In 2007, the Food and Drug Administration (FDA) was granted the authority to require pharmaceutical manufacturers to develop risk evaluation and mitigation strategies (REMS), if deemed necessary. This was made possible by the FDA Amendment Act, which also authorized the FDA to declare a medication product as misbranded and to forbid the utilization of interstate commerce for that product, as well as to financially penalize manufactures of REMS-issued medications if they do not comply with the requirements. REMS are intended as a way to mitigate potentially serious risks associated with certain pharmaceuticals and to maximize the benefit of these high-risk medications. A number of different elements can be employed to achieve the risk mitigation that is intended with medication-specific REMS, which include a medication guide, a communication plan and/or Elements to Assure Safe Use (ETASU).
• A medication guide is patient-directed educational material with a goal of increasing awareness on the safe use of the pharmaceutical product. Reasons why medication guides would be required include if access to this educational information has the potential to influence factors including serious medication adverse events, the patient’s decision to use the pharmaceutical product and patient compliance. A medication guide must be given to the patient each time the drug is dispensed, including refills.
• A communication plan is another element of REMS and is a means of providing education on the safe and appropriate use of pharmaceutical products to health care providers. A communication plan is implemented by the manufacturer and involves contacting healthcare providers or professional societies, usually via letters, to encourage compliance with the REMS elements.
• An ETASU may be required as parts of REMS if the FDA determines the other elements are incapable of guaranteeing the safe use of the medication. An ETASU may involve attainment of special certification of prescribers and pharmacies that are involved with the dispensing of these pharmaceutical products, or may restrict the use of these medications only to patients who are enrolled in registries, receive treatment in specific settings or with documentation of certain safety requirements.
In transplantation, the costimulation inhibitor, belatacept (Nulojix®), has required a medication guide and a communication plan for its REMS since June 2011. In September 2012, the mycophenolic acid derivatives (mycophenolate mofetil [CellCept®] and its generic products and enteric-coated mycophenolic acid [Myfortic®]), which are T-cell proliferation inhibitors, were issued a REMS requirement that included a medication guide and an ETASU. In general nephrology, there are REMS in place for the erythropoietin-stimulating agents (i.e. epoietin alfa [Epogen® and Procrit®], darbepoietin [Aranesp®] and peginesatide [Omentys®]). The REMS epoietin alfa products and darbepoietin each contain a medication guide, communication plan and ETASU. However, the ETASU is meant only for those patients using one of these agents for anemia associated with malignancy. The peginesatide REMS only contains a communication plan. It is vital for nephrologists to realize that there may be other medications that prescribe on a routine basis in your practice that contain a REMS, besides the ones listed above.
It is important to keep in mind that the overall goal of REMS is to increase patient safety in regards to the use of high-risk pharmaceutical products. The FDA tries to limit the burden that REMS puts on health care providers and patients. However, a result of REMS may be the decreased utilization of specific high-risk medications to avoid the REMS requirements. This is an unfortunate and unintended consequence of a program that was created to increase the safe and effective use of medications. The usage patterns of medications the FDA has determined require a medication guide, communication plan, or ETASU, should not be altered to avoid the extra work associated with these elements of REMS.
Steven Gabardi PharmD, FCCP, BCPS, Organ Transplant Clinical Specialist