Eltrombopag is an oral non-peptide thrombopoietin receptor agonist indicated for the treatment of thrombocytopenia in those with persistent or chronic immune thrombocytopenia (ITP) or chronic hepatitis C infection and for the treatment of severe aplastic anemia. There are 2 salt forms available, eltrombopag olamine and eltrombopag choline; these products are not substitutable on a milligram per milligram basis. Eltrombopag may increase the risk of severe and potentially life-threatening hepatotoxicity. In patients with chronic hepatitis C, eltrombopag in combination with interferon and ribavirin may increase the risk of hepatic decompensation. Safety and efficacy have not been established in combination with direct-acting antiviral agents used without interferon for treatment of chronic hepatitis C infection. Hepatic function monitoring is necessary. Eltrombopag is not indicated for the treatment of patients with myelodysplastic syndromes (MDS).
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-Eltrombopag is available in different dosage forms and tablet strengths. Eltrombopag olamine and eltrombopag choline are not substitutable on a milligram per milligram basis.
-Administer without a meal or with a meal low in calcium (50 mg or less).
-Administer at least 2 hours before or 4 hours after other medications (e.g., antacids), calcium-rich foods containing more than 50 mg calcium (e.g., dairy, calcium-fortified juices, certain fruits and vegetables), or supplements containing polyvalent cations such as iron, calcium, aluminum, magnesium, selenium, and zinc.
Oral Solid Formulations
-Swallow tablets whole; do not split, chew, or crush tablets and mix with food or liquids.
Oral Liquid Formulations
Eltrombopag Olamine Powder for Oral Suspension
-Ensure that the enclosed mixing bottle, cap, lid, and oral syringe are dry prior to reconstitution.
-Avoid contact of the medication with skin; if contact occurs, wash the area immediately with soap and water. Advise caregivers and/or patients to contact their healthcare provider if a skin reaction occurs.
-To prevent staining of skin, consider wearing disposable gloves during preparation and clean up.
-Fill the oral dosing syringe with 20 mL of cool or cold drinking water; do not use hot water. Use a new (single-dose) oral dosing syringe to prepare each dose.
-Place the water into the mixing bottle and add the powder from the appropriate number of packets for the dose.
-Tighten the lid onto the mixing bottle and gently shake for at least 20 seconds; avoid vigorous shaking to prevent the mixture from foaming.
-Transfer the mixture into the oral dosing syringe, withdrawing the appropriate volume for the prescribed dose. The reconstituted suspension will be dark brown.
-Place the tip of the oral dosing syringe into the patient's mouth against the inside of the cheek and slowly eject the dose.
-Carefully clean up any spill of the powder or suspension with a damp paper towel or disposable cloth. Rinse the mixing bottle and lid and allow to air dry.
-Storage: Administer immediately; discard the mixture if not used within 30 minutes of reconstitution. May be stored at room temperature (20 to 25 degrees C [68 to 77 degrees F]) for up to 30 minutes. Discard remaining admixture in the mixing bottle in the trash. Do not pour down the drain. Discard the used oral dosing syringe.
Eltrombopag is a thrombopoietin (TPO) receptor agonist, and TPO-receptor agonists increase the risk for development or progression of reticulin fiber deposition and subsequent bone marrow fibrosis. In the extension study in chronic ITP, 151 patients had bone marrow biopsies taken after one year of therapy that were evaluated for collagen fiber deposition and increased reticulin. The majority of patients' (93%) biopsies showed predominately myelofibrosis (MF) Grade 1 or less. There were 7% of patients with MF Grade 2. Four patients had collagen deposition, and 1 patient with pre-existing MF Grade 1 developed MF Grade 2, which necessitated discontinuation of therapy.
In an open-label trial of patients with refractory severe aplastic anemia, 8 patients had a new cytogenetic abnormality reported on therapy, including 5 patients who had complex changes in chromosome 7. Seven patients in the eltrombopag cohort for first-line treatment of severe aplastic anemia had a new cytogenetic abnormality reported; of these, 4 had the loss of chromosome 7 within 6.1 months. Across all cohorts, clonal cytogenetic evolution occurred in 10% (15/153) of patients. Of these 15 patients, 7 had the loss of chromosome 7 (6 within 6.1 months), 4 had chromosomal aberrations which were of unclear significance, 3 had deletion of chromosome 13, and 1 had a follow-up bone marrow assessment at 5 years which showed dysplasia with hypercellularity concerning for potential development of myelodysplastic syndromes. It is unclear whether these findings occurred due to the underlying disease, the immunosuppressive therapy, and/or treatment with eltrombopag. Consider eltrombopag discontinuation if new cytogenetic abnormalities are observed.
During clinical studies of patients with idiopathic thrombocytopenic purpura (ITP), hemorrhage was the most common serious adverse reaction; however, most bleeding occurred after eltrombopag discontinuation. In studies of patients with chronic hepatitis C, anemia was reported at an incidence of 40% in patients receiving eltrombopag in combination with peginterferon/ribavirin compared to 35% of patients receiving placebo in combination with peginterferon/ribavirin.
Eltrombopag raises platelet counts; patients with excessive increases in platelet counts may experience thromboembolism. Follow dose adjustment guidelines to achieve and maintain target platelet counts. If a thromboembolic event (e.g., deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction) occurs during treatment of severe aplastic anemia, discontinue eltrombopag but continue horse antithymocyte globulin and cyclosporine. Among all patients treated in the 7 persistent or chronic ITP trials, thromboembolic events were reported in 6% of eltrombopag-treated patients compared to 0% of patients receiving placebo. Thrombotic microangiopathy with acute renal failure (unspecified) was reported in less than 1% of those receiving eltrombopag and in 0% of patients receiving placebo. In clinical trials of patients with chronic hepatitis C and thrombocytopenia, a thrombotic event occurred in 3% (31/955) of patients treated with eltrombopag compared to 1% (5/484) on placebo. The majority of events were of the portal venous system (1% in patients treated with eltrombopag vs. less than 1% for placebo). In the ELEVATE study, a placebo-controlled clinical trial of eltrombopag for thrombocytopenia due to chronic liver disease, 6 patients (4%) in the eltrombopag arm developed portal venous system thromboses. Two patients in the placebo arm experienced a thrombotic event of the portal venous system. The trial was terminated early upon these findings. In the trial, patients received eltrombopag 75 mg or placebo by mouth once daily for 14 days prior to an elective invasive procedure in an attempt to increase the platelet count to a level sufficient to alleviate the need for platelet transfusions. Patients with mild, moderate, and severe hepatic impairment were enrolled in the trial. Platelet counts were 200,000 cells/mm3 or more in 5 out of 6 patients receiving eltrombopag who developed the thromboses.
Gastrointestinal-related adverse reactions are among the most common associated with eltrombopag use. Nausea (4% to 33%), vomiting (6%), diarrhea (9% to 21%), anorexia (18%), oropharyngeal pain (4% to 14%), and abdominal pain (12%) were reported during eltrombopag clinical trials. Abdominal pain (8%), oropharyngeal pain (8%), dental pain (reported as toothache, 6%), and diarrhea (9%) were reported in pediatric clinical trials.
Eltrombopag may increase the risk of severe and potentially life-threatening hepatotoxicity. Monitor hepatic function and discontinue dosing as recommended. In patients with chronic hepatitis C, eltrombopag in combination with interferon and ribavirin may increase the risk of hepatic decompensation. A single patient (less than 1%) with persistent or chronic ITP and 11 patients (1%) with chronic hepatitis C who were treated with eltrombopag in clinical trials experienced drug-induced liver injury. Ascites and encephalopathy occurred more frequently in the arm receiving eltrombopag plus antivirals (7%) than placebo plus antivirals (4%) in clinical trials in patients with chronic hepatitis C and thrombocytopenia. Hepatic failure was reported in 0.8% of eltrombopag-treated patients and 0.4% of the placebo-treated patients. Discontinue eltrombopag if antiviral therapy is discontinued. In controlled persistent or chronic ITP trials, elevated hepatic enzymes (predominantly Grade 2 or less) were reported in 11% and 7% of the eltrombopag- and placebo-treated patients, respectively. In an extension trial, 17 of the patients with hepatobiliary abnormalities in the controlled trials were re-exposed to eltrombopag; of these patients, 8 experienced liver function test abnormalities (Grade 3 or less) resulting in discontinuation of therapy in 1 patient. An additional 6 patients discontinued therapy due to liver function test abnormalities in the extension trial. ALT and AST elevations were reported in 6% and 4%, respectively, of pediatric patients receiving eltrombopag for persistent or chronic ITP in clinical trials. Hyperbilirubinemia was reported in 3% to 8% of adult patients. In trials in patients with chronic hepatitis C, ALT or AST (3 times or more the upper limit of normal (ULN)) was reported in 34% and 38% of the eltrombopag- and placebo-placebo treated patients, respectively. Total bilirubin 1.5 times or more the ULN was reported in 76% and 50% of patients receiving eltrombopag and placebo, respectively. In an open-label trial where eltrombopag was used as first-line treatment for severe aplastic anemia, ALT, AST, and bilirubin increased in 29%, 17%, and 17% of patients, respectively. New or worsening liver function abnormalities (Grade 3 and 4) were 15% and 2% for AST, 26% and 4% for ALT, and 12% and 1% for bilirubin, respectively. In the pediatric cohort, increased ALT, AST, and bilirubin were reported in 23%, 12%, and 12% of patients. In an open-label trial in patients with refractory severe aplastic anemia, elevated hepatic enzymes and hyperbilirubinemia were reported in 12% and 7% of patients, respectively; ALT or AST more than 3 times the ULN with total bilirubin more than 1.5 times the ULN were reported in 5% of patients. Total bilirubin more than 1.5 the ULN occurred in 14% of patients.
In clinical studies of patients with persistent or chronic immune thrombocytopenia (ITP), cataracts developed or worsened in 15 (7%) patients receiving eltrombopag and in 8 (7%) patients in the placebo group. In the extension study, cataracts developed or worsened in 11% of patients who underwent a baseline ocular examination. The majority of patients (72%) had risk factors for developing cataracts, including corticosteroid use. In clinical trials in patients with chronic hepatitis C and thrombocytopenia, cataracts developed or worsened in 8% of patients treated with eltrombopag and 5% of patients treated with placebo. In patients with severe aplastic anemia, cataracts were reported in 2% of patients receiving eltrombopag. In pediatric trials, cataracts developed or worsened in 2 (1%) patients treated with eltrombopag; both patients had received chronic oral corticosteroids.
