Immune Thrombocytopenia (ITP)

Promacta® (eltrombopag olamine) is an oral small molecule thrombopoietin receptor agonist (TPO-RA). It increases platelet synthesis by interacting with the TPO receptor’s transmembrane domain, also called cMpl.1

Promacta was approved by the FDA in 2008 for use in adult patients with immune thrombocytopenia. In 2015, the FDA approved Promacta for pediatric patients aged 1 year and above. Promacta is manufactured by Novartis in East Hanover, New Jersey.4


Promacta is recommended in the treatment of thrombocytopenia in adult and pediatric patients aged 1 year and above with chronic immune thrombocytopenia (ITP) who have not responded adequately to corticosteroids, immunoglobulins, or splenectomy.2 ITP is a bleeding disorder that occurs due to a deficiency of platelets in the blood. The drug does not provide a cure for ITP, and platelet count does not return to normal.3 

Only patients whose degree of thrombocytopenia and clinical state increase the risk of bleeding should be treated with Promacta. This medication is useful for maintaining a platelet count of at least 50×109/L and should not be utilized to normalize platelet count. The drug has also been approved by the US Food and Drug Administration (FDA) to treat thrombocytopenia in patients with chronic hepatitis C and patients with severe aplastic anemia.2

Mechanism of Action

Promacta simulates the action of the natural hormone thrombopoietin and instructs the bone marrow to produce more blood cells in counteraction of the platelet destruction and impaired platelet production that occurs in ITP.5,6 Eltrombopag is an orally bioavailable, small-molecule TPO receptor agonist that binds with the human TPO receptor’s transmembrane domain and sets off signaling cascades that cause bone marrow progenitor cells to divide and differentiate into megakaryocytes.7 

The nonimmunosuppressive Promacta and the body’s natural TPO function in a synergistic manner. While natural TPO binds to the extracellular domain, Promacta only binds to the transmembrane domain. It supports platelet formation by working in collaboration with endogenous or natural TPO rather than competing with it. Promacta, a small molecule, reaches the bone marrow more efficiently than endogenous TPO, promoting the synthesis of platelets without inducing neutralizing antibodies.5

Read more about ITP experimental therapies


The medication is available in the form of tablets and an oral suspension. The medication should be started at 50 mg once daily for the majority of adult and pediatric patients who are at least 6 years of age or 25 mg once daily for children aged 1 to 5 years. Patients with liver problems and some patients of East Asian descent require dose reductions. Platelet count should be maintained at 50×109/L or higher. The maximum dose of Promacta is 75 mg per day.2

Any drugs or products with polyvalent cations, such as antacids, calcium-rich meals, and mineral supplements, must be taken at least 2 hours before or 4 hours after Promacta. The drug should be taken without food or with a meal that is low in calcium (≤50 mg).5

Read more about ITP treatment

Adverse Effects

The most common adverse effects in adult patients with ITP are nausea, vomiting, diarrhea, upper respiratory tract infection, vomiting, myalgia, elevated levels of ALT, and urinary tract infection. The most common adverse effects in children aged 1 year and above are upper respiratory tract infection and nasopharyngitis.2 Other adverse effects that have been noted with the use of Promacta include hemorrhage, cataracts, menorrhagia, and paresthesia.1

Get full prescribing information for Promacta on MPR

Warning and Precautions 

Promacta has the potential to cause liver damage. Therefore, levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin should be measured before starting treatment, followed by repeat tests every 2 weeks during the dose-adjustment phase and once in a month when a stable dose is established. In case of raised bilirubin values, fractionation must be performed. In case of abnormal serum liver parameter values, tests should be repeated within 3 to 5 days. After confirmation of abnormalities on serum liver tests, follow-up tests should be performed every week until the abnormal values normalize. If ALT levels reach 3 times the upper limit of normal and are progressive, persistent for ≥4 weeks, accompanied by a rise in direct bilirubin, or accompanied by clinical signs of liver damage or any form of hepatic decompensation, it is advised that the patient stops taking Promacta.7 

As Promacta is a TPO-RA medication, there is an increased risk of reticulin fiber deposition developing or progressing in the bone marrow. Peripheral blood smears should be frequently examined for signs of bone marrow fibrosis.7

Drug discontinuation may cause the thrombocytopenia to deteriorate further compared to levels before starting therapy. It is important to continue monitoring weekly complete blood counts, including platelet counts, for a minimum of 4 weeks following discontinuation.7

Promacta overdoses may cause platelet counts to rise to the extent that they cause thrombotic/thromboembolic problems.7

The medication can increase the risk of hematologic cancers, particularly in patients with myelodysplastic syndrome. Thus, it is advised to do weekly follow-ups with complete blood counts, including platelet counts and peripheral blood smear examinations, during the dose-adjustment phase and then once a month after a stable dose has been established.7

Animal studies have shown evidence of fetal harm from Promacta, yet its safe use in human pregnancy remains uncertain, due to a lack of controlled data. Thus, it should be used during pregnancy only when the benefit outweighs the risk. In most cases, while using this medication and for at least 7 days following the last dose, effective contraception is recommended. Use of this medication while nursing is also not advised, due to lack of controlled data.3 

Safety and Efficacy in Clinical Trials

Studies on Adults with ITP

FDA approval was based on the efficacy and safety profile of Promacta in adults with ITP as evidenced in 2 randomized, double-blind, placebo-controlled trials and an open-label extension trial.2

