Eltrombopag Olamine
Eltrombopag · Tablet, Film Coated · Oral
Uses
Eltrombopag tablets are 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. Eltrombopag tablets should be used only in patients with ITP whose degree of thrombocytopenia and clinical condition increase the risk for bleeding. (1.1) for the treatment of thrombocytopenia in patients with chronic hepatitis C to allow the initiation and maintenance of interferon-based therapy. Eltrombopag tablets should be used only in patients with chronic hepatitis C whose degree of thrombocytopenia prevents the initiation of interferon-based therapy or limits the ability to maintain interferon-based therapy. (1.2) in combination with standard immunosuppressive therapy for the first- line treatment of adult and pediatric patients 2 years and older with severe aplastic anemia. (1.3) for the treatment of patients with severe aplastic anemia who have had an insufficient response to immunosuppressive therapy. (1.3) Limitations of Use: Eltrombopag tablets are not indicated for the treatment of patients with myelodysplastic syndrome (MDS). (1.4) Safety and efficacy have not been established in combination with direct-acting antiviral agents used without interferon for treatment of chronic hepatitis C infection. (1.4) 1.1 Treatment of Thrombocytopenia in Patients With Persistent or Chronic Immune Thrombocytopenia Eltrombopag tablets are 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. Eltrombopag tablets should be used only in patients with ITP whose degree of thrombocytopenia and clinical condition increase the risk for bleeding. 1.2 Treatment of Thrombocytopenia in Patients With Hepatitis C Infection Eltrombopag tablets are indicated for the treatment of thrombocytopenia in patients with chronic hepatitis C to allow the initiation and maintenance of interferon-based therapy. Eltrombopag tablets should be used only in patients with chronic hepatitis C whose degree of thrombocytopenia prevents the initiation of interferon-based therapy or limits the ability to maintain interferon-based therapy. 1.3 Treatment of Severe Aplastic Anemia Eltrombopag tablets are indicated in combination with standard immunosuppressive therapy (IST) for the first-line treatment of adult and pediatric patients 2 years and older with severe aplastic anemia. Eltrombopag tablets are indicated for the treatment of patients with severe aplastic anemia who have had an insufficient response to immunosuppressive therapy. 1.4 Limitations of Use Eltrombopag tablets are not indicated for the treatment of patients with myelodysplastic syndromes (MDS) [see Warnings and Precautions (5.3)] . Safety and efficacy have not been established in combination with direct-acting antiviral agents used without interferon for treatment of chronic hepatitis C infection.
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 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.
Dosage forms and strengths
Tablets 12.5 mg tablets —– White to off-white, round, biconvex film-coated tablets with "I" debossed on one side. Each tablet, for oral administration, contains eltrombopag olamine, equivalent to 12.5 mg of eltrombopag free acid. 25 mg tablets —– Orange to brown, round, biconvex film-coated tablets with "II" debossed on one side. Each tablet, for oral administration, contains eltrombopag olamine, equivalent to 25 mg of eltrombopag free acid. 50 mg tablets —– Blue, round, biconvex film-coated tablets with "III" debossed on one side. Each tablet, for oral administration, contains eltrombopag olamine, equivalent to 50 mg of eltrombopag free acid. 75 mg tablets —– Red to brown, round, biconvex film-coated tablets with "IV" debossed on one side. Each tablet, for oral administration, contains eltrombopag olamine, equivalent to 75 mg of eltrombopag free acid. Tablets: 12.5 mg, 25 mg, 50 mg, and 75 mg (3)
Contraindications
None. None. (4)
Warnings and precautions
Hepatotoxicity: Monitor liver function before and during therapy. (5.2) Increased Risk of Death and Progression of Myelodysplastic Syndromes to Acute Myeloid Leukemia. (5.3) Thrombotic/Thromboembolic Complications: Portal vein thrombosis has been reported in patients with chronic liver disease receiving eltrombopag tablets. Monitor platelet counts regularly. (5.4) 5.1 Hepatic Decompensation in Patients With Chronic Hepatitis C In patients with chronic hepatitis C, eltrombopag tablets in combination with interferon and ribavirin may increase the risk of hepatic decompensation. In two controlled clinical trials in patients with chronic hepatitis C and thrombocytopenia, ascites and encephalopathy occurred more frequently on the arm receiving treatment with eltrombopag tablets plus antivirals (7%) than the placebo plus antivirals arm (4%). Patients with low albumin levels (less than 3.5 g/dL) or Model for End-Stage Liver Disease (MELD) score greater than or equal to 10 at baseline had a greater risk for hepatic decompensation on the arm receiving treatment with eltrombopag tablets plus antivirals. Discontinue eltrombopag tablets if antiviral therapy is discontinued. 