Fatigue (5% to 28%), insomnia (16%), dizziness (14%), and paresthesias (3%) were reported during clinical trials of eltrombopag.
Headache was reported at an incidence of 10% to 21% in clinical trials of eltrombopag.
Fever (14% to 30%), influenza-like illness (3% to 18%), cough (15% to 23%), chills (14%), rhinorrhea (12%), pharyngitis (4%), and infection including upper respiratory tract infection (7%) and urinary tract infection (5%) have been reported in clinical trials of eltrombopag. Upper respiratory tract infection (7% to 17%), nasopharyngitis (12%), fever (9%), cough (9%), and rhinorrhea (4%) were reported in pediatric clinical trials.
Pain in extremity (19%), asthenia (16%), muscle cramps (12%), arthralgia (12%), back pain (3%), and myalgia (5% to 12%) have been reported in clinical trials of eltrombopag.
Alopecia (10%), pruritus (15%), rash (3% to 9%), and skin discoloration including skin hyperpigmentation (5%) have been reported in clinical trials of eltrombopag. In a pediatric cohort, rash (12%) was among the most frequent serious adverse reactions reported. Skin hyperpigmentation and skin yellowing have been reported during postmarketing use.
In clinical trials of patients with chronic hepatitis C, peripheral edema was reported in 10% of patients receiving eltrombopag in combination with peginterferon/ribavirin compared to 5% of patients receiving placebo combined with peginterferon/ribavirin.
Eltrombopag may increase the risk of severe and potentially life-threatening hepatotoxicity; use with caution in any patient with preexisting hepatic disease. In patients with chronic hepatitis C infection, use of eltrombopag in combination with interferon and ribavirin may increase the risk of hepatic decompensation. This risk is further increased in those with hypoalbuminemia (albumin less than 3.5 g/dL) or a Model for End-Stage Liver Disease (MELD) score of 10 or more at baseline. In patients being treated for ITP, chronic hepatitis C-associated thrombocytopenia, and refractory severe aplastic anemia measure serum ALT, AST, and bilirubin at baseline, every 2 weeks during dose adjustment, and then monthly once a stable dose is achieved. If bilirubin is elevated, fractionation should be performed. Evaluate abnormalities with repeat testing in 3 to 5 days. If confirmed, monitor liver function tests (LFTs) weekly until the abnormalities resolve or stabilize. Discontinue eltrombopag if ALT increases to 3 times or more the upper limit of normal (ULN) in patients with normal liver function. In patients with pretreatment transaminase elevations, discontinue eltrombopag if ALT increases 3 times or more baseline (or more than 5 times the ULN, whichever is less) and are either progressively increasing, persistent for 4 weeks or more, accompanied by increased direct bilirubin, or accompanied by clinical symptoms of liver injury or evidence of hepatic decompensation. Consider reinitiating eltrombopag only if the potential benefit outweighs the risk of hepatotoxicity. If reinitiated, monitor LFTs weekly during the dose adjustment phase. Permanently discontinue treatment if LFT abnormalities persist, worsen, or recur. When eltrombopag olamine (Promacta) is used as first-line treatment for severe aplastic anemia, measure ALT, AST, and bilirubin at baseline, every other day while hospitalized for horse antithymocyte (h-ATG) therapy, and then every 2 weeks during treatment. If baseline ALT or AST concentrations are more than 6 times the ULN, do not initiate eltrombopag until values decline to less than 5 times the ULN. If ALT or AST increase to more than 6 times the ULN during treatment, discontinue eltrombopag and reinitiate at the same dose when values decline to less than 5 time the ULN. If ALT or AST increase to more than 6 times the ULN after reinitiation, discontinue treatment and monitor LFTs at least every 3 to 4 days. Reinitiate eltrombopag at a reduced daily dose once ALT and AST are less than 5 times the ULN. If ALT or AST return to values more than 6 times the ULN on the reduced dose, reduce the daily dose until ALT or AST is less than 5 times the ULN.
Safety and efficacy of eltrombopag in patients with renal impairment have not been established; monitor patients with renal impairment closely.
Thrombocytopenia and risk of bleeding may reoccur upon discontinuation of eltrombopag. This risk is increased if the drug is discontinued while the person is on antiplatelet or anticoagulant therapy. Advise people to avoid situations or medications that may increase risk for bleeding.
Use caution when administering eltrombopag to anyone with known risk factors for thrombotic or thromboembolic disease (e.g., Factor V Leiden, antithrombin III deficiency, antiphospholipid syndrome, chronic liver disease). Excessive doses of eltrombopag may increase platelet concentrations to a level that produces thrombotic or thromboembolic complications. Do not use eltrombopag in an effort to normalize platelet counts. Eltrombopag is not indicated for the treatment of thrombocytopenia due to chronic liver disease and a lower starting dose is needed in patients with moderate or severe liver disease.
Eltrombopag is not indicated in patients with myelodysplastic syndromes (MDS). Stimulation of the TPO-receptor on the surface of hematopoietic cells may increase the risk of hematologic neoplastic disease. A multicenter trial of patients with International Prognostic Scoring System (IPSS) intermediate-1, intermediate-2, or high risk MDS with thrombocytopenia receiving azacitidine in combination with either eltrombopag (n = 179) or placebo (n = 177) was terminated early due to lack of efficacy and safety concerns. Among those receiving eltrombopag, relative risk of death was increased by 42% and relative risk of progression to acute myeloid leukemia was increased by 166%.
Eltrombopag may increase the risk of cataracts; monitor patients with cataracts for worsening symptoms. A baseline ocular examination should be performed prior to treatment with eltrombopag and routinely throughout therapy.
Eltrombopag concentrations in East/Southeast-Asian ancestry adults with persistent or chronic immune thrombocytopenia (ITP) or chronic hepatitis C were 50% to 55% higher compared with non-Asian subjects. East/Southeast-Asian ancestry pediatric patients with ITP had approximately 43% higher plasma eltrombopag AUC values as compared to non-Asian patients. Reduce the initial dose of eltrombopag for treatment of ITP or severe aplastic anemia. No reduction in the initial dose is recommended for Asian patients with chronic hepatitis C.
During clinical trials of eltrombopag for ITP and severe aplastic anemia, 18% to 22% of patients were 65 years of age and older, and 3% to 9% were 75 years of age and older. Among patients in clinical trials for hepatitis C and thrombocytopenia, 7% were 65 years of age and older, and less than 1% were 75 years of age and older. No overall differences in efficacy or safety were observed between young and geriatric patients. However, greater sensitivity of some older individuals to the effects of eltrombopag cannot be ruled out.
Limited data from published case reports and postmarketing experience with eltrombopag use in human pregnancy 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, embryolethality and reduced fetal weights occurred when eltrombopag was given to rats in maternally toxic doses (6 times the human clinical exposure based on AUC in patients with persistent or chronic immune thrombocytopenia at 75 mg/day and 3 times the AUC in patients with chronic hepatitis C at 100 mg/day).
There are no data regarding the presence of eltrombopag or its metabolites in human breast milk, the effects on the breast-fed child, or the effects on milk production. Eltrombopag was detected in the pups of lactating rats at 10 days postpartum, suggesting the potential for transfer during lactation. Breast-feeding is not recommended during eltrombopag treatment due to the potential for serious adverse reactions in the breast-fed child from eltrombopag.
Eltrombopag is associated with reproductive risk. Discuss contraception requirements. Patients with reproductive potential should use effective contraception (methods that result in less than 1% pregnancy rates) during eltrombopag therapy and for at least 7 days after stopping treatment.
For the treatment of thrombocytopenia in persons with chronic hepatitis C to allow the initiation and maintenance of interferon-based therapy:
Oral dosage (eltrombopag choline):
Adults: 18 mg PO once daily, initially. Adjust dose by 18 mg/day PO every 2 weeks as necessary to achieve the target platelet count. Use the lowest effective dose to achieve and maintain a platelet count necessary to initiate and maintain antiviral therapy with pegylated interferon and ribavirin. Max: 72 mg/day.
Oral dosage (eltrombopag olamine):
Adults: 25 mg PO once daily, initially. Adjust dose by 25 mg/day PO every 2 weeks as necessary to achieve the target platelet count. Use the lowest effective dose to achieve and maintain a platelet count necessary to initiate and maintain antiviral therapy with pegylated interferon and ribavirin. Max: 100 mg/day.
For the treatment of persistent or chronic immune thrombocytopenic purpura (ITP) in persons who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy and whose degree of thrombocytopenia and clinical condition increase the risk of bleeding:
NOTE: Eltrombopag has been designated as an orphan drug by the FDA for this indication.
Oral dosage (eltrombopag choline):
Adults: 36 mg PO once daily, initially; for persons of East/Southeast-Asian ancestry, 18 mg PO once daily, initially. Adjust dose to achieve the target platelet count. Use the lowest effective dose to maintain platelet count and reduce risk for bleeding. Max: 54 mg/day.
Children and Adolescents 6 to 17 years: 36 mg PO once daily, initially; for persons of East/Southeast-Asian ancestry, 18 mg PO once daily, initially. Adjust dose to achieve the target platelet count. Use the lowest effective dose to maintain platelet count and reduce risk for bleeding. Max: 54 mg/day.
Oral dosage (eltrombopag olamine):
Adults: 50 mg PO once daily, initially; for persons of East/Southeast-Asian ancestry, 25 mg PO once daily, initially. Adjust dose to achieve the target platelet count. Use the lowest effective dose to maintain platelet count and reduce risk for bleeding. Max: 75 mg/day.
Children and Adolescents 6 to 17 years: 50 mg PO once daily, initially; for persons of East/Southeast-Asian ancestry, 25 mg PO once daily, initially. Adjust dose to achieve the target platelet count. Use the lowest effective dose to maintain platelet count and reduce risk for bleeding. Max: 75 mg/day.
Children 1 to 5 years: 25 mg PO once daily, initially. Adjust dose to achieve the target platelet count. Use the lowest effective dose to maintain platelet count and reduce risk for bleeding. Max: 75 mg/day.
For the treatment of severe aplastic anemia:
NOTE: Eltrombopag has been designated as an orphan drug by the FDA for this indication.
