Women of childbearing potential / Contraception in males and females 

 

Revolade is not recommended in women of childbearing potential not using contraception. 

 

Breast-feeding 

 

It is not known whether eltrombopag/metabolites are excreted in human milk. Studies in animals have 

shown that eltrombopag is likely secreted into milk (see section 5.3); therefore a risk to the suckling 

child cannot be excluded. A decision must be made whether to discontinue breast-feeding or to 

continue/abstain from Revolade therapy, taking into account the benefit of breast-feeding for the child 

and the benefit of therapy for the woman. 

 

Fertility 

 

Fertility was not affected in male or female rats at exposures that were comparable to those in humans. 

However a risk for humans cannot be ruled out (see section 5.3). 

 

4.7 Effects on ability to drive and use machines 
 

Eltrombopag has negligible influence on the ability to drive and use machines. The clinical status of 

the patient and the adverse reaction profile of eltrombopag, including dizziness and lack of alertness, 

should be borne in mind when considering the patient’s ability to perform tasks that require 

judgement, motor and cognitive skills. 

 



49 

4.8 Undesirable effects 

 

Summary of the safety profile 

Immune thrombocytopenia in adult and paediatric patients 

 

The safety of Revolade was assessed using the pooled double-blind, placebo-controlled studies 

TRA100773A and B, TRA102537 (RAISE) and TRA113765, in which 403 patients were exposed to 

Revolade and 179 to placebo, in addition to data from the completed open-label studies TRA108057, 

TRA105325 (EXTEND) and TRA112940. Patients received study medication for up to 8 years (in 

EXTEND). The most important serious adverse reactions were hepatotoxicity and 

thrombotic/thromboembolic events. The most common adverse reactions occurring in at least 10% of 

patients included nausea, diarrhoea and increased alanine aminotransferase. 

 

The safety of Revolade in paediatric patients (aged 1 to 17 years) with previously treated ITP has been 

demonstrated in two studies. PETIT2 (TRA115450) was a 2-part, double-blind and open-label, 

randomised, placebo-controlled study. Patients were randomised 2:1 and received Revolade (n=63) or 

placebo (n=29) for up to 13 weeks in the randomised period of the study. PETIT (TRA108062) was a 

3-part, staggered-cohort, open-label and double-blind, randomised, placebo-controlled study. Patients 

were randomised 2:1 and received Revolade (n=44) or placebo (n=21), for up to 7 weeks. The profile 

of adverse reactions was comparable to that seen in adults with some additional adverse reactions, 

marked ♦ in the table below. The most common adverse reactions in paediatric ITP patients 1 year and 

older (≥3% and greater than placebo) were upper respiratory tract infection, nasopharyngitis, cough, 

pyrexia, abdominal pain, oropharyngeal pain, toothache and rhinorrhoea. 

 

Thrombocytopenia with HCV infection in adult patients 

 

ENABLE 1 (TPL103922 n=716) and ENABLE 2 (TPL108390 n=805) were randomised, double-

blind, placebo-controlled, multicentre studies to assess the efficacy and safety of Revolade in 

thrombocytopenic patients with HCV infection who were otherwise eligible to initiate antiviral 

therapy. In the HCV studies the safety population consisted of all randomised patients who received 

double-blind study medicinal product during Part 2 of ENABLE 1 (Revolade treatment n=450, 

placebo treatment n=232) and ENABLE 2 (Revolade treatment n=506, placebo treatment n=253). 

Patients are analysed according to the treatment received (total safety double-blind population, 

Revolade n=955 and placebo n=484). The most important serious adverse reactions identified were 

hepatotoxicity and thrombotic/thromboembolic events. The most common adverse reactions occurring 

in at least 10% of patients included headache, anaemia, decreased appetite, cough, nausea, diarrhoea, 

hyperbilirubinaemia, alopecia, pruritus, myalgia, pyrexia, fatigue, influenza-like illness, asthenia, 

chills and oedema. 

 

Severe aplastic anaemia in adult patients 

 

The safety of eltrombopag in severe aplastic anaemia was assessed in a single-arm, open-label study 

(N=43) in which 11 patients (26%) were treated for >6 months and 7 patients (16%) were treated for 

>1 year. The most important serious adverse reactions were febrile neutropenia and sepsis/infection. 

The most common adverse reactions occurring in at least 10% of patients included headache, 

dizziness, cough, oropharyngeal pain, nausea, diarrhoea, abdominal pain, transaminases increased, 

arthralgia, pain in extremity, fatigue and pyrexia. 

 

  



50 

List of adverse reactions 

 

The adverse reactions in the adult ITP studies (N=763), paediatric ITP studies (N=171), the HCV 

studies (N=1,520), the SAA studies (N=43) and post-marketing reports are listed below by MedDRA 

system organ class and by frequency. Within each system organ class, the adverse drug reactions are 

ranked by frequency, with the most frequent reactions first. The corresponding frequency category for 

each adverse drug reaction is based on the following convention (CIOMS III): very common (≥1/10); 

common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); not known 

(cannot be estimated from the available data). 

 

ITP study population 

 

System organ class Frequency Adverse reaction 

Infections and infestations Very 

common 

Nasopharyngitis♦, upper respiratory tract infection♦ 

Common Pharyngitis, influenza, oral herpes, pneumonia, sinusitis, tonsillitis, 

respiratory tract infection, gingivitis 

Uncommon Skin infection 

Neoplasms benign, malignant 

and unspecified (incl cysts 

and polyps) 

Uncommon Rectosigmoid cancer 

Blood and lymphatic system 

disorders 

Common Anaemia, eosinophilia, leukocytosis, thrombocytopenia, 

haemoglobin decreased, white blood cell count decreased 

Uncommon Anisocytosis, haemolytic anaemia, myelocytosis, band neutrophil 

count increased, myelocyte present, platelet count increased, 

haemoglobin increased 

Immune system disorders Uncommon Hypersensitivity 

Metabolism and nutrition 

disorders 

Common Hypokalaemia, decreased appetite, blood uric acid increased 

Uncommon Anorexia, gout, hypocalcaemia 

Psychiatric disorders Common Sleep disorder, depression 

Uncommon Apathy, mood altered, tearfulness 

Nervous system disorders Common Paraesthesia, hypoaesthesia, somnolence, migraine 

Uncommon Tremor, balance disorder, dysaesthesia, hemiparesis, migraine 

with aura, neuropathy peripheral, peripheral sensory neuropathy, 

speech disorder, toxic neuropathy, vascular headache 

Eye disorders Common Dry eye, vision blurred, eye pain, visual acuity reduced 

Uncommon Lenticular opacities, astigmatism, cataract cortical, lacrimation 

increased, retinal haemorrhage, retinal pigment epitheliopathy, 

visual impairment, visual acuity tests abnormal, blepharitis, 

keratoconjunctivitis sicca 

Ear and labyrinth disorders Common Ear pain, vertigo 

Cardiac disorders Uncommon Tachycardia, acute myocardial infarction, cardiovascular disorder, 

cyanosis, sinus tachycardia, electrocardiogram QT prolonged 



51 

Vascular disorders Common Deep vein thrombosis, haematoma, hot flush 

Uncommon Embolism, hot flush, thrombophlebitis superficial, flushing 

Respiratory, thoracic and 

mediastinal disorders 

Very 

common 

Cough♦ 

Common Oropharyngeal pain, rhinorrhoea♦ 

Uncommon Pulmonary embolism, pulmonary infarction, nasal discomfort, 

oropharyngeal blistering, sinus disorder, sleep apnoea syndrome 

Gastrointestinal disorders Very 

common 

Nausea, diarrhoea♦ 

Common Mouth ulceration, toothache♦, vomiting, abdominal pain*, mouth 

haemorrhage, flatulence 

* Very common in paediatric ITP 

Uncommon Dry mouth, glossodynia, abdominal tenderness, faeces 

discoloured, food poisoning, frequent bowel movements, 

haematemesis, oral discomfort 

Hepatobiliary disorders Very 

common 

Alanine aminotransferase increased† 

Common Aspartate aminotransferase increased†, hyperbilirubinaemia, 

hepatic function abnormal 

Uncommon Cholestasis, hepatic lesion, hepatitis, drug-induced liver injury 

Skin and subcutaneous tissue 

disorders 

Common Rash, alopecia, hyperhidrosis, pruritus generalised, petechiae 

Uncommon Urticaria, dermatosis, cold sweat, erythema, melanosis, 

pigmentation disorder, skin discolouration, skin exfoliation 

Musculoskeletal and 

connective tissue disorders 

Common Myalgia, muscle spasm, musculoskeletal pain, bone pain, back 

pain 

Uncommon Muscular weakness 

Renal and urinary disorders Common Proteinuria, blood creatinine increased, thrombotic 

microangiopathy with renal failure‡ 

Uncommon Renal failure, leukocyturia, lupus nephritis, nocturia, blood urea 

increased, urine protein/creatinine ratio increased 

Reproductive system and 

breast disorders 

Common Menorrhagia 

General disorders and 

administration site conditions 

Common Pyrexia*, chest pain, asthenia 

*Very common in paediatric ITP 

Uncommon Feeling hot, vessel puncture site haemorrhage, feeling jittery, 

inflammation of wound, malaise, sensation of foreign body 

Investigations Common Blood alkaline phosphatase increased 

Uncommon Blood albumin increased, protein total increased, blood albumin 

decreased, pH urine increased 

Injury, poisoning and 

procedural complications 

Uncommon Sunburn 

♦ Additional adverse reactions observed in paediatric studies (aged 1to 17 years). 
† Increase of alanine aminotransferase and aspartate aminotransferase may occur simultaneously, 

although at a lower frequency. 
‡ Grouped term with preferred terms acute kidney injury and renal failure 

 

HCV study population (in combination with anti-viral interferon and ribavirin therapy) 

 

System organ class Frequency Adverse reaction 

Infections and infestations Common Urinary tract infection, upper respiratory tract infection, 

bronchitis, nasopharyngitis, influenza, oral herpes 

Uncommon Gastroenteritis, pharyngitis 

Neoplasms benign, malignant 

and unspecified (incl cysts and 

polyps) 

Common Hepatic neoplasm malignant 



52 

Blood and lymphatic system 

disorders 

Very 

common 

Anaemia 

Common Lymphopenia 

Uncommon Haemolytic anaemia 

Metabolism and nutrition 

disorders 

Very 

common 

Decreased appetite 

Common Hyperglycaemia, abnormal loss of weight 

Psychiatric disorders Common Depression, anxiety, sleep disorder 

Uncommon Confusional state, agitation 

Nervous system disorders Very 

common 

Headache 

Common Dizziness, disturbance in attention, dysgeusia, hepatic 

encephalopathy, lethargy, memory impairment, paraesthesia 

Eye disorders Common Cataract, retinal exudates, dry eye, ocular icterus, retinal 

haemorrhage 

Ear and labyrinth disorders Common Vertigo 

Cardiac disorders Common Palpitations 

Respiratory, thoracic and 

mediastinal disorders 

Very 

common 

Cough 

Common Dyspnoea, oropharyngeal pain, dyspnoea exertional, productive 

cough 

Gastrointestinal disorders Very 

common 

Nausea, diarrhoea 

Common Vomiting, ascites, abdominal pain, abdominal pain upper, 

dyspepsia, dry mouth, constipation, abdominal distension, 

toothache, stomatitis, gastrooesophagal reflux disease, 

haemorrhoids, abdominal discomfort, varices oesophageal 

Uncomon Oesophageal varices haemorrhage, gastritis, aphthous stomatitis 

Hepatobiliary disorders Common Hyperbilirubinaemia, jaundice, drug-induced liver injury 

Uncommon Portal vein thrombosis, hepatic failure 

Skin and subcutaneous tissue 

disorders 

Very 

common 

Pruritus 

Common Rash, dry skin, eczema, rash pruritic, erythema, hyperhidrosis, 

pruritus generalised, alopecia 

Uncommon Skin lesion, skin discolouration, skin hyperpigmentation, night 

sweats 

Musculoskeletal and 

connective tissue disorder 

Very 

common 

Myalgia 

Common Arthralgia, muscle spasms, back pain, pain in extremity, 

musculoskeletal pain, bone pain 

Renal and urinary disorders Uncommon Thrombotic microangiopathy with acute renal failure†, dysuria 

General disorders and 

administration site conditions 

Very 

common 

Pyrexia, fatigue, influenza-like illness, asthenia, chills 

Common Irritability, pain, malaise, injection site reaction, non-cardiac chest 

pain, oedema, oedema peripheral 

Uncommon Injection site pruritus, injection site rash, chest discomfort 

Investigations Common Blood bilirubin increased, weight decreased, white blood cell 

count decreased, haemoglobin decreased, neutrophil count 

decreased, international normalised ratio increased, activated 

partial thromboplastin time prolonged, blood glucose increased, 

blood albumin decreased 

Uncommon Electrocardiogram QT prolonged 
† Grouped term with preferred terms oliguria, renal failure and renal impairment 

 



53 

SAA study population 

 

System organ class Frequency Adverse reaction 

Blood and lymphatic system 

disorders 

Common Neutropenia, splenic infarction 

Metabolism and nutrition 

disorders 

Common Iron overload, decreased appetite, hypoglycaemia, increased 

appetite 

Psychiatric disorders Common Anxiety, depression 

Nervous system disorders Very 

common 

Headache, dizziness 

Common Syncope 

Eye disorders Common Dry eye, cataract, ocular icterus, vision blurred, visual 

impairment, vitreous floaters 

Respiratory, thoracic and 

mediastinal disorders 

Very 

common 

Cough, oropharyngeal pain, rhinorrhoea 

Common Epistaxis 

Gastrointestinal disorders Very 

common 

Diarrhoea, nausea, gingival bleeding, abdominal pain 

Common Oral mucosal blistering, oral pain, vomiting, abdominal 

discomfort, constipation, abdominal distension, dysphagia, faeces 

discoloured, swollen tongue, gastrointestinal motility disorder, 

flatulence 

Hepatobiliary disorders Very 

common 

Transaminases increased 

Common Blood bilirubin increased (hyperbilirubinemia), jaundice 

Not known Drug-induced liver injury* 

* Cases of drug-induced liver injury have been reported in 

patients with ITP and HCV 

Skin and subcutaneous tissue 

disorders 

Common Petechiae, rash, pruritus, urticaria, skin lesion, rash macular 

Not known Skin discolouration, skin hyperpigmentation 

Musculosketal and connective 

tissue disorders 

Very 

common 

Arthralgia, pain in extremity, muscle spasms 

Common Back pain, myalgia, bone pain 

Renal and urinary disorders Common Chromaturia 

General disorders and 

administration site conditions 

Very 

common 

Fatigue, pyrexia, chills 

Common Asthenia, oedema peripheral, malaise 

Investigations Common Blood creatine phosphokinase increased 

 

Description of selected adverse reactions 

 

Thrombotic/thromboembolic events (TEEs) 

 

In 3 controlled and 2 uncontrolled clinical studies among adult ITP patients receiving eltrombopag 

(n=446), 17 patients experienced a total of 19 TEEs, which included (in descending order of 

occurrence) deep vein thrombosis (n=6), pulmonary embolism (n=6), acute myocardial infarction 

(n=2), cerebral infarction (n=2), embolism (n=1) (see section 4.4). 

 

In a placebo-controlled study (n=288, Safety population), following 2 weeks’ treatment in preparation 

for invasive procedures, 6 of 143 (4%) adult patients with chronic liver disease receiving eltrombopag 

experienced 7 TEEs of the portal venous system and 2 of 145 (1%) patients in the placebo group 

experienced 3 TEEs. Five of the 6 patients treated with eltrombopag experienced the TEE at a platelet 

count >200,000/µl. 

 

No specific risk factors were identified in those patients who experienced a TEE with the exception of 

platelet counts ≥200,000/µl (see section 4.4). 



54 

 

In controlled studies in thrombocytopenic patients with HCV (n=1439), 38 out of 955 patients (4%) 

treated with eltrombopag experienced a TEE and 6 out of 484 patients (1%) in the placebo group 

experienced TEEs. Portal vein thrombosis was the most common TEE in both treatment groups (2% in 

patients treated with eltrombopag versus <1% for placebo) (see section 4.4). Patients with low albumin 

levels (≤35 g/l) or MELD ≥10 had a 2-fold greater risk of TEEs than those with higher albumin levels; 

those aged ≥60 years had a 2-fold greater risk of TEEs compared to younger patients. 

