For:
Pediatric Chronic Immune Thrombocytopenia in Patients ≥1 Year of Age
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 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

Time to Response

PROMACTA RAISED PLATELET LEVELS TO ≥50,000/mcL AFTER INITIAL THERAPY FAILED1

Platelet Levels Increased in a Majority of Patients1

PETIT Response Rates
  • At baseline, ~51% of patients had platelet counts ≤15,000/mcL1
  • At Week 1, 24% of patients achieved platelet levels ≥50,000/mcL vs 14% with placebo2
  • Response rates on treatment with PROMACTA® (eltrombopag) were consistent across all age groups1,2
  • Primary end point was the proportion of patients who achieved a response (defined as platelet count ≥50,000/mcL) at least once between Weeks 1 and 6 of the randomized, double-blind period1
Rapid: Responses seen as early as Week 1

Study Design1,2

  • Phase 2, 7-week, double-blind trial in children ≥1 year of age with relapsed or refractory ITP, followed by a 17- or 24-week open-label extension phase for patients from the PROMACTA and placebo arms of the double-blind phase, respectively
  • Sixty-seven patients were randomized 2:1 to PROMACTA (n=45) or placebo (n=22) and were permitted to use maintenance therapy, including (but not limited to) corticosteroids, azathioprine, danazol, cyclosporine, and mycophenolate mofetil
  • Platelet response was evaluated for 3 age cohorts: 1) 12 to 17 years, 2) 6 to 11 years, and 3) 1 to 5 years

Length of Response

PLATELET LEVELS ≥50,000/mcL WERE MAINTAINED AFTER INITIAL THERAPY FAILED1,3

41% of PROMACTA Patients Experienced Platelet Level Increases for ≥6 of 8 Weeks1

PETIT 2 Response Rates
  • At baseline, ~62% of patients had platelet counts ≤15,000/mcL1
  • Response rates on treatment with PROMACTA were consistent across all age groups1,3
  • Primary end point was the proportion of patients who achieved a response (defined as platelet count ≥50,000/mcL) for at least 6 of the 8 weeks between Weeks 5 and 12 of the double-blind period1
Durable: Responses maintained for ≥6 weeks

Study Design1,3

  • Phase 3, 13-week, double-blind trial to assess the efficacy and safety of PROMACTA in children ≥1 year of age with relapsed or refractory chronic ITP, followed by a 24-week open-label extension phase
  • Ninety-two patients were randomized 2:1 to PROMACTA (n=63) or placebo (n=29) and were permitted to use maintenance therapy, including corticosteroids, intravenous immunoglobulin, cyclosporine, mycophenolate, azathioprine, and dapsone
  • Platelet response was evaluated for 3 age cohorts: 1) 12 to 17 years, 2) 6 to 11 years, and 3) 1 to 5 years

*In the extension phase of the study, platelet levels ≥50,000/mcL were maintained for a mean of 8.6 weeks and a median of 6 weeks.3

Effect on Concomitant Medications

PROMACTA REDUCED THE NEED FOR CONCOMITANT MEDICATIONS1

Many Patients Were Able to Reduce or Discontinue Concomitant ITP Medications During the Open-Label Extension Phases of Both Pediatric Trials

Reductions in Concomitant Medications

Less Need for Rescue Treatment

  • Fewer patients who received PROMACTA required rescue treatment in the placebo-controlled phase vs those who received placebo
Less need for Rescue Treatment

ITP, immune thrombocytopenia.

References:

  1. Promacta [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2019.
  2. Data on file. Study TRA108062 (PETIT). Novartis Pharmaceuticals Corp; July 2014.
  3. Data on file. Study TRA115450 (PETIT 2). Novartis Pharmaceuticals Corp; July 2014.

Indication for PROMACTA® (eltrombopag)
PROMACTA is indicated for the treatment of thrombocytopenia in adult and pediatric patients 1 year and older with 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 (ULN) 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 on an empty stomach (1 hour before or 2 hours after a meal)

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 chronic ITP patients (≥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 chronic ITP patients 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.