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...+

See More

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

Proven Platelet Response

PROMACTA was proven to rapidly increase platelet levels in adult patients with persistent or chronic ITP who failed their first therapy1,2

88% OF PATIENTS REACHED TARGET LEVELS AT WEEK 21,2

  • The primary end point, response at Day 43, was 70% (19/27) with the 50-mg starting dose vs 11% (3/27) for placebo2*
Chart showing percentage of patients responding (TRA100773A pivotal trial)

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

  • 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® (eltrombopag) and placebo groups, respectively1

Only PROMACTA provided up to 7 years of durable platelet response1,3-6

LONGEST RESULTS EVER REPORTED

  • For second-line patients who want a durable response, ASH guidelines suggest a TPO-RA7†
  • In the primary end point of the EXTEND study, no new adverse reactions were identified at 6 years of therapy1,3
Graph showing median platelet count (extended long-term trial)

The open-label EXTEND study evaluated long-term safety and efficacy of eltrombopag in adults with ITP who had completed a previous eltrombopag study.1,3,8 Interim results showed that treatment with eltrombopag was effective in maintaining platelet counts up to 3 years.8 This study reviewed more than 8 years of continuous treatment.3,8 Of 302 patients enrolled, 135 (45%) completed the study; 60% were treated at least 2 years and 35% at least 3 years.3,8 The “n” value represents the total number of patients, with median platelet counts ≥50,000/mcL by Week 2 and at least that throughout.1,3,8

 
PROMACTA reported the longest results in the largest trial (EXTEND) ever in persistent or chronic ITP1,3-6

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

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.7

Proven Effect on Bleeding Events

PROMACTA was proven to rapidly reduce grades 2-4 bleeding events9

AS EARLY AS DAY 15: 64% REDUCTION IN GRADES 2-4 BLEEDING EVENTS9

  • 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)10
Chart showing clinical trial grades 2-4 bleeding events at day 15 (RAISE pivotal trail)

Phase 3, 6-month, double-blind, randomized, placebo-controlled study of 197 patients with previously treated ITP and baseline platelet counts <30,000/mcL.1,10 The primary end point was the odds of response, defined as a platelet count ≥50,000/mcL and ≤400,000/mcL, during treatment.1,10

  • For all grades, the percentage of patients receiving PROMACTA experiencing bleeding events was reduced by 47% at Day 15 (73% at baseline vs 39%) and by 12% at Day 15 for patients receiving placebo experiencing bleeding events (77% at baseline vs 68%)9

WHO GRADES 2-4 ARE CLINICALLY SIGNIFICANT3,9

  • Grade 2 Mild blood loss
  • Grade 3 Gross blood loss
  • Grade 4 Debilitating blood loss

PROMACTA was proven to provide durable reductions in grades 2-4 bleeding events3

AT YEAR 1: 76% REDUCTION IN GRADES 2-4 BLEEDING EVENTS1,3

Chart showing clinical trial grades 2-4 bleeding events at year 1 (EXTEND long-term trial)

The open-label EXTEND study evaluated long-term safety and efficacy of eltrombopag in adults with ITP who had completed a previous eltrombopag study.1,3,8 Interim results showed that treatment with eltrombopag was effective in maintaining platelet counts up to 3 years.8

  • For all grades, the percentage of patients experiencing bleeding events was reduced by 72% at Year 1 (57% at baseline vs 16%)3

SEE THE ADDITIONAL BENEFITS OF PROMACTA

34% permanently stopped ≥1 ITP medication, usually corticosteroids (n=34/101).  71% maintained levels ≥30,000/mcL for ≥25 weeks without a change in treatment (n=183/257)

aDefined as the need for a new ITP medication, increased dose of any concomitant ITP medication, platelet transfusion, or splenectomy.8

 
Offer your patients the nonimmunosuppressive control of PROMACTA,1 the #1 prescribed TPO-RA11‡
Source: IQVIA market sizing TRx monthly equivalents, R3M, January 2019 through November 2020.11

Effect on Quality of Life

PATIENTS REPORTED IMPROVEMENTS IN KEY PHYSICAL AND MENTAL HEALTH PARAMETERS9,10

  • Patients self-reported improvements at Week 26
Chart showing changes in physical health parameters for the RAISE pivotal clinical trial
Chart showing changes in mental health parameters for the RAISE pivotal clinical trial

P values represent significance with PROMACTA vs baseline.
aPatients in both arms were permitted local SOC, including but not limited to corticosteroids, IVIg, danazol, azathioprine, mycophenolate, anti-D, cyclosporine, cyclophosphamide, rituximab, and vincristine/vinblastine.
bThe vitality domain is defined as physical or mental fatigue.

The prespecified domain analyses were observational in nature; as such, there were no prespecified statistical procedures controlling for type 1 errors.9

  • Patients receiving PROMACTA reported significant improvement from baseline on 5 of the 8 domains of the Short Form 36 Health Survey, version 2 (SF-36v2)§ that measure HRQoL (P<0.05)9,10
    • Domains included physical and mental function
    • Significant changes were also shown in both summary scores|| and in the Functional Assessment of Cancer Therapy–Thrombocytopenia (FACT-Th6) score

CHANGES PERSISTED UP TO 5 YEARS IN FATIGUE, BLEEDING, AND BRUISING3,12

  • ~80% of patients self-reported improvements in at least 1 measure of HRQoL in the EXTEND study12
Chart showing changes in fatigue, bleeding, and bruising in the EXTEND long-term clinical trial
 
Consider PROMACTA as a first choice in second-line treatment1

anti-D, anti-D (ρ) immunoglobulin; ASH, American Society of Hematology; FACIT-Fatigue, Functional Assessment of Chronic Illness Therapy–Fatigue; HRQoL, health-related quality of life; ITP, immune thrombocytopenia; IVIg, intravenous immunoglobulin; R3M, rolling 3 months; SOC, standard of care; TPO-RA, thrombopoietin receptor agonist; TRx, total prescription.

§The acute recall version of the SF-36v2 questionnaire was used to measure HRQoL expressed in 8 domain scores and 2 component summary scores (physical and mental). These domains included physical function, physical role (role limitations due to physical health), bodily pain, general health, vitality (physical or mental fatigue), social function, emotional role (role limitations due to emotional problems), and mental health.9,10

||Physical and mental component summary scores were normalized to the 1998 US Census.10

References:

  1. Promacta [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2021.
  2. Data on file. Study TRA100773A. Novartis Pharmaceuticals Corp; October 2007.
  3. Data on file. Study TRA105325 (EXTEND). Novartis Pharmaceuticals Corp; March 2016.
  4. 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.
  5. 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.
  6. Bussel JB, Arnold DM, Boxer MA, et al. Long-term fostamatinib treatment of adults with immune thrombocytopenia during the phase 3 clinical trial program. Am J Hematol. 2019;94(5):546-553.
  7. Neunert C, Terrell DR, Arnold DM, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019;3(23):3829-3866. 
  8. 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.
  9. Data on file. Study TRA102537 (RAISE). Novartis Pharmaceuticals Corp; February 2009.
  10. 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.
  11. Data on file. IQVIA market sizing TRx monthly equivalents, R3M, January 2019 through November 2020. Novartis Pharmaceuticals Corp; March 2021.
  12. Khelif A, Saleh MN, Salama A, et al. Changes in health-related quality of life with long-term eltrombopag treatment in adults with persistent/chronic immune thrombocytopenia: findings from the EXTEND study. Am J Hematol. 2019;94(2):200-208.

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)

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.