 

Hepatic decompensation (use with interferon) 

 

Chronic HCV patients with cirrhosis may be at risk of hepatic decompensation when receiving alfa 

interferon therapy. In 2 controlled clinical studies in thrombocytopenic patients with HCV, hepatic 

decompensation (ascites, hepatic encephalopathy, variceal haemorrhage, spontaneous bacterial 

peritonitis) was reported more frequently in the eltrombopag arm (11%) than in the placebo arm (6%). 

In patients with low albumin levels (≤35 g/l) or MELD score ≥10 at baseline, there was a 3-fold 

greater risk of hepatic decompensation and an increase in the risk of a fatal adverse event compared to 

those with less advanced liver disease. Eltrombopag should only be administered to such patients after 

careful consideration of the expected benefits in comparison with the risks. Patients with these 

characteristics should be closely monitored for signs and symptoms of hepatic decompensation (see 

section 4.4). 

 

Hepatotoxixity 

 

In the controlled clinical studies in chronic ITP with eltrombopag, increases in serum ALT, AST and 

bilirubin were observed (see section 4.4). 

 

These findings were mostly mild (Grade 1-2), reversible and not accompanied by clinically significant 

symptoms that would indicate an impaired liver function. Across the 3 placebo-controlled studies in 

adults with chronic ITP, 1 patient in the placebo group and 1 patient in the eltrombopag group 

experienced a Grade 4 liver test abnormality. In two placebo-controlled studies in paediatric patients 

(aged 1 to 17 years) with chronic ITP, ALT 3 x ULN was reported in 4.7% and 0% of the 

eltrombopag and placebo groups, respectively. 

 

In 2 controlled clinical studies in patients with HCV, ALT or AST 3 x ULN was reported in 34% and 

38% of the eltrombopag and placebo groups, respectively. Most patients receiving eltrombopag in 

combination with peginterferon / ribavirin therapy will experience indirect hyperbilirubinaemia. 

Overall, total bilirubin ≥1.5 x ULN was reported in 76% and 50% of the eltrombopag and placebo 

groups, respectively. 

 

In the single-arm phase II monotherapy refractory SAA study, concurrent ALT or AST >3 x ULN 

with total (indirect) bilirubin >1.5 x ULN were reported in 5% of patients. Total bilirubin >1.5 x ULN 

occurred in 14% of patients. 

 

Thrombocytopenia following discontinuation of treatment 

 

In the 3 controlled clinical ITP studies, transient decreases in platelet counts to levels lower than 

baseline were observed following discontinuation of treatment in 8% and 8% of the eltrombopag and 

placebo groups, respectively (see section 4.4). 

 

Increased bone marrow reticulin 

 

Across the programme, no patients had evidence of clinically relevant bone marrow abnormalities or 

clinical findings that would indicate bone marrow dysfunction. In a small number of ITP patients, 

eltrombopag treatment was discontinued due to bone marrow reticulin (see section 4.4). 

 



55 

Cytogenetic abnormalities 

 

In the phase II refractory SAA clinical study with eltrombopag with a starting dose of 50 mg/day 

(escalated every 2 weeks to a maximum of 150 mg/day) (ELT112523), the incidence of new 

cytogenetic abnormalities was observed in 17.1% of adult patients [7/41 (where 4 of them had changes 

in chromosome 7)]. The median time on study to a cytogenetic abnormality was 2.9 months. 

 

In the phase II refractory SAA clinical study with eltrombopag at a dose of 150 mg/day (with ethnic or 

age related modifications as indicated) (ELT116826), the incidence of new cytogenetic abnormalities 

was observed in 22.6% of adult patients [7/31 (where 3 of them had changes in chromosome 7)]. All 

7 patients had normal cytogenetics at baseline. Six patients had cytogenetic abnormality at Month 3 of 

eltrombopag therapy and one patient had cytogenetic abnormality at Month 6. 

 

Haematologic malignancies 

 

In the single-arm, open-label study in SAA, three (7%) patients were diagnosed with MDS following 

treatment with eltrombopag, in the two ongoing studies (ELT116826 and ELT116643), 1/28 (4%) and 

1/62 (2%) patient has been diagnosed with MDS or AML in each study. 

 

Reporting of suspected adverse reactions 

 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the national reporting system 

listed in Appendix V. 

 

4.9 Overdose 
 

In the event of overdose, platelet counts may increase excessively and result in 

thrombotic/thromboembolic complications. In case of an overdose, consideration should be given to 

oral administration of a metal cation-containing preparation, such as calcium, aluminium, or 

magnesium preparations to chelate eltrombopag and thus limit absorption. Platelet counts should be 

closely monitored. Treatment with eltrombopag should be reinitiated in accordance with dosing and 

administration recommendations (see section 4.2). 

 

In the clinical studies there was one report of overdose where the patient ingested 5000 mg of 

eltrombopag. Reported adverse reactions included mild rash, transient bradycardia, ALT and AST 

elevation, and fatigue. Liver enzymes measured between Days 2 and 18 after ingestion peaked at a 

1.6-fold ULN in AST, a 3.9-fold ULN in ALT, and a 2.4-fold ULN in total bilirubin, The platelet 

counts were 672,000/µl on Day 18 after ingestion and the maximum platelet count was 929,000/µl. All 

events were resolved without sequelae following treatment. 

 

Because eltrombopag is not significantly renally excreted and is highly bound to plasma proteins, 

haemodialysis would not be expected to be an effective method to enhance the elimination of 

eltrombopag. 

 

 

  



56 

5. PHARMACOLOGICAL PROPERTIES 
 

5.1 Pharmacodynamic properties 
 

Pharmacotherapeutic group: Antihemorrhagics, other systemic hemostatics. ATC code: B02BX 05. 

 

Mechanism of action 

 

TPO is the main cytokine involved in regulation of megakaryopoiesis and platelet production, and is 

the endogenous ligand for the TPO-R. Eltrombopag interacts with the transmembrane domain of the 

human TPO-R and initiates signalling cascades similar but not identical to that of endogenous 

thrombopoietin (TPO), inducing proliferation and differentiation from bone marrow progenitor cells. 

 

Clinical efficacy and safety 

 

Immune (primary) thrombocytopenia (ITP) studies 

 

Two phase III, randomised, double-blind, placebo-controlled studies RAISE (TRA102537) and 

TRA100773B and two open-label studies REPEAT (TRA108057) and EXTEND (TRA105325) 

evaluated the safety and efficacy of eltrombopag in adult patients with previously treated ITP. Overall, 

eltrombopag was administered to 277 ITP patients for at least 6 months and 202 patients for at least 

1 year. 

 

Double-blind placebo-controlled studies 

RAISE: 197 ITP patients were randomised 2:1, eltrombopag (n=135) to placebo (n=62), and 

randomisation was stratified based upon splenectomy status, use of ITP medicinal products at baseline 

and baseline platelet count. The dose of eltrombopag was adjusted during the 6 month treatment 

period based on individual platelet counts. All patients initiated treatment with eltrombopag 50 mg. 

From Day 29 to the end of treatment, 15 to 28% of eltrombopag treated patients were maintained on 

≤25 mg and 29 to 53% received 75 mg. 

 

In addition, patients could taper off concomitant ITP medicinal products and receive rescue treatments 

as dictated by local standard of care. More than half of all patients in each treatment group had ≥3 

prior ITP therapies and 36% had a prior splenectomy. 

 

Median platelet counts at baseline were 16,000/l for both treatment groups and in the eltrombopag 

group were maintained above 50,000/µl at all on-therapy visits starting at Day 15; in contrast, median 

platelet counts in the placebo group remained <30,000/µl throughout the study. 

 

Platelet count response between 50,000-400,000/l in the absence of rescue treatment was achieved by 

significantly more patients in the eltrombopag treated group during the 6 month treatment period, 

p <0.001. Fifty-four percent of the eltrombopag-treated patients and 13% of placebo-treated patients 

achieved this level of response after 6 weeks of treatment. A similar platelet response was maintained 

throughout the study, with 52% and 16% of patients responding at the end of the 6-month treatment 

period. 

 



57 

Table 4 Secondary efficacy results from RAISE 

 

 

Eltrombopag 

N=135 

Placebo 

N=62 

Key secondary endpoints 

Number of cumulative weeks with platelet counts 

50,000-400,000/µl, Mean (SD) 
11.3 (9.46) 2.4 (5.95) 

Patients with ≥75% of assessments in the target range (50,000 to 

400,000/l), n (%) 

p-value a 

51 (38) 4 (7) 

<0.001 

Patients with bleeding (WHO Grades 1-4) at any time during 

6 months, n (%) 

 p-value a 

106 (79) 56 (93) 

0.012 

Patients with bleeding (WHO Grades 2-4) at any time during 

6 months, n (%) 

 p-value a 

44 (33) 32 (53) 

0.002 

Requiring rescue therapy, n (%) 

 p-value a 

24 (18) 25 (40) 

0.001 

Patients receiving ITP therapy at baseline (n) 63 31 

Patients who attempted to reduce or discontinue baseline 

therapy, n (%)b 

 p-value a 

37 (59) 10 (32) 

0.016 

a Logistic regression model adjusted for randomisation stratification variables 

b 21 out of 63 (33%) patients treated with eltrombopag who were taking an ITP medicinal product 

at baseline permanently discontinued all baseline ITP medicinal products. 

 

At baseline, more than 70% of ITP patients in each treatment group reported any bleeding (WHO 

Grades 1-4) and more than 20% reported clinically significant bleeding (WHO Grades 2-4), 

respectively. The proportion of eltrombopag-treated patients with any bleeding (Grades 1-4) and 

clinically significant bleeding (Grades 2-4) was reduced from baseline by approximately 50% from 

Day 15 to the end of treatment throughout the 6-month treatment period. 

 

TRA100773B: The primary efficacy endpoint was the proportion of responders, defined as ITP 

patients who had an increase in platelet counts to 50,000/l at Day 43 from a baseline of <30,000/l; 

patients who withdrew prematurely due to a platelet count 200,000/l were considered responders, 

those that discontinued for any other reason were considered non-responders irrespective of platelet 

count. A total of 114 patients with previously treated ITP were randomised 2:1 eltrombopag (n=76) to 

placebo (n=38). 

 

Table 5 Efficacy results from TRA100773B 

 

 

Eltrombopag 

N=74 

Placebo 

N=38 

Key primary endpoints 

Eligible for efficacy analysis, n 73 37 

Patients with platelet count 50,000/l after up to 42 days 

of dosing (compared to a baseline count of <30,000/l), n 

(%) 

 

p-valuea 

43 (59) 6 (16) 

<0.001 

Key secondary endpoints 

Patients with a Day 43 bleeding assessment, n 51 30 

Bleeding (WHO Grades 1-4) n (%) 

 

p-valuea 

20 (39) 18 (60) 

0.029 

a Logistic regression model adjusted for randomisation stratification variables 



58 

 

In both RAISE and TRA100773B the response to eltrombopag relative to placebo was similar 

irrespective of ITP medicinal product use, splenectomy status and baseline platelet count (≤15,000/µl, 

>15,000/µl) at randomisation. 

 

In RAISE and TRA100773B studies, in the subgroup of ITP patients with baseline platelet count 

≤15,000/μl the median platelet counts did not reach the target level (>50,000/l), although in both 

studies 43% of these patients treated with eltrombopag responded after 6 weeks of treatment. In 

addition, in the RAISE study, 42% of patients with baseline platelet count ≤15,000/μl treated with 

eltrombopag responded at the end of the 6 month treatment period. Forty-two to 60% of the 

eltrombopag-treated patients in the RAISE study were receiving 75 mg from Day 29 to the end of 

treatment. 

 

An open-label, repeat-dose study (3 cycles of 6 weeks of treatment, followed by 4 weeks off 

treatment) showed that episodic use with multiple courses of eltrombopag has demonstrated no loss of 

response. 

 

Eltrombopag was administered to 302 ITP patients in the open-label extension study EXTEND 

(TRA105325), 218 patients completed 1 year, 180 completed 2 years, 107 completed 3 years, 75 

completed 4 years, 34 completed 5 years and 18 completed 6 years. The median baseline platelet count 

was 19,000/l prior to eltrombopag administration. Median platelet counts at 1, 2, 3, 4, 5, 6 and 

7 years on study were 85,000/l, 85,000/l, 105,000/l, 64,000/l, 75,000/l, 119,000/l and 

76,000/l, respectively. 

 

Clinical studies comparing eltrombopag to other treatment options (e.g. splenectomy) have not been 

conducted. The long-term safety of eltrombopag should be considered prior to starting therapy. 

 

Paediatric population (aged 1 to 17 years) 

The safety and efficacy of eltrombopag in paediatric patients have been investigated two studies. 

 

TRA115450 (PETIT2): The primary endpoint was a sustained response, defined as the proportion of 

patients receiving eltrombopag, compared to placebo, achieving platelet counts ≥50,000/µl for at least 

6 out of 8 weeks (in the absence of rescue therapy), between weeks 5 to 12 during the double-blind 

randomised period. Patients were diagnosed with chronic ITP for at least 1 year and were refractory or 

relapsed to at least one prior ITP therapy or unable to continue other ITP treatments for a medical 

reason and had platelet count <30,000/µl. Ninety-two patients were randomised by three age cohort 

strata (2:1) to eltrombopag (n=63) or placebo (n=29). The dose of eltrombopag could be adjusted 

based on individual platelet counts. 

 

Overall, a significantly greater proportion of eltrombopag patients (40%) compared with placebo 

patients (3%) achieved the primary endpoint (Odds Ratio: 18.0 [95% CI: 2.3, 140.9] p <0.001) which 

was similar across the three age cohorts (Table 6). 

 

Table 6 Sustained platelet response rates by age cohort in paediatric patients with chronic 

ITP 

 

 Eltrombopag 

n/N (%) 

[95% CI] 

Placebo 

n/N (%) 

[95% CI] 

Cohort 1 (12 to 17 years) 

 

Cohort 2 (6 to 11 years) 

 

Cohort 3 (1 to 5 years) 

9/23 (39%) 

[20%, 61%] 

11/26 (42%) 

[23%, 63%] 

5/14 (36%) 

[13%, 65%] 

1/10 (10%) 

[0%, 45%] 

0/13 (0%) 

[N/A] 

0/6 (0%) 

[N/A] 

 



59 

Statistically fewer eltrombopag patients required rescue treatment during the randomised period 

compared to placebo patients (19% [12/63] vs. 24% [7/29], p=0.032). 

 

At baseline, 71% of patients in the eltrombopag group and 69% in the placebo group reported any 

bleeding (WHO Grades 1-4). At Week 12, the proportion of eltrombopag patients reporting any 

bleeding was decreased to half of baseline (36%). In comparison, at Week 12, 55% of placebo patients 

reported any bleeding. 

 

Patients were permitted to reduce or discontinue baseline ITP therapy only during the open-label phase 

of the study and 53% (8/15) of patients were able to reduce (n=1) or discontinue (n=7) baseline ITP 

therapy, mainly corticosteroids, without needing rescue therapy. 

 

TRA108062 (PETIT): The primary endpoint was the proportion of patients achieving platelet counts 

≥50,000/µl at least once between weeks 1 and 6 of the randomised period. Patients were diagnosed 

with ITP for at least 6 months and were refractory or relapsed to at least one prior ITP therapy with a 

platelet count <30,000/µl (n=67). During the randomised period of the study, patients were 

randomised by three age cohort strata (2:1) to eltrombopag (n=45) or placebo (n=22). The dose of 

eltrombopag could be adjusted based on individual platelet counts. 

 

Overall, a significantly greater proportion of eltrombopag patients (62%) compared with placebo 

patients (32%) met the primary endpoint (Odds Ratio: 4.3 [95% CI: 1.4, 13.3] p=0.011). 

 

Sustained response was seen in 50% of the initial responders during 20 out of 24 weeks in the 

PETIT 2 study and 15 out of 24 weeks in the PETIT Study. 