-for the treatment of severe aplastic anemia in combination with standard immunosuppressive therapy:
Oral dosage (eltrombopag olamine):
Adults: 150 mg PO once daily, initially; for persons of East/Southeast-Asian ancestry, 75 mg PO once daily, initially. Treat for 6 months. Reduce dose based on platelet count and hepatic enzyme concentrations. Use the lowest effective dose to achieve and maintain a hematological response. Do not exceed initial dose.
Children and Adolescents 12 to 17 years: 150 mg PO once daily, initially; for persons of East/Southeast-Asian ancestry, 75 mg PO once daily, initially. Treat for 6 months. Reduce dose based on platelet count and hepatic enzyme concentrations. Use the lowest effective dose to achieve and maintain a hematological response. Do not exceed initial dose.
Children 6 to 11 years: 75 mg PO once daily, initially; for persons of East/Southeast-Asian ancestry, 37.5 mg PO once daily, initially. Treat for 6 months. Reduce dose based on platelet count and hepatic enzyme concentrations. Use the lowest effective dose to achieve and maintain a hematological response. Do not exceed initial dose.
Children 2 to 5 years: 2.5 mg/kg/dose PO once daily, initially; for persons of East/Southeast-Asian ancestry, 1.25 mg/kg/dose PO once daily, initially. Treat for 6 months. Reduce dose based on platelet count and hepatic enzyme concentrations. Use the lowest effective dose to achieve and maintain a hematological response. Do not exceed initial dose.
-for the treatment of refractory severe aplastic anemia in persons who have had an insufficient response to immunosuppressive therapy:
Oral dosage (eltrombopag choline):
Adults: 36 mg PO once daily, initially; for persons of East/Southeast-Asian ancestry, 18 mg PO once daily, initially. Adjust dose by 36 mg/day every 2 weeks as necessary to achieve the target platelet count. Use the lowest effective dose to achieve and maintain a hematological response. Max: 108 mg/day.
Oral dosage (eltrombopag olamine):
Adults: 50 mg PO once daily, initially; for patients of East/Southeast-Asian ancestry, 25 mg PO once daily, initially. Adjust dose by 50 mg/day PO every 2 weeks as necessary to achieve the target platelet count. Use the lowest effective dose to achieve and maintain a hematological response. Max: 150 mg/day.
Therapeutic Drug Monitoring:
Monitor complete blood counts (CBCs) with differentials, including platelet counts, weekly until a stable platelet count has been achieved, then monthly. Platelet counts generally increase within 1 to 2 weeks of initiation and decrease within 1 to 2 weeks of discontinuation. Use the lowest effective dose to maintain the target platelet count and reduce risk for bleeding; however, do not use eltrombopag to normalize platelet concentrations. Obtain CBCs with differentials, including platelet counts, weekly for at least 4 weeks after discontinuation of eltrombopag.
When switching between the oral suspension and tablet, monitor platelet count weekly for 2 weeks, then monthly.
Persistent or chronic immune thrombocytopenic purpura
Eltrombopag choline:
-For platelet count less than 50,000/mm3 after at least 2 weeks of treatment: Increase the dose by 18 mg/day PO; do not exceed 54 mg/day. For persons receiving 9 mg/day, increase the dose to 18 mg/day before increasing the dose by 18 mg/day.
-For platelet count 50,000/mm3 to less than 200,000/mm3: Continue current dose.
-For platelet count 200,000 to 400,000/mm3: Reduce dose by 18 mg/day PO; wait 2 weeks to assess the effects of any dosage adjustments. For persons taking 18 mg/day, reduce dose to 9 mg/day.
-For platelet count more than 400,000/mm3: Stop therapy and increase the frequency of platelet monitoring to twice weekly. Once the platelet count is less than 150,000/mm3, reinitiate therapy at a dose reduced by 18 mg/day PO. For persons taking 18 mg/day, reinitiate therapy at 9 mg/day. If platelet count is more than 400,000/mm3 after 2 weeks at the lowest dose, discontinue eltrombopag.
Eltrombopag olamine:
-For platelet count less than 50,000/mm3 after at least 2 weeks of treatment: Increase the dose by 25 mg/day PO; do not exceed 75 mg/day. For persons taking 12.5 mg/day, increase the dose to 25 mg/day before increasing the dose by 25 mg/day.
-For platelet count 50,000/mm3 to less than 200,000/mm3: Continue current dose.
-For platelet count 200,000 to 400,000/mm3: Reduce dose by 25 mg/day PO; wait 2 weeks to assess the effects of any dosage adjustments. For persons taking 25 mg/day, reduce dose to 12.5 mg/day.
-For platelet count more than 400,000/mm3: Stop therapy and increase the frequency of platelet monitoring to twice weekly. Once the platelet count is less than 150,000/mm3, reinitiate therapy at a dose reduced by 25 mg/day PO. For persons taking 25 mg/day, reinitiate therapy at 12.5 mg/day. If platelet count is more than 400,000/mm3 after 2 weeks at the lowest dose, discontinue eltrombopag.
Discontinue eltrombopag if the platelet count does not increase to a level sufficient to avoid clinically important bleeding after 4 weeks of therapy at the maximum daily dosage.
Chronic hepatitis C-associated thrombocytopenia
Eltrombopag choline:
-For platelet count less than 50,000/mm3 after at least 2 weeks of treatment: increase the dose by 18 mg/day PO; do not exceed 72 mg/day.
-For platelet count 50,000/mm3 to less than 200,000/mm3: Continue current dose.
-For platelet count 200,000 to 400,000/mm3: Reduce dose by 18 mg/day PO; wait 2 weeks to assess the effects of any dosage adjustments.
-For platelet count more than 400,000/mm3: Stop therapy and increase the frequency of platelet monitoring to twice weekly. Once the platelet count is less than 150,000/mm3, reinitiate therapy at a dose reduced by 18 mg/day PO. For persons taking 18 mg/day, reinitiate therapy at 9 mg/day. If platelet count is more than 400,000/mm3 after 2 weeks at the lowest dose, discontinue eltrombopag.
Eltrombopag olamine:
-For platelet count less than 50,000/mm3 after at least 2 weeks of treatment: Increase the dose by 25 mg/day PO; do not exceed 100 mg/day.
-For platelet count 50,000/mm3 to less than 200,000/mm3: Continue current dose.
-For platelet count 200,000 to 400,000/mm3: Reduce dose by 25 mg/day PO; wait 2 weeks to assess the effects of any dosage adjustments.
-For platelet count more than 400,000/mm3: Stop therapy and increase the frequency of platelet monitoring to twice weekly. Once the platelet count is less than 150,000/mm3, reinitiate therapy at a dose reduced by 25 mg/day PO. For persons taking 25 mg/day, reinitiate therapy at 12.5 mg/day. If platelet count is more than 400,000/mm3 after 2 weeks at the lowest dose, discontinue eltrombopag.
Discontinue eltrombopag when antiviral therapy is discontinued.
First-line severe aplastic anemia
Eltrombopag olamine:
-For platelet count 50,000/mm3 to less than 200,000/mm3: Continue current dose.
-For platelet count 200,000 to 400,000/mm3: Reduce dose by 25 mg/day PO every 2 weeks to the lowest dose that maintains platelet count of 50,000/mm3 or more. In children 2 to 12 years, reduce dose by 12.5 mg/day.
-For platelet count more than 400,000/mm3: Stop therapy for 1 week. Once the platelet count is less than 200,000/mm3, reinitiate therapy at a dose reduced by 25 mg/day PO. In children 2 to 12 years, reduce dose by 12.5 mg/day.
Discontinue eltrombopag but continue horse antithymocyte globulin and cyclosporine if a thromboembolic event (e.g., deep vein thrombosis, pulmonary embolus, stroke, myocardial infarction) occurs.
Refractory severe aplastic anemia
Eltrombopag choline:
-For platelet count less than 50,000/mm3 after at least 2 weeks of treatment: Increase the dose by 36 mg/day PO; do not exceed 108 mg/day. For persons taking 18 mg/day, increase the dose to 36 mg/day before increasing the dose by 36 mg/day.
-For platelet count 50,000/mm3 to less than 200,000/mm3: Continue current dose.
-For platelet count 200,000 to 400,000/mm3: Reduce dose by 36 mg/day PO; wait 2 weeks to assess the effects of any dosage adjustments.
-For platelet count more than 400,000/mm3: Stop therapy for 1 week. Once the platelet count is less than 150,000/mm3, reinitiate therapy at a dose reduced by 36 mg/day PO. If platelet count is more than 400,000/mm3 after 2 weeks at the lowest dose, discontinue eltrombopag.
Eltrombopag olamine:
-For platelet count less than 50,000/mm3 after at least 2 weeks of treatment: Increase the dose by 50 mg/day PO; do not exceed 150 mg/day. For persons taking 25 mg/day, increase the dose to 50 mg/day before increasing the dose by 50 mg/day.
-For platelet count 50,000/mm3 to less than 200,000/mm3: Continue current dose.
-For platelet count 200,000 to 400,000/mm3: Reduce dose by 50 mg/day PO; wait 2 weeks to assess the effects of any dosage adjustments.
-For platelet count more than 400,000/mm3: Stop therapy for 1 week. Once the platelet count is less than 150,000/mm3, reinitiate therapy at a dose reduced by 50 mg/day PO. If platelet count is more than 400,000/mm3 after 2 weeks at the lowest dose, discontinue eltrombopag.
For persons who achieve tri-linage response, including transfusion independence, lasting at least 8 weeks, the dose of eltrombopag may be reduced by 50%. If platelet count remains stable for 8 weeks at the reduced dose, then discontinue eltrombopag and monitor blood counts. If platelet count decreases to less than 30,000/mm3, hemoglobin to less than 9 g/dL, or absolute neutrophil count (ANC) to less than 500/mm3, eltrombopag may be reinitiated at the previous effective dose.
Discontinue eltrombopag if no hematologic response has occurred after 16 weeks of therapy. Consider discontinuation of eltrombopag if new cytogenetic abnormalities are observed.
Maximum Dosage Limits:
-Adults
Eltrombopag choline: 54 mg/day PO for idiopathic thrombocytopenic purpura; 72 mg/day PO for chronic hepatitis C-associated thrombocytopenia; 108 mg/day PO for aplastic anemia.
Eltrombopag olamine: 75 mg/day PO for idiopathic thrombocytopenic purpura; 100 mg/day PO for chronic hepatitis C-associated thrombocytopenia; 150 mg/day PO for aplastic anemia.
-Geriatric
Eltrombopag choline: 54 mg/day PO for idiopathic thrombocytopenic purpura; 72 mg/day PO for chronic hepatitis C-associated thrombocytopenia; 108 mg/day PO for aplastic anemia.
