ALVAIZ
Generic: ELTROMBOPAG
Basic Information
Manufacturer
Teva Pharmaceuticals, Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
ed51e463-7a03-4858-bbd2-882ce4753d5a
Indications & Usage
1 INDICATIONS AND USAGE ALVAIZ is a thrombopoietin receptor agonist indicated: for the treatment of thrombocytopenia in adult and pediatric patients 6 years and older with persistent or chronic immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.
ALVAIZ 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 adult patients with chronic hepatitis C to allow the initiation and maintenance of interferon-based therapy.
ALVAIZ 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 ) for the treatment of adult patients with severe aplastic anemia who have had an insufficient response to immunosuppressive therapy.
( 1.3 ) Limitations of Use: ALVAIZ is 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 ALVAIZ ® (eltrombopag tablets) are indicated for the treatment of thrombocytopenia in adult and pediatric patients 6 years and older with persistent or chronic immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.
ALVAIZ 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 ALVAIZ is indicated for the treatment of thrombocytopenia in adult patients with chronic hepatitis C to allow the initiation and maintenance of interferon-based therapy.
ALVAIZ 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 ALVAIZ is indicated for the treatment of adult patients with severe aplastic anemia who have had an insufficient response to immunosuppressive therapy.
1.4 Limitations of Use ALVAIZ is 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.
ALVAIZ 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 adult patients with chronic hepatitis C to allow the initiation and maintenance of interferon-based therapy.
ALVAIZ 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 ) for the treatment of adult patients with severe aplastic anemia who have had an insufficient response to immunosuppressive therapy.
( 1.3 ) Limitations of Use: ALVAIZ is 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 ALVAIZ ® (eltrombopag tablets) are indicated for the treatment of thrombocytopenia in adult and pediatric patients 6 years and older with persistent or chronic immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.
ALVAIZ 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 ALVAIZ is indicated for the treatment of thrombocytopenia in adult patients with chronic hepatitis C to allow the initiation and maintenance of interferon-based therapy.
ALVAIZ 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 ALVAIZ is indicated for the treatment of adult patients with severe aplastic anemia who have had an insufficient response to immunosuppressive therapy.
1.4 Limitations of Use ALVAIZ is 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.
Adverse Reactions
6 ADVERSE REACTIONS The following clinically significant adverse reactions associated with ALVAIZ 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 Teva at 1-888-838-2872 or 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.
The safety of ALVAIZ has been established based on adequate and well-controlled studies of eltrombopag olamine in adult and pediatric patients 6 years and older with persistent or chronic ITP, adult patients with chronic hepatitis C-associated thrombocytopenia, and adult patients with refractory severe aplastic anemia.
Below is a display of the adverse reactions of eltrombopag olamine in these adequate and well-controlled studies.
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.
Other serious adverse reactions included thrombotic/thromboembolic complications [see Warnings and Precautions ( 5.4 )] .
The data described below reflect exposure of eltrombopag 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 was administered to 330 patients for at least 6 months and 218 patients for at least 1 year.
Table 4 presents the most common adverse drug reactions (experienced by greater than or equal to 3% of patients receiving eltrombopag) from the three placebo-controlled trials, with a higher incidence in eltrombopag versus placebo.
Table 4.
Adverse Reactions (≥ 3%) From Three Placebo-controlled Trials in Adults with Persistent or Chronic Immune Thrombocytopenia Adverse Reaction Eltrombopag 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 and in no patients who received placebo.
Among 302 patients with persistent or chronic ITP who received eltrombopag in the single-arm extension trial, the adverse reactions occurred in a pattern similar to that seen in the placebo-controlled trials.
Table 5 presents the most common treatment-related adverse reactions (experienced by greater than or equal to 3% of patients receiving eltrombopag) from the extension trial.
Table 5.
Treatment-related Adverse Reactions (≥3%) From Extension Trial in Adults with Persistent or Chronic Immune Thrombocytopenia Adverse Reaction Eltrombopag 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 and placebo, respectively.
Four patients (1%) treated with eltrombopag and three patients in the placebo group (2%) discontinued treatment due to hepatobiliary laboratory abnormalities.
Seventeen of the patients treated with eltrombopag in the controlled trials with hepatobiliary laboratory abnormalities were re-exposed to eltrombopag 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 in one patient.
In the extension persistent or chronic ITP trial, six additional patients had eltrombopag 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 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.
Seventy-two percent of patients had preexisting risk factors, including corticosteroid use.
The safety of eltrombopag was also assessed in all patients treated in 7 adult persistent or chronic ITP clinical trials (N = 763 eltrombopag-treated patients and 179 placebo-treated patients).