 

Chronic hepatitis C associated thrombocytopenia studies 

 

The efficacy and safety of eltrombopag for the treatment of thrombocytopenia in patients with HCV 

infection were evaluated in two randomised, double-blind, placebo-controlled studies. ENABLE 1 

utilised peginterferon alfa-2a plus ribavirin for antiviral treatment and ENABLE 2 utilised 

peginterferon alfa-2b plus ribavirin. Patients did not receive direct acting antiviral agents. In both 

studies, patients with a platelet count of <75,000/µl were enrolled and stratified by platelet count 

(<50,000/µl and ≥50,000/µl to <75,000/µl), screening HCV RNA (<800,000 IU/ml and 

≥800,000 IU/ml), and HCV genotype (genotype 2/3, and genotype 1/4/6). 

 

Baseline disease characteristics were similar in both studies and were consistent with compensated 

cirrhotic HCV patient population. The majority of patients were HCV genotype 1 (64%) and had 

bridging fibrosis/cirrhosis. Thirty-one percent of patients had been treated with prior HCV therapies, 

primarily pegylated interferon plus ribavirin. The median baseline platelet count was 59,500/µl in both 

treatment groups: 0.8%, 28% and 72% of the patients recruited had platelet counts <20,000/µl, 

<50.000/µl and ≥50,000/µl respectively. 

 

The studies consisted of two phases – a pre-antiviral treatment phase and an antiviral treatment phase. 

In the pre-antiviral treatment phase, patients received open-label eltrombopag to increase the platelet 

count to ≥90,000/µl for ENABLE 1 and ≥100,000/µl for ENABLE 2. The median time to achieve the 

target platelet count ≥90,000/µl (ENABLE 1) or ≥100,000/µl (ENABLE 2) was 2 weeks. 

 

The primary efficacy endpoint for both studies was sustained virologic response (SVR), defined as the 

percentage of patients with no detectable HCV-RNA at 24 weeks after completion of the planned 

treatment period. 

 

In both HCV studies, a significantly greater proportion of patients treated with eltrombopag (n=201, 

21%) achieved SVR compared to those treated with placebo (n=65, 13%) (see Table 7). The 

improvement in the proportion of patients who achieved SVR was consistent across all subgroups in 

the randomisation strata (baseline platelet counts (<50,000 vs. >50,000), viral load (<800,000 IU/ml 

vs. ≥800,000 IU/ml) and genotype (2/3 vs. 1/4/6)). 

 



60 

Table 7 Virologic response in HCV patients in ENABLE 1 and ENABLE 2 

 

 Pooled data ENABLE 1a ENABLE 2b 

Patients achieving 

target platelet counts 

and initiating antiviral 

therapy c 

 

1,439/1,520 (95%) 

 

680/715 (95%) 

 

759/805 (94%) 

 Eltrombopag Placebo Eltrombopag Placebo Eltrombopag Placebo 

Total number of 

patients entering 

antiviral treatment 

phase 

n=956 n=485 n=450 n=232 n=506 n=253 

 % patients achieving virologic response 

Overall SVR d  21 13 23 14 19 13 

HCV RNA Genotype       

Genotype 2/3 35 25 35 24 34 25 

Genotype 1/4/6e 15 8 18 10 13 7 

Albumin levels f    

≤35g/l 11 8 

>35g/l 25 16 

MELD scoref   

≥10 18 10 

<10 23 17 

a Eltrombopag given in combination with peginterferon alfa-2a (180 μg once weekly for 

48 weeks for genotypes 1/4/6; 24 weeks for genotype 2/3) plus ribavirin (800 to 1200 mg daily 

in 2 divided doses orally) 

b Eltrombopag given in combination with peginterferon alfa-2b (1.5 μg/kg once weekly for 

48 weeks for genotype 1/4/6; 24 weeks for genotype 2/3) plus ribavirin (800 to 1400 mg orally 

in 2 divided doses) 

c Target platelet count was 90,000/µl for ENABLE 1 and 100,000/µl for ENABLE 2. For 

ENABLE 1, 682 patients were randomised to the antiviral treatment phase; however 2 patients 

then withdrew consent prior to receiving antiviral therapy. 

d p-value <0.05 for eltrombopag versus placebo 

e 64% patients participating in ENABLE 1 and ENABLE 2 were genotype 1 

f Post-hoc analyses 

 

Other secondary findings of the studies included the following: significantly fewer patients treated 

with eltrombopag prematurely discontinued antiviral therapy compared to placebo (45% vs. 60%, 

p=<0.0001). A greater proportion of patients on eltrombopag did not require any antiviral dose 

reduction as compared to placebo (45% vs. 27%). Eltrombopag treatment delayed and reduced the 

number of peginterferon dose reductions. 

 

Severe aplastic anaemia 

 

Eltrombopag was studied in a single-arm, single-centre open-label study in 43 patients with severe 

aplastic anaemia with refractory thrombocytopenia following at least one prior immunosuppressive 

therapy (IST) and who had a platelet count ≤30,000/µl. 

 

The majority of patients, 33 (77%), were considered to have ‘primary refractory disease’, defined as 

having no prior adequate response to IST in any lineage. The remaining 10 patients had insufficient 

platelet response to prior therapies. All 10 had received at least 2 prior IST regimens and 50% had 

received at least 3 prior IST regimens. Patients with diagnosis of Fanconi anaemia, infection not 

responding to appropriate therapy, PNH clone size in neutrophils of ≥50%, where excluded from 

participation. 

 

  



61 

At baseline the median platelet count was 20,000/µl, haemoglobin was 8.4 g/dl, ANC was 0.58 x 109/l 

and absolute reticulocyte count was 24.3 x109/l. Eighty-six percent of patients were RBC transfusion 

dependent, and 91% were platelet transfusion dependent. The majority of patients (84%) had received 

at least 2 prior immunosuppressive therapies. Three patients had cytogenetic abnormalities at baseline. 

 

The primary endpoint was haematological response assessed after 12 weeks of eltrombopag treatment. 

Haematological response was defined as meeting one or more of the following criteria: 1) platelet 

count increases to 20,000/µl above baseline or stable platelet counts with transfusion independence for 

a minimum of 8 weeks; 2) haemoglobin increase by >1.5g/dl, or a reduction in ≥4 units of red blood 

cell (RBC) transfusions for 8 consecutive weeks; 3) absolute neutrophil count (ANC) increase of 

100% or an ANC increase >0.5 x 109/l. 

 

The haematological response rate was 40% (17/43 patients; 95 % CI 25, 56), the majority were 

unilineage responses (13/17, 76%) whilst there were 3 bilineage and 1 trilineage responses at week 12. 

Eltrombopag was discontinued after 16 weeks if no haematological response or transfusion 

independence was observed. Patients who responded continued therapy in an extension phase of the 

study. A total of 14 patients entered the extension phase of the trial. Nine of these patients achieved a 

multi-lineage response, 4 of the 9 remain on treatment and 5 tapered off treatment with eltrombopag 

and maintained the response (median follow up: 20.6 months, range: 5.7 to 22.5 months). The 

remaining 5 patients discontinued treatment, three due to relapse at the month 3 extension visit. 

 

During treatment with eltrombopag 59% (23/39) became platelet transfusion independent (28 days 

without platelet transfusion) and 27% (10/37) became RBC transfusion independent (56 days without 

RBC transfusion). The longest platelet transfusion-free period for non-responders was 27 days 

(median). The longest platelet transfusion-free period for responders was 287 days (median). The 

longest RBC transfusion-free period for non-responders was 29 days (median). The longest RBC 

transfusion-free period for responders was 266 days (median). 

 

Over 50% of responders who were transfusion-dependent at baseline, had >80% reduction in both 

platelet and RBC transfusion requirements compared to baseline. 

 

Preliminary results from a supportive study (Study ELT116826), an ongoing non-randomised, 

phase II, single-arm, open-label study in refractory SAA patients, showed consistent results. Data are 

limited to 21 out of the planned 60 patients with haematological responses reported by 52% of patients 

at 6 months. Multilineage responses were reported by 45% of patients. 

 

5.2 Pharmacokinetic properties 
 

Pharmacokinetics 

 

The plasma eltrombopag concentration-time data collected in 88 patients with ITP in studies 

TRA100773A and TRA100773B were combined with data from 111 healthy adult subjects in a 

population PK analysis. Plasma eltrombopag AUC(0-) and Cmax estimates for ITP patients are 

presented (Table 8). 

 

Table 8 Geometric mean (95% confidence intervals) of steady-state plasma eltrombopag 

pharmacokinetic parameters in adults with ITP 

 

Eltrombopag dose, once 

daily 

N AUC(0-)a, g.h/ml Cmaxa, g/ml 

30 mg 28 47 (39, 58) 3.78 (3.18, 4.49) 

50 mg 34 108 (88, 134) 8.01 (6.73, 9.53) 

75 mg 26 168 (143, 198) 12.7 (11.0, 14.5) 

a AUC(0-) and Cmax based on population PK post-hoc estimates. 

 

  



62 

Plasma eltrombopag concentration-time data collected in 590 patients with HCV enrolled in phase III 

studies TPL103922/ENABLE 1 and TPL108390/ENABLE 2 were combined with data from patients 

with HCV enrolled in the phase II study TPL102357 and healthy adult subjects in a population PK 

analysis. Plasma eltrombopag Cmax and AUC(0-) estimates for patients with HCV enrolled in the 

phase III studies are presented for each dose studied in Table 9. 

 

Table 9 Geometric mean (95% CI) steady-state plasma eltrombopag pharmacokinetic 

parameters in patients with chronic HCV 

 

Eltrombopag dose 

(once daily) 

N AUC(0-) 

(g.h/ml) 

Cmax 

(g/ml) 

25 mg 330 118 

(109, 128) 

6.40 

(5.97, 6.86) 

50 mg 119 166 

(143, 192) 

9.08 

(7.96, 10.35) 

75 mg 45 301 

(250, 363) 

16.71 

(14.26, 19.58) 

100 mg 96 354 

(304, 411) 

19.19 

(16.81, 21.91) 

Data presented as geometric mean (95% CI). 

AUC (0-) and Cmax based on population PK post-hoc estimates at the highest dose in the data for each 

patient. 

 

Absorption and bioavailability 

 

Eltrombopag is absorbed with a peak concentration occurring 2 to 6 hours after oral administration. 

Administration of eltrombopag concomitantly with antacids and other products containing polyvalent 

cations such as dairy products and mineral supplements significantly reduces eltrombopag exposure 

(see section 4.2). In a relative bioavailability study in adults, the eltrombopag powder for oral 

suspension delivered 22% higher plasma AUC(0-) than the film-coated tablet formulation. The 

absolute oral bioavailability of eltrombopag after administration to humans has not been established. 

Based on urinary excretion and metabolites eliminated in faeces, the oral absorption of drug-related 

material following administration of a single 75 mg eltrombopag solution dose was estimated to be at 

least 52%. 

 

Distribution 

 

Eltrombopag is highly bound to human plasma proteins (>99.9%), predominantly to albumin. 

Eltrombopag is a substrate for BCRP, but is not a substrate for P-glycoprotein or OATP1B1. 

 

Biotransformation 

 

Eltrombopag is primarily metabolised through cleavage, oxidation and conjugation with glucuronic 

acid, glutathione, or cysteine. In a human radiolabel study, eltrombopag accounted for approximately 

64% of plasma radiocarbon AUC0-. Minor metabolites due to glucuronidation and oxidation were 

also detected. In vitro studies suggest that CYP1A2 and CYP2C8 are responsible for oxidative 

metabolism of eltrombopag. Uridine diphosphoglucuronyl transferase UGT1A1 and UGT1A3 are 

responsible for glucuronidation, and bacteria in the lower gastrointestinal tract may be responsible for 

the cleavage pathway. 

 

  



63 

Elimination 

 

Absorbed eltrombopag is extensively metabolised. The predominant route of eltrombopag excretion is 

via faeces (59%) with 31% of the dose found in the urine as metabolites. Unchanged parent compound 

(eltrombopag) is not detected in urine. Unchanged eltrombopag excreted in faeces accounts for 

approximately 20% of the dose. The plasma elimination half-life of eltrombopag is approximately 

21-32 hours. 

 

Pharmacokinetic interactions 

 

Based on a human study with radiolabelled eltrombopag, glucuronidation plays a minor role in the 

metabolism of eltrombopag. Human liver microsome studies identified UGT1A1 and UGT1A3 as the 

enzymes responsible for eltrombopag glucuronidation. Eltrombopag was an inhibitor of a number of 

UGT enzymes in vitro. Clinically significant drug interactions involving glucuronidation are not 

anticipated due to limited contribution of individual UGT enzymes in the glucuronidation of 

eltrombopag. 

 

Approximately 21% of an eltrombopag dose could undergo oxidative metabolism. Human liver 

microsome studies identified CYP1A2 and CYP2C8 as the enzymes responsible for eltrombopag 

oxidation. Eltrombopag does not inhibit or induce CYP enzymes based on in vitro and in vivo data 

(see section 4.5). 

 

In vitro studies demonstrate that eltrombopag is an inhibitor of the OATP1B1 transporter and an 

inhibitor of the BCRP transporter and eltrombopag increased exposure of the OATP1B1 and BCRP 

substrate rosuvastatin in a clinical drug interaction study (see section 4.5). In clinical studies with 

eltrombopag, a dose reduction of statins by 50% was recommended. 

 

Eltrombopag chelates with polyvalent cations such as iron, calcium, magnesium, aluminium, selenium 

and zinc (see sections 4.2 and 4.5). 

 

In vitro studies demonstrated that eltrombopag is not a substrate for the organic anion transporter 

polypeptide, OATP1B1, but is an inhibitor of this transporter (IC50 value of 2.7 μM (1.2 μg/ml). In 

vitro studies also demonstrated that eltrombopag is a breast cancer resistance protein (BCRP) substrate 

and inhibitor (IC50 value of 2.7 μM (1.2 μg/ml). 

 

Special patient populations 

 

Renal impairment 

 

The pharmacokinetics of eltrombopag have been studied after administration of eltrombopag to adult 

patients with renal impairment. Following administration of a single 50 mg dose, the AUC0- of 

eltrombopag was 32% to 36% lower in patients with mild to moderate renal impairment, and 60% 

lower in patients with severe renal impairment compared with healthy volunteers. There was 

substantial variability and significant overlap in exposures between patients with renal impairment and 

healthy volunteers. Unbound eltrombopag (active) concentrations for this highly protein-bound 

medicinal product were not measured. Patients with impaired renal function should use eltrombopag 

with caution and close monitoring, for example by testing serum creatinine and/or urine analysis (see 

section 4.2). The efficacy and safety of eltrombopag have not been established in patients with both 

moderate to severe renal impairment and hepatic impairment. 

 

  



64 

Hepatic impairment 

 

The pharmacokinetics of eltrombopag have been studied after administration of eltrombopag to adult 

patients with hepatic impairment. Following the administration of a single 50 mg dose, the AUC0- of 

eltrombopag was 41% higher in patients with mild hepatic impairment and 80% to 93% higher in 

patients with moderate to severe hepatic impairment compared with healthy volunteers. There was 

substantial variability and significant overlap in exposures between patients with hepatic impairment 

and healthy volunteers. Unbound eltrombopag (active) concentrations for this highly protein-bound 

medicinal product were not measured. 

 

The influence of hepatic impairment on the pharmacokinetics of eltrombopag following repeat 

administration was evaluated using a population pharmacokinetic analysis in 28 healthy adults and 

714 patients with hepatic impairment (673 patients with HCV and 41 patients with chronic liver 

disease of other aetiology). Of the 714 patients, 642 were with mild hepatic impairment, 67 with 

moderate hepatic impairment, and 2 with severe hepatic impairment. Compared to healthy volunteers, 

patients with mild hepatic impairment had approximately 111% (95% CI: 45% to 283%) higher 

plasma eltrombopag AUC(0-) values and patients with moderate hepatic impairment had 

approximately 183% (95% CI: 90% to 459%) higher plasma eltrombopag AUC(0-) values. 

 

Therefore, eltrombopag should not be used in ITP patients with hepatic impairment (Child-Pugh score 

≥5) unless the expected benefit outweighs the identified risk of portal venous thrombosis (see 

sections 4.2 and 4.4). For patients with HCV initiate eltrombopag at a dose of 25 mg once daily (see 

section 4.2). 