Eltrombopag olamine: 75 mg/day PO for idiopathic thrombocytopenic purpura; 100 mg/day PO for chronic hepatitis C-associated thrombocytopenia; 150 mg/day PO for aplastic anemia.
-Adolescents
Eltrombopag choline: 54 mg/day PO for idiopathic thrombocytopenic purpura.
Eltrombopag olamine: 75 mg/day PO for idiopathic thrombocytopenic purpura; 150 mg/day PO for severe aplastic anemia.
-Children
Eltrombopag choline:
6 to 12 years: 54 mg/day PO for idiopathic thrombocytopenic purpura.
1 to 5 years: Safety and efficacy have not been established.
Eltrombopag olamine:
12 years: 75 mg/day PO for idiopathic thrombocytopenic purpura; 150 mg/day PO for aplastic anemia.
6 to 11 years: 75 mg/day PO for idiopathic thrombocytopenic purpura; 75 mg/day PO for aplastic anemia.
2 to 5 years: 75 mg/day PO for idiopathic thrombocytopenic purpura; 2.5 mg/kg/day PO for aplastic anemia.
1 year: 75 mg/day PO for idiopathic thrombocytopenic purpura; safety and efficacy have not been established for other indications.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Mild to severe hepatic impairment (Child-Pugh Class A, B, or C) when treating idiopathic thrombocytopenic purpura (ITP), chronic hepatitis C-associated thrombocytopenia, and severe refractory aplastic anemia:
Eltrombopag choline:
-ITP: Reduce the initial dose to 18 mg PO once daily and do not increase the dose more frequently than every 3 weeks. Consider reducing the initial dose to 9 mg PO once daily for persons of East/Southeaster-Asian ancestry.
-Hepatitis C: No dose adjustment needed.
-Refractory severe aplastic anemia: Reduce initial dose to 18 mg PO once daily.
Eltrombopag olamine:
-ITP: Reduce the initial dose to 25 mg PO once daily and do not increase the dose more frequently than every 3 weeks. Consider reducing the initial dose to 12.5 mg PO once daily for persons of East/Southeast-Asian ancestry.
-Hepatitis C: No dose adjustment needed.
-Refractory severe aplastic anemia: Reduce the initial dose to 25 mg PO once daily.
Monitor ALT, AST, and bilirubin at baseline, every 2 weeks during dose adjustment, and monthly after the establishment of a stable dose. If abnormalities are confirmed, monitor weekly until resolved or stabilized. Discontinue eltrombopag if ALT concentrations increase to 3 times or more the upper limit of normal (ULN) in persons with normal liver function at baseline. In persons with pretreatment elevations in transaminases, discontinue eltrombopag if ALT concentrations increase to 3 times or more baseline (or more than 5 times ULN, whichever is least) and the increases are progressive, or persistent for 4 weeks or more, or accompanied by increased direct bilirubin, or clinical symptoms of liver injury, or evidence of hepatic decompensation. If potential benefit for reinitiating treatment with eltrombopag is considered to outweigh the risk, measure serum liver function tests weekly during the dose adjustment phase. Hepatotoxicity may reoccur with reinitiation. If liver abnormalities persist, worsen, or recur, then permanently discontinue eltrombopag.
Mild to severe hepatic impairment (Child-Pugh Class A, B, or C) when treating severe aplastic anemia first-line:
Eltrombopag olamine:
-12 years and older: Reduce the initial dose to 75 mg PO once daily.
-6 to 11 years: Reduce the initial dose to 37.5 mg PO once daily.
-2 to 5 years: Reduce the initial dose to 1.25 mg/kg/dose PO once daily.
Do not initiate treatment until transaminase concentrations are less than 5 times the ULN. Monitor ALT, AST, and bilirubin at baseline, every other day while hospitalized for horse antithymocyte globulin therapy, and then every 2 weeks. Discontinue eltrombopag if ALT/AST concentrations increase more than 6 times the ULN; may reinitiate treatment at the same dose once the AST/ALT is less than 5 times the ULN. If concentrations increase more than 6 times the ULN after reinitiation, discontinue eltrombopag and monitor liver function tests at least every 3 to 4 days. Once ALT/AST are less than 5 times the ULN, reinitiate treatment at a dose reduced by 25 mg/day compared to the previous dose. If the ALT/AST returns to more than 6 times the ULN on the reduced dose, reduce the dose by 25 mg/day until the ALT/AST is less than 5 times the ULN. In children 2 to 11 years, reduce the daily dose by at least 15% to the nearest dose that can be administered.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Acetaminophen: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. Acetaminophen is a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of acetaminophen are possible. Monitor patients for adverse reactions if these drugs are coadministered.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. Acetaminophen is a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of acetaminophen are possible. Monitor patients for adverse reactions if these drugs are coadministered.
Acetaminophen; Aspirin: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. Acetaminophen is a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of acetaminophen are possible. Monitor patients for adverse reactions if these drugs are coadministered.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. Acetaminophen is a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of acetaminophen are possible. Monitor patients for adverse reactions if these drugs are coadministered.
Acetaminophen; Caffeine: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. Acetaminophen is a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of acetaminophen are possible. Monitor patients for adverse reactions if these drugs are coadministered.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. Acetaminophen is a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of acetaminophen are possible. Monitor patients for adverse reactions if these drugs are coadministered.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. Acetaminophen is a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of acetaminophen are possible. Monitor patients for adverse reactions if these drugs are coadministered.
Acetaminophen; Chlorpheniramine: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. Acetaminophen is a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of acetaminophen are possible. Monitor patients for adverse reactions if these drugs are coadministered.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. Acetaminophen is a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of acetaminophen are possible. Monitor patients for adverse reactions if these drugs are coadministered.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. Acetaminophen is a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of acetaminophen are possible. Monitor patients for adverse reactions if these drugs are coadministered.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. Acetaminophen is a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of acetaminophen are possible. Monitor patients for adverse reactions if these drugs are coadministered.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. Acetaminophen is a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of acetaminophen are possible. Monitor patients for adverse reactions if these drugs are coadministered.
Acetaminophen; Codeine: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. Acetaminophen is a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of acetaminophen are possible. Monitor patients for adverse reactions if these drugs are coadministered.
Acetaminophen; Dextromethorphan: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. Acetaminophen is a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of acetaminophen are possible. Monitor patients for adverse reactions if these drugs are coadministered.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. Acetaminophen is a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of acetaminophen are possible. Monitor patients for adverse reactions if these drugs are coadministered.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. Acetaminophen is a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of acetaminophen are possible. Monitor patients for adverse reactions if these drugs are coadministered.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. Acetaminophen is a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of acetaminophen are possible. Monitor patients for adverse reactions if these drugs are coadministered.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. Acetaminophen is a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of acetaminophen are possible. Monitor patients for adverse reactions if these drugs are coadministered.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. Acetaminophen is a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of acetaminophen are possible. Monitor patients for adverse reactions if these drugs are coadministered.
Acetaminophen; Diphenhydramine: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. Acetaminophen is a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of acetaminophen are possible. Monitor patients for adverse reactions if these drugs are coadministered.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. Acetaminophen is a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of acetaminophen are possible. Monitor patients for adverse reactions if these drugs are coadministered.
Acetaminophen; Hydrocodone: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. Acetaminophen is a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of acetaminophen are possible. Monitor patients for adverse reactions if these drugs are coadministered.
Acetaminophen; Ibuprofen: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. Acetaminophen is a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of acetaminophen are possible. Monitor patients for adverse reactions if these drugs are coadministered. (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Acetaminophen; Oxycodone: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. Acetaminophen is a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of acetaminophen are possible. Monitor patients for adverse reactions if these drugs are coadministered.
Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. Acetaminophen is a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of acetaminophen are possible. Monitor patients for adverse reactions if these drugs are coadministered.
Acetaminophen; Phenylephrine: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. Acetaminophen is a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of acetaminophen are possible. Monitor patients for adverse reactions if these drugs are coadministered.
Acetaminophen; Pseudoephedrine: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. Acetaminophen is a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of acetaminophen are possible. Monitor patients for adverse reactions if these drugs are coadministered.
Alpelisib: (Major) Avoid coadministration of alpelisib with eltrombopag due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and eltrombopag is a BCRP inhibitor.
Aluminum Hydroxide: (Major) Eltrombopag chelates polyvalent cations (e.g., calcium, aluminum, and magnesium) in food, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as aluminum salts, (like aluminum hydroxide), calcium salts, (including calcium carbonate), and magnesium salts.
Aluminum Hydroxide; Magnesium Carbonate: (Major) Eltrombopag chelates polyvalent cations (e.g., calcium, aluminum, and magnesium) in food, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as aluminum salts, (like aluminum hydroxide), calcium salts, (including calcium carbonate), and magnesium salts.
Aluminum Hydroxide; Magnesium Hydroxide: (Major) Eltrombopag chelates polyvalent cations (e.g., calcium, aluminum, and magnesium) in food, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as aluminum salts, (like aluminum hydroxide), calcium salts, (including calcium carbonate), and magnesium salts.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Major) Eltrombopag chelates polyvalent cations (e.g., calcium, aluminum, and magnesium) in food, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as aluminum salts, (like aluminum hydroxide), calcium salts, (including calcium carbonate), and magnesium salts.
Aluminum Hydroxide; Magnesium Trisilicate: (Major) Eltrombopag chelates polyvalent cations (e.g., calcium, aluminum, and magnesium) in food, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as aluminum salts, (like aluminum hydroxide), calcium salts, (including calcium carbonate), and magnesium salts.
Amlodipine; Atorvastatin: (Moderate) Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as atorvastatin, may exhibit an increase in systemic exposure if coadministered with eltrombopag; monitor patients for adverse reactions if these drugs are coadministered.
Amlodipine; Celecoxib: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Amlodipine; Olmesartan: (Moderate) Use caution and monitor blood pressure closely if eltrombopag and olmesartan are coadministered. Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as olmesartan, may exhibit an increase in systemic exposure if coadministered with eltrombopag.
Amlodipine; Valsartan: (Moderate) Use caution and monitor blood pressure closely if eltrombopag and valsartan are coadministered. Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as valsartan, may exhibit an increase in systemic exposure if coadministered with eltrombopag.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Use caution and monitor blood pressure closely if eltrombopag and valsartan are coadministered. Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as valsartan, may exhibit an increase in systemic exposure if coadministered with eltrombopag.
