Eltrombopagdosage

Take eltrombopag tablets without a meal or with a meal low in calcium (≤ 50 mg). Take eltrombopag tablets at least 2 hours before or 4 hours after any medications or products containing polyvalent cations, such as antacids, calcium-rich foods, and mineral supplements.

Persistent or Chronic ITP: Initiate eltrombopag tablets at 50 mg orally once daily for most adult and pediatric patients 6 years and older, and at 25 mg orally once daily for pediatric patients aged 1 to 5 years. Dose reductions are needed for patients with hepatic impairment and some patients of East-/Southeast-Asian ancestry. Adjust to maintain platelet count greater than or equal to 50 x 10 9 /L. Do not exceed 75 mg per day.

Chronic Hepatitis C-associated Thrombocytopenia: Initiate eltrombopag tablets at 25 mg orally once daily for all patients. Adjust to achieve target platelet count required to initiate antiviral therapy. Do not exceed a daily dose of 100 mg.

First-line Severe Aplastic Anemia: Initiate eltrombopag tablets orally once daily at 2.5 mg/kg (in pediatric patients aged 2 to 5 years old), 75 mg (pediatric patients aged 6 to 11 years old) or 150 mg for patients aged 12 years and older concurrently with standard immunosuppressive therapy. Reduce initial dose in patients of East-/Southeast-Asian ancestry. Modify dosage for toxicity or elevated platelet counts.

Refractory Severe Aplastic Anemia: Initiate eltrombopag tablets orally at 50 mg once daily. Reduce initial dose in patients with hepatic impairment or patients of East-/Southeast-Asian ancestry. Adjust to maintain platelet count greater than 50 x 10 9 /L. Do not exceed 150 mg per day.

2.1 Persistent or

Chronic Immune Thrombocytopenia Use the lowest dose of eltrombopag tablets to achieve and maintain a platelet count greater than or equal to 50 x 10 9 /L as necessary to reduce the risk for bleeding. Dose adjustments are based upon the platelet count response. Do not use eltrombopag tablets to normalize platelet counts. In clinical trials, platelet counts generally increased within 1 to 2 weeks after starting eltrombopag tablets and decreased within 1 to 2 weeks after discontinuing eltrombopag tablets. Initial Dose Regimen Adult and Pediatric Patients 6 Years and Older with ITP Initiate eltrombopag tablets at a dose of 50 mg orally once daily, except in patients who are of East-/Southeast-Asian ancestry or who have mild to severe hepatic impairment (Child-Pugh class A, B, C). For patients of East-/Southeast-Asian ancestry with ITP, initiate eltrombopag tablets at a reduced dose of 25 mg orally once daily. For patients with ITP and mild, moderate, or severe hepatic impairment (Child-Pugh class A, B, C), initiate eltrombopag tablets at a reduced dose of 25 mg orally once daily. For patients of East-/Southeast-Asian ancestry with ITP and hepatic impairment (Child-Pugh class A, B, C), consider initiating eltrombopag tablets at a reduced dose of 12.5 mg orally once daily. Pediatric Patients with ITP Aged 1 to 5 Years Initiate eltrombopag tablets at a dose of 25 mg orally once daily. Monitoring and Dose Adjustment After initiating eltrombopag tablets, adjust the dose to achieve and maintain a platelet count greater than or equal to 50 x 10 9 /L as necessary to reduce the risk for bleeding. Do not exceed a dose of 75 mg daily. Monitor clinical hematology and liver tests regularly throughout therapy with eltrombopag tablets and modify the dosage regimen of eltrombopag tablets based on platelet counts as outlined in Table 1. During therapy with eltrombopag tablets, assess complete blood counts (CBCs) with differentials, including platelet counts, weekly until a stable platelet count has been achieved. Obtain CBCs with differentials, including platelet counts, monthly thereafter. When switching between the oral suspension and tablet, assess platelet counts weekly for 2 weeks, and then follow standard monthly monitoring.