 

Race 

 

The influence of Asian ethnicity (such as Japanese, Chinese, Taiwanese and Korean) on the 

pharmacokinetics of eltrombopag was evaluated using a population pharmacokinetic analysis in 111 

healthy adults (31 Asians) and 88 patients with ITP (18 Asians). Based on estimates from the 

population pharmacokinetic analysis, Asian ITP patients had approximately 49% higher plasma 

eltrombopag AUC(0-) values as compared to non-Asian patients who were predominantly Caucasian 

(see section 4.2). 

 

The influence of Asian ethnicity (such as Chinese, Japanese, Taiwanese, Korean, and Thai) on the 

pharmacokinetics of eltrombopag was evaluated using a population pharmacokinetic analysis in 

635 patients with HCV (145 Asians and 69 South Asians). Based on estimates from the population 

pharmacokinetic analysis, Asian patients had approximately 55% higher plasma eltrombopag AUC(0-) 

values as compared to patients of other races who were predominantly Caucasian (see section 4.2). 

 

Gender 

 

The influence of gender on the pharmacokinetics of eltrombopag was evaluated using a population 

pharmacokinetic analysis in 111 healthy adults (14 females) and 88 patients with ITP (57 females). 

Based on estimates from the population pharmacokinetic analysis, female ITP patients had 

approximately 23% higher plasma eltrombopag AUC(0-) as compared to male patients, without 

adjustment for body weight differences. 

 

The influence of gender on eltrombopag pharmacokinetics was evaluated using population 

pharmacokinetics analysis in 635 patients with HCV (260 females). Based on model estimate, female 

HCV patient had approximately 41% higher plasma eltrombopag AUC(0-) as compared to male 

patients. 

 

  



65 

Age 

 

The influence of age on eltrombopag pharmacokinetics was evaluated using population 

pharmacokinetics analysis in 28 healthy subjects, 673 patients with HCV, and 41 patients with chronic 

liver disease of other aetiology ranging from 19 to 74 years old. There are no PK data on the use of 

eltrombopag in patients ≥75 years. Based on model estimate, elderly (≥65 years) patients had 

approximately 41% higher plasma eltrombopag AUC(0-) as compared to younger patients (see 

section 4.2). 

 

Paediatric Population (aged 1 to 17 years) 

 

The pharmacokinetics of eltrombopag have been evaluated in 168 paediatric ITP patients dosed once 

daily in two studies, TRA108062/PETIT and TRA115450/PETIT-2. Plasma eltrombopag apparent 

clearance following oral administration (CL/F) increased with increasing body weight. The effects of 

race and sex on plasma eltrombopag CL/F estimates were consistent between paediatric and adult 

patients. Asian paediatric ITP patients had approximately 43% higher plasma eltrombopag AUC(0-) 

values as compared to non-Asian patients. Female paediatric ITP patients had approximately 25% 

higher plasma eltrombopag AUC(0-) values as compared to male patients. 

 

The pharmacokinetic parameters of eltrombopag in paediatric patients with ITP are shown in 

Table 10. 

 

Table 10 Geometric mean (95% CI) steady-state plasma eltrombopag pharmacokinetic 

parameters in paediatric patients with ITP (50 mg once daily dosing regimen) 

 

Age Cmax 
(µg/ml) 

AUC(0-) 
(µg.hr/ml) 

12 to 17 years (n=62) 6.80 

(6.17, 7.50) 

103 

(91.1, 116) 

6 to 11 years (n=68) 10.3 

(9.42, 11.2) 

153 

(137, 170) 

1 to 5 years (n=38) 11.6 

(10.4, 12.9) 

162 

(139, 187) 

Data presented as geometric mean (95% CI). AUC(0-) and Cmax based on population PK post-hoc 

estimates 

 

5.3 Preclinical safety data 
 

Safety pharmacology and repeat-dose toxicity 

 

Eltrombopag does not stimulate platelet production in mice, rats or dogs because of unique TPO 

receptor specificity. Therefore, data from these animals do not fully model potential adverse effects 

related to the pharmacology of eltrombopag in humans, including the reproduction and carcinogenicity 

studies. 

 

Treatment-related cataracts were detected in rodents and were dose and time-dependent. At ≥6 times 

the human clinical exposure in adult ITP patients at 75 mg/day and 3 times the human clinical 

exposure in adult HCV patients at 100 mg/day, based on AUC, cataracts were observed in mice after 

6 weeks and rats after 28 weeks of dosing. At 4 times the human clinical exposure in ITP patients at 

75 mg/day and 2 times the human exposure in HCV patients at 100 mg/day, based on AUC, cataracts 

were observed in mice after 13 weeks and in rats after 39 weeks of dosing. At non-tolerated doses in 

pre-weaning juvenile rats dosed from days 4-32 (approximately equating to a 2-year-old human at the 

end of the dosing period), ocular opacities were observed (histology not performed) at 9 times the 

maximum human clinical exposure in paediatric ITP patients at 75 mg/day, based on AUC. However, 

cataracts were not observed in juvenile rats given tolerated doses at 5 times the human clinical 

exposure in paediatric ITP patients, based on AUC. Cataracts have not been observed in adult dogs 

after 52 weeks of dosing at 2 times the human clinical exposure in adult or paediatric ITP patients at 



66 

75 mg/day and equivalent to the human clinical exposure in HCV patients at 100 mg/day, based on 

AUC). 

 

Renal tubular toxicity was observed in studies of up to 14 days duration in mice and rats at exposures 

that were generally associated with morbidity and mortality. Tubular toxicity was also observed in a 

2-year oral carcinogenicity study in mice at doses of 25, 75 and 150 mg/kg/day. Effects were less 

severe at lower doses and were characterised by a spectrum of regenerative changes. The exposure at 

the lowest dose was 1.2 or 0.8 times the human clinical exposure based on AUC in adult or paediatric 

ITP patients at 75 mg/day and 0.6 times the human clinical exposure in HCV patients at 100 mg/day, 

based on AUC. Renal effects were not observed in rats after 28 weeks or in dogs after 52 weeks at 

exposures 4 and 2 times the human clinical exposure in adult ITP patients and 3 and 2 times the 

human clinical exposure in paediatric ITP patients at 75 mg/day and 2 times and equivalent to the 

human clinical exposure in HCV patients at 100 mg/day, based on AUC. 

 

Hepatocyte degeneration and/or necrosis, often accompanied by increased serum liver enzymes, was 

observed in mice, rats and dogs at doses that were associated with morbidity and mortality or were 

poorly tolerated. No hepatic effects were observed after chronic dosing in rats (28 weeks) and in dogs 

(52 weeks) at 4 or 2 times the human clinical exposure in adult ITP and 3 or 2 times the human 

clinical exposure in paediatric ITP patients at 75 mg/day and 2 times and equivalent to the human 

clinical exposure in HCV patients at 100 mg/day, based on AUC. 

 

At poorly tolerated doses in rats and dogs (>10 or 7 times the human clinical exposure in adult or 

paediatric ITP patients at 75 mg/day and>4 times the human clinical exposure in HCV patients at 

100 mg/day, based on AUC), decreased reticulocyte counts and regenerative bone marrow erythroid 

hyperplasia (rats only) were observed in short-term studies. There were no effects of note on red cell 

mass or reticulocyte counts after dosing for up to 28 weeks in rats, 52 weeks in dogs and 2 years in 

mice or rats at maximally tolerated doses which were 2 to 4 times human clinical exposure in adult or 

paediatric ITP patients at 75 mg/day and ≤2 times the human clinical exposure in HCV patients at 

100 mg/day, based on AUC. 

 

Endosteal hyperostosis was observed in a 28-week toxicity study in rats at a non-tolerated dose of 

60 mg/kg/day (6 times or 4 times the human clinical exposure in adult or paediatric ITP patients at 

75 mg/day and 3 times the human clinical exposure in HCV patients at 100 mg/day, based on AUC). 

There were no bone changes observed in mice or rats after lifetime exposure (2 years) at 4 times or 

2 times the human clinical exposure in adult or paediatric ITP patients at 75 mg/day and 2 times the 

human clinical exposure in HCV patients at 100 mg/day, based on AUC. 

 

Carcinogenicity and mutagenicity 

 

Eltrombopag was not carcinogenic in mice at doses up to 75 mg/kg/day or in rats at doses up to 

40 mg/kg/day (exposures up to 4 or 2 times the human clinical exposure in adult or paediatric ITP 

patients at 75 mg/day and 2 times the human clinical exposure in HCV patients at 100 mg/day, based 

on AUC). Eltrombopag was not mutagenic or clastogenic in a bacterial mutation assay or in two in 

vivo assays in rats (micronucleus and unscheduled DNA synthesis, 10 times or 8 times the human 

clinical exposure in adult or paediatric ITP patients at 75 mg/day and 7 times the human clinical 

exposure in HCV patients at 100 mg/day, based on Cmax). In the in vitro mouse lymphoma assay, 

eltrombopag was marginally positive (<3-fold increase in mutation frequency). These in vitro and in 

vivo findings suggest that eltrombopag does not pose a genotoxic risk to humans. 

 

  



67 

Reproductive toxicity 

 

Eltrombopag did not affect female fertility, early embryonic development or embryofoetal 

development in rats at doses up to 20 mg/kg/day (2 times the human clinical exposure in adult or 

adolescent (12-17 years) ITP patients at 75 mg/day and equivalent to the human clinical exposure in 

HCV patients at 100 mg/day, based on AUC). Also there was no effect on embryofoetal development 

in rabbits at doses up to 150 mg/kg/day, the highest dose tested (0.3 to 0.5 times the human clinical 

exposure in ITP patients at 75 mg/day and HCV patients at 100 mg/day, based on AUC). However, at 

a maternally toxic dose of 60 mg/kg/day (6 times the human clinical exposure in ITP patients at 

75 mg/day and 3 times the human clinical exposure in HCV patients at 100 mg/day, based on AUC) in 

rats, eltrombopag treatment was associated with embryo lethality (increased pre- and post-

implantation loss), reduced foetal body weight and gravid uterine weight in the female fertility study 

and a low incidence of cervical ribs and reduced foetal body weight in the embryofoetal development 

study. Eltrombopag should be used during pregnancy only if the expected benefit justifies the potential 

risk to the foetus (see section 4.6). Eltrombopag did not affect male fertility in rats at doses up to 

40 mg/kg/day, the highest dose tested (3 times the human clinical exposure in ITP patients at 

75 mg/day and 2 times the human clinical exposure in HCV patients at 100 mg/day, based on AUC). 

In the pre- and post-natal development study in rats, there were no undesirable effects on pregnancy, 

parturition or lactation of F0 female rats at maternally non-toxic doses (10 and 20 mg/kg/day) and no 

effects on the growth, development, neurobehavioural or reproductive function of the offspring (F1). 

Eltrombopag was detected in the plasma of all F1 rat pups for the entire 22 hour sampling period 

following administration of medicinal product to the F0 dams, suggesting that rat pup exposure to 

eltrombopag was likely via lactation. 

 

Phototoxicity 

 

In vitro studies with eltrombopag suggest a potential phototoxicity risk; however, in rodents there was 

no evidence of cutaneous phototoxicity (10 or 7 times the human clinical exposure in adult or 

paediatric ITP patients at 75 mg/day and 5 times the human clinical exposure in HCV patients at 

100 mg/day, based on AUC) or ocular phototoxicity (4 times the human clinical exposure in adult or 

paediatric ITP patients at 75 mg/day and 3 times the human clinical exposure in HCV patients at 

100 mg/day, based on AUC). Furthermore, a clinical pharmacology study in 36 subjects showed no 

evidence that photosensitivity was increased following administration of eltrombopag 75 mg. This was 

measured by delayed phototoxic index. Nevertheless, a potential risk of photoallergy cannot be ruled 

out since no specific preclinical study could be performed. 

 

Juvenile animal studies 

 

At non-tolerated doses in pre-weaning rats, ocular opacities were observed. At tolerated doses, no 

ocular opacities were observed (see above subsection ‘Safety pharmacology and repeat-dose toxicity’). 

In conclusion, taking into account the exposure margins based on AUC, a risk of eltrombopag-related 

cataracts in paediatric patients cannot be excluded. There are no findings in juvenile rats to suggest a 

greater risk of toxicity with eltrombopag treatment in paediatric vs. adult ITP patients. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Mannitol (E421) 

Sucralose 

Xanthan gum 

 

6.2 Incompatibilities 
 

Not applicable. 

 



68 

6.3 Shelf life 
 

2 years. 

 

Following reconstitution, the medicinal product should be administered immediately but may be 

stored for a maximum period of 30 minutes. 

 

6.4 Special precautions for storage 
 

This medicinal product does not require any special storage conditions. 

 

For storage conditions after reconstitution of the medicinal product, see section 6.3. 

 

6.5 Nature and contents of container 

 

Heat-sealed foil laminate sachets. The laminate material is comprised of polyester (PET) / orientated 

polyamide (OPA) / 9 µm aluminium foil (AL) / low density polyethylene heat seal layer (LDPE). The 

product contact material is the polyethylene heat seal layer. The sachets are co-packaged in a kit with a 

40 ml HDPE mixing bottle, and 30 single-use 20 ml oral dosing syringes (polypropylene/silicon 

rubber) with 1 ml graduations. In addition, a screw cap (ethylene vinyl acetate / LDPE) with syringe-

port capability is provided. 

 

Pack size of 30 sachets. 

 

6.6 Special precautions for disposal 
 

Instructions for use 

 

Avoid direct contact with the medicine. Wash any exposed area immediately with soap and water. 

 

Preparation and administration of the powder for oral suspension: 

 Administer the oral suspension immediately after preparation. Discard suspension if not 
administered within 30 minutes after preparation. 

 Prepare the suspension with water only. 

 Add 20 ml of water and the contents of the prescribed number of sachets (depending on the 
recommended dose) to the provided mixing bottle and mix gently. 

 Give the entire contents of the bottle to the patient using one of the accompanying oral syringes. 

 IMPORTANT: Because some medicine will remain in the mixing bottle, complete the 
following steps. 

 Add 10 ml of water to the mixing bottle and mix gently. 

 Give the entire contents of the bottle to the patient using the same oral syringe. 
 

Cleaning of the mixing equipment: 

 Discard the used oral syringe. 

 Rinse the mixing bottle and lid, under running water. (The mixing bottle may become stained 
from the medicine. This is normal.) 

 Let all the equipment dry in the air. 

 Wash your hands with soap and water. 
 

Do not re-use the oral dosing syringe. A new single-use oral dosing syringe should be used to prepare 

each dose of Revolade for oral suspension. 

 

For more details on preparation and administration of the suspension, see Instructions for Use in the 

package leaflet. 

 



69 

Disposal 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/10/612/013 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 11 March 2010 

Date of latest renewal: 15 January 2015 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu/. 
  



70 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 
 

A. MANUFACTURERS RESPONSIBLE FOR BATCH 

RELEASE 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 

PRODUCT 

 



71 

A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturers responsible for batch release 

 

Revolade 12.5 mg, 25 mg, 50 mg and 75 mg film-coated tablets: 

 

Novartis Farmacéutica SA 

Ronda de Santa Maria 158 

08210 Barberà del Vallès (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 

 

Revolade 25 mg powder for oral suspension: 

 

Lek d.d 

Verovskova Ulica 57 

Ljubljana 1526 

Slovenia 

 

Novartis Pharma GmbH 

Roonstraße 25 

D-90429 Nuremberg 

Germany 

 

The printed package leaflet of the medicinal product must state the name and address of the 

manufacturer responsible for the release of the concerned batch. 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

Medicinal product subject to restricted medical prescription. (see Annex I: Summary of Product 

Characteristics, section 4.2). 

 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 

 Periodic Safety Update Reports 
 

The requirements for submission of periodic safety update reports for this medicinal product are set 

out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 

2001/83/EC and any subsequent updates published on the European medicines web-portal. 

 

  



72 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

 Risk Management Plan (RMP) 
 

The MAH shall perform the required pharmacovigilance activities and interventions detailed in 

the agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed 

subsequent updates of the RMP. 

 

An updated RMP should be submitted: 

 At the request of the European Medicines Agency; 

 Whenever the risk management system is modified, especially as the result of new information 
being received that may lead to a significant change to the benefit/risk profile or as the result of 

an important (pharmacovigilance or risk minimisation) milestone being reached. 