Amobarbital: (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inducers of CYP1A2, such as barbiturates, on the systemic exposure of eltrombopag has not been established. Monitor patients for a decrease in the efficacy of eltrombopag if these drugs are coadministered.
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inducers of CYP1A2, such as omeprazole, on the systemic exposure of eltrombopag has not been established. Monitor patients for a decrease in the efficacy of eltrombopag if these drugs are coadministered.
Anticoagulants: (Moderate) Use caution when discontinuing eltrombopag in patients receiving anticoagulants (e.g., warfarin, enoxaparin, dabigatran, rivaroxaban). The risk of bleeding and recurrent thrombocytopenia is increased in patients receiving these drugs when eltrombopag is discontinued.
Antithrombin III: (Moderate) Use caution when discontinuing eltrombopag in patients receiving anticoagulants (e.g., warfarin, enoxaparin, dabigatran, rivaroxaban). The risk of bleeding and recurrent thrombocytopenia is increased in patients receiving these drugs when eltrombopag is discontinued.
Apixaban: (Moderate) Use caution when discontinuing eltrombopag in patients receiving anticoagulants (e.g., warfarin, enoxaparin, dabigatran, rivaroxaban). The risk of bleeding and recurrent thrombocytopenia is increased in patients receiving these drugs when eltrombopag is discontinued.
Argatroban: (Moderate) Use caution when discontinuing eltrombopag in patients receiving anticoagulants (e.g., warfarin, enoxaparin, dabigatran, rivaroxaban). The risk of bleeding and recurrent thrombocytopenia is increased in patients receiving these drugs when eltrombopag is discontinued.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inducers of CYP1A2, such as barbiturates, on the systemic exposure of eltrombopag has not been established. Monitor patients for a decrease in the efficacy of eltrombopag if these drugs are coadministered.
Aspirin, ASA; Caffeine: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. Acetaminophen is a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of acetaminophen are possible. Monitor patients for adverse reactions if these drugs are coadministered.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Major) Eltrombopag chelates polyvalent cations (e.g., antacids) in food, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as magaldrate.
Aspirin, ASA; Omeprazole: (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inducers of CYP1A2, such as omeprazole, on the systemic exposure of eltrombopag has not been established. Monitor patients for a decrease in the efficacy of eltrombopag if these drugs are coadministered.
Atazanavir: (Moderate) Eltrombopag is metabolized by CYP2C8. The significance of administering weak inhibitors of CYP2C8, such as atazanavir, on the systemic exposure of eltrombopag has not been established. Monitor patients for signs of eltrombopag toxicity if these drugs are coadministered.
Atazanavir; Cobicistat: (Moderate) Eltrombopag is metabolized by CYP2C8. The significance of administering weak inhibitors of CYP2C8, such as atazanavir, on the systemic exposure of eltrombopag has not been established. Monitor patients for signs of eltrombopag toxicity if these drugs are coadministered.
Atogepant: (Major) Limit the dose of atogepant to 10 or 30 mg PO once daily for episodic migraine or 30 mg PO once daily for chronic migraine if coadministered with eltrombopag. Concurrent use may increase atogepant exposure and the risk of adverse effects. Atogepant is a substrate of OATP1B1 and OATP1B3 and eltrombopag is an OATP inhibitor. Coadministration with an OATP1B1/3 inhibitor resulted in a 2.85-fold increase in atogepant overall exposure and a 2.23-fold increase in atogepant peak concentration.
Atorvastatin: (Moderate) Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as atorvastatin, may exhibit an increase in systemic exposure if coadministered with eltrombopag; monitor patients for adverse reactions if these drugs are coadministered.
Barbiturates: (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inducers of CYP1A2, such as barbiturates, on the systemic exposure of eltrombopag has not been established. Monitor patients for a decrease in the efficacy of eltrombopag if these drugs are coadministered.
Bempedoic Acid; Ezetimibe: (Moderate) Use caution and monitor for adverse reactions if eltrombopag and ezetimibe are coadministered. Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as ezetimibe, may exhibit an increase in systemic exposure if coadministered with eltrombopag.
Benzhydrocodone; Acetaminophen: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. Acetaminophen is a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of acetaminophen are possible. Monitor patients for adverse reactions if these drugs are coadministered.
Betrixaban: (Moderate) Use caution when discontinuing eltrombopag in patients receiving anticoagulants (e.g., warfarin, enoxaparin, dabigatran, rivaroxaban). The risk of bleeding and recurrent thrombocytopenia is increased in patients receiving these drugs when eltrombopag is discontinued.
Bivalirudin: (Moderate) Use caution when discontinuing eltrombopag in patients receiving anticoagulants (e.g., warfarin, enoxaparin, dabigatran, rivaroxaban). The risk of bleeding and recurrent thrombocytopenia is increased in patients receiving these drugs when eltrombopag is discontinued.
Bosentan: (Moderate) Use caution and monitor for adverse reactions if eltrombopag and bosentan are coadministered. Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as bosentan, may exhibit an increase in systemic exposure if coadministered with eltrombopag.
Brincidofovir: (Moderate) Postpone the administration of eltrombopag for at least three hours after brincidofovir administration and increase monitoring for brincidofovir-related adverse reactions (i.e., elevated hepatic enzymes and bilirubin, diarrhea, other gastrointestinal adverse events) if concomitant use of brincidofovir and eltrombopag is necessary. Brincidofovir is an OATP1B1 substrate and eltrombopag is an OATP1B1 inhibitor. In a drug interaction study, the mean AUC and Cmax of brincidofovir increased by 374% and 269%, respectively, when administered with another OATP1B1 inhibitor.
Bupivacaine; Meloxicam: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Butalbital; Acetaminophen: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. Acetaminophen is a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of acetaminophen are possible. Monitor patients for adverse reactions if these drugs are coadministered. (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inducers of CYP1A2, such as barbiturates, on the systemic exposure of eltrombopag has not been established. Monitor patients for a decrease in the efficacy of eltrombopag if these drugs are coadministered.
Butalbital; Acetaminophen; Caffeine: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. Acetaminophen is a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of acetaminophen are possible. Monitor patients for adverse reactions if these drugs are coadministered. (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inducers of CYP1A2, such as barbiturates, on the systemic exposure of eltrombopag has not been established. Monitor patients for a decrease in the efficacy of eltrombopag if these drugs are coadministered.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. Acetaminophen is a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of acetaminophen are possible. Monitor patients for adverse reactions if these drugs are coadministered. (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inducers of CYP1A2, such as barbiturates, on the systemic exposure of eltrombopag has not been established. Monitor patients for a decrease in the efficacy of eltrombopag if these drugs are coadministered.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inducers of CYP1A2, such as barbiturates, on the systemic exposure of eltrombopag has not been established. Monitor patients for a decrease in the efficacy of eltrombopag if these drugs are coadministered.
Calcium Acetate: (Major) Eltrombopag chelates polyvalent cations (e.g., calcium, aluminum, and magnesium) in food, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as aluminum salts, (like aluminum hydroxide), calcium salts, (including calcium carbonate), and magnesium salts.
Calcium Carbonate: (Major) Eltrombopag chelates polyvalent cations (e.g., calcium, aluminum, and magnesium) in food, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as aluminum salts, (like aluminum hydroxide), calcium salts, (including calcium carbonate), and magnesium salts.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Major) Eltrombopag chelates polyvalent cations (e.g., calcium, aluminum, and magnesium) in food, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as aluminum salts, (like aluminum hydroxide), calcium salts, (including calcium carbonate), and magnesium salts.
Calcium Carbonate; Magnesium Hydroxide: (Major) Eltrombopag chelates polyvalent cations (e.g., calcium, aluminum, and magnesium) in food, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as aluminum salts, (like aluminum hydroxide), calcium salts, (including calcium carbonate), and magnesium salts.
Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Major) Eltrombopag chelates polyvalent cations (e.g., calcium, aluminum, and magnesium) in food, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as aluminum salts, (like aluminum hydroxide), calcium salts, (including calcium carbonate), and magnesium salts.
Calcium Carbonate; Simethicone: (Major) Eltrombopag chelates polyvalent cations (e.g., calcium, aluminum, and magnesium) in food, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as aluminum salts, (like aluminum hydroxide), calcium salts, (including calcium carbonate), and magnesium salts.
Calcium Chloride: (Major) Eltrombopag chelates polyvalent cations (e.g., calcium, aluminum, and magnesium) in food, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as aluminum salts, (like aluminum hydroxide), calcium salts, (including calcium carbonate), and magnesium salts.
Calcium Gluconate: (Major) Eltrombopag chelates polyvalent cations (e.g., calcium, aluminum, and magnesium) in food, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as aluminum salts, (like aluminum hydroxide), calcium salts, (including calcium carbonate), and magnesium salts.
Calcium: (Major) Eltrombopag chelates polyvalent cations (e.g., calcium, aluminum, and magnesium) in food, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as aluminum salts, (like aluminum hydroxide), calcium salts, (including calcium carbonate), and magnesium salts.
Calcium; Vitamin D: (Major) Eltrombopag chelates polyvalent cations (e.g., calcium, aluminum, and magnesium) in food, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as aluminum salts, (like aluminum hydroxide), calcium salts, (including calcium carbonate), and magnesium salts.
Calcium; Vitamin D: (Major) Eltrombopag chelates polyvalent cations (e.g., calcium, aluminum, and magnesium) in food, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as aluminum salts, (like aluminum hydroxide), calcium salts, (including calcium carbonate), and magnesium salts.
Carbamazepine: (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inducers of CYP1A2, such as carbamazepine, on the systemic exposure of eltrombopag has not been established. Monitor patients for a decrease in the efficacy of eltrombopag if these drugs are coadministered.
Celecoxib: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Celecoxib; Tramadol: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Chlorpheniramine; Pseudoephedrine: (Major) Eltrombopag chelates polyvalent cations (e.g., zinc salts) in foods, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag 2 hours before or 4 hours after any oral products containing zinc salts.
Chromium: (Major) Eltrombopag chelates polyvalent cations (e.g., calcium, aluminum, and magnesium) in food, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as aluminum salts, (like aluminum hydroxide), calcium salts, (including calcium carbonate), and magnesium salts.
Cimetidine: (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inhibitors of CYP1A2, such as cimetidine, on the systemic exposure of eltrombopag has not been established. Monitor patients for signs of eltrombopag toxicity if these drugs are coadministered.