Thromboembolic events were reported in 6% of eltrombopag-treated patients versus 0% of placebo-treated patients and thrombotic microangiopathy with acute renal failure was reported in < 1% of eltrombopag-treated patients versus 0% of placebo-treated patients.
In a placebo-controlled trial of eltrombopag in patients with chronic liver disease and thrombocytopenia not related to ITP, six patients treated with eltrombopag and one patient in the placebo group developed portal vein thromboses [see Warnings and Precautions ( 5.4 )] .
Pediatric Patients: The data described below reflect median exposure to eltrombopag of 91 days for 107 pediatric patients (aged 1 to 17 years) with persistent or chronic ITP, of whom 53% were female, across the randomized phase of two placebo-controlled trials.
ALVAIZ is not indicated for pediatric patients <6 years of age with persistent or chronic ITP.
Table 6 presents the most common adverse drug reactions (experienced by greater than or equal to 3% of pediatric patients 1 year and older receiving eltrombopag) across the two placebo-controlled trials, with a higher incidence for eltrombopag versus placebo.
Table 6.
Adverse Reactions (≥ 3%) with a Higher Incidence for Eltrombopag Versus Placebo from Two Placebo-controlled Trials in Pediatric Patients 1 Year and Older with Persistent or Chronic Immune Thrombocytopenia Adverse Reaction Eltrombopag n = 107 (%) Placebo n = 50 (%) Upper respiratory tract infection 17 6 Nasopharyngitis 12 4 Cough 9 0 Diarrhea 9 2 Pyrexia 9 8 Abdominal pain 8 4 Oropharyngeal pain 8 2 Toothache 6 0 ALT increased a 6 0 Rash 5 2 AST increased 4 0 Rhinorrhea 4 0 Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase.
a Includes adverse reactions or laboratory abnormalities > 3 x ULN.
In the two controlled clinical persistent or chronic ITP trials, cataracts developed or worsened in 2 (1%) patients treated with eltrombopag.
Both patients had received chronic oral corticosteroids, a risk factor for cataractogenesis.
Chronic Hepatitis C-associated Thrombocytopenia: In the two placebo-controlled trials, 955 patients with chronic hepatitis C-associated thrombocytopenia received eltrombopag.
Table 7 presents the most common adverse drug reactions (experienced by greater than or equal to 10% of patients receiving eltrombopag compared with placebo).
Table 7.
Adverse Reactions (≥ 10% and Greater Than Placebo) from Two Placebo-controlled Trials in Adults with Chronic Hepatitis C Adverse Reaction Eltrombopag + Peginterferon/Ribavirin n = 955 (%) Placebo + Peginterferon/Ribavirin n = 484 (%) Anemia 40 35 Pyrexia 30 24 Fatigue 28 23 Headache 21 20 Nausea 19 14 Diarrhea 19 11 Decreased appetite 18 14 Influenza-like illness 18 16 Insomnia a 16 15 Asthenia 16 13 Cough 15 12 Pruritus 15 13 Chills 14 9 Myalgia 12 10 Alopecia 10 6 Peripheral edema 10 5 a Includes PTs of insomnia, initial insomnia, and poor quality sleep.
Rash was reported in 9% and 7% of patients receiving eltrombopag and placebo, respectively.
In the two controlled clinical trials in patients with chronic hepatitis C, hyperbilirubinemia was reported in 8% of patients receiving eltrombopag compared with 3% for placebo.
Total bilirubin greater than or equal to 1.5 x ULN was reported in 76% and 50% of patients receiving eltrombopag and placebo, respectively.
ALT or AST greater than or equal to 3 x ULN was reported in 34% and 38% of patients for eltrombopag and placebo, respectively.
In the two controlled clinical trials in patients with chronic hepatitis C, cataracts developed or worsened in 8% of patients treated with eltrombopag and 5% of patients treated with placebo.
The safety of eltrombopag was also assessed in all patients treated with eltrombopag in the two controlled trials, including patients who initially received eltrombopag in the pre-antiviral treatment phase of the trial and were later randomized to the placebo arm (N = 1520 eltrombopag-treated patients).
Hepatic failure was reported in 0.8% of eltrombopag-treated patients and 0.4% of placebo-treated patients.
Severe Aplastic Anemia: Refractory Severe Aplastic Anemia In the single-arm, open-label trial, 43 patients with refractory severe aplastic anemia received eltrombopag.
Eleven patients (26%) were treated for greater than 6 months and 7 patients (16%) were treated for greater than 1 year.
The most common adverse reactions (greater than or equal to 20%) were nausea, fatigue, cough, diarrhea, and headache.
Table 8.
