For:
Pediatric Chronic Immune (Idiopathic) Thrombocytopenia in Patients ≥1 Year of Age
Important Safety Information

RISK FOR HEPATIC DECOMPENSATION IN PATIENTS WITH CHRONIC HEPATITIS C - PROMACTA in combination with interferon and ribavirin may increase the risk of hepatic decompensation... +

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Indication
PROMACTA is indicated for the treatment of thrombocytopenia in adult and pediatric patients 1 year and older with chronic immune (idiopathic) 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).

PROMACTA should be used only in patients with ITP whose degree of thrombocytopenia and clinical condition increase the risk for bleeding.

Pediatric Chronic Immune (Idiopathic) Thrombocytopenia in Patients ≥1 Year of Age

ABOUT PROMACTA

PROMACTA® (eltrombopag): PROVEN EFFICACY FOR PEDIATRIC PATIENTS DEMONSTRATED IN 2 PIVOTAL TRIALS1

PETIT Study Design: Results from a 7-week, double-blind, phase 2 trial to assess the efficacy, safety, and dosing of PROMACTA in children ≥1 year of age with relapsed or refractory chronic ITP. Sixty-seven patients were randomized 2:1 to treatment with PROMACTA (n=45) or placebo (n=22) and were permitted to use stable maintenance ITP therapy, including (but not limited to) corticosteroids, azathioprine, danazol, cyclosporin A, and mycophenolate mofetil. At baseline, 51% of patients had platelet counts ≤15 × 109/L; 84% of PROMACTA-treated and 86% of placebo-treated patients had received ≥2 prior ITP therapies; and 5 patients in the PROMACTA group had had a prior splenectomy. Efficacy was determined by the proportion of patients who achieved a platelet count ≥50 × 109/L at least once between Weeks 1 and 6 of the randomized period.1,2

PETIT 2 Study Design: Results from a 13-week, double-blind, phase 3 trial to assess the efficacy, safety, and dosing of PROMACTA in children ≥1 year of age with relapsed or refractory chronic ITP. Ninety-two patients were randomized 2:1 to treatment with PROMACTA (n=63) or placebo (n=29) and were permitted to use stable maintenance ITP therapy, including (but not limited to) corticosteroids, azathioprine, danazol, cyclosporin A, and mycophenolate mofetil. At baseline, 62% of patients had platelet counts ≤15 × 109/L; 73% of PROMACTA-treated and 90% of placebo-treated patients had received ≥2 prior ITP therapies and 4 patients in the PROMACTA group had undergone prior splenectomy. The primary end point was the proportion of patients who achieved a platelet count ≥50 × 109/L for at least 6 of the 8 weeks between Weeks 5 and 12 of the double-blind period.1,3

EFFICACY PROFILES

PROMACTA SIGNIFICANTLY RAISED PLATELET LEVELS OVER 7 WEEKS1

Response seen as early as Week 12*

Response rates

*Response rates at Week 1 were 24.4% for PROMACTA vs 13.6% for placebo.2
Please see study design above.

  • Platelet counts with PROMACTA were consistent across all age groups2
  • In these clinical trials, platelet counts generally increased within 1 to 2 weeks after starting PROMACTA and decreased within 1 to 2 weeks after discontinuation1
  • In the PETIT trial, response was defined as platelet count ≥50 × 109/L at least once between Weeks 1 and 6 of the randomized, double-blind period1

 

PROMACTA SIGNIFICANTLY SUSTAINED PLATELET LEVELS OVER 13 WEEKS1

Response seen as early as Week 13*

Response rates

*Response rates at Week 1 were 15.9% for PROMACTA vs <1% for placebo.3
Please see study design above.

  • In the PETIT 2 trial, response was defined as platelet count ≥50 × 109/L for at least 6 of 8 weeks between Weeks 5 and 12 of the randomized, double-blind period1

 

PATIENTS MAY BE ABLE TO DISCONTINUE CONCOMITANT THERAPIES

During the open-label phase of both trials, many patients were able to reduce or discontinue concomitant ITP medications1

 

 

Less need for rescue treatment 

In the randomized, double-blind period, fewer PROMACTA-treated patients required rescue therapy vs those who received placebo.1

  • PETIT: Only 13% (6/45) required rescue treatment
  • PETIT 2: Only 19% (12/63) required rescue treatment

