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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Indications for PROMACTA® (eltrombopag) Tablets
PROMACTA is indicated in combination with standard immunosuppressive therapy for the first-line treatment of adult and pediatric patients 2 years and older with severe aplastic anemia.

PROMACTA is indicated for the treatment of patients with severe aplastic anemia who have had an insufficient response to immunosuppressive therapy.

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.

Disease Information

Unmet Need in SAA

STANDARD IST* ALONE MAY NOT BE OPTIMAL FOR YOUR PATIENTS WITH TREATMENT-NAIVE SAA1-4

17% complete response was reported in a combined analysis of 2 separate NHLBI trials (2003-2005 and 2005-2010) in 102 patients with SAA receiving h-ATG + CsA.5

In addition:

  • ~30% of patients with SAA do not respond to standard IST alone1
  • ~40% of responders relapse, causing symptoms to return2
  • >50% of patients are unable to experience a long-term benefit from IST3,4

 

 

CsA, cyclosporine A; h-ATG, horse antithymocyte globulin; IST, immunosuppressive therapy; NHLBI, National Heart, Lung, and Blood Institute; r-ATG, rabbit antithymocyte globulin; SAA, severe aplastic anemia.

*h-ATG or r-ATG and CsA.6

PROMACTA in First-Line SAA

PROMACTA IS THE ONLY TPO-RA PROVEN EFFECTIVE IN TREATMENT-NAIVE PATIENTS7-9

The First and Only:

  • TPO-RA approved to treat SAA in patients as young as 2 years old7-9
  • SAA treatment option approved by the FDA in nearly 30 years7,10,11
  • TPO-RA with a proven trilineage response in SAA7-9,12-14

FDA, US Food and Drug Administration; SAA, severe aplastic anemia; TPO-RA, thrombopoietin receptor agonist.

 

References:

  1. Desmond R, Townsley DM, Dumitriu B, et al. Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug. Blood. 2014;123(12):1818-1825.
  2. Scheinberg P. Current management of severe acquired aplastic anemia. Einstein (Sao Paulo). 2011;9(2, pt 1):229-235.
  3. Rosenfeld S, Follman D, Nunez O, Young NS. Antithymocyte globulin and cyclosporine for severe aplastic anemia: association between hematologic response and long-term outcome. JAMA. 2003;289(9):1130-1135.
  4. Young NS, Calado RT, Scheinberg P. Current concepts in the pathophysiology and treatment of aplastic anemia. Blood. 2006;108(8):2509-2519.
  5. Townsley DM, Scheinberg P, Winkler T, et al. Eltrombopag added to standard immunosuppression for aplastic anemia. N Engl J Med. 2017;376(16):1540-1550, S1-S39. doi:10.1056/NEJMoa1613878.
  6. Jeong DC, Chung NG, Cho B, et al. Long-term outcome after immunosuppressive therapy with horse or rabbit antithymocyte globulin and cyclosporine for severe aplastic anemia in children. Haematologica. 2014;99(4):664-671.
  7. Promacta [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2019.
  8. Nplate [prescribing information]. Thousand Oaks, CA: Amgen Inc; 2017.
  9. Doptelet [prescribing information]. Durham, NC: Dova Pharmaceuticals Inc; 2018.
  10. Passweg JR, Tichelli A. Immunosuppressive treatment for aplastic anemia: are we hitting the ceiling? Haematologica. 2009;94(3):310-312.
  11. ClinicalTrials.gov. Bethesda, MD: US National Library of Medicine, National Institutes of Health; 2000. https://clinicaltrials.gov/ct2/results?cond=severe+aplastic+anemia &Search=Apply&recrs=e&age_v=&gndr=&type=&rslt=. Accessed October 5, 2018.
  12. Lum SH, Grainger JD. Eltrombopag for the treatment of aplastic anemia: current perspectives. Drug Des Devel Ther. 2016;10:2833-2843.
  13. Data on file. Study ETB115AUS01T. Novartis Pharmaceuticals Corp; July 2018.
  14. Lengline E, Drenou B, Peterlin P, et al. Nationwide survey on the use of eltrombopag in patients with severe aplastic anemia: a report on behalf of the French Reference Center for Aplastic Anemia. Haematologica. 2018;103(2):212-220.

Indications for PROMACTA® (eltrombopag) Tablets
PROMACTA is indicated in combination with standard immunosuppressive therapy for the first-line treatment of adult and pediatric patients 2 years and older with severe aplastic anemia.

PROMACTA is indicated for the treatment of patients with severe aplastic anemia who have had an insufficient response to immunosuppressive therapy.

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) Tablets

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

First-line treatment of severe aplastic anemia

  • ALT, AST, and bilirubin should be measured prior to initiation of PROMACTA
  • During treatment, increases in ALT levels should be managed based on recommendation in Dosing and Administration section for hepatic impairment  
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
  • Monitor clinical hematology tests regularly throughout therapy with PROMACTA and modify the dosage regimen of PROMACTA based on platelet counts
  • Hematologic response may take up to 16 weeks after starting PROMACTA. If no hematologic response has occurred after 16 weeks with PROMACTA, discontinue therapy
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 (≥5%) in a single-arm trial of 92 patients 2 years and older with severe aplastic anemia (SAA) who had not received prior immunosuppressive therapy were increased ALT (29%) and AST (17%), blood bilirubin increased (17%), rash (8%), and skin discoloration including hyperpigmentation (5%). Upper respiratory infection, particularly in pediatric patients, was also reported. The most common adverse reactions (≥20%) in a single-arm, open-label trial in 43 patients with refractory SAA who received PROMACTA were nausea (33%), fatigue (28%), cough (23%), diarrhea (21%), and headache (21%). In this trial, patients had bone marrow aspirates evaluated for cytogenetic abnormalities. Eight patients had a new cytogenetic abnormality reported, including 5 patients who had complex changes in chromosome 7. If new cytogenetic abnormalities are observed, consider discontinuation of PROMACTA.

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