Table 1: Dose Adjustments of Eltrombopag Tablets in Patients With Persistent or Chronic Immune Thrombocytopenia Platelet count result Dose adjustment or response < 50 x 10 9 /L following at least 2 weeks of eltrombopag tablets Increase daily dose by 25 mg to a maximum of 75 mg/day. For patients taking 12.5 mg once daily, increase the dose to 25 mg daily before increasing the dose amount by 25 mg. ≥ 200 x 10 9 /L to ≤ 400 x 10 9 /L at any time Decrease the daily dose by 25 mg. Wait 2 weeks to assess the effects of this and any subsequent dose adjustments. For patients taking 25 mg once daily, decrease the dose to 12.5 mg once daily. > 400 x 10 9 /L Stop eltrombopag tablets; increase the frequency of platelet monitoring to twice weekly. Once the platelet count is < 150 x 10 9 /L, reinitiate therapy at a daily dose reduced by 25 mg. For patients taking 25 mg once daily, reinitiate therapy at a daily dose of 12.5 mg. > 400 x 10 9 /L after 2 weeks of therapy at lowest dose of eltrombopag tablets Discontinue eltrombopag tablets. In patients with ITP and hepatic impairment (Child-Pugh class A, B, C), after initiating eltrombopag tablets or after any subsequent dosing increase, wait 3 weeks before increasing the dose. Modify the dosage regimen of concomitant ITP medications, as medically appropriate, to avoid excessive increases in platelet counts during therapy with eltrombopag tablets. Do not administer more than one dose of eltrombopag tablets within any 24-hour period. Discontinuation Discontinue eltrombopag tablets if the platelet count does not increase to a level sufficient to avoid clinically important bleeding after 4 weeks of therapy with eltrombopag tablets at the maximum daily dose of 75 mg. Excessive platelet count responses, as outlined in Table 1, or important liver test abnormalities (e.g., transaminases and/or bilirubin) also necessitate discontinuation of eltrombopag tablets. Obtain CBCs with differentials, including platelet counts, weekly for at least 4 weeks following discontinuation of eltrombopag tablets.

2.2 Chronic

Hepatitis C-Associated Thrombocytopenia Use the lowest dose of eltrombopag tablets to achieve and maintain a platelet count necessary to initiate and maintain antiviral therapy with pegylated interferon and ribavirin. Dose adjustments are based upon the platelet count response. Do not use eltrombopag tablets to normalize platelet counts. In clinical trials, platelet counts generally began to rise within the first week of treatment with eltrombopag tablets. Initial Dose Regimen Initiate eltrombopag tablets at a dose of 25 mg orally once daily. Monitoring and Dose Adjustment Adjust the dose of eltrombopag tablets in 25 mg increments every 2 weeks as necessary to achieve the target platelet count required to initiate antiviral therapy. Monitor platelet counts every week prior to starting antiviral therapy. During antiviral therapy, adjust the dose of eltrombopag tablets to avoid dose reductions of peginterferon. Monitor CBCs with differentials, including platelet counts, weekly during antiviral therapy until a stable platelet count is achieved. Monitor platelet counts monthly thereafter. Do not exceed a dose of 100 mg daily. Monitor clinical hematology and liver tests (e.g., transaminases and bilirubin) regularly throughout therapy with eltrombopag tablets. For specific dosage instructions for peginterferon or ribavirin, refer to their respective prescribing information.