Studies 1 (TRA100773B) and 2 (TRA100773A) (NCT00102739)

In Study 1 (773B), 114 participants were randomly assigned to receive 50 mg of Promacta or a placebo. In Study 2 (773A), 117 participants were randomly assigned to receive either a placebo or 1 of 3 daily doses of Promacta: 30 mg, 50 mg, or 75 mg.8 The maximum treatment time with Promacta was 6 weeks, which was followed by a 6-week break from medication. In the event that the platelet count exceeded 200×109/L, Promacta or the placebo was stopped. Response rate, which was measured as any change from the baseline platelet count of 50×109/L during the treatment period, served as the primary efficacy endpoint. In Study 1, the response rate was 59% in the Promacta (50 mg) arm as compared to 16% in the placebo group.1 In Study 2, the response rate was 70% in the Promacta (50 mg) arm compared to 11% in the placebo group.2

RAISE Study (NCT00370331) 

In the RAISE study,9 197 patients were randomly assigned (2:1) to receive 50 mg of Promacta once a day or a placebo for 6 months, during which the dosage could be changed in accordance with the patients’ platelet counts. The effectiveness of Promacta was assessed in this trial by the probability of achieving a platelet count of ≥50×109/L and ≤400×109/L as compared to placebo. A sustained platelet response was defined as a platelet count of ≥50×109/L and ≤400×109/L in 6 of the last 8 weeks of the 26-week treatment period without the use of rescue medication at any point. In 134 patients who completed 26 weeks of treatment, 60% of patients receiving Promacta achieved this, compared to 10% of those receiving the placebo. Compared to patients who received placebo, those who received Promacta had a considerably higher chance of achieving a platelet count between 50×109/L and 400×109/L during the course of the 6-month treatment period.2

EXTEND Study (NCT00351468)

Participants who successfully completed a Promacta trial were allowed to enroll in the open-label, single-arm EXTEND study (NCT00351468).10 The goal of the trial was to either reduce the dosage of any concomitant ITP drugs or eliminate the need for them altogether.1 

Studies on Children with ITP

The efficacy and safety of Promacta in children aged 1 year and above with persistent or chronic ITP have been assessed in 2 double-blind, placebo-controlled trials, PETIT and PETIT2.2

PETIT Study (NCT00908037)

PETIT (NCT00908037) was a phase 2, multicenter, 3-part clinical trial.11 The percentage of participants who attained a platelet count of 50×109/L without rescue medication at least once between weeks 1 and 6 was the primary endpoint, and this was achieved by 63% of patients receiving Promacta and 18% of patients given placebo. The secondary efficacy endpoint was a reduced need for rescue treatment as a clinically significant benefit, with reported values of 14% in individuals receiving Promacta and 59% in participants given placebo.12

PETIT2 Study (NCT01520909)

PETIT2 (NCT01520909) was a phase 3 multicenter, 2-part study.13 The primary endpoint was the percentage of participants who attained a platelet count of 50×109/L for at least 6 out of 8 weeks between weeks 5 and 12 of part 1 of the study without rescue medication, and this was fulfilled by 43% of patients given Promacta and 4% of patients given placebo. The secondary efficacy endpoint was a reduced need for rescue treatment, similar to the above trial, with values of 18% in patients receiving Promacta and 22% in patients given placebo.12

Both trials showed consistent safety with the known safety profile of Promacta in adults with chronic ITP and in the population under study.12 

Read more about ITP clinical trials


  1. Promacta (eltrombopag). CenterWatch. Accessed October 26, 2022. 
  2. Promacta. Prescribing information. GlaxoSmithKline; 2015. Accessed October 26, 2022.
  3. Promacta. March 2008. Accessed October 26, 2022.
  4. FDA extends use of Promacta (eltrombopag) in pediatric patients with immune thrombocytopenic purpura. August 24, 2015. Accessed October 26, 2022.
  5. Promacta (eltrombopag): mechanism of action. Novartis. Accessed October 26, 2022.
  6. Promacta (eltrombopag). GoodRx. Accessed October 26, 2022.
  7. Promacta. Prescribing information. GlaxoSmithKline; 2008. Accessed October 26, 2022.
  8. SB-497115 (oral thrombopoietin receptor agonist) versus placebo in adults with refractory immune thrombocytopenic purpura (ITP). February 2, 2005. Updated April 15, 2013. Accessed October 26, 2022.
  9. RAISE: randomized placebo-controlled idiopathic thrombocytopenic purpura (ITP) study with eltrombopag (RAISE). August 31, 2006. Updated April 18, 2017. Accessed October 26, 2022.
  10. EXTEND (eltrombopag extended dosing study) (EXTEND). July 12, 2006. Updated April 17, 2017. Accessed October 26, 2022.
  11. Efficacy and safety study of eltrombopag in pediatric patients with thrombocytopenia from chronic idiopathic thrombocytopenic purpura (ITP) (PETIT). May 25, 2009. Updated October 12, 2018. Accessed October 26, 2022.
  12. FDA approves Promacta for new pediatric chronic immune thrombocytopenia (cITP) indication. June 12, 2015. Accessed October 26, 2022.
  13. Study of a new medication for childhood chronic immune thrombocytopenia (ITP), a blood disorder of low platelet counts that can lead to bruising easily, bleeding gums, and/or bleeding inside the body. (PETIT2). January 30, 2012. Updated March 10, 2015. Accessed October 26, 2022.

Reviewed by Kyle Habet, MD, on 10/27/2022.