5.2 Hepatotoxicity Eltrombopag tablets may increase the risk of severe and potentially life-threatening hepatotoxicity [see Adverse Reactions (6.1)] . One patient (< 1%) with ITP treated with eltrombopag tablets in clinical trials experienced drug-induced liver injury. Eleven patients (1%) with chronic hepatitis C treated with eltrombopag tablets in clinical trials experienced drug-induced liver injury. Treatment of ITP, Chronic Hepatitis C-associated Thrombocytopenia, and Refractory Severe Aplastic Anemia Measure serum ALT, AST, and bilirubin prior to initiation of eltrombopag tablets, every 2 weeks during the dose adjustment phase, and monthly following establishment of a stable dose [see Drug Interactions (7.5)] . Eltrombopag tablets inhibits UDP-glucuronosyltransferase (UGT)1A1 and organic anion-transporting polypeptide (OATP)1B1, which may lead to indirect hyperbilirubinemia. If bilirubin is elevated, perform fractionation. Evaluate abnormal serum liver tests with repeat testing within 3 to 5 days. If the abnormalities are confirmed, monitor serum liver tests weekly until resolved or stabilized. Discontinue eltrombopag tablets if ALT levels increase to greater than or equal to 3 x ULN in patients with normal liver function or greater than or equal to 3 x baseline (or greater than 5 x ULN, whichever is the lower) in patients with pre-treatment elevations in transaminases and are: progressively increasing, or persistent for greater than or equal to 4 weeks, or accompanied by increased direct bilirubin, or accompanied by clinical symptoms of liver injury or evidence for hepatic decompensation. If the potential benefit for reinitiating treatment with eltrombopag tablets is considered to outweigh the risk for hepatotoxicity, then consider cautiously reintroducing eltrombopag tablets and measure serum liver tests weekly during the dose adjustment phase. Hepatotoxicity may reoccur if eltrombopag tablets is reinitiated. If liver test abnormalities persist, worsen, or recur, then permanently discontinue eltrombopag tablets. First-Line Treatment of Severe Aplastic Anemia Measure ALT, AST, and bilirubin prior to initiation of eltrombopag tablets, 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. 5.3 Increased Risk of Death and Progression of Myelodysplastic Syndromes to Acute Myeloid Leukemia A randomized, double-blind, placebo-controlled, multicenter trial in patients with International Prognostic Scoring System (IPSS) intermediate-1, intermediate-2 or high risk MDS with thrombocytopenia, receiving azacitidine in combination with either eltrombopag tablets (n = 179) or placebo (n = 177) was terminated due to lack of efficacy and safety reasons, including increased progression to acute myeloid leukemia (AML). Patients received eltrombopag tablets or placebo at a starting dose of 200 mg once daily, up to a maximum of 300 mg once daily, in combination with azacitidine for at least six cycles. The incidence of death (overall survival) was 32% (57/179) in the eltrombopag tablets arm versus 29% (51/177) in the placebo arm (HR [95% CI] = 1.42 [0.97, 2.08], showing an increased relative risk of death in this trial by 42% in the eltrombopag tablets arm). The incidence of progression to AML was 12% (21/179) in the eltrombopag tablets arm versus 6% (10/177) in the placebo arm (HR [95% CI] = 2.66 [1.31, 5.41], showing an increased relative risk of progression to AML in this trial by 166% in the eltrombopag tablets arm). 5.4 Thrombotic/Thromboembolic Complications Thrombotic/thromboembolic complications may result from increases in platelet counts with eltrombopag tablets. Reported thrombotic/thromboembolic complications included both venous and arterial events and were observed at low and at normal platelet counts. Consider the potential for an increased risk of thromboembolism when administering eltrombopag tablets to patients with known risk factors for thromboembolism (e.g., Factor V Leiden, ATIII deficiency, antiphospholipid syndrome, chronic liver disease). To minimize the risk for thrombotic/thromboembolic complications, do not use eltrombopag tablets in an attempt to normalize platelet counts. Follow the dose adjustment guidelines to achieve and maintain target platelet counts [see Dosage and Administration (2.1, 2.2, 2.3)] . In two controlled clinical trials in patients with chronic hepatitis C and thrombocytopenia, 3% (31/955) treated with eltrombopag tablets experienced a thrombotic event compared with 1% (5/484) on placebo. The majority of events were of the portal venous system (1% in patients treated with eltrombopag tablets versus less than 1% for placebo).