Ciprofloxacin: (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inhibitors of CYP1A2, such as ciprofloxacin, on the systemic exposure of eltrombopag has not been established. Monitor patients for signs of eltrombopag toxicity if these drugs are coadministered.
Dabigatran: (Moderate) Use caution when discontinuing eltrombopag in patients receiving anticoagulants (e.g., warfarin, enoxaparin, dabigatran, rivaroxaban). The risk of bleeding and recurrent thrombocytopenia is increased in patients receiving these drugs when eltrombopag is discontinued.
Dalteparin: (Moderate) Use caution when discontinuing eltrombopag in patients receiving anticoagulants (e.g., warfarin, enoxaparin, dabigatran, rivaroxaban). The risk of bleeding and recurrent thrombocytopenia is increased in patients receiving these drugs when eltrombopag is discontinued.
Diclofenac: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Diclofenac; Misoprostol: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Diflunisal: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Diphenhydramine; Ibuprofen: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Diphenhydramine; Naproxen: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Edoxaban: (Moderate) Use caution when discontinuing eltrombopag in patients receiving anticoagulants (e.g., warfarin, enoxaparin, dabigatran, rivaroxaban). The risk of bleeding and recurrent thrombocytopenia is increased in patients receiving these drugs when eltrombopag is discontinued.
Elagolix: (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as eltrombopag is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Eltrombopag is an inhibitor of OATP1B1 in vitro and can increase the systemic exposure of other drugs that are substrates of OATP1B1. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density.
Elagolix; Estradiol; Norethindrone acetate: (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as eltrombopag is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Eltrombopag is an inhibitor of OATP1B1 in vitro and can increase the systemic exposure of other drugs that are substrates of OATP1B1. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density.
Eluxadoline: (Major) When administered concurrently with eltrombopag, the dose of eluxadoline must be reduced to 75 mg PO twice daily, and the patient should be closely monitored for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity). Eluxadoline is a substrate of the organic anion-transporting peptide (OATP1B1); eltrombopag is an in vitro inhibitor of OATP1B1. Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known.
Enoxaparin: (Moderate) Use caution when discontinuing eltrombopag in patients receiving anticoagulants (e.g., warfarin, enoxaparin, dabigatran, rivaroxaban). The risk of bleeding and recurrent thrombocytopenia is increased in patients receiving these drugs when eltrombopag is discontinued.
Etodolac: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Ezetimibe: (Moderate) Use caution and monitor for adverse reactions if eltrombopag and ezetimibe are coadministered. Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as ezetimibe, may exhibit an increase in systemic exposure if coadministered with eltrombopag.
Ezetimibe; Simvastatin: (Moderate) Use caution and monitor for adverse reactions if eltrombopag and ezetimibe are coadministered. Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as ezetimibe, may exhibit an increase in systemic exposure if coadministered with eltrombopag. (Moderate) Use caution and monitor for adverse reactions if eltrombopag and simvastatin are coadministered. Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as simvastatin, may exhibit an increase in systemic exposure if coadministered with eltrombopag.
Fenoprofen: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Ferric Maltol: (Major) Eltrombopag chelates polyvalent cations (e.g., iron) in foods and mineral supplements. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as iron salts, multivitamins that contain iron, or polysaccharide-iron complex.
Fexofenadine: (Moderate) Monitor patients for fexofenadine adverse reactions if coadministered with eltrombopag. Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as fexofenadine, may exhibit an increase in systemic exposure if coadministered with eltrombopag.
Fexofenadine; Pseudoephedrine: (Moderate) Monitor patients for fexofenadine adverse reactions if coadministered with eltrombopag. Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as fexofenadine, may exhibit an increase in systemic exposure if coadministered with eltrombopag.
Flurbiprofen: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Fluvastatin: (Moderate) Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as fluvastatin, may exhibit an increase in systemic exposure if coadministered with eltrombopag; monitor patients for adverse reactions if these drugs are coadministered.
Fluvoxamine: (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inhibitors of CYP1A2, such as fluvoxamine, on the systemic exposure of eltrombopag has not been established. Monitor patients for signs of eltrombopag toxicity if these drugs are coadministered.
Fondaparinux: (Moderate) Use caution when discontinuing eltrombopag in patients receiving anticoagulants (e.g., warfarin, enoxaparin, dabigatran, rivaroxaban). The risk of bleeding and recurrent thrombocytopenia is increased in patients receiving these drugs when eltrombopag is discontinued.
Food: (Major) Eltrombopag chelates polyvalent cations (e.g., calcium, aluminum, and magnesium) in food. Systemic exposure to eltrombopag may be decreased when it is coadministered with a polyvalent cation-containing product. Eltrombopag should not be taken within 4 hours of any oral products containing polyvalent cations, such as aluminum salts, (like aluminum hydroxide), calcium salts, (including calcium carbonate), and magnesium salts. (Major) Eltrombopag chelates polyvalent cations (e.g., calcium, aluminum, and magnesium) in food. Systemic exposure to eltrombopag may be decreased when it is coadministered with a polyvalent cation-containing product. Eltrombopag should not be taken within 4 hours of any oral products containing polyvalent cations, such as calcium salts.
Gemfibrozil: (Moderate) Eltrombopag is metabolized by CYP2C8. The significance of administering inhibitors of CYP2C8, such as gemfibrozil, on the systemic exposure of eltrombopag has not been established. Monitor patients for signs of eltrombopag toxicity if these drugs are coadministered.
Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of glecaprevir and eltrombopag as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of organic anion transporting polypeptide (OATP) 1B1 and breast cancer resistance protein (BCRP); eltrombopag is an inhibitor of OATP1B1 and BCRP. (Moderate) Caution is advised with the coadministration of pibrentasvir and eltrombopag as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of breast cancer resistance protein (BCRP); eltrombopag is an inhibitor of BCRP.
Glyburide: (Moderate) Use caution and monitor blood glucose carefully if eltrombopag and glyburide are coadministered. Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as glyburide, may exhibit an increase in systemic exposure if coadministered with eltrombopag.
Glyburide; Metformin: (Moderate) Use caution and monitor blood glucose carefully if eltrombopag and glyburide are coadministered. Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as glyburide, may exhibit an increase in systemic exposure if coadministered with eltrombopag.
Heparin: (Moderate) Use caution when discontinuing eltrombopag in patients receiving anticoagulants (e.g., warfarin, enoxaparin, dabigatran, rivaroxaban). The risk of bleeding and recurrent thrombocytopenia is increased in patients receiving these drugs when eltrombopag is discontinued.
Hydrocodone; Ibuprofen: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Ibuprofen: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Ibuprofen; Famotidine: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Ibuprofen; Oxycodone: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Ibuprofen; Pseudoephedrine: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Imatinib: (Moderate) Use caution and monitor for adverse reactions if eltrombopag and imatinib, STI-571 are coadministered. Eltrombopag is an inhibitor of Breast Cancer Resistance Protein (BCRP). Drugs that are substrates for this transporter, such as imatinib, may exhibit an increase in systemic exposure if coadministered with eltrombopag.
Indomethacin: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Iron Salts: (Major) Eltrombopag chelates polyvalent cations (e.g., iron) in foods and mineral supplements. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as iron salts, multivitamins that contain iron, or polysaccharide-iron complex.
Iron Salts: (Major) Eltrombopag chelates polyvalent cations (e.g., iron) in foods and mineral supplements. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as iron salts, multivitamins that contain iron, or polysaccharide-iron complex.
Iron: (Major) Eltrombopag chelates polyvalent cations (e.g., iron) in foods and mineral supplements. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as iron salts, multivitamins that contain iron, or polysaccharide-iron complex.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Eltrombopag is metabolized by CYP1A2 and CYP2C8. The significance of administering inducers of CYP1A2 and CYP2C8, such as rifampin, on the systemic exposure of eltrombopag has not been established. Additionally, eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as rifampin, may exhibit an increase in systemic exposure if coadministered with eltrombopag. Monitor patients for a decrease in the efficacy of eltrombopag and for an increase in adverse reactions of rifampin if these drugs are coadministered.
Isoniazid, INH; Rifampin: (Major) Eltrombopag is metabolized by CYP1A2 and CYP2C8. The significance of administering inducers of CYP1A2 and CYP2C8, such as rifampin, on the systemic exposure of eltrombopag has not been established. Additionally, eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as rifampin, may exhibit an increase in systemic exposure if coadministered with eltrombopag. Monitor patients for a decrease in the efficacy of eltrombopag and for an increase in adverse reactions of rifampin if these drugs are coadministered.
Ketoprofen: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Ketorolac: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Lapatinib: (Moderate) Use caution and monitor for signs of lapatinib toxicity if these drugs are coadministered; a lapatinib dosage reduction may be necessary.
Letermovir: (Moderate) Closely monitor for letermovir-related adverse events (i.e., tachycardia, atrial fibrillation, and gastrointestinal events) if administered with eltrombopag, as use of these drugs together may result in elevated letermovir plasma concentration. Letermovir is a substrate of the organic anion-transporting polypeptide (OATP1B1); eltrombopag is an inhibitor of OATP1B1.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Major) Eltrombopag chelates polyvalent cations (e.g., iron) in foods and mineral supplements. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as iron salts, multivitamins that contain iron, or polysaccharide-iron complex.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Major) Eltrombopag chelates polyvalent cations (e.g., iron) in foods and mineral supplements. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as iron salts, multivitamins that contain iron, or polysaccharide-iron complex.
Lopinavir; Ritonavir: (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inducers of CYP1A2, such as ritonavir, on the systemic exposure of eltrombopag has not been established. Monitor patients for a decrease in the efficacy of eltrombopag if these drugs are coadministered.
Magnesium Salts: (Major) Eltrombopag chelates polyvalent cations (e.g., calcium, aluminum, and magnesium) in food, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as aluminum salts, (like aluminum hydroxide), calcium salts, (including calcium carbonate), and magnesium salts.
Magnesium: (Major) Eltrombopag chelates polyvalent cations (e.g., calcium, aluminum, and magnesium) in food, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as aluminum salts, (like aluminum hydroxide), calcium salts, (including calcium carbonate), and magnesium salts.
Maraviroc: (Moderate) Use caution and closely monitor for increased adverse effects during concurrent administration of maraviroc and eltrombopag as increased maraviroc concentrations may occur. Maraviroc is a substrate of organic anion-transporting polypeptide (OATP1B1); eltrombopag is an inhibitor of OATP1B1. The effects of this transporter on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
Meclofenamate Sodium: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Mefenamic Acid: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Meloxicam: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Metformin; Repaglinide: (Moderate) Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as repaglinide, may exhibit an increase in systemic exposure if coadministered with eltrombopag; monitor patients for adverse reactions if these drugs are coadministered.