Adverse Reactions (≥ 10%) From One Open-label Trial in Adults with Refractory Severe Aplastic Anemia Adverse Reaction Eltrombopag n = 43 (%) Nausea 33 Fatigue 28 Cough 23 Diarrhea 21 Headache 21 Pain in extremity 19 Pyrexia 14 Dizziness 14 Oropharyngeal pain 14 Abdominal pain 12 Muscle spasms 12 Transaminases increased 12 Arthralgia 12 Rhinorrhea 12 Rash and hyperbilirubinemia were reported in 7% of patients; cataract was reported in 2% of patients.
In this trial, concurrent ALT or AST greater than 3 x ULN with total bilirubin greater than 1.5 x ULN were reported in 5% of patients.
Total bilirubin greater than 1.5 x ULN occurred in 14% of patients.
In this trial, patients had bone marrow aspirates evaluated for cytogenetic abnormalities.
Eight patients had a new cytogenetic abnormality reported on therapy, including 5 patients who had complex changes in chromosome 7.
6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of eltrombopag.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure.
Skin and Subcutaneous Tissue Disorders: Skin discoloration, including hyperpigmentation and skin yellowing.
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 Teva at 1-888-838-2872 or 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.
The safety of ALVAIZ has been established based on adequate and well-controlled studies of eltrombopag olamine in adult and pediatric patients 6 years and older with persistent or chronic ITP, adult patients with chronic hepatitis C-associated thrombocytopenia, and adult patients with refractory severe aplastic anemia.
Below is a display of the adverse reactions of eltrombopag olamine in these adequate and well-controlled studies.
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.
Other serious adverse reactions included thrombotic/thromboembolic complications [see Warnings and Precautions ( 5.4 )] .
The data described below reflect exposure of eltrombopag 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 was administered to 330 patients for at least 6 months and 218 patients for at least 1 year.
Table 4 presents the most common adverse drug reactions (experienced by greater than or equal to 3% of patients receiving eltrombopag) from the three placebo-controlled trials, with a higher incidence in eltrombopag versus placebo.
Table 4.
Adverse Reactions (≥ 3%) From Three Placebo-controlled Trials in Adults with Persistent or Chronic Immune Thrombocytopenia Adverse Reaction Eltrombopag 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 and in no patients who received placebo.
Among 302 patients with persistent or chronic ITP who received eltrombopag in the single-arm extension trial, the adverse reactions occurred in a pattern similar to that seen in the placebo-controlled trials.
Table 5 presents the most common treatment-related adverse reactions (experienced by greater than or equal to 3% of patients receiving eltrombopag) from the extension trial.
Table 5.
Treatment-related Adverse Reactions (≥3%) From Extension Trial in Adults with Persistent or Chronic Immune Thrombocytopenia Adverse Reaction Eltrombopag 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 and placebo, respectively.
Four patients (1%) treated with eltrombopag and three patients in the placebo group (2%) discontinued treatment due to hepatobiliary laboratory abnormalities.
Seventeen of the patients treated with eltrombopag in the controlled trials with hepatobiliary laboratory abnormalities were re-exposed to eltrombopag 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 in one patient.
In the extension persistent or chronic ITP trial, six additional patients had eltrombopag 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 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.
Seventy-two percent of patients had preexisting risk factors, including corticosteroid use.
The safety of eltrombopag was also assessed in all patients treated in 7 adult persistent or chronic ITP clinical trials (N = 763 eltrombopag-treated patients and 179 placebo-treated patients).
Thromboembolic events were reported in 6% of eltrombopag-treated patients versus 0% of placebo-treated patients and thrombotic microangiopathy with acute renal failure was reported in < 1% of eltrombopag-treated patients versus 0% of placebo-treated patients.
In a placebo-controlled trial of eltrombopag in patients with chronic liver disease and thrombocytopenia not related to ITP, six patients treated with eltrombopag and one patient in the placebo group developed portal vein thromboses [see Warnings and Precautions ( 5.4 )] .
Pediatric Patients: The data described below reflect median exposure to eltrombopag of 91 days for 107 pediatric patients (aged 1 to 17 years) with persistent or chronic ITP, of whom 53% were female, across the randomized phase of two placebo-controlled trials.
ALVAIZ is not indicated for pediatric patients <6 years of age with persistent or chronic ITP.
Table 6 presents the most common adverse drug reactions (experienced by greater than or equal to 3% of pediatric patients 1 year and older receiving eltrombopag) across the two placebo-controlled trials, with a higher incidence for eltrombopag versus placebo.
Table 6.