Side effects
The following clinically significant adverse reactions associated with eltrombopag tablets are described in other sections. Hepatic Decompensation in Patients with Chronic Hepatitis C [see Warnings and Precautions (5.1)] Hepatotoxicity [see Warnings and Precautions (5.2)] Increased Risk of Death and Progression of Myelodysplastic Syndromes to Acute Myeloid Leukemia [see Warnings and Precautions (5.3)] Thrombotic/Thromboembolic Complications [see Warnings and Precautions (5.4)] Cataracts [see Warnings and Precautions (5.5)] Across all indications, the most common adverse reactions (≥ 20% in any indication) were: anemia, nausea, pyrexia, alanine aminotransferase increased, cough, fatigue, headache, and diarrhea. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Somerset Therapeutics, LLC at 1-800-417-9175 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. Persistent or Chronic Immune Thrombocytopenia Adults: In clinical trials, hemorrhage was the most common serious adverse reaction and most hemorrhagic reactions followed discontinuation of eltrombopag tablets. Other serious adverse reactions included thrombotic/thromboembolic complications [see Warnings and Precautions (5.4)] . The data described below reflect exposure of eltrombopag tablets to patients with persistent or chronic ITP aged 18 to 85 years, of whom 66% were female, in three placebo-controlled trials and one open-label extension trial [see Clinical Studies (14.1)] . Eltrombopag tablets was administered to 330 patients for at least 6 months and 218 patients for at least 1 year. Table 8 presents the most common adverse drug reactions (experienced by greater than or equal to 3% of patients receiving eltrombopag tablets) from the three placebo-controlled trials, with a higher incidence in eltrombopag tablets versus placebo. Table 8. Adverse Reactions (≥ 3%) From Three Placebo-controlled Trials in Adults With Persistent or Chronic Immune Thrombocytopenia Adverse reaction Eltrombopag tablets 50 mg n = 241 (%) Placebo n = 128 (%) Nausea 9 3 Diarrhea 9 7 Upper respiratory tract infection 7 6 Vomiting 6 < 1 Urinary tract infection a 5 4 Increased ALT 5 3 Myalgia 5 2 Oropharyngeal pain 4 3 Increased AST 4 2 Pharyngitis 4 2 Back pain 3 2 Influenza 3 2 Paresthesia 3 2 Rash 3 2 Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase. a Includes PTs of urinary tract infection, cystitis, urinary tract infection bacterial, and bacteriuria. In the three controlled clinical persistent or chronic ITP trials, alopecia, musculoskeletal pain, blood alkaline phosphatase increased, and dry mouth were the adverse reactions reported in 2% of patients treated with eltrombopag tablets and in no patients who received placebo. Among 302 patients with persistent or chronic ITP who received eltrombopag tablets in the single-arm extension trial, the adverse reactions occurred in a pattern similar to that seen in the placebo-controlled trials. Table 9 presents the most common treatment-related adverse reactions (experienced by greater than or equal to 3% of patients receiving eltrombopag tablets) from the extension trial. Table 9. Treatment-related Adverse Reactions (≥ 3%) From Extension Trial in Adults With Persistent or Chronic Immune Thrombocytopenia Adverse reaction Eltrombopag tablets 50 mg n = 302 (%) Headache 10 ALT increased 5 AST increased 5 Cataract 5 Fatigue 5 Blood bilirubin increased 4 Nausea 4 Hyperbilirubinemia 3 Diarrhea 3 Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase. In the three controlled persistent or chronic ITP trials, serum liver test abnormalities (predominantly Grade 2 or less in severity) were reported in 11% and 7% of patients for eltrombopag tablets and placebo, respectively. Four patients (1%) treated with eltrombopag tablets and three patients in the placebo group (2%) discontinued treatment due to hepatobiliary laboratory abnormalities. Seventeen of the patients treated with eltrombopag tablets in the controlled trials with hepatobiliary laboratory abnormalities were re-exposed to eltrombopag tablets in the extension trial. Eight of these patients again experienced liver test abnormalities (less than or equal to Grade 3) resulting in discontinuation of eltrombopag tablets in one patient. In the extension persistent or chronic ITP trial, six additional patients had eltrombopag tablets discontinued due to liver test abnormalities (less than or equal to Grade 3). In the three controlled persistent or chronic ITP trials, cataracts developed or worsened in 7% of patients treated with eltrombopag tablets and 7% of patients in the placebo group. All patients had documented, preexisting risk factors for cataractogenesis, including corticosteroid use. In the extension trial, cataracts developed or worsened in 11% of patients who underwent ocular examination prior to therapy with eltrombopag tablets. Seventy-two percent of patients had preexisting risk factors, including corticosteroid use. The safety of eltrombopag tablets was also assessed in all patients treated in 7 adult persistent or chronic ITP clinical trials (N = 763 eltrombopag tablets-treated patients and 179 placebo-treated patients). Thromboembolic events were reported in 6% of eltrombopag tablets-treated patients versus 0% of placebo-treated patients and thrombotic microangiopathy with acute renal failure was reported in < 1% of eltrombopag tablets-treated patients versus 0% of placebo-treated patients.