Table 2: Dose Adjustments of Eltrombopag Tablets in Adults With Thrombocytopenia Due to Chronic Hepatitis C Platelet count result Dose adjustment or response < 50 x 10 9 /L following at least 2 weeks of eltrombopag tablets Increase daily dose by 25 mg to a maximum of 100 mg/day. ≥ 200 x 10 9 /L to ≤ 400 x 10 9 /L at any time Decrease the daily dose by 25 mg. Wait 2 weeks to assess the effects of this and any subsequent dose adjustments. > 400 x 10 9 /L Stop eltrombopag tablets; increase the frequency of platelet monitoring to twice weekly. Once the platelet count is < 150 x 10 9 /L, reinitiate therapy at a daily dose reduced by 25 mg. For patients taking 25 mg once daily, reinitiate therapy at a daily dose of 12.5 mg. > 400 x 10 9 /L after 2 weeks of therapy at lowest dose of eltrombopag tablets Discontinue eltrombopag tablets. Discontinuation The prescribing information for pegylated interferon and ribavirin include recommendations for antiviral treatment discontinuation for treatment futility. Refer to pegylated interferon and ribavirin prescribing information for discontinuation recommendations for antiviral treatment futility. Eltrombopag tablets should be discontinued when antiviral therapy is discontinued. Excessive platelet count responses, as outlined in Table 2, or important liver test abnormalities also necessitate discontinuation of eltrombopag tablets.

2.3 Severe Aplastic

Anemia First-Line Severe Aplastic Anemia Initiate eltrombopag tablets concurrently with standard immunosuppressive therapy. Initial Dose Regimen The recommended initial dose regimen is listed in Table 3. Do not exceed the initial dose of eltrombopag tablets.

Table 3: Recommended Initial Eltrombopag Tablets Dose Regimen in the First-Line Treatment of Severe Aplastic Anemia Age Dose regimen Patients 12 years and older 150 mg orally once daily for 6 months Pediatric patients 6 to 11 years 75 mg orally once daily for 6 months Pediatric patients 2 to 5 years 2.5 mg/kg orally once daily for 6 months For patients with severe aplastic anemia of East-/Southeast-Asian ancestry or those with mild, moderate or severe hepatic impairment (Child-Pugh class A, B, C), decrease the initial eltrombopag tablets dose by 50% as listed in Table 4. If baseline alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels are > 6 x upper limit of normal (ULN), do not initiate eltrombopag tablets until transaminase levels are < 5 x ULN. Determine the initial dose for these patients based on Table 3 or Table 4.

Table 4: Recommended Initial Eltrombopag Tablets Dose Regimen for Patients of East-/Southeast-Asian Ancestry or Those With Mild, Moderate, or Severe Hepatic Impairment (Child-Pugh class A, B, C) in the First-Line Treatment of Severe Aplastic Anemia Age Dose regimen Patients 12 years and older 75 mg orally once daily for 6 months Pediatric patients 6 to 11 years 37.5 mg orally once daily for 6 months Pediatric patients 2 to 5 years 1.25 mg/kg orally once daily for 6 months Monitoring and Dose Adjustment for Eltrombopag Tablets Perform clinical hematology and liver tests regularly throughout therapy with eltrombopag tablets. Modify the dosage regimen of eltrombopag tablets based on platelet counts as outlined in Table 5.

Table 5: Dose Adjustments of Eltrombopag Tablets for Elevated Platelet Counts in the First-Line Treatment of Severe Aplastic Anemia Platelet count result Dose adjustment or response > 200 x 10 9 /L to ≤ 400 x 10 9 /L Decrease the daily dose by 25 mg every 2 weeks to lowest dose that maintains platelet count ≥ 50 x 10 9 /L. In pediatric patients under 12 years of age, decrease the dose by 12.5 mg. > 400 x 10 9 /L Discontinue eltrombopag tablets for one week. Once the platelet count is < 200 x 10 9 /L, reinitiate eltrombopag tablets at a daily dose reduced by 25 mg (or 12.5 mg in pediatric patients under 12 years of age). Table 6 summarizes the recommendations for dose interruption, reduction or discontinuation of eltrombopag tablets in the management of elevated liver transaminase levels and thromboembolic events.