SAFETY PROFILE

DEMONSTRATED A STRONG SAFETY PROFILE 

Only 8 of 159 (5%) patients treated with PROMACTA discontinued due to adverse events in all phases of both trials1-3

Adverse reactions (≥3%)*PROMACTA (n=107)Placebo (n=50)
Upper respiratory tract infection 17% 6%
Nasopharyngitis 12% 4%
Cough 9% 0%
Pyrexia 9% 8%
Diarrhea 9% 2%
Rhinitis 9% 6%
Abdominal Pain 8% 4%
Oropharyngeal pain 8% 2%
Toothache 6% 0%
Increased ALT 6% 0%
Rash 5% 2%
Increased AST
4% 0%
Rhinorrhea 4% 0%

*The adverse events listed above were pooled from the PETIT and PETIT 2 clinical trials.
Includes adverse reactions or laboratory abnormalities 3 × upper limit of normal.
  ALT=alanine aminotransferase.
  AST=aspartate aminotransferase.

  • PETIT: 6.8% grade 3 and 4.5% grade 4 adverse events2
  • PETIT 2: 12.7% grades 3 and 4 adverse events, combined3

DOSING AND ADMINISTRATION

CONVENIENCE OF ONCE-DAILY ORAL PROMACTA FOR YOUR PATIENTS1

Dosing options to meet your patients’ needs, in a single tablet they can take at school, home, or on the go

  • Tablets are available in 4 strengths for titration within an active lifestyle

 

 

No injections

 

The recommended initial starting dosage for patients aged 1 to 5 years is 25 mg once daily1

 

  • The recommended initial starting dosage for patients aged 6 years and older is 50 mg once daily1
  • Consider initiating PROMACTA at a reduced dosage of 25 mg once daily for patients aged 6 years and older of East Asian ancestry or who have mild to severe hepatic impairment1
  • For East Asian patients aged 6 years and older with hepatic impairment, consider initiating PROMACTA at a reduced dosage of 12.5 mg once daily1
  • PROMACTA has a maximum dosage of 75 mg per day1

 

Dosing considerations1

Prior to initiating PROMACTA, monitor liver tests (ALT, AST, and bilirubin). During PROMACTA therapy, assess platelet counts weekly for 2 weeks until a stable platelet count has been achieved, then follow standard monthly monitoring.

  

Less need for rescue treatment1

  • In the randomized, double-blind period, fewer PROMACTA-treated patients required rescue therapy vs those who received placebo

 

 

  • Modify the dosage regimen of concomitant ITP medications, as medically appropriate, to avoid excessive increases in platelet counts during therapy with PROMACTA
  • Use the lowest dose of PROMACTA to achieve and maintain a platelet count ≥50 × 109/L as necessary to reduce the risk for bleeding
  • Do not use PROMACTA to normalize platelet counts
  • Discontinue PROMACTA if the platelet count does not increase to a level sufficient to avoid clinically important bleeding after 4 weeks of therapy with PROMACTA at the maximum daily dose of 75 mg
  • Excessive platelet count responses, as outlined in Table 1 of the Prescribing Information, or important liver test abnormalities also necessitate discontinuation of PROMACTA

 

DIETARY GUIDELINES1,4

50 mg of calcium examples (check labels of all food/supplements):

  • Dairy products (yogurt, cheese, milk, ice cream)
  • Calcium-fortified foods (orange juice, dry cereal, bread)
  • Leafy green vegetables (collard greens, spinach)

*This includes calcium-rich foods, other medications (such as antacids), or supplements containing polyvalent cations such as iron, calcium, aluminum, magnesium, selenium, and zinc.4

 

How should your patients take PROMACTA?

  • Take exactly as prescribed
  • Take PROMACTA on an empty stomach
  • Take tablets whole. Do not crush or mix with liquids
  • If a dose is missed, wait until the next scheduled dose

MECHANISM OF ACTION

In Chronic Immune (Idiopathic) Thrombocytopenia

Multiple processes are responsible for decreased platelet levels5-8

Thrombopoietin (TPO) is a vital growth factor for platelet production5,9

  • TPO works by stimulating megakaryocytes and their precursors in the bone marrow, leading to proliferation and differentiation of these cells
  • Normally, when there is a drop in platelet levels, more circulating TPO becomes available to stimulate platelet production
  • In patients with ITP, there is no compensatory increase in TPO synthesis to stimulate platelet production