Adverse Reactions (≥ 3%) with a Higher Incidence for Eltrombopag Versus Placebo from Two Placebo-controlled Trials in Pediatric Patients 1 Year and Older with Persistent or Chronic Immune Thrombocytopenia Adverse Reaction Eltrombopag n = 107 (%) Placebo n = 50 (%) Upper respiratory tract infection 17 6 Nasopharyngitis 12 4 Cough 9 0 Diarrhea 9 2 Pyrexia 9 8 Abdominal pain 8 4 Oropharyngeal pain 8 2 Toothache 6 0 ALT increased a 6 0 Rash 5 2 AST increased 4 0 Rhinorrhea 4 0 Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase.
a Includes adverse reactions or laboratory abnormalities > 3 x ULN.
In the two controlled clinical persistent or chronic ITP trials, cataracts developed or worsened in 2 (1%) patients treated with eltrombopag.
Both patients had received chronic oral corticosteroids, a risk factor for cataractogenesis.
Chronic Hepatitis C-associated Thrombocytopenia: In the two placebo-controlled trials, 955 patients with chronic hepatitis C-associated thrombocytopenia received eltrombopag.
Table 7 presents the most common adverse drug reactions (experienced by greater than or equal to 10% of patients receiving eltrombopag compared with placebo).
Table 7.
Adverse Reactions (≥ 10% and Greater Than Placebo) from Two Placebo-controlled Trials in Adults with Chronic Hepatitis C Adverse Reaction Eltrombopag + Peginterferon/Ribavirin n = 955 (%) Placebo + Peginterferon/Ribavirin n = 484 (%) Anemia 40 35 Pyrexia 30 24 Fatigue 28 23 Headache 21 20 Nausea 19 14 Diarrhea 19 11 Decreased appetite 18 14 Influenza-like illness 18 16 Insomnia a 16 15 Asthenia 16 13 Cough 15 12 Pruritus 15 13 Chills 14 9 Myalgia 12 10 Alopecia 10 6 Peripheral edema 10 5 a Includes PTs of insomnia, initial insomnia, and poor quality sleep.
Rash was reported in 9% and 7% of patients receiving eltrombopag and placebo, respectively.
In the two controlled clinical trials in patients with chronic hepatitis C, hyperbilirubinemia was reported in 8% of patients receiving eltrombopag compared with 3% for placebo.
Total bilirubin greater than or equal to 1.5 x ULN was reported in 76% and 50% of patients receiving eltrombopag and placebo, respectively.
ALT or AST greater than or equal to 3 x ULN was reported in 34% and 38% of patients for eltrombopag and placebo, respectively.
In the two controlled clinical trials in patients with chronic hepatitis C, cataracts developed or worsened in 8% of patients treated with eltrombopag and 5% of patients treated with placebo.
The safety of eltrombopag was also assessed in all patients treated with eltrombopag in the two controlled trials, including patients who initially received eltrombopag in the pre-antiviral treatment phase of the trial and were later randomized to the placebo arm (N = 1520 eltrombopag-treated patients).
Hepatic failure was reported in 0.8% of eltrombopag-treated patients and 0.4% of placebo-treated patients.
Severe Aplastic Anemia: Refractory Severe Aplastic Anemia In the single-arm, open-label trial, 43 patients with refractory severe aplastic anemia received eltrombopag.
Eleven patients (26%) were treated for greater than 6 months and 7 patients (16%) were treated for greater than 1 year.
The most common adverse reactions (greater than or equal to 20%) were nausea, fatigue, cough, diarrhea, and headache.
Table 8.
Adverse Reactions (≥ 10%) From One Open-label Trial in Adults with Refractory Severe Aplastic Anemia Adverse Reaction Eltrombopag n = 43 (%) Nausea 33 Fatigue 28 Cough 23 Diarrhea 21 Headache 21 Pain in extremity 19 Pyrexia 14 Dizziness 14 Oropharyngeal pain 14 Abdominal pain 12 Muscle spasms 12 Transaminases increased 12 Arthralgia 12 Rhinorrhea 12 Rash and hyperbilirubinemia were reported in 7% of patients; cataract was reported in 2% of patients.
In this trial, concurrent ALT or AST greater than 3 x ULN with total bilirubin greater than 1.5 x ULN were reported in 5% of patients.
Total bilirubin greater than 1.5 x ULN occurred in 14% of patients.
In this trial, patients had bone marrow aspirates evaluated for cytogenetic abnormalities.
Eight patients had a new cytogenetic abnormality reported on therapy, including 5 patients who had complex changes in chromosome 7.
6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of eltrombopag.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure.
Skin and Subcutaneous Tissue Disorders: Skin discoloration, including hyperpigmentation and skin yellowing.