Methohexital: (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inducers of CYP1A2, such as barbiturates, on the systemic exposure of eltrombopag has not been established. Monitor patients for a decrease in the efficacy of eltrombopag if these drugs are coadministered.
Methotrexate: (Moderate) Eltrombopag is an inhibitor of OATP1B1 and Breast Cancer Resistance Protein (BCRP). Drugs that are substrates for these transporters, such as methotrexate, may exhibit an increase in systemic exposure if coadministered with eltrombopag; monitor patients for increased methotrexate toxicity if these drugs are coadministered. In a clinical study, administration of a single dose of rosuvastatin, another substrate of both OATP1B1 and BCRP, in combination with eltrombopag increased plasma rosuvastatin AUC by 55% and the Cmax by 103%. A 50% rosuvastatin dosage reduction was recommended.
Mexiletine: (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inhibitors of CYP1A2, such as mexiletine, on the systemic exposure of eltrombopag has not been established. Monitor patients for signs of eltrombopag toxicity if these drugs are coadministered.
Mitoxantrone: (Moderate) Use caution and monitor for adverse reactions if eltrombopag and mitoxantrone are coadministered. Eltrombopag is an inhibitor of Breast Cancer Resistance Protein (BCRP). Drugs that are substrates for this transporter, such as mitoxantrone, may exhibit an increase in systemic exposure if coadministered with eltrombopag.
Nabumetone: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Naproxen: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Naproxen; Esomeprazole: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Naproxen; Pseudoephedrine: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Nateglinide: (Moderate) Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as nateglinide, may exhibit an increase in systemic exposure if coadministered with eltrombopag; monitor patients for adverse reactions if these drugs are coadministered.
Nebivolol; Valsartan: (Moderate) Use caution and monitor blood pressure closely if eltrombopag and valsartan are coadministered. Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as valsartan, may exhibit an increase in systemic exposure if coadministered with eltrombopag.
Nirmatrelvir; Ritonavir: (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inducers of CYP1A2, such as ritonavir, on the systemic exposure of eltrombopag has not been established. Monitor patients for a decrease in the efficacy of eltrombopag if these drugs are coadministered.
Nonsteroidal antiinflammatory drugs: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Major) Eltrombopag chelates polyvalent cations (e.g., iron) in foods and mineral supplements. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as iron salts, multivitamins that contain iron, or polysaccharide-iron complex.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Major) Eltrombopag chelates polyvalent cations (e.g., iron) in foods and mineral supplements. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as iron salts, multivitamins that contain iron, or polysaccharide-iron complex.
Olmesartan: (Moderate) Use caution and monitor blood pressure closely if eltrombopag and olmesartan are coadministered. Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as olmesartan, may exhibit an increase in systemic exposure if coadministered with eltrombopag.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Use caution and monitor blood pressure closely if eltrombopag and olmesartan are coadministered. Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as olmesartan, may exhibit an increase in systemic exposure if coadministered with eltrombopag.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Use caution and monitor blood pressure closely if eltrombopag and olmesartan are coadministered. Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as olmesartan, may exhibit an increase in systemic exposure if coadministered with eltrombopag.
Omeprazole: (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inducers of CYP1A2, such as omeprazole, on the systemic exposure of eltrombopag has not been established. Monitor patients for a decrease in the efficacy of eltrombopag if these drugs are coadministered.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inducers of CYP1A2, such as omeprazole, on the systemic exposure of eltrombopag has not been established. Monitor patients for a decrease in the efficacy of eltrombopag if these drugs are coadministered.
Omeprazole; Sodium Bicarbonate: (Major) Eltrombopag chelates polyvalent cations (e.g., antacids) in food, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as magaldrate. (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inducers of CYP1A2, such as omeprazole, on the systemic exposure of eltrombopag has not been established. Monitor patients for a decrease in the efficacy of eltrombopag if these drugs are coadministered.
Oxaprozin: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Paclitaxel: (Moderate) Monitor patients for paclitaxel adverse reactions if coadministered with eltrombopag. Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as paclitaxel, may exhibit an increase in systemic exposure if coadministered with eltrombopag.
Pazopanib: (Major) Avoid administering pazopanib with strong breast cancer resistance protein (BCRP) inhibitors, such as eltrombopag. The concomitant use of pazopanib, a BCRP substrate,and eltrombopag, a BCRP inhibitor, may result in increased pazopanib concentrations.
Pentobarbital: (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inducers of CYP1A2, such as barbiturates, on the systemic exposure of eltrombopag has not been established. Monitor patients for a decrease in the efficacy of eltrombopag if these drugs are coadministered.
Pentosan: (Moderate) Use caution when discontinuing eltrombopag in patients receiving anticoagulants (e.g., warfarin, enoxaparin, dabigatran, rivaroxaban). The risk of bleeding and recurrent thrombocytopenia is increased in patients receiving these drugs when eltrombopag is discontinued.
Phenobarbital: (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inducers of CYP1A2, such as barbiturates, on the systemic exposure of eltrombopag has not been established. Monitor patients for a decrease in the efficacy of eltrombopag if these drugs are coadministered.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inducers of CYP1A2, such as barbiturates, on the systemic exposure of eltrombopag has not been established. Monitor patients for a decrease in the efficacy of eltrombopag if these drugs are coadministered.
Piroxicam: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Pitavastatin: (Moderate) Use caution and monitor for adverse reactions if eltrombopag and pitavastatin are coadministered. Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as pitavastatin, may exhibit an increase in systemic exposure if coadministered with eltrombopag.
Pravastatin: (Moderate) Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as pravastatin, may exhibit an increase in systemic exposure if coadministered with eltrombopag; monitor patients for adverse reactions if these drugs are coadministered.
Primidone: (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inducers of CYP1A2, such as barbiturates, on the systemic exposure of eltrombopag has not been established. Monitor patients for a decrease in the efficacy of eltrombopag if these drugs are coadministered.
Pyridoxine, Vitamin B6: (Major) Eltrombopag chelates polyvalent cations (e.g., calcium, aluminum, and magnesium) in food, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as aluminum salts, (like aluminum hydroxide), calcium salts, (including calcium carbonate), and magnesium salts.
Quinine: (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inducers of CYP1A2, such as quinine, on the systemic exposure of eltrombopag has not been established. Monitor patients for a decrease in the efficacy of eltrombopag if these drugs are coadministered.
Repaglinide: (Moderate) Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as repaglinide, may exhibit an increase in systemic exposure if coadministered with eltrombopag; monitor patients for adverse reactions if these drugs are coadministered.
Resmetirom: (Major) Avoid concomitant use of resmetirom and eltrombopag due to the risk for increased resmetirom exposure which may increase the risk for resmetirom-related adverse effects. Resmetirom is an OATP1B1 substrate and eltrombopag is an OATP1B1 inhibitor.
Revefenacin: (Major) Coadministration of revefenacin is not recommended with eltrombopag because it could lead to an increase in systemic exposure of the active metabolite of revefenacin and an increased potential for anticholinergic adverse effects. The active metabolite of revefenacin is a substrate of OATP1B1 and OATP1B3; eltrombopag is an inhibitor of OATP1B1.
Rifampin: (Major) Eltrombopag is metabolized by CYP1A2 and CYP2C8. The significance of administering inducers of CYP1A2 and CYP2C8, such as rifampin, on the systemic exposure of eltrombopag has not been established. Additionally, eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as rifampin, may exhibit an increase in systemic exposure if coadministered with eltrombopag. Monitor patients for a decrease in the efficacy of eltrombopag and for an increase in adverse reactions of rifampin if these drugs are coadministered.
Ritonavir: (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inducers of CYP1A2, such as ritonavir, on the systemic exposure of eltrombopag has not been established. Monitor patients for a decrease in the efficacy of eltrombopag if these drugs are coadministered.
Rivaroxaban: (Moderate) Use caution when discontinuing eltrombopag in patients receiving anticoagulants (e.g., warfarin, enoxaparin, dabigatran, rivaroxaban). The risk of bleeding and recurrent thrombocytopenia is increased in patients receiving these drugs when eltrombopag is discontinued.
Rosuvastatin: (Moderate) Use caution and monitor for signs of rosuvastatin toxicity if this drug is coadministered with eltrombopag. In clinical trials, a 50% dose reduction of rosuvastatin was recommended. Eltrombopag is an inhibitor of OATP1B1 and BCRP, and rosuvastatin is a substrate of both of these transporters. In a clinical study, administration of a single dose of rosuvastatin with eltrombopag increased plasma rosuvastatin AUC by 55% and the Cmax by 103%.
Rosuvastatin; Ezetimibe: (Moderate) Use caution and monitor for adverse reactions if eltrombopag and ezetimibe are coadministered. Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as ezetimibe, may exhibit an increase in systemic exposure if coadministered with eltrombopag. (Moderate) Use caution and monitor for signs of rosuvastatin toxicity if this drug is coadministered with eltrombopag. In clinical trials, a 50% dose reduction of rosuvastatin was recommended. Eltrombopag is an inhibitor of OATP1B1 and BCRP, and rosuvastatin is a substrate of both of these transporters. In a clinical study, administration of a single dose of rosuvastatin with eltrombopag increased plasma rosuvastatin AUC by 55% and the Cmax by 103%.
Sacubitril; Valsartan: (Moderate) Use caution and monitor blood pressure closely if eltrombopag and valsartan are coadministered. Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as valsartan, may exhibit an increase in systemic exposure if coadministered with eltrombopag.
Secobarbital: (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inducers of CYP1A2, such as barbiturates, on the systemic exposure of eltrombopag has not been established. Monitor patients for a decrease in the efficacy of eltrombopag if these drugs are coadministered.
Selenium: (Major) Eltrombopag chelates polyvalent cations (e.g., selenium) in foods, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag 2 hours before or 4 hours after any oral products containing selenium.
Simvastatin: (Moderate) Use caution and monitor for adverse reactions if eltrombopag and simvastatin are coadministered. Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as simvastatin, may exhibit an increase in systemic exposure if coadministered with eltrombopag.
Sodium Bicarbonate: (Major) Eltrombopag chelates polyvalent cations (e.g., antacids) in food, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as magaldrate.