Drug interactions
7.1 Polyvalent Cations (Chelation) Eltrombopag chelates polyvalent cations (such as iron, calcium, aluminum, magnesium, selenium, and zinc) in foods, mineral supplements, and antacids. Take eltrombopag tablets at least 2 hours before or 4 hours after any medications or products containing polyvalent cations, such as antacids, dairy products, and mineral supplements to avoid significant reduction in absorption of eltrombopag tablets due to chelation [see Dosage and Administration (2.4), Clinical Pharmacology (12.3)] . 7.2 Transporters Use caution when concomitantly administering eltrombopag tablets and drugs that are substrates of OATP1B1 (e.g., atorvastatin, bosentan, ezetimibe, fluvastatin, glyburide, olmesartan, pitavastatin, pravastatin, rosuvastatin, repaglinide, rifampin, simvastatin acid, SN-38 [active metabolite of irinotecan], valsartan) or breast cancer resistance protein (BCRP) (e.g., imatinib, irinotecan, lapatinib, methotrexate, mitoxantrone, rosuvastatin, sulfasalazine, topotecan). Monitor patients closely for signs and symptoms of excessive exposure to the drugs that are substrates of OATP1B1 or BCRP and consider reduction of the dose of these drugs, if appropriate. In clinical trials with eltrombopag tablets, a dose reduction of rosuvastatin by 50% was recommended. 7.3 Protease Inhibitors HIV Protease Inhibitors: No dose adjustment is recommended when eltrombopag tablets are coadministered with lopinavir/ritonavir (LPV/RTV). Drug interactions with other HIV protease inhibitors have not been evaluated. Hepatitis C Virus Protease Inhibitors: No dose adjustments are recommended when eltrombopag tablets are coadministered with boceprevir or telaprevir. Drug interactions with other hepatitis C virus (HCV) protease inhibitors have not been evaluated. 7.4 Peginterferon Alfa-2a/b Therapy No dose adjustments are recommended when eltrombopag tablets are coadministered with peginterferon alfa-2a (PEGASYS ® ) or -2b (PEGINTRON ® ). 7.5 Interference with Clinical Laboratory Tests Eltrombopag is highly colored and can cause patient sample discoloration, which is reported to interfere with some clinical laboratory tests, including, but not limited to bilirubin and creatinine. Bilirubin Testing : Eltrombopag can cause both positive and negative interference with bilirubin assays. If the laboratory results for bilirubin are inconsistent with clinical observations, further evaluation of liver function should be performed to clarify the clinical status of the patient. Evaluating contemporaneous aminotransferase values (AST, ALT) may help determine the validity of normal total bilirubin levels in the presence of clinical jaundice. Creatinine Testing : Eltrombopag can cause positive interference with creatinine measurements, leading to falsely elevated creatinine levels. In the event of an unexpected serum creatinine test result, further evaluation of renal function should be performed. Blood urea should be evaluated if serum creatinine is unexpectedly high. Communicate to the lab conducting testing if the patient is taking eltrombopag tablets. Re-testing using other methods may also help in determining the validity of the test results.
Use in specific populations
Lactation: Advise women not to breastfeed during treatment. (8.2) 8.1 Pregnancy Risk Summary Available data from a small number of published case reports and postmarketing experience with eltrombopag tablets use in pregnant women are insufficient to assess any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction and developmental toxicity studies, oral administration of eltrombopag to pregnant rats during organogenesis resulted in embryolethality and reduced fetal weights at maternally toxic doses. These effects were observed at doses resulting in exposures that were six times the human clinical exposure based on area under the curve (AUC) in patients with persistent or chronic ITP at 75 mg/day, and three times the AUC in patients with chronic hepatitis C at 100 mg/day (see Data). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In an early embryonic development study, female rats received oral eltrombopag at doses of 10, 20, or 60 mg/kg/day (0.8, 2, and 6 times, respectively, the human clinical exposure based on AUC in patients with ITP at 75 mg/day and 0.3, 1, and 3 times, respectively, the human clinical exposure based on AUC in patients with chronic hepatitis C at 100 mg/day). Increased pre- and post-implantation loss and reduced fetal weight were observed at the highest dose which also caused maternal toxicity. In an embryo-fetal development study eltrombopag was administered orally to pregnant rats during the period of organogenesis at doses of 10, 20, or 60 mg/kg/day (0.8, 2, and 6 times, respectively, the human clinical exposure based on AUC in patients with ITP at 75 mg/day and 0.3, 1, and 3 times, respectively, the human clinical exposure based on AUC in patients with chronic hepatitis C at 100 mg/day). Decreased fetal weights (6% to 7%) and a slight increase in the presence of cervical ribs were observed at the highest dose which also caused maternal toxicity. However, no evidence of major structural malformations was observed. In an embryo-fetal development study eltrombopag was administered orally to pregnant rabbits during the period of organogenesis at doses of 30, 80, or 150 mg/kg/day (0.04, 0.3, and 0.5 times, respectively, the human clinical exposure based on AUC in patients with ITP at 75 mg/day and 0.02, 0.1, and 0.3 times, respectively, the human clinical exposure based on AUC in patients with chronic hepatitis C at 100 mg/day). No evidence of fetotoxicity, embryolethality, or teratogenicity was observed. In a pre- and post-natal developmental toxicity study in pregnant rats (F0), oral eltrombopag was administered from gestation Day 6 through lactation Day 20. No adverse effects on maternal