WARNING: RISK FOR HEPATIC DECOMPENSATION IN PATIENTS WITH CHRONIC HEPATITIS C - In patients with chronic hepatitis C, PROMACTA in combination with interferon and ribavirin may increase the risk of...+
Mechanism of Action
Mechanism of Action
Nonimmunosuppressive PROMACTA works synergistically with the body's endogenous TPO1,2
- PROMACTA® (eltrombopag) uniquely binds to the transmembrane domain, while endogenous TPO binds to the extracellular domain1,2
- By not competing with endogenous TPO, PROMACTA can work together with endogenous TPO to promote platelet production2
As a small molecule,1 PROMACTA:
- Enters the bone marrow more effectively than endogenous TPO, stimulating platelet production2,4
- Does not promote neutralizing antibodies4,5
PROMACTA has been proven to effectively restore bone marrow cellularity1,2
- PROMACTA increases proliferation and differentiation of stem cells into red blood cells, white blood cells, and platelets1,2
Illustrations are for representative purposes only.
ITP, immune thrombocytopenia; TPO, thrombopoietin.
- Promacta [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2021.
- Lum SH, Grainger JD. Eltrombopag for the treatment of aplastic anemia: current perspectives. Drug Des Devel Ther. 2016;10:2833-2843.
- McCrae K. Immune thrombocytopenia: no longer ‘idiopathic.’ Cleve Clin J Med. 2011;78(6):358-373.
- Kuter DJ. The biology of thrombopoietin and thrombopoietin receptor agonists. Int J Hematol. 2013;98(1):10-23.
- Cheng G. Eltrombopag, a thrombopoietin-receptor agonist in the treatment of adult chronic immune thrombocytopenia: a review of the efficacy and safety profile. Ther Adv Hematol. 2012;3(3):155-164.
Indication and Important Safety Information
Indication for PROMACTA® (eltrombopag)
PROMACTA is indicated for the treatment of thrombocytopenia in adult and pediatric patients 1 year and older with persistent or chronic immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. PROMACTA should be used only in patients with ITP whose degree of thrombocytopenia and clinical condition increase the risk for bleeding.
Limitations of Use
PROMACTA is not indicated for the treatment of patients with myelodysplastic syndromes (MDS).
Safety and efficacy have not been established in combination with direct-acting antiviral agents used without interferon for treatment of chronic hepatitis C infection.
Important Safety Information for PROMACTA® (eltrombopag)
PROMACTA may increase the risk of severe and potentially life-threatening hepatotoxicity.
Treatment of ITP, chronic hepatitis C, and refractory severe aplastic anemia
- Measure serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin prior to initiation of PROMACTA, every 2 weeks during the dose-adjustment phase, and monthly following establishment of a stable dose
- PROMACTA inhibits UGT1A1 and OATP1B1, which may lead to indirect hyperbilirubinemia. If bilirubin is elevated, perform fractionation
- Evaluate abnormal serum liver tests with repeat testing within 3 to 5 days. If the abnormalities are confirmed, monitor serum liver tests weekly until resolved or stabilized
- Discontinue PROMACTA if ALT levels increase to ≥3 times the upper limit of normal in patients with normal liver function or ≥3 times baseline in patients with pretreatment elevations in transaminases and are progressively increasing; or persistent for ≥4 weeks; or accompanied by increased direct bilirubin; or accompanied by clinical symptoms of liver injury or evidence for hepatic decompensation
- If the potential benefit for reinitiating treatment with PROMACTA outweighs the risk for hepatotoxicity, then consider cautiously reintroducing PROMACTA and measure serum liver tests weekly during the dose-adjustment phase. Hepatotoxicity may reoccur if PROMACTA is reinitiated. If liver test abnormalities persist, worsen, or recur, then permanently discontinue PROMACTA
- Thrombotic/thromboembolic complications may result from increases in platelet counts with PROMACTA
- Reported thrombotic/thromboembolic complications included both venous and arterial events, and were observed at low and at normal platelet counts
- Portal vein thrombosis has been reported in patients with chronic liver disease receiving PROMACTA
- To minimize the risk for thrombotic/thromboembolic complications, do not use PROMACTA in an attempt to normalize platelet counts. Follow the dose-adjustment guidelines to achieve and maintain target platelet counts
Increased Risk of Death and Progression of Myelodysplastic Syndromes (MDS) to Acute Myeloid Leukemia (AML)
- In a clinical trial of patients with intermediate- to high-risk MDS and thrombocytopenia receiving PROMACTA, an increased number of progressions from MDS to AML and deaths have been observed compared to placebo
- PROMACTA is not indicated for the treatment of patients with MDS
- Development or worsening of cataracts with PROMACTA has been reported with a frequency of 5% to 11% in 6 clinical studies
- Perform a baseline ocular examination prior to initiating PROMACTA. Regularly monitor patients for signs and symptoms of cataracts while on PROMACTA
- Monitor serum liver tests
- During therapy with PROMACTA, assess complete blood counts (CBCs) with differentials, including platelet counts, weekly until a stable platelet count has been achieved. Monitor platelet counts monthly thereafter
- Obtain CBCs with differentials, including platelet counts, weekly for at least 4 weeks following discontinuation of PROMACTA
- When switching between the oral suspension and tablet, assess platelet counts weekly for 2 weeks, then follow standard monthly monitoring
Drug/Drug and Drug/Food Interactions
- PROMACTA must be taken at least 2 hours before or 4 hours after any medications or products containing polyvalent cations such as antacids, calcium-rich foods, and mineral supplements
- Take PROMACTA without a meal or with a meal low in calcium (≤50 mg)
Across all indications, the most common adverse reactions (≥20% in any indication) were anemia, nausea, pyrexia, ALT increased, cough, fatigue, headache, and diarrhea.
The most common adverse reactions in 3 placebo-controlled clinical trials in patients with persistent or chronic ITP (≥3% and greater than placebo) for PROMACTA were nausea (9%), diarrhea (9%), upper respiratory tract infection (7%), vomiting (6%), increased ALT (5%), myalgia (5%), urinary tract infection (5%), oropharyngeal pain (4%), increased AST (4%), pharyngitis (4%), back pain (3%), influenza (3%), paresthesia (3%), and rash (3%).
The most common adverse reactions in 2 placebo-controlled clinical trials in patients with persistent or chronic ITP 1 year and older (≥3% and greater than placebo) for PROMACTA were upper respiratory tract infection (17%), nasopharyngitis (12%), cough (9%), diarrhea (9%), pyrexia (9%), abdominal pain (8%), oropharyngeal pain (8%), toothache (6%), ALT increased (6%), rash (5%), AST increased (4%), and rhinorrhea (4%).