 

  



73 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

  



74 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 

  



75 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON OF 12.5 mg – 14, 28, 84 (3 PACKS of 28) TABLETS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Revolade 12.5 mg film-coated tablets 

 

eltrombopag 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

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

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 film-coated tablets 

28 film-coated tablets 

Multipack containing 84 (3 packs of 28) film-coated tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. Oral use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

  



76 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/10/612/010 (14 film-coated tablets) 

EU/1/10/612/011 (28 film-coated tablets) 

EU/1/10/612/012 84 film-coated tablets (3 packs of 28) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

revolade 12.5 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 
 

  



77 

 

PARTICULARS TO APPEAR ON INTERMEDIATE CARTON 

 

Multipacks of 84 (3 packs of 28 film-coated tablets) – without blue box – 12.5 mg film-coated 

tablets 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Revolade 12.5 mg film-coated tablets 

 

eltrombopag 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

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

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

28 film-coated tablets. Component of a multipack, can’t be sold separately. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. Oral use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

  



78 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/10/612/012 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

revolade 12.5 mg 

 

  



79 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

Blister 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Revolade 12.5 mg film-coated tablets 

 

eltrombopag 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

  



80 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON OF 25 mg – 14, 28, 84 (3 PACKS of 28) TABLETS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Revolade 25 mg film-coated tablets 

 

eltrombopag 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

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

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 film-coated tablets 

28 film-coated tablets 

Multipack containing 84 (3 packs of 28) film-coated tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. Oral use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

  



81 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/10/612/001 (14 film-coated tablets) 

EU/1/10/612/002 (28 film-coated tablets) 

EU/1/10/612/003 84 film-coated tablets (3 packs of 28) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

revolade 25 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

  



82 

 

PARTICULARS TO APPEAR ON INTERMEDIATE CARTON 

 

Multipacks of 84 (3 packs of 28 film-coated tablets) – without blue box – 25 mg film-coated 

tablets 

 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Revolade 25 mg film-coated tablets 

 

eltrombopag 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

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

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

28 film-coated tablets. Component of a multipack, can’t be sold separately. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. Oral use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

  



83 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/10/612/003 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

revolade 25 mg 

 

  



84 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

Blister 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Revolade 25 mg film-coated tablets 

 

eltrombopag 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

  



85 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON OF 50 mg – 14, 28, 84 (3 PACKS of 28) TABLETS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Revolade 50 mg film-coated tablets 

 

eltrombopag 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

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

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 film-coated tablets 

28 film-coated tablets 

Multipack containing 84 (3 packs of 28) film-coated tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. Oral use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

  



86 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/10/612/004 (14 film-coated tablets) 

EU/1/10/612/005 (28 film-coated tablets) 

EU/1/10/612/006 84 film-coated tablets (3 packs of 28) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

revolade 50 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

  



87 

 

PARTICULARS TO APPEAR ON INTERMEDIATE CARTON 

 

Multipacks of 84 (3 packs of 28 film-coated tablets) – without blue box – 50 mg film-coated 

tablets 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Revolade 50 mg film-coated tablets 

 

eltrombopag 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

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

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

28 film-coated tablets. Component of a multipack, can’t be sold separately. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. Oral use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

  



88 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/10/612/006 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

revolade 50 mg 

 

 

  



89 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

Blister 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Revolade 50 mg film-coated tablets 

 

eltrombopag 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

  



90 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON OF 75 mg – 14, 28, 84 (3 PACKS of 28) TABLETS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Revolade 75 mg film-coated tablets 

 

eltrombopag 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains eltrombopag olamine equivalent to 75 mg eltrombopag 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 film-coated tablets 

28 film-coated tablets 

Multipack containing 84 (3 packs of 28) film-coated tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. Oral use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

  



91 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/10/612/007 (14 film-coated tablets) 

EU/1/10/612/008 (28 film-coated tablets) 

EU/1/10/612/009 84 film-coated tablets (3 packs of 28) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

revolade 75 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 
 

  



92 

 

PARTICULARS TO APPEAR ON INTERMEDIATE CARTON 

 

Multipacks of 84 (3 packs of 28 film-coated tablets) – without blue box –75 mg film-coated 

tablets 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Revolade 75 mg film-coated tablets 

 

eltrombopag 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains eltrombopag olamine equivalent to 75 mg eltrombopag 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

28 film-coated tablets. Component of a multipack, can’t be sold separately. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. Oral use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

  



93 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/10/612/009 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

revolade 75 mg 

 

 

  



94 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

Blister 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Revolade 75 mg film-coated tablets 

 

eltrombopag 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

  



95 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

Carton of 25 mg powder for oral suspension 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Revolade 25 mg powder for oral suspension 

 

eltrombopag 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each sachet contains eltrombopag olamine equivalent to 25 mg of eltrombopag. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

30 sachets and 1 mixing bottle + 30 single-use oral syringes 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

Use within 30 minutes of reconstitution. 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

  



96 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/10/612/013 (30 sachets of powder for oral suspension) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

revolade 25 mg sachets 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 
 

  



97 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

Carton of 25 mg powder for oral suspension – without blue box – 30 sachets 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Revolade 25 mg powder for oral suspension 

 

eltrombopag 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each sachet contains eltrombopag olamine equivalent to 25 mg of eltrombopag. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

30 sachets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

Use within 30 minutes of reconstitution. 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

  



98 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/10/612/013 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

revolade 25 mg sachets 

 

  



99 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

SACHET 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Revolade 25 mg powder for oral suspension 

 

eltrombopag 

 

Oral use 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

  



100 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 



101 

Package Leaflet: Information for the patient 

 

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 all of this leaflet carefully before you start taking this medicine because it contains 

important information for you. 
- 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 of the side effects talk to your doctor or pharmacist. This includes any possible 
side effects not listed in this leaflet. See section 4 

 

What is in this leaflet: 

1. What Revolade is and what it is used for 

2. What you need to know before you take Revolade 

3. How to take Revolade 

4. Possible side effects 

5. How to store Revolade 

6. Contents of the pack and other information 

 

 

1. What Revolade is and what it is used for 

 

Revolade contains eltrombopag, which belongs to a group of medicines called thrombopoietin 

receptor agonists. It is used to help increase the number of platelets in your blood. Platelets are blood 

cells that help to reduce or prevent bleeding. 

 

 Revolade is used to treat a bleeding disorder called immune (primary) thrombocytopenia (ITP) 
in patients aged 1 year and above who have already taken other medicines (corticosteroids or 

immunoglobulins), which have not worked. 

 

ITP is caused by a low blood platelet count (thrombocytopenia). People with ITP have an 

increased risk of bleeding. Symptoms patients with ITP may notice include petechiae (pinpoint-

sized flat round red spots under the skin), bruising, nosebleeds, bleeding gums and not being 

able to control bleeding if they are cut or injured. 

 

 Revolade can also be used to treat low platelet count (thrombocytopenia) in adults with 
hepatitis C virus (HCV) infections, if they have had problems with side effects while on 

interferon treatment. Many people with hepatitis C have low platelet counts, not only as a result 

of the disease, but also due to some of the antiviral medicines that are used to treat it. Taking 

Revolade may make it easier for you to complete a full course of antiviral medicine 

(peginterferon and ribavirin). 

 

 Revolade may also be used to treat adult patients with low blood counts caused by severe 
aplastic anaemia (SAA). SAA is a disease in which the bone marrow is damaged, causing a 

deficiency of the red blood cells (anaemia), white blood cells (leukopenia) and platelets 

(thrombocytopenia). 

 



102 

 

2. What you need to know before you take Revolade 

 

Do not take Revolade 

 if you are allergic to eltrombopag or any of the other ingredients of this medicine (listed in 
section 6 under ‘What Revolade contains’). 

 Check with your doctor if you think this applies to you. 
 

Warnings and precautions 

Talk to your doctor before taking Revolade: 

 if you have liver problems. People who have low platelet counts as well as advanced chronic 
(long-term) liver disease are more at risk of side effects, including life-threatening liver damage 

and blood clots. If your doctor considers that the benefits of taking Revolade outweigh the risks, 

you will be closely monitored during treatment. 

 if you are at risk of blood clots in your veins or arteries, or you know that blood clots are 
common in your family. 

You may be at higher risk of blood clots: 

- as you get older 
- if you have had to stay in bed for a long time 
- if you have cancer 
- if you are taking the contraceptive birth control pill or hormone replacement therapy 
- if you have recently had surgery or received a physical injury 
- if you are very overweight (obese) 
- if you are a smoker 
- if you have advanced chronic liver disease 
 If any of these apply to you, tell your doctor before starting treatment. You should not 

take Revolade unless your doctor considers that the expected benefits outweigh the risk of 

blood clots. 

 if you have cataracts (the lens of the eye getting cloudy) 

 if you have another blood condition, such as myelodysplastic syndrome (MDS). Your doctor 
will carry out tests to check that you do not have this blood condition before you start Revolade. 

If you have MDS and take Revolade, your MDS may get worse. 

 Tell your doctor if any of these apply to you. 
 

Eye examinations 
Your doctor will recommend that you are checked for cataracts. If you do not have routine eye-tests 

your doctor should arrange regular testing. You may also be checked for the occurrence of any 

bleeding in or around your retina (the light-sensitive layer of cells at the back of the eye). 

 

You will need regular tests 

Before you start taking Revolade, your doctor will carry out blood tests to check your blood cells, 

including platelets. These tests will be repeated at intervals while you are taking it. 

 

Blood tests for liver function 

Revolade can cause blood test results that may be signs of liver damage - an increase of some liver 

enzymes, especially bilirubin and alanine / aspartate transaminases. If you are taking interferon-based 

treatments together with Revolade to treat low platelet count due to hepatitis C, some liver problems 

can get worse. 

 

You will have blood tests to check your liver function before you start taking Revolade and at 

intervals while you are taking it. You may need to stop taking Revolade if the amount of these 

substances increases too much, or if you get other signs of liver damage. 

 Read the information ‘Liver problems’ in section 4 of this leaflet. 
 

  



103 

Blood tests for platelet count 

If you stop taking Revolade, your blood platelet count is likely to become low again within several 

days. The platelet count will be monitored, and your doctor will discuss appropriate precautions with 

you. 

 

A very high blood platelet count may increase the risk of blood clotting. However blood clots can also 

form with normal or even low platelet counts. Your doctor will adjust your dose of Revolade to ensure 

that your platelet count does not become too high. 

 

 Get medical help immediately if you have any of these signs of a blood clot: 

 swelling, pain or tenderness in one leg 

 sudden shortness of breath especially together with sharp pain in the chest or rapid breathing 

 abdominal (stomach) pain, enlarged abdomen, blood in your stools 
 

Tests to check your bone marrow 

In people who have problems with their bone marrow, medicines like Revolade could make the 

problems worse. Signs of bone marrow changes may show up as abnormal results in your blood tests. 

Your doctor may also carry out tests to directly check your bone marrow during treatment with 

Revolade. 

 

Checks for digestive bleeding 

If you are taking interferon-based treatments together 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 it necessary to monitor your heart during treatment with Revolade and carry 

out an electrocardiogram (ECG) test. 

 

Older people (65 years and above) 

There are limited data on the use of Revolade in patients aged 65 years and older. Care should be 

taken when using Revolade if you are aged 65 years or above. 

 

Children and adolescents 

Revolade is not recommended for children aged under 1 year who have ITP. It is also not 

recommended for people under 18 years with low platelet counts due to hepatitis C or severe aplastic 

anaemia. 

 

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 prescription and vitamins. 

 

Some everyday medicines interact with Revolade – including prescription and non-prescription 

medicines and minerals. These include: 

 antacid medicines to treat indigestion, heartburn or stomach ulcers (see also ‘When to take it’ 
in section 3) 

 medicines called statins, to lower cholesterol 

 some medicines to treat HIV infection, such as lopinavir and/or ritonavir 

 ciclosporin used in the context of transplantations or immune diseases 

 minerals such as iron, calcium, magnesium, aluminium, selenium and zinc which may be found 
in vitamin and mineral supplements (see also ‘When to take it’ in section 3) 

 medicines such as methotrexate and topotecan, to treat cancer 
 Talk to your doctor if you take any of these. Some of them are not to be taken with Revolade, 

or the dose may need adjusting, or you may need to alter the timing of when you take them. 

Your doctor will review the medicines you are taking, and suggest suitable replacements if 

necessary. 

 



104 

If you are also taking medicines to prevent blood clots there is a greater risk of bleeding. 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 

to stop taking them while you are taking Revolade. 

 

Revolade with food and drink 

Do not take Revolade with dairy foods or drinks as the calcium in dairy products affects the absorption 

of the medicine. For more information, see ‘When to take it’ in section 3. 

 

Pregnancy and breast-feeding 

Don’t use Revolade if you are pregnant unless 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 are planning to have a 
baby. 

 Use a reliable method of contraception while you’re taking Revolade, to prevent pregnancy 

 If you do become pregnant during treatment with Revolade, tell your doctor. 
 

Don’t breast-feed while you are taking Revolade. It is not known whether Revolade passes into 

breast-milk. 

 If you are breast-feeding or planning to breast-feed, tell your doctor. 
 

Driving and using machines 

Revolade can make you dizzy and have other side effects that make you less alert. 

 Don’t drive or use machines unless you are sure you’re not affected. 
 

 

3. How to take Revolade 

 

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 

if you are not sure. Do not change the dose or schedule for taking Revolade unless your doctor or 

pharmacist advises you to. While you are taking Revolade, you will be under the care of a doctor with 

specialist experience in treating your condition. 

 

How much to take 

For ITP 

Adults and children (6 to 17 years) – the usual starting dose for ITP is one 50 mg tablet of Revolade 

a day. If you are of Asian origin (Chinese, Japanese, Taiwanese, Thai or Korean) you may need to 

start at a lower dose of 25 mg. 

 

Children (1 to 5 years) — the usual starting dose for ITP is one 25 mg tablet of Revolade a day. 

 

For hepatitis C 

Adults - the usual starting dose for hepatitis C is one 25 mg tablet of Revolade a day. If you are of 

Asian origin (Chinese, Japanese, Taiwanese, Thai or Korean) you will start on the same 25 mg dose. 

 

For SAA 

Adults - the usual starting dose for SAA is one 50 mg tablet of Revolade a day. If you are of Asian 

origin (Chinese, Japanese, Taiwanese, Thai or Korean) you may need to start at a lower dose of 

25 mg. 

 

Revolade may take 1 to 2 weeks to work. Based on your response to Revolade your doctor may 

recommend that your daily dose is changed. 

 

  



105 

How to take the tablets 
Swallow the tablet whole, with some water. 

 

When to take it 

 

Make sure that – 

 in the 4 hours before you take Revolade 

 and the 2 hours after you take Revolade 

 

you don’t consume any of the following: 

 dairy foods such as cheese, butter, yoghurt or ice cream 

 milk or milk shakes, drinks containing milk, yoghurt or cream 

 antacids, a type of medicine for indigestion and heartburn 

 some mineral and vitamin supplements including iron, calcium, magnesium, aluminium, 
selenium and zinc 

 

If you do, the medicine will not be properly absorbed into your body. 

 

 
 

For more advice about suitable foods and drinks, talk to your doctor. 

 

If you take more Revolade than you should 

Contact a doctor or pharmacist immediately. If possible show them the pack, or this leaflet. 

Youwill be monitored for any signs or symptoms of side effects and given appropriate 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 in one day. 

 

If you stop taking Revolade 

Don’t stop taking Revolade without talking to your doctor. If your doctor advises you to stop 

treatment, your platelet count will then be checked each week for four weeks. See also ‘Bleeding or 

bruising after you stop treatment’ in section 4. 

 

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

 

 

  

NO dairy products, antacids 
or mineral supplements 

Take Revolade 

For 4 hours 
before you  
take 

Revolade... 

    ...  and for 

2 hours after 



106 

4. Possible side effects 
 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

Symptoms needing attention: see a doctor 

People taking Revolade for either ITP or low blood platelet counts due to hepatitis C could develop 

signs of potentially serious side effects. It is important to tell a doctor if you develop these 

symptoms. 

 

Higher risk of blood clots 

Certain people may have a higher risk of blood clots, and medicines like Revolade could make this 

problem worse. The sudden blocking of a blood vessel by a blood clot is an uncommon side effect and 

may affect up to 1 in 100 people. 