reproductive function or on the development of the offspring (F1) were observed at doses up to 20 mg/kg/day (2 times the human clinical exposure based on AUC in patients with ITP at 75 mg/day and similar to the human clinical exposure based on AUC in patients with chronic hepatitis C at 100 mg/day). Eltrombopag was detected in the plasma of offspring (F1). The plasma concentrations in pups increased with dose following administration of drug to the F0 dams. 8.2 Lactation Risk Summary There are no data regarding the presence of eltrombopag or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production. However, eltrombopag was detected in the pups of lactating rats 10 days postpartum suggesting the potential for transfer during lactation. Due to the potential for serious adverse reactions in a breastfed child from eltrombopag tablets, breastfeeding is not recommended during treatment. 8.3 Females and Males of Reproductive Potential Contraception Based on animal reproduction studies, eltrombopag tablets can cause fetal harm when administered to a pregnant woman. Sexually-active females of reproductive potential should use effective contraception (methods that result in less than 1% pregnancy rates) when using eltrombopag tablets during treatment and for at least 7 days after stopping treatment with eltrombopag tablets. 8.4 Pediatric Use The safety and efficacy of eltrombopag tablets have been established in pediatric patients 1 year and older with persistent or chronic ITP and in pediatric patients 2 years and older with IST-naïve severe aplastic anemia (in combination with h-ATG and cyclosporine). Safety and efficacy in pediatric patients below the age of 1 year with ITP have not been established. Safety and efficacy in pediatric patients with thrombocytopenia associated with chronic hepatitis C and refractory severe aplastic anemia have not been established. The safety and efficacy of eltrombopag tablets in pediatric patients 1 year and older with persistent or chronic ITP were evaluated in two double-blind, placebo-controlled trials [see Adverse Reactions (6.1), Clinical Studies (14.1)] . The pharmacokinetics of eltrombopag have been evaluated in 168 pediatric patients 1 year and older with ITP dosed once daily [see Clinical Pharmacology (12.3)] . See Dosage and Administration (2.1) for dosing recommendations for pediatric patients 1 year and older. The safety and efficacy of eltrombopag tablets in combination with h-ATG and cyclosporine for the first-line treatment of severe aplastic anemia in pediatric patients 2 years and older were evaluated in a single-arm, open-label trial [see Adverse Reactions (6.1), Clinical Studies (14.3)] . A total of 26 pediatric patients (ages 2 to < 17 years) were evaluated; 12 children (aged 2 to < 12 years) and 14 adolescents (aged 12 to < 17).
Pregnancy
8.1 Pregnancy Risk Summary Available data from a small number of published case reports and postmarketing experience with eltrombopag tablets use in pregnant women are insufficient to assess any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction and developmental toxicity studies, oral administration of eltrombopag to pregnant rats during organogenesis resulted in embryolethality and reduced fetal weights at maternally toxic doses. These effects were observed at doses resulting in exposures that were six times the human clinical exposure based on area under the curve (AUC) in patients with persistent or chronic ITP at 75 mg/day, and three times the AUC in patients with chronic hepatitis C at 100 mg/day (see Data). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In an early embryonic development study, female rats received oral eltrombopag at doses of 10, 20, or 60 mg/kg/day (0.8, 2, and 6 times, respectively, the human clinical exposure based on AUC in patients with ITP at 75 mg/day and 0.3, 1, and 3 times, respectively, the human clinical exposure based on AUC in patients with chronic hepatitis C at 100 mg/day). Increased pre- and post-implantation loss and reduced fetal weight were observed at the highest dose which also caused maternal toxicity. In an embryo-fetal development study eltrombopag was administered orally to pregnant rats during the period of organogenesis at doses of 10, 20, or 60 mg/kg/day (0.8, 2, and 6 times, respectively, the human clinical exposure based on AUC in patients with ITP at 75 mg/day and 0.3, 1, and 3 times, respectively, the human clinical exposure based on AUC in patients with chronic hepatitis C at 100 mg/day). Decreased fetal weights (6% to 7%) and a slight increase in the presence of cervical ribs were observed at the highest dose which also caused maternal toxicity. However, no evidence of major structural malformations was observed. In an embryo-fetal development study eltrombopag was administered orally to pregnant rabbits during the period of organogenesis at doses of 30, 80, or 150 mg/kg/day (0.04, 0.3, and 0.5 times, respectively, the human clinical exposure based on AUC in patients with ITP at 75 mg/day and 0.02, 0.1, and 0.3 times, respectively, the human clinical exposure based on AUC in patients with chronic hepatitis C at 100 mg/day). No evidence of fetotoxicity, embryolethality, or teratogenicity was observed. In a pre- and post-natal developmental toxicity study in pregnant rats (F0), oral eltrombopag was administered from gestation Day 6 through lactation Day 20. No adverse effects on maternal reproductive function or on the development of the offspring (F1) were observed at doses up to 20 mg/kg/day (2 times the human clinical exposure based on AUC in patients with ITP at 75 mg/day and similar to the human clinical exposure based on AUC in patients with chronic hepatitis C at 100 mg/day). Eltrombopag was detected in the plasma of offspring (F1). The plasma concentrations in pups increased with dose following administration of drug to the F0 dams.