PROMACTA—The First and Only Approved Oral TPO Receptor Agonist That Works to Increase Platelet Production1,9

PROMACTA is a not a corticosteroid or an immunosuppressant1

PROMACTA is a nonpeptide TPO receptor agonist that works to increase platelet production by1,8,9:

  • Interacting with the transmembrane domain of TPO receptors on megakaryocytes to induce an intracellular signal
  • Triggering the proliferation and differentiation of megakaryocytes from bone marrow progenitor cells

PROMACTA SUPPORT AND SERVICES

The Universal Co-pay Card

At Novartis Oncology, we’ve made it easier for patients to access co-pay assistance on their prescription costs for almost all Novartis Oncology products. Patients may be eligible for immediate co-pay savings on their next prescription:

  • Commercially insured patients pay only $25 per month
  • Novartis will pay the remaining co-pay, up to $15,000 per calendar year

Encourage your patients to find out if they are eligible to enroll in the Universal Co-Pay Program by visiting www.CoPay.NovartisOncology.com or calling 1-877-577-7756.

Limitations apply. Offer is not valid under Medicare, Medicaid, or any other federal or state program. Novartis reserves the right to rescind, revoke, or amend this program without notice.

 

Patient services

Patient Assistance Now Oncology (PANO) assists with all aspects of access, from insurance verification, to information about financial assistance, to a supportive call center.

To learn more, call 1-800-282-7630.

 

Terms and Conditions
This offer is valid only for those with commercial insurance. Offer not valid under Medicare, Medicaid, or any other federal or state program. Not valid for cash payments, where product is not covered by patient’s commercial insurance, or where plan reimburses you for entire cost of your prescription drug. Offer is not valid where prohibited by law. Valid only in the United States and Puerto Rico. This program is not health insurance. Offer may not be combined with any other rebate, coupon, or offer. The card is the property of Novartis Pharmaceuticals Corporation and must be returned upon request. Novartis reserves the right to rescind, revoke, or amend the program without notice. Patient certifies responsibility for complying with applicable limitations, if any, of any commercial insurance and reporting receipt of program rewards, if necessary, to any commercial insurer. This offer expires on December 31, 2018. Additional Terms and Conditions may apply.

References

  1. Promacta [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2017.
  2. Data on file. PROMACTA TRA108062 PETIT Clinical Study Report. Novartis Pharmaceuticals Corp; June 2014.
  3. Data on file. PROMACTA TRA115450 PETIT 2 Clinical Study Report. Novartis Pharmaceuticals Corp; June 2014.
  4. Data on file. Ad Com Briefing Doc. Promacta (eltrombopag tablets). FDA oncologic drug advisory committee briefing document. Novartis Pharmaceuticals Corp; 2008.
  5. George JN. Challenges and priorities for patients with immune thrombocytopenic purpura and their physicians. Pharm Policy Law. 2009;11(4):299-305.
  6. Cines DB, McMillan R. Management of adult idiopathic thrombocytopenic purpura. Annu Rev Med. 2005;56:425-442.
  7. Gernsheimer T. Chronic idiopathic thrombocytopenic purpura: mechanisms of pathogenesis. Oncologist. 2009;14(1):12-21.
  8. Kühne T, Imbach P. Eltrombopag: an update on the novel, non-peptide thrombopoietin receptor agonist for the treatment of immune thrombocytopenia. Ann Hematol. 2010;89(suppl 1):S67-S74.
  9. Bussel JB, Cheng G, Saleh MN, et al. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med. 2007;357(22):2237-2247.

Indication
PROMACTA is indicated for the treatment of thrombocytopenia in adult and pediatric patients 1 year and older with chronic immune (idiopathic) 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).

PROMACTA should be used only in patients with ITP whose degree of thrombocytopenia and clinical condition increase the risk for bleeding.

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. (See Section 5.1 of the full Prescribing Information for additional information.)

RISK OF HEPATOTOXICITY
PROMACTA may increase the risk of severe and potentially life-threatening hepatotoxicity. Monitor hepatic function and discontinue dosing as recommended. (See Section 5.2 of the full Prescribing Information for additional information.)

Hepatotoxicity
PROMACTA may increase the risk of severe and potentially life-threatening hepatotoxicity. 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.

