For:

Adult Persistent or Chronic Immune Thrombocytopenia

IMPORTANT SAFETY INFORMATION, INCLUDING BOXED WARNING, AND INDICATION

Important Safety Information

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...+

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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.

Efficacy

3+ months ITP is defined as persistent (3-12 months) or chronic (>12 months) ITP.⁴
*Clinical trials include: TRA100773A (N=117), TRA100773B (N=114), RAISE (N=197), and EXTEND (N=302).¹

Rapid Response

PROMACTA worked fast—patients achieved response as early as Week 1, with most patients responding at Week 2^1,2

The primary end point, response at Day 43, was 70% (19/27) with the 50-mg dose vs 11% (3/27) with placebo^2†
Response rate at Day 8 was 44% (12/27) vs 7% (2/27) with placebo²
The incidence of adverse events was consistent across all groups while on treatment²
In the 3 placebo-controlled pivotal trials, serum liver test abnormalities (predominantly grade 2 or lower in severity) were reported in 11% and 7% of patients in the PROMACTA and placebo groups, respectively²

TRA100773A was a phase 2, 12-week, double-blind, placebo-controlled trial of 117 adult patients with previously treated ITP.^1,2 Response was defined as a shift from baseline platelet count <30,000/mcL to ≥50,000/mcL at any time during the treatment period up to 42 days of dosing with 30 mg, 50 mg, or 75 mg of eltrombopag.^1,2

Rapid reduction in grades 2-4 bleeding events⁵

The primary end point, odds of response, was 8 times greater for PROMACTA throughout the 6-month treatment period (odds ratio 8.2; 99% CI, 3.59-18.73; P<0.0001)⁶
WHO grades 2-4 are clinically significant (grade 2: Mild blood loss; grade 3: Gross blood loss; grade 4: Debilitating blood loss)⁵
For all grades, PROMACTA provided a 47% reduction in bleeding events (73% at baseline vs 39% at Day 15), while placebo provided a 12% reduction (77% at baseline vs 68% at Day 15)⁵

RAISE was a phase 3, 6-month, double-blind, randomized, placebo-controlled study of 197 patients with previously treated ITP and baseline platelet counts <30,000/mcL.^1,6 The primary end point was the odds of response, defined as a platelet count ≥50,000/mcL and ≤400,000/mcL, during treatment.^1,6

^†Response rates with the 30-mg and 75-mg doses were 28% (8/29) and 81% (21/26), respectively.²

Durable Response

Up to 7 years of continuous response in the EXTEND trial—the longest results ever reported in persistent or chronic ITP^1,3,7-9

In the primary end point of the EXTEND study, no new adverse reactions were identified at 6 years of therapy^1,3

The open-label EXTEND study evaluated long-term safety and efficacy of eltrombopag in adults with ITP who had completed a previous eltrombopag study.^1,3,10 The median baseline platelet count was 19,000/mcL prior to administration of PROMACTA.^1,3 This study reviewed more than 8 years of continuous treatment.^3,10 PROMACTA was administered to 302 patients in EXTEND; 218 completed 1 year, 180 completed 2 years, 107 completed 3 years, 75 completed 4 years, 34 completed 5 years, and 18 completed 6 years of therapy, with 3 patients evaluable at Year 7.^1,3 Median platelet counts ≥50,000/mcL by Week 2 and at least that throughout.^1,3,10 The primary end points were safety and tolerability.³

See an interactive story about helping to choose a treatment for your patient

ASH guidelines suggest a TPO-RA for patients with ITP in second line who prefer a durable response^4‡

^‡The 2019 ASH guidelines define durable response as a platelet count ≥30,000/mcL and at least doubling of the baseline count at 6 months.⁴

Reduction in Concomitant ITP Therapies

Consider PROMACTA as a first choice in second-line treatment¹

ASH, American Society of Hematology; ITP, immune thrombocytopenia; TPO-RA, thrombopoietin receptor agonist; WHO, World Health Organization.

References:

Promacta [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp.
Data on file. Study TRA100773A. Novartis Pharmaceuticals Corp; October 2007.
Data on file. Study TRA105325 (EXTEND). Novartis Pharmaceuticals Corp; March 2016.
Neunert C, Terrell DR, Arnold DM, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019;3(23):3829-3866.
Data on file. Study TRA102537 (RAISE). Novartis Pharmaceuticals Corp; February 2009.
Cheng G, Saleh MN, Marcher C, et al. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study. Lancet. 2011;377(9763):393-402.
Jurczak W, Chojnowski K, Mayer J, et al. Phase 3 randomised study of avatrombopag, a novel thrombopoietin receptor agonist for the treatment of chronic immune thrombocytopenia. Br J Haematol. 2018;183(3):479-490.
Cooper N, Altomare I, Thomas MR, et al. Assessment of thrombotic risk during long-term treatment of immune thrombocytopenia with fostamatinib. Ther Adv Hematol. 2021;12:1-12. doi:1177/20406207211010875.
Kuter DJ, Bussel JB, Newland A, et al. Long-term treatment with romiplostim in patients with chronic immune thrombocytopenia: safety and efficacy. Br J Haematol. 2013;161(3):411-423.
Wong RSM, Saleh MN, Khelif A, et al. Safety and efficacy of long-term treatment of chronic/persistent ITP with eltrombopag: final results of the EXTEND study. Blood. 2017;130(23):2527-2536.

Indication and Important Safety Information

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)

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 hepatic decompensation.

RISK OF HEPATOTOXICITY
PROMACTA may increase the risk of severe and potentially life-threatening hepatotoxicity. Monitor hepatic function and discontinue dosing as recommended.

Hepatotoxicity
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

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

Cataracts

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

Laboratory Monitoring

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)

Adverse Reactions
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%).

Please see full Prescribing Information for PROMACTA, including Boxed WARNING, and Medication Guide.