Pediatric use
8.4 Pediatric Use The safety and efficacy of eltrombopag tablets have been established in pediatric patients 1 year and older with persistent or chronic ITP and in pediatric patients 2 years and older with IST-naïve severe aplastic anemia (in combination with h-ATG and cyclosporine). Safety and efficacy in pediatric patients below the age of 1 year with ITP have not been established. Safety and efficacy in pediatric patients with thrombocytopenia associated with chronic hepatitis C and refractory severe aplastic anemia have not been established. The safety and efficacy of eltrombopag tablets in pediatric patients 1 year and older with persistent or chronic ITP were evaluated in two double-blind, placebo-controlled trials [see Adverse Reactions (6.1), Clinical Studies (14.1)] . The pharmacokinetics of eltrombopag have been evaluated in 168 pediatric patients 1 year and older with ITP dosed once daily [see Clinical Pharmacology (12.3)] . See Dosage and Administration (2.1) for dosing recommendations for pediatric patients 1 year and older. The safety and efficacy of eltrombopag tablets in combination with h-ATG and cyclosporine for the first-line treatment of severe aplastic anemia in pediatric patients 2 years and older were evaluated in a single-arm, open-label trial [see Adverse Reactions (6.1), Clinical Studies (14.3)] . A total of 26 pediatric patients (ages 2 to < 17 years) were evaluated; 12 children (aged 2 to < 12 years) and 14 adolescents (aged 12 to < 17). See Dosage and Administration (2.3) for dosing recommendations for pediatric patients 2 years and older. The safety and efficacy of eltrombopag tablets in combination with h-ATG and cyclosporine in pediatric patients younger than 2 years for the first-line treatment of severe aplastic anemia have not yet been established. In patients 2 to 16 years of age, 69% of patients experienced serious adverse events compared to 42% in patients 17 years and older. Among the 12 patients who were 2 to 11 years of age in the eltrombopag tablets D1-M6 cohort and reached the 6-month assessment or withdrew earlier, the complete response rate at Month 6 was 8% versus 46% in patients age 12 to 16 years and 50% in patients 17 years of age and older.
Geriatric use
8.5 Geriatric Use Of the 106 patients in two randomized clinical trials of eltrombopag tablets, 50 mg in persistent or chronic ITP, 22% were 65 years of age and over, while 9% were 75 years of age and over. Of the 1439 patients in two randomized clinical trials of eltrombopag tablets in patients with chronic hepatitis C and thrombocytopenia, 7% were 65 years of age and over, while < 1% were 75 years of age and over. Of the 196 patients who received eltrombopag tablets for the treatment of severe aplastic anemia, 18% were 65 years of age and over, while 3% were 75 years of age and over. No overall differences in safety or effectiveness were observed between these patients and younger patients.
Overdosage
In the event of overdose, platelet counts may increase excessively and result in thrombotic/thromboembolic complications. In one report, a subject who ingested 5000 mg of eltrombopag tablets had a platelet count increase to a maximum of 929 x 10 9 /L at 13 days following the ingestion. The patient also experienced rash, bradycardia, ALT/AST elevations, and fatigue. The patient was treated with gastric lavage, oral lactulose, intravenous fluids, omeprazole, atropine, furosemide, calcium, dexamethasone, and plasmapheresis; however, the abnormal platelet count and liver test abnormalities persisted for 3 weeks. After 2 months' follow-up, all events had resolved without sequelae. In case of an overdose, consider oral administration of a metal cation-containing preparation, such as calcium, aluminum, or magnesium preparations to chelate eltrombopag and thus limit absorption. Closely monitor platelet counts. Reinitiate treatment with eltrombopag tablets in accordance with dosing and administration recommendations [see Dosage and Administration (2.1, 2.2)] . Consider contacting the Poison Help line (1- 800-222-1222) or a medical toxicologist for additional overdose management recommendations.