Sodium Ferric Gluconate Complex; ferric pyrophosphate citrate: (Major) Eltrombopag chelates polyvalent cations (e.g., iron) in foods and mineral supplements. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as iron salts, multivitamins that contain iron, or polysaccharide-iron complex.
Sodium Sulfate; Magnesium Sulfate; Potassium Chloride: (Major) Eltrombopag chelates polyvalent cations (e.g., calcium, aluminum, and magnesium) in food, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as aluminum salts, (like aluminum hydroxide), calcium salts, (including calcium carbonate), and magnesium salts.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) Eltrombopag is metabolized by CYP2C8. The significance of administering inhibitors of CYP2C8, such as trimethoprim, on the systemic exposure of eltrombopag has not been established. Monitor patients for signs of eltrombopag toxicity if these drugs are coadministered.
Sulfasalazine: (Moderate) Use caution and monitor for adverse reactions if eltrombopag and sulfasalazine are coadministered. Eltrombopag is an inhibitor of Breast Cancer Resistance Protein (BCRP). Drugs that are substrates for this transporter, such as sulfasalazine, may exhibit an increase in systemic exposure if coadministered with eltrombopag.
Sulindac: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Sumatriptan; Naproxen: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Talazoparib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of eltrombopag is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a BCRP substrate and eltrombopag is a BCRP inhibitor.
Teriflunomide: (Moderate) In vitro studies indicate that teriflunomide is a substrate of ABCG2 (breast cancer resistance protein, BCRP). Drugs that are inhibitors of BCRP, such as eltrombopag, may cause increases in teriflunomide plasma concentrations. Monitor patients for adverse effects, including symptoms serious liver injury and immunosuppression.
Tipranavir: (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inducers of CYP1A2, such as tipranavir, on the systemic exposure of eltrombopag has not been established. Monitor patients for a decrease in the efficacy of eltrombopag if these drugs are coadministered.
Tolmetin: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID.
Topotecan: (Major) Avoid coadministration of eltrombopag with oral topotecan due to increased topotecan exposure; eltrombopag may be administered with intravenous topotecan. Oral topotecan is a substrate of the Breast Cancer Resistance Protein (BCRP) and eltrombopag is a BCRP inhibitor. Coadministration increases the risk of topotecan-related adverse reactions.
Tramadol; Acetaminophen: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. Acetaminophen is a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of acetaminophen are possible. Monitor patients for adverse reactions if these drugs are coadministered.
Trimethoprim: (Moderate) Eltrombopag is metabolized by CYP2C8. The significance of administering inhibitors of CYP2C8, such as trimethoprim, on the systemic exposure of eltrombopag has not been established. Monitor patients for signs of eltrombopag toxicity if these drugs are coadministered.
Ubrogepant: (Major) Limit the initial and second dose of ubrogepant to 50 mg if coadministered with eltrombopag. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a substrate of the BCRP drug transporter; eltrombopag is a BCRP inhibitor.
Valsartan: (Moderate) Use caution and monitor blood pressure closely if eltrombopag and valsartan are coadministered. Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as valsartan, may exhibit an increase in systemic exposure if coadministered with eltrombopag.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Use caution and monitor blood pressure closely if eltrombopag and valsartan are coadministered. Eltrombopag is an inhibitor of the transporter OATP1B1. Drugs that are substrates for this transporter, such as valsartan, may exhibit an increase in systemic exposure if coadministered with eltrombopag.
Warfarin: (Moderate) Use caution when discontinuing eltrombopag in patients receiving anticoagulants (e.g., warfarin, enoxaparin, dabigatran, rivaroxaban). The risk of bleeding and recurrent thrombocytopenia is increased in patients receiving these drugs when eltrombopag is discontinued.
Zafirlukast: (Moderate) Eltrombopag is metabolized by CYP2C8. The significance of administering inhibitors of CYP2C8, such as zafirlukast, on the systemic exposure of eltrombopag has not been established. Monitor patients for signs of eltrombopag toxicity if these drugs are coadministered.
Zileuton: (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inhibitors of CYP1A2, such as zileuton, on the systemic exposure of eltrombopag has not been established. Monitor patients for signs of eltrombopag toxicity if these drugs are coadministered.
Zinc Salts: (Major) Eltrombopag chelates polyvalent cations (e.g., zinc salts) in foods, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag 2 hours before or 4 hours after any oral products containing zinc salts.
Zinc: (Major) Eltrombopag chelates polyvalent cations (e.g., zinc salts) in foods, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag 2 hours before or 4 hours after any oral products containing zinc salts.
Eltrombopag is a non-peptide thrombopoietin (TPO) receptor agonist that interacts with the transmembrane domain of the human TPO receptor. Specifically, eltrombopag binds to the TPO receptor (also known as cMpl) and causes proliferation and differentiation of megakaryocytes leading to increased platelet production. Additionally, it may bind to a location that is distinct from where endogenous TPO binds to the receptor; in vitro data suggest that eltrombopag's effects may be additive to TPO. In animal and early clinical studies, eltrombopag caused dose-dependent increases in platelet counts without affecting platelet function.
Eltrombopag is administered orally. The concentration in blood cells is 50% to 79% of plasma concentrations; in vitro studies indicate more than 99% protein binding. Eltrombopag undergoes extensive metabolism, predominantly through cleavage, oxidation, and conjugation with glucuronic acid, glutathione, or cysteine. In vitro studies have found that CYP1A2 and CYP2C8 are responsible for the oxidative metabolism of eltrombopag, and UGT1A1 and UGT1A3 are responsible for glucuronidation. Elimination occurs primarily by the feces (59%) and the urine (31%); unchanged drug accounts for approximately 20% of the dose in the feces, and unchanged drug is not detected in the urine. The plasma elimination half-life is 21 to 32 hours in healthy subjects.
Affected cytochrome P450 isoenzymes and drug transporters: CYP1A2, CYP2C8, CYP2C9, BCRP, OATP1B1, UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, UGT2B7, UGT2B15
In vitro studies suggest that eltrombopag has the potential to inhibit CYP2C8 and CYP2C9, the organic anion transporting peptide OATP1B1, the breast cancer resistance protein (BCRP), and the UDP-glucuronyltransferases UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, UGT2B7, and UGT2B15. The effects on eltrombopag of coadministration of moderate or strong inhibitors or inducers of CYP1A2, CYP2C8, UGT1A1, and UGT1A3 have not been adequately assessed.
-Route-Specific Pharmacokinetics
Oral Route
Eltrombopag demonstrates dose-proportional increases in exposure between doses of 50 to 150 mg/day in healthy adult subjects. AUC is approximately 1.7-fold, 2.8-fold, and 3.2-fold higher in patients with chronic immune thrombocytopenia, hepatitis C, and immunosuppressive therapy-naive severe aplastic anemia, respectively, compared to healthy subjects.
Eltrombopag choline
After oral administration, peak plasma concentrations occur within 1.5 to 5.5 hours under fasting conditions and 1 to 8 hours under fed conditions (high-fat, high-calorie meal). The AUC and Cmax decrease by approximately 36% and 39% and the Tmax is delayed by 0.5 hour after a high fat, high calorie meal.
Eltrombopag olamine
After oral administration, peak plasma concentrations occur approximately 2 to 6 hours under fasting conditions. After administration of a 75 mg oral suspension dose, approximately 52% of drug-related material is absorbed. The oral suspension delivers a 22% higher plasma AUC than the tablet formulation. When administered with a polyvalent cation antacid (aluminum hydroxide; aluminum carbonate; sodium alginate), the AUC of eltrombopag olamine is decreased by approximately 70%. Similarly, when administered with a high-fat meal, the AUC is decreased by 59%, the Cmax is decreased by 65%, and the Tmax is delayed by 1 hour. Administration of a single 25 mg dose of the oral suspension to adults with a high-calcium, moderate-fat meal reduced the AUC by 75% and the Cmax by 79%. Administration of a single 25 mg dose of the oral suspension 2 hours before and 2 hours after the high-calcium meal reduced the AUC by 20% and 47%, respectively, while the Cmax was reduced by 14% and 48%, respectively.
-Special Populations
Hepatic Impairment
Patients with hepatic impairment experience higher eltrombopag exposure. AUC was 41% higher in patients with mild hepatic impairment (Child-Pugh Class A) compared to those with normal hepatic function. AUC was approximately 2-fold higher, and half-life was prolonged 2-fold in patients with moderate and severe impairment (Child-Pugh Class B and C). After repeated doses of eltrombopag in thrombocytopenic patients with chronic liver disease, the AUC was 87% to 110% higher in patients with mild hepatic impairment and 141% to 240% higher in those with moderate hepatic impairment. Half-life was prolonged 3-fold in patients with mild hepatic impairment and 4-fold in those with moderate hepatic impairment. Patients with chronic hepatitis C and mild hepatic impairment had approximately 100% to 144% higher plasma AUC compared to healthy subjects.
Renal Impairment
Average total plasma AUC was 32% to 36% lower in patients with mild to moderate renal impairment (CrCl 30 to 80 mL/minute) and 60% lower in those with severe renal impairment (CrCl less than 30 mL/minute) compared with healthy subjects during pharmacokinetic trials.
Pediatrics
Plasma clearance of eltrombopag increases with increasing body weight. Pediatric patients of East/Southeast-Asian ancestry have approximately 43% higher AUC values compared to non-Asian patients. During clinical trials, mean eltrombopag Cmax and AUC in pediatric patients 12 to 17 years were similar to those seen in adults, while mean Cmax and AUC in pediatric patients 1 to 11 years was slightly higher than those of older pediatric patients and adults. Mean steady-state eltrombopag Cmax concentrations in patients 1 to 5 years, 6 to 11 years, 12 to 17 years, and adults were 11.6 mcg/mL, 10.3 mcg/mL, 6.8 mcg/mL, and 7.03 mcg/mL, respectively; mean steady-state AUC was 162 mcg x hour/mL, 153 mcg x hour/mL, 103 mcg x hour/mL, and 101 mcg x hour/mL, respectively.
Ethnic Differences
In patients of East/Southeast-Asian ancestry, eltrombopag concentrations were 50% to 55% higher compared to non-Asian subjects. A 40% increase in eltrombopag exposure was noted in Black subjects compared to White subjects; the effect of African American ethnicity on exposure has not been established.
Other
Immune Thrombocytopenic Purpura (ITP)
The plasma elimination half-life is 26 to 35 hours in patients with ITP compared to 21 to 32 hours in healthy patients.