 

Get medical help immediately if you develop signs and symptoms of a blood clot, such as: 

 swelling, pain, heat, redness, or tenderness in one leg 

 sudden shortness of breath, especially together with sharp pain in the chest or rapid breathing 

 abdominal (stomach) pain, enlarged abdomen, blood in your stools. 
 

Liver problems 

Revolade can cause changes that show up in blood tests, and may be signs of liver damage. Liver 

problems (increased enzymes showing up in blood tests) are common and may affect up to 1 in 

10 people. Other liver problems (bile not flowing properly) are uncommon and may affect up to 1 in 

100 people. 

 

If you have either of these signs of liver problems: 

 yellowing of the skin or the whites of the eyes (jaundice) 

 unusually dark-coloured urine 
 tell your doctor immediately. 
 

Bleeding or bruising after you stop treatment 

Within two weeks of stopping Revolade, your blood platelet count will usually drop back down to 

what it was before starting Revolade. The lower platelet count may increase the risk of bleeding or 

bruising. Your doctor will check your platelet count for at least 4 weeks after you stop taking 

Revolade. 

 Tell your doctor if you have any bleeding or bruising after stopping Revolade. 
 

Some people have bleeding in the digestive system after they stop taking peginterferon, ribavirin, and 

Revolade. Symptoms include: 

 black tarry stools (discoloured bowel movements are a uncommon side effect that may affect up 
to 1 in 100 people) 

 blood in your stools 

 vomiting blood or something that looks like coffee grounds 
 Tell your doctor immediately if you have any of these symptoms. 
 

The following side effects have been reported to be associated with treatment with Revolade in 

adult patients with ITP: 

 

Very common side effects 

These may affect more than 1 in 10 people: 

 common cold 

 feeling sick (nausea) 

 diarrhoea 

 cough 

 infection in the nose, sinuses, throat and upper airways, common cold (upper respiratory tract 
infection) 



107 

 

Very common side effects that may show up in blood tests: 

 increased of liver enzymes (alanine aminotransferase (ALT)) 
 

Common side effects 

These may affect up to 1 in 10 people: 

 muscle pain, muscle spasm, muscle weakness 

 back pain 

 bone pain 

 heavy menstrual period 

 sore throat and discomfort when swallowing  

 eye problems including abnormal eye test, dry eye, eye pain and blurred vision 

 vomiting 

 flu (influenza) 

 cold sore 

 pneumonia 

 irritation and inflammation (swelling) of the sinuses 

 inflammation (swelling) and infection of the tonsils infection of the lungs, sinuses, tonsils, nose 
and throat 

 inflammation of the gum tissue 

 loss of appetite 

 feeling of tingling, prickling or numbness, commonly called “pins and needles” 

 feeling drowsy 

 ear pain 

 pain, swelling and tenderness in one of your legs (usually the calf) with warm skin in the 
affected area (signs of a blood clot in a deep vein) 

 localised swelling filled with blood from a break in a blood vessel (haematoma) 

 mouth problems including dry mouth, sore mouth, sensitive tongue, bleeding gums, mouth 
ulcers 

 runny nose 

 toothache 

 stomach pain and tenderness 

 liver problems 

 skin changes including excessive sweating, itching bumpy rash, red spots, changes in 
appearance of the skin 

 hair loss 

 foamy, frothy or bubbly-looking urine (signs of protein in urine) 

 generally feeling unwell, high temperature, feeling hot 

 chest pain 

 problems sleeping, depression 

 migraine 

 decreased vision 

 spinning sensation (vertigo) 

 digestive wind/gas 
 

Common side effects that may show up in blood test: 

 decreased number of red blood cells (anaemia) 

 decreased number of platelets (thrombocytopenia) 

 decreased number of white blood cells 

 decreased haemaglobin level 

 decreased number of eosinophils 

 increased number of white blood cells (leukocytosis) 

 increased levels of uric acid 

 decreased levels of potassium 



108 

 increased levels of creatinine 

 increased levels of alkaline phosphatase 

 increase of liver enzymes (aspartate aminotransferase (AST)) 

 increase in bilirubin (a substance produced by the liver) 

 increased levels of some proteins 
 

Uncommon side effects 

These may affect up to 1 in 100 people: 

 interruption of blood supply to part of the heart 

 sudden shortness of breath, especially when accompanied with sharp pain in the chest and /or 
rapid breathing, which could be signs of a blood clot in the lungs (see ‘Higher risk of blood 

clots’ earlier in section 4) 

 the loss of function of part of the lung caused by a blockage in the lung artery 

 including yellowing of the eyes and skin (see ‘Liver problems’ earlier in section 4) 

 liver injury due to medication 

 heart beating faster, irregular heartbeat, bluish discolouration of the skin 

 disturbances of heart rhythm (QT prolongation) 

 blood clot 

 painful swollen joints caused by uric acid (gout) 

 lack of interest, mood changes 

 problems with balance, speech and nerve function, shaking 

 eye problems including increased production of tears, cloudy lens in the eye (cataract), bleeding 
of the retina 

 problems with the nose, throat and sinuses, breathing problems when sleeping 

 digestive system problems including frequent bowel movements, food poisoning, blood in stool 

 rectal bleeding, blood in your stool, abdominal bloating, constipation 

 mouth problems, including dry or sore mouth, sensitive tongue, bleeding gums 

 sunburn 

 redness or swelling around, a woundbleeding around a catheter (if present) into the 
skinsensation of a foreign body 

 kidney problems including inflammation of the kidney, excessive urination at night, kidney 
failure, white cells in urine 

 cold sweat 

 infection of the skin 

 skin changes including change in colour, peeling, redness, itching and sweating 
 

Uncommon side effects that may show up in laboratory tests: 

 changes in the shape of red blood cells 

 increased number of platelets 

 decreased levels of calcium 

 decreased number of red blood cells (anaemia) cause by excessive destruction of red blood cells 
(haemolytic anaemia) 

 increased number of myelocytes 

 increased band neutrophils 

 increased blood urea 

 increased levels of blood albumin 

 increased levels of total protein 

 decreased levels of blood albumin 

 increased pH of urine 

 increased haemaglobin level 
 



109 

The following additional side effects have been reported to be associated with treatment with 

Revolade in children (aged 1 to 17 years) with ITP: 

If these side effects become severe, please tell your doctor, pharmacist or nurse. 

 

Very common side effects 

These may affect more than 1 in 10 children: 

 infection in the nose, sinuses, throat and upper airways, common cold (upper respiratory tract 
infection) 

 diarrhoea 

 abdominal pain 

 cough 

 high temperature 

 feeling sick (nausea) 
 

Common side effects 

These may affect up to 1 in 10 children: 

 difficulty in sleeping (insomnia) 

 toothache 

 pain in the nose and throat 

 itchy, 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 to be associated with treatment with Revolade in 

combination with peginterferon and ribavirin in patients with HCV: 

 

Very common side effects 

These may affect more than 1 in 10 people: 

 headache 

 decreased appetite 

 cough 

 feeling sick (nausea), diarrhoea 

 muscle pain, muscle weakness 

 itching 

 lack of energy 

 high temperature 

 unusual hair loss 

 feeling weak 

 flu-like illness 

 swelling in the hands or feet 

 chills 
 

Very common side effects that may show up in blood tests: 

 decreased number of red blood cells (anaemia) 
 

Common side effects 

These may affect up to 1 in 10 people: 

 infection of the urinary system 

 inflammation of the nasal passages, throat and mouth, flu-like symptoms, dry mouth, sore or 
inflamed mouth, toothache 

 weight loss 

 sleep disorders, abnormal drowsiness, depression, anxiety 

 dizziness, problems with attention and memory, change in mood 

 tingling or numbness of the hands or feet 



110 

 fever, headache 

 eye problems, including cloudy lens in the eye (cataract), dry eye, small yellow deposits in the 
retina, yellowing of the whites of the eye 

 bleeding of the retina 

 spinning sensation (vertigo) 

 fast or irregular heartbeat (palpitations), shortness of breath 

 cough bringing up phlegm, runny nose, flu, cold sore, sore throat and discomfort when 
swallowing 

 digestive system problems, including being sick (vomiting), stomach pain, indigestion, 
constipation, swollen stomach, taste disturbances, inflammation of the stomach, piles 

(haemorrhoids), irritation of the gut 

 toothache 

 liver problems, including blood clot, tumour in the liver (see ‘Liver problems’ earlier in 
section 4) 

 skin changes, including rash, dry skin, eczema, redness of the skin, itching, excessive sweating, 
unusual skin growths 

 joint pain, back pain, bone pain, pain in the hands or feet, muscle spasms 

 irritability, generally feeling unwell, chest pain and discomfort 

 infection in the nose, sinuses, throat and upper airways, common cold (upper respiratory tract 
infection) 

 depression, anxiety, sleep problems, nervousness 
 

Common side effects that may show up in blood tests: 

 increased blood sugar (glucose) 

 decreased number of white blood cells 

 decreased level of blood proteins 

 increased levels of blood bilirubin (a substance produced by the liver) 

 changes in the enzymes that control blood clotting 
 

Uncommon side effects 

These may affect up to 1 in 100 people: 

 painful urination 

 disturbances of heart rhythm (QT prolongation) 

 stomach flu (gastroenteritis) 

 skin changes including change in colour, peeling, redness, itching and sweating. 

 yellowing of the whites of the eyes or skin (jaundice) 

 swollen blood vessels and bleeding in the gullet (oesophagus) 

 rash, bruising at the injection site 

 decreased number of red blood cells (anaemia) caused by excessive destruction of red blood 
cells (haemolytic anaemia) 

 confusion, agitation 

 liver injury due to medication 
 

The following side effects have been reported to be associated with treatment with Revolade in 

patients with severe aplastic anaemia (SAA): 

If these side effects become severe, please tell your doctor, pharmacist or nurse. 

 

Very common side effects 

These may affect more than 1 in 10 people. 

 cough 

 headache 

 pain in the nose and throat 

 diarrhoea 

 nausea 

 joint pain (arthralgia) 



111 

 pain in extremities (arms, legs, hands and feet) 

 dizziness 

 feeling very tired (fatigue) 

 fever 

 chills 

 itchy eyes 

 blisters in the mouth 

 abdominal pain 

 muscle spasms 
 

Very common side effects that may show up in the blood tests 

 abnormal changes to the cells in your bone marrow 
 

Common side effects 

These may affect up to 1 in 10 people. 

 anxiety 

 depression 

 feeling cold 

 feeling unwell 

 eye problems including blurred vision, cloudy lens in the eye (cataract), spots or deposits in eye 
(vitreous floaters), dry eye, itchy eye, yellowing of the whites of the eyes or skin 

 nose bleed 

 bleeding of the gums 

 digestive system problems including being sick (vomiting), change in appetite (increased or 
decreased), stomach pain/discomfort, swollen stomach, passing wind, change in stool colour 

 fainting 

 skin problems including small red or purple spots caused by bleeding into the skin (petechiae) 
rash, itching, skin lesion 

 back pain 

 muscle pain 

 bone pain 

 weakness (asthenia) 

 swelling of the lower limbs due to the accumulation of fluids 

 abnormal colored urine 

 interruption in blood supply to spleen (splenic infarction) 

 runny nose 
 

Common side effects that may show up in the blood tests 

 increase in enzymes due to muscle breakdown (creatine phosphokinase) 

 accumulation of iron in the body (iron overload) 

 decrease in blood sugar levels (hypoglycaemia) 

 increased levels of bilirubin (a substance produced by the liver) 

 increased levels of liver enzymes (aspartate aminotransferase (AST)) 

 decreased levels of white blood cells 
 

Side effects with frequency not known 

Frequency cannot be estimated from the available data 

 skin discolouration 

 darkening of the skin 

 yellowing of the skin and eyes, tenderness around the liver 
 

  



112 

Reporting of side effects 

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 

effects not listed in this leaflet. You can also report side effects directly via the national reporting 

system listed in Appendix V. By reporting side effects you can help provide more information on the 

safety of this medicine. 

 

 

5. How to store Revolade 
 

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

 

Do not use this medicine after the expiry date which is stated on the carton and the blister. 

 

This medicine does not require any special storage conditions. 

 

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 

throw away medicines you no longer use. These measures will help protect the environment. 

 

 

6. Contents of the pack and other information 

 

What Revolade contains 

The active substance in Revolade is eltrombopag. 

 

12.5 mg film-coated tablets 

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

 

25 mg film-coated tablets 

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

 

50 mg film-coated tablets 

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

 
75 mg film-coated tablets 

Each film-coated tablet contains eltrombopag olamine equivalent to 75 mg eltrombopag. 

 
The other ingredients are: hypromellose, macrogol 400, magnesium stearate, mannitol (E421), 

microcrystalline cellulose, povidone, sodium starch glycolate, 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 iron oxide red (E172) and iron oxide yellow (E172). 

 

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

 

What Revolade looks like and contents of the pack 

Revolade 12.5 mg film-coated tablets are round, biconvex, white, debossed with ‘GS MZ1’ and ‘12.5’ 

on one side. 

 

Revolade 25 mg film-coated tablets are round, biconvex, white, debossed with ‘GS NX3’ and ‘25’ on 

one side. 

 

Revolade 50 mg film-coated tablets are round, biconvex, brown, debossed with ‘GS UFU’ and ‘50’ on 

one side. 

 

Revolade 75 mg film-coated tablets are round, biconvex, pink, debossed with ‘GS FFS’ and ‘75’ on 

one side. 



113 

 

They are supplied in aluminum blisters in a carton containing 14 or 28 film-coated tablets and 

multipacks containg 84 (3 packs of 28) film-coated tablets). 

 

Not all pack sizes may be available in your country. 

 

Marketing authorisation holder 
Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

Manufacturer 
Novartis Farmacéutica SA 

Ronda de Santa Maria 158 

08210 Barberà del Vallès (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 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien 

Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Lietuva 

SIA “Novartis Baltics” Lietuvos filialas 

Tel: +370 5 269 16 50 

 

България 

Novartis Bulgaria EOOD 

Тел: +359 2 489 98 28 

 

Luxembourg/Luxemburg 

Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Česká republika 

Novartis s.r.o. 

Tel: +420 225 775 111 

 

Magyarország 

Novartis Hungária Kft. 

Tel.: +36 1 457 65 00 

Danmark 

Novartis Healthcare A/S 

Tlf: +45 39 16 84 00 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2122 2872 

Deutschland 

Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Nederland 

Novartis Pharma B.V. 

Tel: +31 26 37 82 555 

Eesti 

SIA Novartis Baltics Eesti filiaal 

Tel: +372 66 30 810 

 

Norge 

Novartis Norge AS 

Tlf: +47 23 05 20 00 



114 

Ελλάδα 

Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

 

Österreich 

Novartis Pharma GmbH 

Tel: +43 1 86 6570 

España 

Novartis Farmacéutica, S.A. 

Tel: +34 93 306 42 00 

 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 

France 

Novartis Pharma S.A.S. 

Tél: +33 1 55 47 66 00 

 

Portugal 

Novartis Farma - Produtos Farmacêuticos, S.A. 

Tel: +351 21 000 8600 

Hrvatska 

Novartis Hrvatska d.o.o. 

Tel. +385 1 6274 220 

 

România 

Novartis Pharma Services Romania SRL 

Tel: +40 21 31299 01 

Ireland 

Novartis Ireland Limited 

Tel: +353 1 260 12 55 

 

Slovenija 

Novartis Pharma Services Inc. 

Tel: +386 1 300 75 50 

Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Novartis Slovakia s.r.o. 

Tel: +421 2 5542 5439 

 

Italia 

Novartis Farma S.p.A. 

Tel: +39 02 96 54 1 

Suomi/Finland 

Novartis Finland Oy 

Puh/Tel: +358 (0)10 6133 200 

 

Κύπρος 

Novartis Pharma Services Inc. 