Table 6: Recommended Dose Modifications for Eltrombopag Tablets for ALT or AST Elevations and Thromboembolic Events Event Recommendation ALT or AST elevations Increase in ALT or AST > 6 x ULN Discontinue eltrombopag tablets. Once ALT or AST is < 5 x ULN, reinitiate eltrombopag tablets at the same dose. Increase in ALT or AST > 6 x ULN after reinitiating eltrombopag tablets Discontinue eltrombopag tablets and monitor ALT or AST at least every 3 to 4 days. Once ALT or AST is < 5 x ULN, reinitiate eltrombopag tablets at a daily dose reduced by 25 mg compared to the previous dose. If ALT or AST returns to > 6 x ULN on the reduced dose Reduce the daily dose of eltrombopag tablets by 25 mg until ALT or AST is < 5 x ULN. In pediatric patients under 12 years of age, reduce the daily dose by at least 15% to the nearest dose that can be administered. Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolus, stroke, myocardial infarction) Discontinue eltrombopag tablets but remain on horse antithymocyte globulin (h-ATG) and cyclosporine.

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; ULN, upper limit of normal. The total duration of eltrombopag tablets treatment is 6 months. Refractory Severe Aplastic Anemia Use the lowest dose of eltrombopag tablets to achieve and maintain a hematologic response. Dose adjustments are based upon the platelet count. Hematologic response requires dose titration, generally up to 150 mg, and may take up to 16 weeks after starting eltrombopag tablets. Initial Dose Regimen Initiate eltrombopag tablets at a dose of 50 mg orally once daily. For patients with severe aplastic anemia of East-/Southeast-Asian ancestry or those with mild, moderate, or severe hepatic impairment (Child-Pugh class A, B, C), initiate eltrombopag tablets at a reduced dose of 25 mg orally once daily. Monitoring and Dose Adjustment Adjust the dose of eltrombopag tablets in 50 mg increments every 2 weeks as necessary to achieve the target platelet count greater than or equal to 50 x 10 9 /L as necessary. Do not exceed a dose of 150 mg daily. Monitor clinical hematology and liver tests regularly throughout therapy with eltrombopag tablets and modify the dosage regimen of eltrombopag tablets based on platelet counts as outlined in Table 7.

Table 7: Dose Adjustments of Eltrombopag Tablets in Patients With Refractory Severe Aplastic Anemia Platelet count result Dose adjustment or response < 50 x 10 9 /L following at least 2 weeks of eltrombopag tablets 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. ≥ 200 x 10 9 /L to ≤ 400 x 10 9 /L at any time Decrease the daily dose by 50 mg. Wait 2 weeks to assess the effects of this and any subsequent dose adjustments. > 400 x 10 9 /L Stop eltrombopag tablets for 1 week. Once the platelet count is < 150 x 10 9 /L, reinitiate therapy at a dose reduced by 50 mg. > 400 x 10 9 /L after 2 weeks of therapy at lowest dose of eltrombopag tablets Discontinue eltrombopag tablets. For patients who achieve tri-lineage response, including transfusion independence, lasting at least 8 weeks: the dose of eltrombopag tablets may be reduced by 50%. If counts remain stable after 8 weeks at the reduced dose, then discontinue eltrombopag tablets and monitor blood counts. If platelet counts drop to less than 30 x 10 9 /L, hemoglobin to less than 9 g/dL, or absolute neutrophil count (ANC) to less than 0.5 x 10 9 /L, eltrombopag tablets may be reinitiated at the previous effective dose. Discontinuation If no hematologic response has occurred after 16 weeks of therapy with eltrombopag tablets, discontinue therapy. If new cytogenetic abnormalities are observed, consider discontinuation of eltrombopag tablets. Excessive platelet count responses (as outlined in Table 7) or important liver test abnormalities also necessitate discontinuation of eltrombopag tablets.

2.4 Administration

Take eltrombopag tablets without a meal or with a meal low in calcium (≤ 50 mg). Take eltrombopag tablets at least 2 hours before or 4 hours after other medications (e.g., antacids), calcium-rich foods (containing > 50 mg calcium e.g., dairy products, calcium-fortified juices, and certain fruits and vegetables), or supplements containing polyvalent cations, such as iron, calcium, aluminum, magnesium, selenium, and zinc. Do not split, chew, or crush tablets and mix with food or liquids.