The FDA approved changes to the Risk Evaluation and Mitigation Strategies (REMS) for both Nplate (romiplostim) and Promacta (eltrombopag). According to an FDA-initiated review of the current information, Nplate and Promacta still pose certain safety risks, but certain restrictive requirements of the REMS programs are no longer required to ensure that the drugs' benefits outweigh their risks. The FDA (Food and Drug Administration, USA) will continue to monitor both medications for safety risks.
Based on continuing clinical trials, agreed post-approval studies by both companies, and a submission to the FDA of adverse event reports, the FDA has concluded that the long term safety of both Nplate and Promacta can be evaluated.
The FDA can demand REMS for certain drugs or biological products to ensure that their benefits outweigh the risks. REMS can include various elements, for example, a medication guide advising patients about important safety information for a drug, or a communication plan to notify health care providers of serious risks linked to a particular drug, as well as demanding that all health professionals who prescribe and dispense these drugs are specially certified.
Major changes to the REMS for Nplate and PromactaUnlike previously, healthcare professionals, including hospitals, specialty care facilities, as well as 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 prescribe, dispense or receive these products.
Furthermore, healthcare professionals no longer need to complete periodic safety forms for patients receiving Nplate or Promacta.
Pharmacies and pharmacists also no longer need to enroll in the Promacta CARES Program, or verify prescriber and patient enrollment prior to Promacta dispensing.
According to the FDA, the modified REMS programs will include a communication plan, informing health care professionals regarding the REMS changes and safety risks relating to each product.
Patients and healthcare professionals should also be aware that the product labels' warnings and precaution sections have been updated to indicate the current understanding of the drugs' safety, and that healthcare professionals should continue to refer to the drug prescribing information for the latest recommendations on prescribing Nplate and Promacta and report adverse events for both products to the FDA MedWatch program. Patients should also read the accompanying Medication Guide of their Nplate or Promacta prescription and contact their healthcare professional if they have any questions or concerns.
Janet Woodcock, M.D., director of FDA's Center for Drug Evaluation and Research stated:
"REMS continue to be vital tools for the agency to employ as we work with companies to address the serious risks associated with drugs and monitor their appropriate and safe use in various health care settings. The agency remains committed to exercising a flexible and responsible regulatory approach that ensures REMS programs are being effectively and efficiently used and not resulting in an unnecessary burden on health care professionals and patients."
Both Nplate and Promacta were approved in 2008 for the treatment in adult patients suffering from chronic immune thrombocytopenia (ITP), who were unresponsive to corticosteroids, immunoglobulins, or to splenectomy (removal of the spleen). ITP, a rare blood disorder that results in a low number of platelets, i.e. blood components that help with clotting, can lead to serious bleeding. Both drugs are designed to stimulate bone marrow to produce the required platelets.
Given that the experience of both drugs was limited at the time of approval, concerns regarding their safety led to the decision for a REMS requirement, which included restricted distribution requirements for each drug in order to ensure that their benefits outweighed their risks. The restricted distribution requirements meant that health care professionals including pharmacies, hospitals, specialty care facilities and patients were required to enroll in a special access program to prescribe, dispense or receive the drugs.
The FDA has continuously monitored specific safety risks related to Nplate and Promacta since the drugs' have been approved. They have monitored various factors, such as higher risk for blood clots, bone marrow changes of collagen deposition (reticulin), increased risk of developing other blood-related cancers (hematological malignancies) resulting from the stimulation of bone marrow cells, the risk of bleeding shortly after drug discontinuation and worsening of low blood platelet count.
Adverse events noted in patients treated with Nplate include: dizziness, headaches, problems in falling or staying asleep (insomnia), pain in the shoulder, joints (arthralgia) and muscle (myalgia), stomach or abdominal pain, dyspepsia (upset stomach), and paresthesia, which is tingling or numbness in the skin.
The following adverse events have been linked to Promacta: nausea, vomiting, diarrhea, rash, flu (influenza), upper respiratory tract infection, sore throat (pharyngitis), back pain, and tingling or numbness in the skin (paresthesia). Promacta could also potentially cause liver injury.
Nplate is manufactured by Amgen, Inc. of Thousand Oaks, Calif.
Promacta is manufactured by Philadelphia-based GlaxoSmithKline.
Written by Petra Rattue