Isolated cases of severe liver injury were identified in clinical trials. The elevation of liver laboratory values occurred approximately 3 months after initiation of PROMACTA. In all cases, the event resolved following PROMACTA discontinuation.

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. Consider the potential for an increased risk of thromboembolism when administering PROMACTA to patients with known risk factors for thromboembolism. 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.

In 2 controlled clinical trials in patients with chronic hepatitis C and thrombocytopenia, 3% (31/955) treated with PROMACTA experienced a thrombotic event compared to 1% (5/484) on placebo. The majority of events were of the portal venous system (1% in patients treated with PROMACTA vs <1% for placebo).

In a controlled trial in patients with chronic liver disease and thrombocytopenia not related to ITP undergoing elective invasive procedures (N=292), 7 thrombotic complications (6 patients) were reported within the group that received PROMACTA and 3 thrombotic complications (2 patients) within the placebo group. All of the thrombotic complications reported in the group that received PROMACTA were portal vein thrombosis, with thrombotic complications occurring in 5 of the 6 patients at a platelet count above 200 x 109/L. PROMACTA is not indicated for the treatment of thrombocytopenia in patients with chronic liver disease in preparation for invasive procedures.

Increased Risk of Death and Progression of Myelodysplastic Syndromes (MDS) to Acute Myeloid Leukemia (AML)
A randomized, double-blind, placebo-controlled, multicenter trial in patients with International Prognostic Scoring System (IPSS) intermediate-1, intermediate-2, or high-risk MDS with thrombocytopenia receiving azacitidine in combination with either PROMACTA (n=179) or placebo (n=177) was terminated due to lack of efficacy and safety reasons, including increased progression to AML. Patients received PROMACTA or placebo at a starting dose of 200 mg once daily, up to a maximum of 300 mg once daily, in combination with azacitidine for at least 6 cycles. The incidence of death (overall survival) was 32% (57/179) in the PROMACTA arm vs 29% (51/177) in the placebo arm (HR=1.42 [95% CI, 0.97-2.08]), showing an increased relative risk of death in this trial by 42% in the PROMACTA arm. The incidence of progression to AML was 12% (21/179) in the PROMACTA arm vs 6% (10/177) in the placebo arm (HR=2.66 [95% CI, 1.31-5.41]), showing an increased relative risk of progression to AML in this trial by 166% in the PROMACTA arm.

Cataracts
In the 3 controlled clinical trials in chronic ITP, cataracts developed or worsened in 15 (7%) patients who received 50-mg PROMACTA daily and 8 (7%) placebo-group patients. In the extension trial, cataracts developed or worsened in 11% of patients who underwent ocular examination prior to therapy with PROMACTA.

In the 2 controlled trials with patients with thrombocytopenia, cataracts developed or worsened in 8% of patients treated with PROMACTA and 5% of patients treated with placebo.

Cataracts were observed in toxicology studies of eltrombopag in rodents. Perform a baseline ocular examination prior to administration of PROMACTA and, during therapy with PROMACTA, regularly monitor patients for signs and symptoms of cataracts.

Laboratory Monitoring
In patients with chronic ITP, 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 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.

Adverse Reactions
The most common adverse reactions in 3 placebo-controlled clinical trials in adult patients with chronic ITP (≥3% and greater than placebo) for PROMACTA vs placebo were nausea (9% vs 3%), diarrhea (9% vs 7%), upper respiratory tract infection (7% vs 6%), vomiting (6% vs <1%), increased ALT (5% vs 3%), myalgia (5% vs 2%), urinary tract infection (5% vs 3%), oropharyngeal pain (4% vs 3%), increased AST (4% vs 2%), pharyngitis (4% vs 2%), back pain (3% vs 2%), influenza (3% vs 2%), paresthesia (3% vs 2%), and rash (3% vs 2%).

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 vs placebo were upper respiratory tract infection (17% vs 6%), nasopharyngitis (12% vs 4%), cough (9% vs 0%), diarrhea (9% vs 2%), pyrexia (9% vs 8%), rhinitis (9% vs 6%), abdominal pain (8% vs 4%), oropharyngeal pain (8% vs 2%), toothache (6% vs 0%), ALT increased (6% vs 0%), rash (5% vs 2%), AST increased (4% vs 0%), and rhinorrhea (4% vs 0%).

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