Τηλ: +357 22 690 690 

 

Sverige 

Novartis Sverige AB 

Tel: +46 8 732 32 00 

 

Latvija 

SIA “Novartis Baltics” 

Tel: +371 67 887 070 

 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

 

 

This leaflet was last revised in 
 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu./ 



115 

Package Leaflet: Information for the patient 

 

Revolade 25 mg powder for oral suspension 

 

eltrombopag 

 

Read all of this leaflet carefully before you start taking this medicine because it contains 

important information for you. 
- 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 of the side effects talk to your doctor or pharmacist. This includes any possible 
side effects not listed in this leaflet. See section 4 

 

What is in this leaflet: 

1. What Revolade is and what it is used for 

2. What you need to know before you take Revolade 

3. How to take Revolade 

4. Possible side effects 

5. How to store Revolade 

6. Contents of the pack and other information 

 Instructions for use 

 

 

1. What Revolade is and what it is used for 

 

Revolade contains eltrombopag, which belongs to a group of medicines called thrombopoietin 

receptor agonists. It is used to help increase the number of platelets in your blood. Platelets are blood 

cells that help to reduce or prevent bleeding. 

 

 Revolade is used to treat a bleeding disorder called immune (primary) thrombocytopenia (ITP) 
in patients aged 1 year and above who have already taken other medicines (corticosteroids or 

immunoglobulins), which have not worked. 

 

ITP is caused by a low blood platelet count (thrombocytopenia). People with ITP have an 

increased risk of bleeding. Symptoms patients with ITP may notice include petechiae (pinpoint-

sized flat round red spots under the skin), bruising, nosebleeds, bleeding gums and not being 

able to control bleeding if they are cut or injured. 

 

 Revolade can also be used to treat low platelet count (thrombocytopenia) in adults with 
hepatitis C virus (HCV) infections, if they have had problems with side effects while on 

interferon treatment. Many people with hepatitis C have low platelet counts, not only as a result 

of the disease, but also due to some of the antiviral medicines that are used to treat it. Taking 

Revolade may make it easier for you to complete a full course of antiviral medicine 

(peginterferon and ribavirin). 

 

 Revolade may also be used to treat adult patients with low blood counts caused by severe 
aplastic anaemia (SAA). SAA is a disease in which the bone marrow is damaged, causing a 

deficiency of the red blood cells (anaemia), white blood cells (leukopenia) and platelets 

(thrombocytopenia). 

 

  



116 

 

2. What you need to know before you take Revolade 

 

Do not take Revolade 

 if you are allergic to eltrombopag or any of the other ingredients of this medicine (listed in 
section 6 under ‘What Revolade contains’). 

 Check with your doctor if you think this applies to you. 
 

Warnings and precautions 

Talk to your doctor before taking Revolade: 

 if you have liver problems. People who have low platelet counts as well as advanced chronic 
(long-term) liver disease are more at risk of side effects, including life-threatening liver damage 

and blood clots. If your doctor considers that the benefits of taking Revolade outweigh the risks, 

you will be closely monitored during treatment. 

 if you are at risk of blood clots in your veins or arteries, or you know that blood clots are 
common in your family. 

You may be at higher risk of blood clots: 

- as you get older 
- if you have had to stay in bed for a long time 
- if you have cancer 
- if you are taking the contraceptive birth control pill or hormone replacement therapy 
- if you have recently had surgery or received a physical injury 
- if you are very overweight (obese) 
- if you are a smoker 
- if you have advanced chronic liver disease 
 If any of these apply to you tell your doctor before starting treatment. You should not 

take Revolade unless your doctor considers that the expected benefits outweigh the risk of 

blood clots. 

 if you have cataracts (the lens of the eye getting cloudy) 

 if you have another blood condition, such as myelodysplastic syndrome (MDS). Your doctor 
will carry out tests to check that you do not have this blood condition before you start Revolade. 

If you have MDS and take Revolade, your MDS may get worse. 

 Tell your doctor if any of these apply to you. 
 

Eye examinations 
Your doctor will recommend that you are checked for cataracts. If you do not have routine eye-tests, 

your doctor should arrange regular testing. You may also be checked for the occurrence of any 

bleeding in or around your retina (the light-sensitive layer of cells at the back of the eye). 

 

You will need regular tests 

Before you start taking Revolade, your doctor will carry out blood tests to check your blood cells, 

including platelets. These tests will be repeated at intervals while you are taking it. 

 

Blood tests for liver function 

Revolade can cause blood test results that may be signs of liver damage - an increase of some liver 

enzymes, especially bilirubin and alanine / aspartate transaminases. If you are taking interferon-based 

treatments together with Revolade to treat low platelet count due to hepatitis C, some liver problems 

can get worse. 

 

You will have blood tests to check your liver function before you start taking Revolade and at 

intervals while you are taking it. You may need to stop taking Revolade if the amount of these 

substances increases too much, or if you get other signs of liver damage. 

 Read the information ‘Liver problems’ in section 4 of this leaflet. 
  



117 

 

Blood tests for platelet count 

If you stop taking Revolade, your blood platelet count is likely to become low again within several 

days. The platelet count will be monitored, and your doctor will discuss appropriate precautions with 

you. 

 

A very high blood platelet count may increase the risk of blood clotting. However blood clots can also 

form with normal or even low platelet counts. Your doctor will adjust your dose of Revolade to ensure 

that your platelet count does not become too high. 

 

 Get medical help immediately if you have any of these signs of a blood clot: 

 swelling, pain or tenderness in one leg 

 sudden shortness of breath especially together with sharp pain in the chest or rapid breathing 

 abdominal (stomach) pain, enlarged abdomen, blood in your stools 
 

Tests to check your bone marrow 

In people who have problems with their bone marrow, medicines like Revolade could make the 

problems worse. Signs of bone marrow changes may show up as abnormal results in your blood tests. 

Your doctor may also carry out tests to directly check your bone marrow during treatment with 

Revolade. 

 

Checks for digestive bleeding 

If you are taking interferon-based treatments together 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 it necessary to monitor your heart during treatment with Revolade and carry 

out an electrocardiogram (ECG) test. 

 

Older people (65 years and above) 

There are limited data on the use of Revolade in patients aged 65 years and older. Care should be 

taken when using Revolade if you are aged 65 years or above. 

 

Children and adolescents 

Revolade is not recommended for children aged under 1 year who have ITP. It is also not 

recommended for people under 18 years with low platelet counts due to hepatitis C or severe aplastic 

anaemia. 

 

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 prescription and vitamins. 

 

Some everyday medicines interact with Revolade – including prescription and non-prescription 

medicines and minerals. These include: 

 antacid medicines to treat indigestion, heartburn or stomach ulcers (see also ‘When to take it’ 
in section 3) 

 medicines called statins, to lower cholesterol 

 some medicines to treat HIV infection, such as lopinavir and/or ritonavir 

 ciclosporin used in the context of transplantations or immune diseases 
 minerals such as iron, calcium, magnesium, aluminium, selenium and zinc which may be found 

in vitamin and mineral supplements (see also ‘When to take it’ in section 3) 

 medicines such as methotrexate and topotecan, to treat cancer 
 Talk to your doctor if you take any of these. Some of them are not to be taken with Revolade, 

or the dose may need adjusting, or you may need to alter the timing of when you take them. 

Your doctor will review the medicines you are taking, and suggest suitable replacements if 

necessary. 



118 

 

If you are also taking medicines to prevent blood clots, there is a greater risk of bleeding. 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 

to stop taking them while you are taking Revolade. 

 

Revolade with food and drink 

Do not take Revolade with dairy foods or drinks as the calcium in dairy products affects the absorption 

of the medicine. For more information, see ‘When to take it’ in section 3. 

 

Pregnancy and breast-feeding 

Don’t use Revolade if you are pregnant unless 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 are planning to have a 
baby. 

 Use a reliable method of contraception while you’re taking Revolade, to prevent pregnancy 

 If you do become pregnant during treatment with Revolade, tell your doctor. 
 

Don’t breast-feed while you are taking Revolade. It is not known whether Revolade passes into 

breast-milk. 

 If you are breast-feeding or planning to breast-feed, tell your doctor. 
 

Driving and using machines 

Revolade can make you dizzy and have other side effects that make you less alert. 

 Don’t drive or use machines unless you are sure you’re not affected. 
 

 

3. How to take Revolade 

 

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 

if you are not sure. Do not change the dose or schedule for taking Revolade unless your doctor or 

pharmacist advises you to. While you are taking Revolade, you will be under the care of a doctor with 

specialist experience in treating your condition. 

 

How much to take 

For ITP 

Adults and children (6 to 17 years) - the usual starting dose for ITP is two 25 mg sachets of 

Revolade a day. If you are of Asian origin (Chinese, Japanese, Taiwanese, Thai or Korean) you may 

need to start at a lower dose of 25 mg. 

 

Children (1 to 5 years) — the usual starting dose for ITP is one 25 mg sachet of Revolade a day. 

 

For hepatitis C 

Adults - the usual starting dose for hepatitis C is one 25 mg sachet of Revolade a day. If you are of 

Asian origin (Chinese, Japanese, Taiwanese, Thai or Korean) you will start on the same 25 mg dose. 

 

For SAA 

Adults - the usual starting dose for SAA is two 25 mg sachets of Revolade a day. If you are of Asian 

origin (Chinese, Japanese, Taiwanese, Thai or Korean) you may need to start at a lower dose of 

25 mg. 
 

Revolade may take 1 to 2 weeks to work. Based on your response to Revolade your doctor may 

recommend that your daily dose is changed. 

 



119 

How to give a dose of medicine 

The powder for oral suspension is in sachets, the contents of which will need to mixed before you can 

take the medicine. After section 6 of this leaflet there are Instructions For Use on how to mix and 

administer the medicine. If you have questions or do not understand the Instructions For Use, talk to 

your doctor, nurse or pharmacist. 

 

IMPORTANT — Use the medicine immediately after you have mixed the powder with water. If 

you do not use it within 30 minutes of mixing it, you will need to mix a new dose. Do not re-use the 

oral dosing syringe. A new single-use oral dosing syringe should be used to prepare each dose of 

Revolade for oral suspension. 

 

When to take it 

 

Make sure – 

 in the 4 hours before you take Revolade 

 and the 2 hours after you take Revolade 

 

you don’t consume any of the following: 

 dairy foods such as cheese, butter, yoghurt or ice cream 

 milk or milk shakes, drinks containing milk, yoghurt or cream 

 antacids, a type of medicine for indigestion and heartburn 

 some mineral and vitamin supplements including iron, calcium, magnesium, aluminium, 

selenium and zinc 

 

If you do, the medicine will not be properly absorbed into your body. 

 

 
 

For more advice about suitable foods and drinks, talk to your doctor. 

 

If you take more Revolade than you should 

Contact a doctor or pharmacist immediately. If possible show them the pack, or this leaflet. 

You will be monitored for any signs or symptoms of side effects and given appropriate treatment 

immediately. 

 

If you forget to take Revolade 

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

 

If you stop taking Revolade 

Don’t stop taking Revolade without talking to your doctor. If your doctor advises you to stop 

treatment, your platelet count will then be checked each week for four weeks. See also ‘Bleeding or 

bruising after you stop treatment’ in section 4. 

 

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

 

 

NO dairy products, antacids 

or mineral supplements 

Take Revolade 

For 4 hours 
before you  
take 

Revolade... 

    ...  and for 

2 hours after 



120 

4. Possible side effects 
 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

Symptoms needing attention: see a doctor 

People taking Revolade for either ITP or low blood platelet counts due to hepatitis C could develop 

signs of potentially serious side effects. It is important to tell a doctor if you develop these 

symptoms. 

 

Higher risk of blood clots 

Certain people may have a higher risk of blood clots, and medicines like Revolade could make this 

problem worse. The sudden blocking of a blood vessel by a blood clot is an uncommon side effect and 

may affect up to 1 in 100 people. 

 

 Get medical help immediately if you develop signs and symptoms of a blood clot, such as: 

 swelling, pain, heat, redness or tenderness in one leg 

 sudden shortness of breath, especially together with sharp pain in the chest or rapid breathing 

 abdominal (stomach) pain, enlarged abdomen, blood in your stools. 
 

Liver problems 

Revolade can cause changes that show up in blood tests, and may be signs of liver damage. Liver 

problems (increased enzymes showing up in blood tests) are common and may affect up to 1 in 

10 people. Other liver problems (bile not flowing properly) are uncommon and may affect up to 1 in 

100 people. 

 

If you have either of these signs of liver problems: 

 yellowing of the skin or the whites of the eyes (jaundice) 

 unusually dark-coloured urine 
 tell your doctor immediately. 
 

Bleeding or bruising after you stop treatment 

Within two weeks of stopping Revolade, your blood platelet count will usually drop back down to 

what it was before starting Revolade. The lower platelet count may increase the risk of bleeding or 

bruising. Your doctor will check your platelet count for at least 4 weeks after you stop taking 

Revolade. 

 Tell your doctor if you have any bleeding or bruising after stopping Revolade. 
 

Some people have bleeding in the digestive system after they stop taking peginterferon, ribavirin, and 

Revolade. Symptoms include: 

- black tarry stools (discoloured bowel movements are a uncommon side effect that may affect up 
to 1 in 100 people) 

- blood in your stools 
- vomiting blood or something that looks like coffee grounds 
 Tell your doctor immediately if you have any of these symptoms. 
 

The following side effects have been reported to be associated with treatment with Revolade in 

adult patients with ITP: 

 

Very common side effects 

These may affect more than 1 in 10 people: 

 common cold 

 feeling sick (nausea) 

 diarrhoea 

 cough 

 infection in the nose, sinuses, throat and upper airways, common cold (upper respiratory tract 
infection) 



121 

 

Very common side effects that may show up in blood tests: 

 increased of liver enzymes (alanine aminotransferase (ALT)) 
 

Common side effects 

These may affect up to 1 in 10 people: 

 muscle pain, muscle spasm, muscle weakness 

 back pain 

 bone pain 

 heavy menstrual period 

 sore throat and discomfort when swallowing  

 eye problems including abnormal eye test, dry eye, eye pain and blurred vision 

 vomiting 

 flu (influenza) 

 cold sore 

 pneumonia 

 irritation and inflammation (swelling) of the sinuses 

 inflammation (swelling) and infection of the tonsils infection of the lungs, sinuses, tonsils, nose 
and throat 

 inflammation of the gum tissue 

 loss of appetite 

 feeling of tingling, prickling or numbness, commonly called “pins and needles” 

 feeling drowsy 

 ear pain 

 pain, swelling and tenderness in one of your legs (usually the calf) with warm skin in the 
affected area (signs of a blood clot in a deep vein) 

 localised swelling filled with blood from a break in a blood vessel (haematoma) 

 mouth problems including dry mouth, sore mouth, sensitive tongue, bleeding gums, mouth 
ulcers 

 runny nose 

 toothache 

 stomach pain and tenderness 

 liver problems 

 skin changes including excessive sweating, itching bumpy rash, red spots, changes in 
appearance of the skin 

 hair loss 

 foamy, frothy or bubbly-looking urine (signs of protein in urine) 

 generally feeling unwell, high temperature, feeling hot 

 chest pain 

 problems sleeping, depression 

 migraine 

 decreased vision 

 spinning sensation (vertigo) 

 digestive wind/gas 
 

Common side effects that may show up in blood test: 

 decreased number of red blood cells (anaemia) 

 decreased number of platelets (thrombocytopenia) 

 decreased number of white blood cells 

 decreased haemaglobin level 

 decreased number of eosinophils 

 increased number of white blood cells (leukocytosis) 

 increased levels of uric acid 

 decreased levels of potassium 



122 

 increased levels of creatinine 

 increased levels of alkaline phosphatase 

 increase of liver enzymes (aspartate aminotransferase (AST)) 

 increase in bilirubin (a substance produced by the liver) 

 increased levels of some proteins 
 

Uncommon side effects 

These may affect up to 1 in 100 people: 

 interruption of blood supply to part of the heart 

 sudden shortness of breath, especially when accompanied with sharp pain in the chest and /or 
rapid breathing, which could be signs of a blood clot in the lungs (see ‘Higher risk of blood 

clots’ earlier in section 4) 

 the loss of function of part of the lung caused by a blockage in the lung artery 

 including yellowing of the eyes and skin (see ‘Liver problems’ earlier in section 4) 

 liver injury due to medication 

 heart beating faster, irregular heartbeat, bluish discolouration of the skin 

 disturbances of heart rhythm (QT prolongation) 

 blood clot 

 painful swollen joints caused by uric acid (gout) 

 lack of interest, mood changes 

 problems with balance, speech and nerve function, shaking 

 eye problems including increased production of tears, cloudy lens in the eye (cataract), bleeding 
of the retina 

 problems with the nose, throat and sinuses, breathing problems when sleeping 

 digestive system problems including frequent bowel movements, food poisoning, blood in stool 

 rectal bleeding, blood in your stool, abdominal bloating, constipation 

 mouth problems, including dry or sore mouth, sensitive tongue, bleeding gums 

 sunburn 

 redness or swelling around, a woundbleeding around a catheter (if present) into the 
skinsensation of a foreign body 

 kidney problems including inflammation of the kidney, excessive urination at night, kidney 
failure, white cells in urine 

 cold sweat 

 infection of the skin 

 skin changes including change in colour, peeling, redness, itching and sweating 
 

Uncommon side effects that may show up in laboratory tests: 

 changes in the shape of red blood cells 

 increased number of platelets 

 decreased levels of calcium 

 decreased number of red blood cells (anaemia) cause by excessive destruction of red blood cells 
(haemolytic anaemia) 

 increased number of myelocytes 

 increased band neutrophils 

 increased blood urea 

 increased levels of blood albumin 

 increased levels of total protein 

 decreased levels of blood albumin 

 increased pH of urine 

 increased haemaglobin level 
 



123 

The following additional side effects have been reported to be associated with treatment with 

Revolade in children (aged 1 to 17 years) with ITP: 

If these side effects become severe, please tell your doctor, pharmacist or nurse. 