Description
Eltrombopag tablets contain eltrombopag olamine, a small molecule thrombopoietin (TPO) receptor agonist for oral administration. Eltrombopag olamine is a biphenyl hydrazone. The chemical name for eltrombopag olamine is 3'-{(2Z)-2-[1-(3,4-dimethylphenyl)-3-methyl-5-oxo-1,5-dihydro-4H-pyrazol-4- ylidene]hydrazino}-2'-hydroxy-3-biphenylcarboxylic acid - 2-aminoethanol (1:2). It has the molecular formula C 25 H 22 N 4 O 4
• 2(C 2 H 7 NO). The molecular weight is 564.65 g/mol for eltrombopag olamine and 442.5 g/mol for eltrombopag free acid. Eltrombopag olamine has the following structural formula: Eltrombopag olamine is practically insoluble in aqueous buffer across a pH range of 1 to 7.4, and is sparingly soluble in water. Eltrombopag tablets contain eltrombopag olamine in the amount equivalent to 12.5 mg, 25 mg, 50 mg, or 75 mg of eltrombopag free acid. The inactive ingredients of eltrombopag tablets are: Tablet Core: microcrystaline cellulose, mannitol, povidone, isomalt, calcium silicate, sodium starch glycolate, and magnesium stearate. Coating: 12.5 mg: hypromellose 2910, titanium dioxide, triacetin. 25 mg: hypromellose 2910, titanium dioxide, triacetin, ferric oxide yellow, ferric oxide red. 50 mg: hypromellose 2910, titanium dioxide, triacetin, FD&C Blue No. 1/brilliant blue FCF aluminum lake, FD&C Blue No. 2/indigo carmine aluminum lake, ferrosoferric oxide. 75 mg: hypromellose 2910, titanium dioxide, triacetin, ferric oxide red. Image
Mechanism of action
12.1 Mechanism of Action Eltrombopag is a TPO-receptor agonist that interacts with the transmembrane domain of the human TPO-receptor (also known as cMpl) and initiates signaling cascades that induce proliferation and differentiation of megakaryocytes leading to increased platelet production.
How supplied
16.1 Tablets The 12.5 mg tablets are white to off-white, round, biconvex film-coated tablets with "I" debossed on one side and are available in bottles of 30: NDC 70069-837-01 The 25 mg tablets are orange to brown, round, biconvex film-coated tablets with "II" debossed on one side and are available in bottles of 30: NDC 70069-838-01 The 50 mg tablets are blue, round, biconvex film-coated tablets with "III" debossed on one side and are available in bottles of 30: NDC 70069-839-01 The 75 mg tablets are red to brown, round, biconvex film-coated tablets with "IV" debossed on one side and are available in bottles of 30: NDC 70069-840-01 Store at room temperature between 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature]. Dispense in original bottle.
Patient information
Advise the patient or caregiver to read the FDA-approved patient labeling (Medication Guide). Prior to treatment, patients should fully understand and be informed of the following risks and considerations for eltrombopag tablets: Risks Hepatotoxicity Therapy with eltrombopag tablets may be associated with hepatobiliary laboratory abnormalities [see Warnings and Precautions (5.2)] . Advise patients with chronic hepatitis C and cirrhosis that they may be at risk for hepatic decompensation when receiving eltrombopag tablets with alfa interferon therapy [see Warnings and Precautions (5.1)] . Advise patients that they should report any of the following signs and symptoms of liver problems to their healthcare provider right away [see Warnings and Precautions (5.2)] . yellowing of the skin or the whites of the eyes (jaundice) unusual darkening of the urine unusual tiredness right upper stomach area pain confusion swelling of the stomach area (abdomen) Risk of Bleeding Upon Eltrombopag Tablets Discontinuation Advise patients that thrombocytopenia and risk of bleeding may reoccur upon discontinuing eltrombopag tablets, particularly if eltrombopag tablets is discontinued while the patient is on anticoagulants or antiplatelet agents. Advise patients that during therapy with eltrombopag tablets, they should continue to avoid situations or medications that may increase the risk for bleeding. Thrombotic/Thromboembolic Complications Advise patients that too much eltrombopag tablets may result in excessive platelet counts and a risk for thrombotic/thromboembolic complications [see Warnings and Precautions (5.4)] . Cataracts Advise patients to have a baseline ocular examination prior to administration of eltrombopag tablets and be monitored for signs and symptoms of cataracts during therapy [see Warnings and Precautions (5.5)] . Drug Interactions Advise patients to take eltrombopag tablets at least 2 hours before or 4 hours after calcium-rich foods, mineral supplements, and antacids which contain polyvalent cations, such as iron, calcium, aluminum, magnesium, selenium, and zinc [see Dosage and Administration (2.4), Drug Interactions (7.1)] . Lactation Advise women not to breastfeed during treatment with eltrombopag tablets [see Use in Specific Populations (8.2)] . Administration of Eltrombopag Tablets For patients with persistent or chronic ITP, therapy with eltrombopag tablets are administered 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 [see Indications and Usage (1.1)] . For patients with chronic hepatitis C, therapy with eltrombopag tablets are administered to achieve and maintain a platelet count necessary to initiate and maintain antiviral therapy with pegylated interferon and ribavirin [see Indications and Usage (1.2)] . Advise patients to take eltrombopag tablets without a meal or with a meal low in calcium (≤ 50 mg) and at least 2 hours before or 4 hours after other medications (e.g., antacids) and calcium-rich foods [see Dosage and Administration (2.4)] . The brands listed are trademarks or registered trademarks of their respective owners.
