Revolade

/ Novartis

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.
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.
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 East Asian ancestry (such as Chinese, Japanese, Taiwanese, Korean or Thai), eltrombopag should be initiated at a reduced dose of 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 at the attached doctor’s leaflet. 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.
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.
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 East Asian ancestry or patients with mild hepatic impairment.
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 anti-viral 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 at the attached doctor’s leaflet).
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. 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 75 mg eltrombopag once daily must not be exceeded.
Discontinuation: If after 2 weeks of eltrombopag therapy at 75 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 (SAA):
First-Line severe aplastic anaemia: Initiate eltrombopag concurrently with standard immunosuppressive therapy.
Initial Dose Regimen: The recommended initial dose regimen is listed below. Do not exceed the initial dose of eltrombopag.
Patients 12 Years and Older: 150 mg once daily for 6 months.
Paediatric Patients 6 to 11 Years: 75 mg once daily for 6 months.
For patients with severe aplastic anaemia of East Asian ancestry (such as Chinese, Japanese, Taiwanese, Korean, or Thai) or those with mild, moderate, or severe hepatic impairment (Child-Pugh Class A, B, C), decrease the initial eltrombopag dose by 50% as listed below:
Patients 12 Years and Older: 75 mg once daily for 6 months.
Paediatric Patients 6 to 11 Years: 75 mg every other day for 6 months.
If baseline alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels are > 6 x upper limit of Normal (ULN), do not initiate eltrombopag until transaminase levels are < 5 x ULN. Determine the initial dose for these patients based on doses above.
Monitoring and Dose Adjustment for eltrombopag: Perform clinical haematology and liver tests regularly throughout therapy with eltrombopag.
Modify the dosage regimen of eltrombopag based on platelet counts as outlined in Table 5 at the attached doctor’s leaflet.
Table 6 at the attached doctor’s leaflet summarizes the recommendations for dose interruption, reduction, or discontinuation of eltrombopag in the management of elevated liver transaminase levels and thromboembolic events.
Refractory severe aplastic anaemia: Use the lowest dose of eltrombopag to achieve and maintain a haematologic response. Dose adjustments are based upon the platelet count. Haematologic response requires dose titration, generally up to 150 mg, and may take up to 16 weeks after starting eltrombopag.
Initial Dose Regimen: Initiate eltrombopag at a dose of 50 mg once daily.
For patients with severe aplastic anaemia of East Asian ancestry or those with mild, moderate, or severe hepatic impairment (Child-Pugh Class A, B, C), initiate eltrombopag at a reduced dose of 25 mg once daily.
Monitoring and Dose Adjustment: Adjust the dose of eltrombopag in 50-mg increments every 2 weeks as necessary to achieve the target platelet count ≥50,000/μl as necessary. Do not exceed a dose of 150 mg daily. Monitor clinical haematology and liver tests regularly throughout therapy with eltrombopag and modify the dosage regimen of eltrombopag based on platelet counts as outlined in Table 7 at the attached doctor’s leaflet.
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 discontinue eltrombopag and monitor blood counts. If platelet counts drop to less than 30,000/μl, hemoglobin to less than 9 g/dL, or ANC to less than 0.5 x 10^9/L, eltrombopag may be reinitiated at the previous effective dose.
Discontinuation: If no haematologic response has occurred after 16 weeks of therapy with eltrombopag, discontinue therapy. If new cytogenetic abnormalities are observed, consider discontinuation of eltrombopag. Excessive platelet count responses (as outlined in Table 7 at the attached doctor’s leaflet) or important liver test abnormalities also necessitate discontinuation of eltrombopag.
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.
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.
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 refractory severe aplastic anaemia patients with hepatic impairment should initiate eltrombopag at a dose of 25 mg once daily. 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.
In a clinical trial in patients with severe aplastic anaemia who had not received prior definitive immunosuppressive therapy, patients with baseline ALT or AST > 5 x ULN were ineligible to participate. If a patient with hepatic impairment (Child-Pugh Class A, B, C) initiates therapy with eltrombopag for the first-line treatment of severe aplastic anaemia, reduce the initial dose.
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.
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.
East Asian patients: For patients of East Asian ancestry (such as Chinese, Japanese, Taiwanese, Korean or Thai), eltrombopag should be initiated at a dose of 25 mg once daily for treatment of ITP, HCV and refractory SAA, and for treatment of patients with 1L SAA refer to Table 4 at the attached doctor’s leaflet. For treatment of patients with hepatic impairment, refer to hepatic impairment section above.
Patient platelet count should continue to be monitored and the standard criteria for further dose modification followed.
Paediatric population: Revolade tablets are not indicated for use in children under the age of 6 years with ITP.
The safety and efficacy of eltrombopag has not been established in children and adolescents (<18 years) with chronic HCV related thrombocytopenia or refractory SAA.
No data are available.
Revolade tablets are indicated for definitive immunosuppressive therapy-naïve SAA aged 6 years and older.
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).

Revolade is indicated for the treatment of patients aged 6 years and above with primary immune thrombocytopenia (ITP) lasting 6 months or longer from diagnosisand who are refractory to other treatments (e.g. corticosteroids, immunoglobulins).
Revolade is indicated for the treatment of thrombocytopenia in adult patients with chronic hepatitis C to allow the initiation and maintenance of interferon-based therapy.
Revolade is indicated in combination with standard immunosuppressive therapy for the first-line treatment of adult and paediatric patients 6 years and older with severe aplastic anaemia.
Revolade is indicated for the treatment of adult patients with severe aplastic anaemia who have had an insufficient response to immunosuppressive therapy.

Hypersensitivity to eltrombopag or to any of the excipients.

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.
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 refractory SAA patients a lower starting dose of eltrombopag should be used. Close monitoring is required when administering to patients with hepatic impairment.
First-line treatment of severe aplastic anaemia: Measure ALT, AST, and bilirubin prior to initiation of eltrombopag, every other day while hospitalized for h-ATG therapy, and then every 2 weeks during treatment. During treatment, manage increases in ALT or AST levels as recommended in Table 6 at the attached doctor’s leaflet.
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. 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. See prescribing information for full details.
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 (≤ 35g/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.
See prescribing information for full details.
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.
See prescribing information for full details.

The most common adverse reactions occurring in at least 10% of patients included: nausea, diarrhoea and increased alanine aminotransferase.
See prescribing information for full details.

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.
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.
Cytochrome P450 substrates: In studies utilising human liver microsomes, eltrombopag (up to 100 µM) 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.
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-τ), 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. 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.
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 AUCinfby 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. 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.
Food interaction: The administration of eltrombopag tablet 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.
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%.
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.

Pragnancy: There are no or limited amount of data from the use of eltrombopag in pregnant women. Revolade is not recommended during pregnancy.
Lactation: It is not known whether eltrombopag/metabolites are excreted in human milk. Studies in animals have shown that eltrombopag is likely secreted into milk; 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.
See prescribing information for full details.

In the event of overdose, platelet counts may increase excessively and result in thrombotic/thromboembolic complications. In case of an overdose, consider oral administration of a metal cation-containing preparation, such as calcium, aluminium, or magnesium preparations to chelate eltrombopag and thus limit absorption. Closely monitor platelet counts. Reinitiate treatment with eltrombopag in accordance with dosing and administration recommendations. In the ITP clinical studies there was one report of overdose where the patient ingested 5000 mg of eltrombopag. Reported adverse events 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.

Storage: Store below 30°C.