 

Very common side effects 

These may affect more than 1 in 10 children: 

 infection in the nose, sinuses, throat and upper airways, common cold (upper respiratory tract 
infection) 

 diarrhoea 

 abdominal pain 

 cough 

 high temperature 

 feeling sick (nausea) 
 

Common side effects 

These may affect up to 1 in 10 children: 

 difficulty in sleeping (insomnia) 

 toothache 

 pain in the nose and throat 

 itchy, 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 to be associated with treatment with Revolade in 

combination with peginterferon and ribavirin in patients with HCV: 

 

Very common side effects 

These may affect more than 1 in 10 people: 

 headache 

 decreased appetite 

 cough 

 feeling sick (nausea), diarrhoea 

 muscle pain, muscle weakness 

 itching 

 lack of energy 

 high temperature 

 unusual hair loss 

 feeling weak 

 flu-like illness 

 swelling in the hands or feet 

 chills 
 

Very common side effects that may show up in blood tests: 

 decreased number of red blood cells (anaemia) 
 

Common side effects 

These may affect up to 1 in 10 people: 

 infection of the urinary system 

 inflammation of the nasal passages, throat and mouth, flu-like symptoms, dry mouth, sore or 
inflamed mouth, toothache 

 weight loss 

 sleep disorders, abnormal drowsiness, depression, anxiety 

 dizziness, problems with attention and memory, change in mood 

 tingling or numbness of the hands or feet 



124 

 fever, headache 

 eye problems, including cloudy lens in the eye (cataract), dry eye, small yellow deposits in the 
retina, yellowing of the whites of the eye 

 bleeding of the retina 

 spinning sensation (vertigo) 

 fast or irregular heartbeat (palpitations), shortness of breath 

 cough bringing up phlegm, runny nose, flu, cold sore, sore throat and discomfort when 
swallowing 

 digestive system problems, including being sick (vomiting), stomach pain, indigestion, 
constipation, swollen stomach, taste disturbances, inflammation of the stomach, piles 

(haemorrhoids), irritation of the gut 

 toothache 

 liver problems, including blood clot, tumour in the liver (see ‘Liver problems’ earlier in 
section 4) 

 skin changes, including rash, dry skin, eczema, redness of the skin, itching, excessive sweating, 
unusual skin growths 

 joint pain, back pain, bone pain, pain in the hands or feet, muscle spasms 

 irritability, generally feeling unwell, chest pain and discomfort 

 infection in the nose, sinuses, throat and upper airways, common cold (upper respiratory tract 
infection) 

 depression, anxiety, sleep problems, nervousness 
 

Common side effects that may show up in blood tests: 

 increased blood sugar (glucose) 

 decreased number of white blood cells 

 decreased level of blood proteins 

 increased levels of blood bilirubin (a substance produced by the liver) 

 changes in the enzymes that control blood clotting 
 

Uncommon side effects 

These may affect up to 1 in 100 people: 

 painful urination 

 disturbances of heart rhythm (QT prolongation) 

 stomach flu (gastroenteritis) 

 skin changes including change in colour, peeling, redness, itching and sweating. 

 yellowing of the whites of the eyes or skin (jaundice) 

 swollen blood vessels and bleeding in the gullet (oesophagus) 

 rash, bruising at the injection site 

 decreased number of red blood cells (anaemia) caused by excessive destruction of red blood 
cells (haemolytic anaemia) 

 confusion, agitation 

 liver injury due to medication 
 

The following side effects have been reported to be associated with treatment with Revolade in 

patients with severe aplastic anaemia (SAA): 

If these side effects become severe, please tell your doctor, pharmacist or nurse. 

 

Very common side effects 

These may affect more than 1 in 10 people. 

 cough 

 headache 

 pain in the nose and throat 

 diarrhoea 

 nausea 

 joint pain (arthralgia) 



125 

 pain in extremities (arms, legs, hands and feet) 

 dizziness 

 feeling very tired (fatigue) 

 fever 

 chills 

 itchy eyes 

 blisters in the mouth 

 abdominal pain 

 muscle spasms 
 

Very common side effects that may show up in the blood tests 

 abnormal changes to the cells in your bone marrow 
 

Common side effects 

These may affect up to 1 in 10 people. 

 anxiety 

 depression 

 feeling cold 

 feeling unwell 

 eye problems including blurred vision, cloudy lens in the eye (cataract), spots or deposits in eye 
(vitreous floaters), dry eye, itchy eye, yellowing of the whites of the eyes or skin 

 nose bleed 

 bleeding of the gums 

 digestive system problems including being sick (vomiting), change in appetite (increased or 
decreased), stomach pain/discomfort, swollen stomach, passing wind, change in stool colour 

 fainting 

 skin problems including small red or purple spots caused by bleeding into the skin (petechiae) 
rash, itching, skin lesion 

 back pain 

 muscle pain 

 bone pain 

 weakness (asthenia) 

 swelling of the lower limbs due to the accumulation of fluids 

 abnormal colored urine 

 interruption in blood supply to spleen (splenic infarction) 

 runny nose 
 

Common side effects that may show up in the blood tests 

 increase in enzymes due to muscle breakdown (creatine phosphokinase) 

 accumulation of iron in the body (iron overload) 

 decrease in blood sugar levels (hypoglycaemia) 

 increased levels of bilirubin (a substance produced by the liver) 

 increased levels of liver enzymes (aspartate aminotransferase (AST)) 

 decreased levels of white blood cells 
 

Side effects with frequency not known 

Frequency cannot be estimated from the available data 

 skin discolouration 

 darkening of the skin 

 yellowing of the skin and eyes, tenderness around the liver 
 

  



126 

Reporting of side effects 

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 

effects not listed in this leaflet. You can also report side effects directly via the national reporting 

system listed in Appendix V. By reporting side effects you can help provide more information on the 

safety of this medicine. 

 

 

5. How to store Revolade 
 

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

 

Do not use this medicine after the expiry date which is stated on the carton and the sachet. 

 

This medicine does not require any special storage conditions. 

 

Do not open the foil sachets until ready for use. After mixing, Revolade oral suspension should be 

administered immediately, but may be stored for no more than 30 minutes at room temperature. 

 

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 

throw away medicines you no longer use. These measures will help protect the environment. 

 

 

6. Contents of the pack and other information 

 

What Revolade contains 

25 mg powder for oral suspension 

The active substance in Revolade is eltrombopag. Each sachet contains a powder for reconstitution 

that delivers 32 mg eltrombopag olamine, equivalent to 25 mg of eltrombopag free acid. 

 

The other ingredients are: mannitol, sucralose and xanthan gum. 

 

What Revolade looks like and contents of the pack 

Revolade 25 mg powder for oral suspension is available in kits containing 30 sachets; each sachet 

contains a reddish-brown to yellow powder. Each pack contains 30 sachets, one 40 ml reusable mixing 

bottle with lid and cap, and 30 single-use oral dosing syringes. 

 

Marketing authorisation holder 
Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

Manufacturer 
Lek d.d 

Verovskova Ulica 57 

Ljubljana 1526 

Slovenia 

 

Novartis Pharma GmbH 

Roonstraße 25 

D-90429 Nuremberg 

Germany 

 

  



127 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien 

Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Lietuva 

SIA “Novartis Baltics” Lietuvos filialas 

Tel: +370 5 269 16 50 

 

България 

Novartis Bulgaria EOOD 

Тел: +359 2 489 98 28 

 

Luxembourg/Luxemburg 

Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Česká republika 

Novartis s.r.o. 

Tel: +420 225 775 111 

 

Magyarország 

Novartis Hungária Kft. 

Tel.: +36 1 457 65 00 

Danmark 

Novartis Healthcare A/S 

Tlf: +45 39 16 84 00 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2122 2872 

Deutschland 

Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Nederland 

Novartis Pharma B.V. 

Tel: +31 26 37 82 555 

Eesti 

SIA Novartis Baltics Eesti filiaal 

Tel: +372 66 30 810 

 

Norge 

Novartis Norge AS 

Tlf: +47 23 05 20 00 

Ελλάδα 

Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

 

Österreich 

Novartis Pharma GmbH 

Tel: +43 1 86 6570 

España 

Novartis Farmacéutica, S.A. 

Tel: +34 93 306 42 00 

 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 

France 

Novartis Pharma S.A.S. 

Tél: +33 1 55 47 66 00 

 

Portugal 

Novartis Farma - Produtos Farmacêuticos, S.A. 

Tel: +351 21 000 8600 

Hrvatska 

Novartis Hrvatska d.o.o. 

Tel. +385 1 6274 220 

 

România 

Novartis Pharma Services Romania SRL 

Tel: +40 21 31299 01 

Ireland 

Novartis Ireland Limited 

Tel: +353 1 260 12 55 

 

Slovenija 

Novartis Pharma Services Inc. 

Tel: +386 1 300 75 50 

Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Novartis Slovakia s.r.o. 

Tel: +421 2 5542 5439 

 

Italia 

Novartis Farma S.p.A. 

Tel: +39 02 96 54 1 

Suomi/Finland 

Novartis Finland Oy 

Puh/Tel: +358 (0)10 6133 200 

 



128 

Κύπρος 

Novartis Pharma Services Inc. 

Τηλ: +357 22 690 690 

 

Sverige 

Novartis Sverige AB 

Tel: +46 8 732 32 00 

 

Latvija 

SIA “Novartis Baltics” 

Tel: +371 67 887 070 

 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

 

 

This leaflet was last revised in. 

 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu./ 



129 

INSTRUCTIONS FOR USE 

 

Revolade 25 mg powder for oral suspension 

 

(eltrombopag) 

 

Read and follow these instructions to prepare a dose of Revolade and give it to the child. If you have 

any questions, or if you damage or lose any of the supplies in your kit, ask your doctor, nurse or 

pharmacist for advice 

 

Before you start 

Read these messages first 
 

 Revolade powder must be mixed only with water at room temperature. 

 Give the medicine to the child immediately after you have mixed the powder with water. If you 

don’t use the medicine within 30 minutes of mixing it, you will need to mix a new dose. 

Dispose of the unused mixture in your household waste; don’t pour it down the drain. 

 

 Try not to let the medicine touch your skin. If this happens, wash the area immediately with 
soap and water. If you get a skin reaction, or if you have any questions, contact the doctor. 

 If you spill any powder or liquid, clean it up with a damp cloth (see step 14 of the instructions). 

 Take care that the child does not play with the bottle, cap, lid or syringes — there is a risk of 
choking if the child puts them in their mouth. 

 

What you need 

Each Revolade powder for oral suspension kit contains: 

 

30 sachets of powder 
 

1 reusable mixing bottle with lid and cap (note — 

the mixing bottle may become stained) 

 
30 single-use oral dosing syringes  

 
 

To prepare and give a dose of Revolade, you need: 

 

 The correct number of sachets your doctor has prescribed (supplied in the kit) 

 1 reusable mixing bottle with lid and cap (supplied in the kit) 

 1 single-use oral dosing syringe (supplied in the kit) 

 1 clean glass or cup filled with drinking water (not supplied) 

 scissors to cut sachet (not supplied) 
 

Cap 

Lid 

Plunger Syringe tip 



130 

Make sure that the bottle, cap and lid are dry before you use them. 

To prepare the dose 

1.  Make sure the lid is not on the mixing bottle. 

2.  Fill the syringe with 20 ml drinking water from the glass or cup. 

A new single-use oral dosing syringe should be used to prepare each 

dose of Revolade for oral suspension. 

 Start with the plunger pushed all the way into the syringe. 

 Put the tip of the syringe all the way into the water 

 Pull back on the plunger to the 20 ml mark on the syringe. 

 
3.  Empty water into open mixing bottle 

 Slowly pushing the plunger all the way into the syringe. 

 
4.  Take only the prescribed number of sachets for one dose out of the kit. 

 25 mg dose — 1 sachet 

 50 mg dose — 2 sachets 

 75 mg dose — 3 sachets 

 

5.  Add the powder from the prescribed number of sachets to 
the bottle. 

 Tap the top of each sachet to make sure the contents fall to 
the bottom 

 Cut off the top of each sachet with scissors 

 Empty all contents of each sachet into the mixing bottle 

 Make sure not to spill the powder outside the mixing bottle. 

 
6.  Screw the lid onto the mixing bottle. Make sure the cap is firmly pushed onto the lid, so it is 

closed. 
 

7.  Gently and slowly shake the mixing bottle backwards and 

forwards for at least 20 seconds to mix the water with the powder. 

 Don’t shake the bottle hard — that could make the medicine 
foam. 

 
To give a dose to a child 

8.  Make sure the plunger is pushed all the way into the syringe. 

 Pull cap off the lid of the mixing bottle 

 Insert the syringe tip into the hole in the bottle lid. 

9.  Fill the syringe with the medicine. 

 Turn the mixing bottle upside-down together with the 
syringe. 

 Pull back the plunger until all the medicine is in the syringe. 

 The medicine is a dark brown liquid. 

 Remove the syringe from the bottle. 

 
  



131 

10.  Give the medicine to the child. Do this straight away when 

you have mixed the dose. 

 Place the tip of the syringe into the inside of the child’s 
cheek. 

 Slowly push the plunger all the way down so the medicine 
goes into the child’s mouth. 

Make sure the child has time to swallow. 

 

 

IMPORTANT: 
You have now given the child nearly all of their dose of medicine. But there will still be some left in 

the bottle, even though you may not be able to see it. 

Now you need to complete steps 11 to 13 to make sure the child receives all of the medicine. 

11.  Again fill the syringe, this time with 10 ml of drinking water. 

 Start with the plunger pushed all the way down into the 
syringe. 

 Put the tip of the syringe all the way into the water 

 Pull back on the plunger to the 10 ml mark on the syringe. 

 
12.  Empty the water into the mixing bottle. 

 Insert the tip of the syringe into the hole in the lid of the 
mixing bottle. 

 Slowly push the plunger all the way into the syringe. 

 Push the cap firmly back on to the lid of the mixing bottle. 

 
13.  Repeat steps 7 to 10 – gently shake the bottle to mix the rest of the medicine, then give all the 

rest of the liquid to the child. 

To clean up 

14.  If you have spilt any powder or mixed medicine, clean it up with a damp disposable cloth. 

You may choose to wear disposable gloves so your skin doesn’t get stained. 

 Dispose of the cloth and gloves used to clean up the spillage in your household waste. 

15.  Clean the mixing equipment. 

 Throw away the used oral dosing syringe. A new oral dosing syringe should be used to 
prepare each dose of Revolade for oral suspension. 

 Rinse the mixing bottle and lid under running water. (The mixing bottle may become stained 
from the medicine. This is normal.) 

 Let all the equipment dry in the air. 

 Wash your hands with soap and water. 

After you have used all 30 sachets in the kit, dispose of the bottle. Always start with a complete 

new kit for each 30 sachets. 

 

Keep Revolade powder for oral suspension, including the dosing kit, and all medicines out of the 

reach of children. 

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET