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Risk Evaluation and Mitigation Strategies
Risk Evaluation and Mitigation Strategies When I was a pharmacy student, our pharmacology professor told our class, “All drugs are poisons!” I suppose literally this is true, but we also learned about the relative toxicities of various drugs and the concept of LD50, the dose of a drug that can kill 50% of a study population. We certainly do not want to do that with the medicines that we prescribe! When the Food and Drug Administration (FDA) reviews a new drug application, it must make a decision about both the safety and efficacy of that drug before approving it for clinical use. There is a delicate balance between the speed with which a drug is approved and the amount of testing that is needed to demonstrate safety. Unfortunately, many serious adverse events associated with a drug are relatively rare and not often revealed in clinical trials. One answer to this dilemma is to strengthen the monitoring of drugs after they are approved and are more widely used in clinical practice and real world settings. This process is called postmarketing surveillance and requires manufacturers to report adverse reactions to their products after approval and encourages practitioners to do likewise through the FDA MedWatch program.1 If a drug is found to be associated with serious adverse reactions, the FDA can
withdraw it from the market, require label changes alerting clinicians of these events, or determine that a risk evaluation and mitigation strategy (REMS) is necessary beyond changes in labeling. REMS may contain any of the following elements:2 • Medication guide—This document written for patients highlights the important safety information about the drug. Medication guides are given to the patient by the pharmacist when a prescription for the drug is filled.
PRESCRIPTION PAD Philip J. Schneider, MS • Communication plan—This plan to educate health care professionals about the safe and appropriate use of the drug includes tools and materials that are distributed to health care professionals.
Table 1. Selected List of Approved Individual REMS Drug name
Date REMS Approved
REMS Components
Advair (fluticaasone proprionate and salmeterol xinofoate inhalation powder)
4/30/2008; modified 1/4/2011, 5/10/2011, 6/27/2012
Communication plan
Advair HFA® (fluticasone proprionate and salmeterol xinofoate inhalation powder)
7/31/2008; modified 9/15/2011, 1/4/2011, 5/10/2011, 6/27/2011
Communication plan
7/1/2011
Communication plan
Avandamet® (rosiglitazone maleate and metformin hydrochloride)
12/2/2008; modified 5/18/2011, 11/13/2011, 5/30/2012
Medication guide, elements to ensure safe use, implementation system
Avandaryl (rosiglitazone maleate and glimepiride) tablets
12/2/2008; modified 5/18/2011, 11/13/2011, 5/30/2012
Medication guide, elements to assure safe use, implementation system
Avandia® (rosiglitazone maleate) tablets
5/18/; modified 11/13/2011, 5/30/2012
Medication guide, elements to assure safe use, implementation system
7/20/2012
Medication guide, communication plan
10/19/2009; modified 4/22/2010, 7/22/2011
Medication guide
Diskus®
Arcapta Neohaler® (indacaterol maleate inhalation powder
BrilintaR (ticagrelor) tablets Chantix®
(varenicline) tablets
www.npjournal.org
The Journal for Nurse Practitioners - JNP
747
JNP Table 1. Selected List of Approved Individual REMS (continued) Drug name
Date REMS Approved
REMS Components
Foradil® (formoterol fumerate) inhalation powder
5/18/2011
Communication plan
Lotronex® (alosetron hydrochloride) tablets
9/2/2010
Medication guide, elements to assure safe use, implementation system
Nucynta ER® (tapentadol) extended release tablets
8/25/2011
Medication guide, elements to assure safe use
Opana ER® (oxymorphone hydrochloride) extended release tablets
12/9/2009
Medication guide, elements to assure safe use, implementation system
Oxycontin® (oxycodone hydrochloride) extended release tablets
4/5/2010; modified 6/29/2010, 11/15/2010
Medication guide, elements to assure safe use
Sabril (vigabatrin) tablets and oral solution
8/21/2009; modified 1/18/2011
Medication guide, elements to assure safe use, implementation system
Serevent Diskus® (salmeterol xinafoate) inhalation powder
11/18/2010; modified 5/10/2011, 6/27/2011
Communication plan
Symbicort® (budesonide and formoterol) inhalation aerosol
2/27/2009; modified 2/16/2011, 8/18/2011
Communication plan
Wellbutrin® (bupropion hydrochloride), including SR (sustained release) and XL (extended release) tablets
2/26/2010
Medication guide
Zyban® (bupropion hydrochloride) sustained release tablets
2/26/2010
Medication guide
• Elements to Assure Safe Use (EASU)—This system of strict control includes requirements to enforce the safe and appropriate use of a drug. Some examples of EASUs include a certification requirement for prescribers, a central registry for patients receiving the drug, and a requirement to dispense the drug through specialty pharmacies. • Implementation plan—This document specifies how the EASU will be executed. • Timetable for submission of assessments— This plan requires manufacturers to assess the performance of their REMS program 18 months after implementation and at 3- and 7year intervals. Based on the results, the REMS program may be modified. There are now 86 approved individual REMSs.3 Table 1 lists the drugs commonly prescribed in a primary care practice. Readers are referred to the FDA website for a complete listing of drugs for which there are REMS requirements and specific REMS components for each.
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The Journal for Nurse Practitioners - JNP
Prescribers should be mindful of patient safety considerations with any drug that is prescribed, particularly those with an REMS program, and follow the requirement specified for that particular drug. References 1. Food and Drug Administration. MedWatch: The FDA Safety Information and Adverse Event Reporting Program. http://www.fda.gov/Safety/MedWatch/default.htm. Accessed June 26, 2012. 2. Paragon Rx. Risk evaluation and mitigation strategies (REMS)—a brief history. http://www.paragonrx.com/rems-hub/rems-history. Accessed June 26, 2012. 3. US Food and Drug Administration. Approved Risk Evaluation and Mitigation Strategies (REMS). http://www.fda.gov/Drugs/DrugSafety/ PostmarketDrugSafetyInformationforPatientsandProviders/ucm11135 0.htm. Accessed June 26, 2012.
Philip J. Schneider, MS, FASHP, FFIP, is professor and associate dean of the College of Pharmacy at the University of Arizona in Phoenix. He can be reached at [email protected]. 1555-4155/$ see front matter © 2012 American College of Nurse Practitioners http://dx.doi.org/10.1016/j.nurpra.2012.06.011
Volume 8, Issue 9, October 2012
withdraw it from the market, require label changes alerting clinicians of these events, or determine that a risk evaluation and mitigation strategy (REMS) is necessary beyond changes in labeling. REMS may contain any of the following elements:2 • Medication guide—This document written for patients highlights the important safety information about the drug. Medication guides are given to the patient by the pharmacist when a prescription for the drug is filled.
PRESCRIPTION PAD Philip J. Schneider, MS • Communication plan—This plan to educate health care professionals about the safe and appropriate use of the drug includes tools and materials that are distributed to health care professionals.
