eltrombopag

2 DOSAGE AND 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 any medications or products containing polyvalent cations, such as antacids, calcium-rich foods, and mineral supplements. ( 2.4 , 7.1 , 12.3 ) 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. ( 2.1 , 8.6 , 8.7 ) 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. ( 2.2 ) 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. ( 2.3 , 8.7 ) 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. ( 2.3 , 8.6 , 8.7 ) 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 [see Warnings and Precautions ( 5.4 )]. 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 [see Clinical Studies ( 14.1 )]. 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 [see Use in Specific Populations ( 8.7 ), Clinical Pharmacology ( 12.3 )]. 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 [see Use in Specific Populations ( 8.6 ), Clinical Pharmacology ( 12.3 )]. 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 [see Clinical Pharmacology ( 12.3 )]. Pediatric Patients with ITP Aged 1 to 5 Years : Initiate eltrombopag tablets at a dose of 25 mg orally once daily [see Use in Specific Populations ( 8.7 ), Clinical Pharmacology ( 12.3 )]. 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 P latelet count result D ose adjustment or response 400 x 10 9 /L Stop eltrombopag tablets; increase the frequency of platelet monitoring to twice weekly. Once the platelet count is 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 [see Warnings and Precautions (5.2 , 5.6 ) and Drug Interactions (7.5 )]. 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 [see Warnings and Precautions ( 5.4 )]. In clinical trials, platelet counts generally began to rise within the first week of treatment with eltrombopag tablets [see Clinical Studies ( 14.2 )]. 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 [see Drug Interactions (7.5) ] . 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 P latelet count result D ose adjustment or response 400 x 10 9 /L Stop eltrombopag tablets; increase the frequency of platelet monitoring to twice weekly. Once the platelet count is 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 [see Warnings and Precautions (5.2 )]. 2.3 Severe Aplastic Anemia First-Line Severe Aplastic Anemia Initiate eltrombopag tablets concurrently with standard immunosuppressive therapy [see Clinical Studies ( 14.3 )]. 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 A ge D ose regimen Patients 12 years and older 150 mg orally once daily for 6 months Pediatric patients 6 to 11 years 75 mgo rally 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 [see Use in Specific Populations ( 8.6 , 8.7 ), Clinical Pharmacology ( 12.3 )]. 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 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 6 x ULN Discontinue eltrombopag tablets. Once ALT or AST is 6 x ULN after reinitiating eltrombopag tablets Discontinue eltrombopagtablets and monitor ALT or AST at least every 3 to 4 days. Once ALT or AST is 6 x ULN on the reduced dose Reduce the daily dose of eltrombopag tablets by 25 mg until ALT or AST is 400 x 10 9 /L Stop eltrombopagtablets for 1 week. Once the platelet count is 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% [see Clinical Studies ( 14.3 )]. 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 [see Adverse Reactions ( 6.1 )]. Excessive platelet count responses (as outlined in Table 7) or important liver test abnormalities also necessitate discontinuation of eltrombopag tablets [see Warnings and Precautions ( 5.2 )]. 2.4 Administration Administration of Tablets : 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 [see Drug Interactions ( 7.1 ), Clinical Pharmacology ( 12.3 )]. Do not split, chew, or crush tablets and mix with food or liquids.

See official label

1 INDICATIONS AND USAGE Eltrombopag tablets are a thrombopoietin receptor agonist indicated: for the treatment of thrombocytopenia in adult and pediatric patients 1 year and older with persistent or chronic immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.