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FDA Drug Safety Communication: Modified Risk Evaluation and Mitigation Strategies (REMS) for Nplate (romiplostim) and Promacta (eltrombopag)


Safety Announcement

Additional Information for Patients
Additional Information for Healthcare Professionals
Data Summary
 

Safety Announcement

[12-6-2011] The U.S. Food and Drug Administration (FDA) has approved modifications to the Risk Evaluation and Mitigation Strategies (REMS) for platelet-booster drugs Nplate (romiplostim) injection and Promacta (eltrombopag) tablets. The modifications include the removal of certain elements of the REMS, including the requirements for restricted distribution and additional safety data collection.

Facts about Nplate and Promacta

  • Used to treat low blood platelet counts in adults with chronic immune (idiopathic) thrombocytopenia (ITP), when certain other medicines, or surgery to remove the spleen, have not worked well enough. 
  • Used to try to keep the platelet count about 50,000 per microliter in order to lower the risk for bleeding.
  • ITP is a condition that may cause unusual bruising or bleeding due to an abnormally low number of platelets in the blood.

Prescribers, healthcare institutions, pharmacies, and patients no longer have to enroll in the REMS programs in order to prescribe, dispense or take these drugs.

Healthcare professionals and patients should be aware, however, that serious risks still exist with Nplate and Promacta. The physician labels and patient Medication Guides have been updated to reflect the current data on the risks with each therapy.

At the time of approval in 2008, experience with both Nplate and Promacta was limited, and safety concerns led to a decision to require a REMS that included restricted distribution and additional safety data collection requirements for each drug to ensure that the benefits of the drugs outweighed their risks. These risks included bone marrow changes, higher risk for blood clots, possible worsening of blood cancers, and worsening low blood platelet count after stopping the drugs. The purpose of the REMS was to promote informed risk-benefit decisions between patients and healthcare professionals prior to starting therapy and while patients remained on treatment to ensure the appropriate use of the drugs, and to establish the long-term safety and safe use of the drugs. However, the underlying medical conditions in patients with chronic immune (idiopathic) thrombocytopenia (ITP) made the safety data collected by the REMS programs difficult to interpret. FDA has determined that the REMS requirements related to safety data collection are not informative and are no longer necessary to ensure that the benefits of the drugs outweigh their risks. FDA has concluded that establishing the long-term safety of Nplate and Promacta is best achieved through ongoing clinical trials, post-approval studies, and post-marketing adverse event reports.  

FDA will continue to monitor these drugs for safety risks and will update the public if it has additional information on the benefits and risks of Nplate and Promacta.


Additional Information for Patients 

  • Patients no longer need to be enrolled in the Nplate NEXUS (Network of Experts Understanding and Supporting Nplate and Patients) Program or the Promacta CARES Program in order to receive Nplate or Promacta.
  • Patients should read the Medication Guide that they get along with their Nplate or Promacta prescription. It explains the risks associated with the use of these drugs.
  • Patients should contact their healthcare professional if they have any questions or concerns about Nplate or Promacta.
  • Patients should report serious side effects from the use of Nplate or Promacta to the FDA MedWatch program, using the information at the bottom of the page in the "Contact Us" box.
     

Additional Information for Healthcare Professionals 

  • Healthcare professionals no longer need to:
      • Enroll in the Nplate NEXUS (Network of Experts Understanding and Supporting Nplate and Patients) Program to prescribe Nplate.
      • Enroll in the Promacta CARES Program to prescribe Promacta.
      • Complete periodic safety forms for patients receiving Nplate or Promacta.
  • Institutions no longer need to:
      • Enroll in the Nplate NEXUS Program.
      • Enroll in the Promacta CARES Program.
      • Verify prescriber and patient enrollment before dispensing Nplate.
  • Pharmacies/pharmacists no longer need to:
      • Enroll in the Promacta CARES Program.
      • Verify prescriber and patient enrollment before dispensing Promacta.
  • Healthcare professionals should should continue to refer to the drug prescribing information for the latest recommendations on prescribing Nplate and Promacta.

  • Healthcare professionals should encourage patients to read the Medication Guide that they get along with their Nplate or Promacta prescription.
  • Healthcare professionals should continue to report adverse events involving Nplate or Promacta to the FDA MedWatch program, using the information at the bottom of the page in the "Contact Us" box.
     

Data Summary 

Nplate (romiplostim) was approved on August 22, 2008 and Promacta (eltrombopag) on November 20, 2008 for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. The clinical trials upon which the approvals were based were small in enrollment and of relatively short duration. These pre-market clinical trials identified several safety concerns for both drugs, including evidence of bone marrow reticulin formation and fibrosis, worsening thrombocytopenia on discontinuation of the drugs, thromboembolic events, and concerns that the marrow stimulatory effects of the drugs could increase the risk of hematological malignancies or progression of malignancy. In addition, Promacta may cause hepatotoxicity. The applications for Nplate and Promacta were discussed at FDA Oncologic Drugs Advisory Committee meetings, held on March 12, 2008 and May 30, 2008, respectively.

Risk Evaluation and Mitigation Strategies (REMS) that included elements to assure safe use (ETASU) were required for both Nplate and Promacta at the time of approval because potential serious risks were not well characterized due to the absence of long-term safety data, and FDA determined that the ETASU were necessary to ensure that the benefits of the drugs outweighed their risks. The goals of the REMS were: (1) to promote informed risk-benefit decisions before initiating treatment and while patients are on treatment to ensure appropriate use of the drugs and; (2) to establish the overall long-term safety and safe use of the drugs through periodic monitoring of all patients who receive them. The ETASU consisted of restricted distribution requirements for prescribers, pharmacists, health care settings, and patients to be enrolled in the programs to prescribe, dispense or receive the drugs, and requirements for healthcare professionals to submit baseline and periodic safety information for patients who received the drugs.

Since 2008, FDA has continued to monitor the safety of Nplate and Promacta, and to evaluate the REMS. FDA’s review has indicated that some of the adverse events of concern with Nplate and Promacta can be part of the natural history of ITP and other serious underlying medical conditions in patients treated with these drugs. Confounding by underlying medical conditions in the treated patient population made the adverse event data collected by the REMS programs challenging to interpret. FDA and the manufacturers of Nplate and Promacta believe that ongoing clinical trials, post-approval studies, and post-marketing adverse event reports will provide the necessary data to continue monitoring the long-term safety of Nplate and Promacta. Based in part on this information, FDA has determined that it is appropriate to modify the REMS for both drugs to remove the requirements for restricted distribution and additional adverse event data collection, because these elements of the REMS are no longer needed to ensure that the benefits of the drugs outweigh their risks.

REMS for Nplate and Promacta are still required. The revised REMS include a communication plan to inform healthcare professionals about the changes to the REMS programs, as well as the serious risks associated with treatment. 

 

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