Table 1. Selected List of Approved Individual REMS Drug name
Date REMS Approved
REMS Components
Advair (fluticaasone proprionate and salmeterol xinofoate inhalation powder)
4/30/2008; modified 1/4/2011, 5/10/2011, 6/27/2012
Communication plan
Advair HFA® (fluticasone proprionate and salmeterol xinofoate inhalation powder)
7/31/2008; modified 9/15/2011, 1/4/2011, 5/10/2011, 6/27/2011
Communication plan
7/1/2011
Communication plan
Avandamet® (rosiglitazone maleate and metformin hydrochloride)
12/2/2008; modified 5/18/2011, 11/13/2011, 5/30/2012
Medication guide, elements to ensure safe use, implementation system
Avandaryl (rosiglitazone maleate and glimepiride) tablets
12/2/2008; modified 5/18/2011, 11/13/2011, 5/30/2012
Medication guide, elements to assure safe use, implementation system
Avandia® (rosiglitazone maleate) tablets
5/18/; modified 11/13/2011, 5/30/2012
Medication guide, elements to assure safe use, implementation system
7/20/2012
Medication guide, communication plan
10/19/2009; modified 4/22/2010, 7/22/2011
Medication guide
Diskus®
Arcapta Neohaler® (indacaterol maleate inhalation powder
BrilintaR (ticagrelor) tablets Chantix®
(varenicline) tablets
www.npjournal.org
The Journal for Nurse Practitioners - JNP
747
JNP Table 1. Selected List of Approved Individual REMS (continued) Drug name
Date REMS Approved
REMS Components
Foradil® (formoterol fumerate) inhalation powder
5/18/2011
Communication plan
Lotronex® (alosetron hydrochloride) tablets
9/2/2010
Medication guide, elements to assure safe use, implementation system
Nucynta ER® (tapentadol) extended release tablets
8/25/2011
Medication guide, elements to assure safe use
Opana ER® (oxymorphone hydrochloride) extended release tablets
12/9/2009
Medication guide, elements to assure safe use, implementation system
Oxycontin® (oxycodone hydrochloride) extended release tablets
4/5/2010; modified 6/29/2010, 11/15/2010
Medication guide, elements to assure safe use
Sabril (vigabatrin) tablets and oral solution
8/21/2009; modified 1/18/2011
Medication guide, elements to assure safe use, implementation system
Serevent Diskus® (salmeterol xinafoate) inhalation powder
11/18/2010; modified 5/10/2011, 6/27/2011
Communication plan
Symbicort® (budesonide and formoterol) inhalation aerosol
2/27/2009; modified 2/16/2011, 8/18/2011
Communication plan
Wellbutrin® (bupropion hydrochloride), including SR (sustained release) and XL (extended release) tablets
2/26/2010
Medication guide
Zyban® (bupropion hydrochloride) sustained release tablets
2/26/2010
Medication guide
• Elements to Assure Safe Use (EASU)—This system of strict control includes requirements to enforce the safe and appropriate use of a drug. Some examples of EASUs include a certification requirement for prescribers, a central registry for patients receiving the drug, and a requirement to dispense the drug through specialty pharmacies. • Implementation plan—This document specifies how the EASU will be executed. • Timetable for submission of assessments— This plan requires manufacturers to assess the performance of their REMS program 18 months after implementation and at 3- and 7year intervals. Based on the results, the REMS program may be modified. There are now 86 approved individual REMSs.3 Table 1 lists the drugs commonly prescribed in a primary care practice. Readers are referred to the FDA website for a complete listing of drugs for which there are REMS requirements and specific REMS components for each.
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The Journal for Nurse Practitioners - JNP
Prescribers should be mindful of patient safety considerations with any drug that is prescribed, particularly those with an REMS program, and follow the requirement specified for that particular drug. References 1. Food and Drug Administration. MedWatch: The FDA Safety Information and Adverse Event Reporting Program. http://www.fda.gov/Safety/MedWatch/default.htm. Accessed June 26, 2012. 2. Paragon Rx. Risk evaluation and mitigation strategies (REMS)—a brief history. http://www.paragonrx.com/rems-hub/rems-history. Accessed June 26, 2012. 3. US Food and Drug Administration. Approved Risk Evaluation and Mitigation Strategies (REMS). http://www.fda.gov/Drugs/DrugSafety/ PostmarketDrugSafetyInformationforPatientsandProviders/ucm11135 0.htm. Accessed June 26, 2012.
Philip J. Schneider, MS, FASHP, FFIP, is professor and associate dean of the College of Pharmacy at the University of Arizona in Phoenix. He can be reached at [email protected]. 1555-4155/$ see front matter © 2012 American College of Nurse Practitioners http://dx.doi.org/10.1016/j.nurpra.2012.06.011
Volume 8, Issue 9, October 2012