Label text from the FDA structured product label by Somerset Therapeutics, LLC (revised Jan 13, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Eltrombopag Olamine in 20 products
Eltrombopag Olamine NDC products (20)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 87564-035 | Eltrombopag Olamine 75 mg/1 Tablet, Film Coated | Amerisyn, LLC | ANDA |
| 87564-034 | Eltrombopag Olamine 50 mg/1 Tablet, Film Coated | Amerisyn, LLC | ANDA |
| 87564-033 | Eltrombopag Olamine 25 mg/1 Tablet, Film Coated | Amerisyn, LLC | ANDA |
| 87564-032 | Eltrombopag Olamine 12.5 mg/1 Tablet, Film Coated | Amerisyn, LLC | ANDA |
| 69238-1416 | Eltrombopag Olamine 25 mg/1 Tablet, Film Coated | Amneal Pharmaceuticals NY LLC | ANDA |
| 69238-1417 | Eltrombopag Olamine 12.5 mg/1 Tablet, Film Coated | Amneal Pharmaceuticals NY LLC | ANDA |
| 69238-1415 | Eltrombopag Olamine 50 mg/1 Tablet, Film Coated | Amneal Pharmaceuticals NY LLC | ANDA |
| 69238-1414 | Eltrombopag Olamine 75 mg/1 Tablet, Film Coated | Amneal Pharmaceuticals NY LLC | ANDA |
| 60219-1417 | Eltrombopag Olamine 12.5 mg/1 Tablet, Film Coated | Amneal Pharmaceuticals NY LLC | ANDA |
| 60219-1416 | Eltrombopag Olamine 25 mg/1 Tablet, Film Coated | Amneal Pharmaceuticals NY LLC | ANDA |
| 60219-1415 | Eltrombopag Olamine 50 mg/1 Tablet, Film Coated | Amneal Pharmaceuticals NY LLC | ANDA |
| 60219-1414 | Eltrombopag Olamine 75 mg/1 Tablet, Film Coated | Amneal Pharmaceuticals NY LLC | ANDA |
| 42291-932 | Eltrombopag Olamine 12.5 mg/1 Tablet, Film Coated | AvKARE | ANDA |
| 42291-935 | Eltrombopag Olamine 75 mg/1 Tablet, Film Coated | AvKARE | ANDA |
| 42291-934 | Eltrombopag Olamine 50 mg/1 Tablet, Film Coated | AvKARE | ANDA |
| 42291-933 | Eltrombopag Olamine 25 mg/1 Tablet, Film Coated | AvKARE | ANDA |
| 70069-837 | Eltrombopag Olamine 12.5 mg/1 Tablet, Film Coated | Somerset Therapeutics, LLC | ANDA |
| 70069-838 | Eltrombopag Olamine 25 mg/1 Tablet, Film Coated | Somerset Therapeutics, LLC | ANDA |
| 70069-839 | Eltrombopag Olamine 50 mg/1 Tablet, Film Coated | Somerset Therapeutics, LLC | ANDA |
| 70069-840 | Eltrombopag Olamine 75 mg/1 Tablet, Film Coated | Somerset Therapeutics, LLC | ANDA |
Frequently asked questions
What is Eltrombopag Olamine used for?
Eltrombopag tablets are 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. Eltrombopag tablets should be used only in patients with ITP whose degree of thrombocytopenia and…
What are the side effects of Eltrombopag Olamine?
The following clinically significant adverse reactions associated with eltrombopag tablets are described in other sections. Hepatic Decompensation in Patients with Chronic Hepatitis C [see Warnings and Precautions (5.1)] Hepatotoxicity [see Warnings and Precautions (5.2)] Increased Risk of Death and Progression of Myelodysplastic Syndromes to Acute Myeloid Leukemia [see Warnings and Precautions… See the full label for the complete list.
Who makes Eltrombopag Olamine?
Eltrombopag Olamine is listed by 4 labelers in the FDA NDC directory, including Amerisyn, LLC, Amneal Pharmaceuticals NY LLC, AvKARE, Somerset Therapeutics, LLC.