Drug Information Center

What are the medication guide distribution requirements as part of REMS?

Guidance from the Food and Drug Administration

Introduction

In 2007, the Food and Drug Amendments Act (FDAAA) was passed which granted the Food and Drug Administration (FDA) the authority to require postmarketing studies or clinical trials for medications as they deem necessary.¹ The Risk Evaluation and Mitigation Strategies (REMS) was created by the FDA to serve as a postmarketing surveillance process that ensures medication safety. The goal is to guarantee that the benefits of a medication outweigh the risks. Components of REMS include one or more of the following: prescriber, pharmacy, and/or dispensing requirements, quantity limits, monitoring requirements, documentation, and medication guides. The REMS requirements are specific for each medication. Although medication guides may be developed separately for some medications, they are the most common component of REMS.² Over 150 medication guides have been FDA-approved between March 2008 and January 2011 and of them, 108 guides are REMS requirements.^2,3

Additional requirements of REMS include:⁴

• All direct-to-consumer advertisements contain information on reporting negative side effects to the FDA
• All drug labeling provide a toll-free telephone number for consumers to report adverse events
• The FDA must have a searchable website for safety information
• Information about newly approved products be posted on the FDA website
• Establishment of an FDA Advisory Committee on Risk Communication to conduct bi-weekly screenings of the Adverse Event Reporting System

Since the establishment of REMS, several questions have arose regarding the distribution of medication guides in various settings, such as inpatient and outpatient clinics, when a drug is dispensed by a healthcare professional.² In a hospital or nursing home setting, medications are dispensed by a pharmacist and administered by a healthcare professional.³ In an outpatient setting, such as a clinic or infusion center, medications are administered by healthcare professionals, with or without the involvement of a dispensing pharmacist. In both cases, a patient may receive a drug several times a day or week. To address these concerns, in November 2011, the FDA published guidance for medication guide distribution requirements under REMS. Below is a summary of the recommendations.

Guidance summary

The guidance, which contains nonbinding recommendations, provides information for industry, healthcare providers, and authorized dispensers of prescription medications.³ Two main topics are addressed in the guidance: when a medication guide must be provided to a patient when the medication is dispensed by a healthcare provider and when a medication guide is required under REMS.

Medication guides are not required in the inpatient setting unless requested by the patient or his or her caregiver.^2,3 When drugs are administered by a healthcare professional in the outpatient setting (e.g., clinic, dialysis unit, or infusion center) medication guides should only be provided under the following circumstances: 1) at the time of first administration; 2) the first time a medication is administered after a medication guide changes; 3) if requested by the patient; or 4) if a patient must be enrolled in a REMS program. However, patient instructions must be provided by the healthcare provider addressing the appropriate use of the medication, potential adverse effects, and follow-up, if needed.³ Table 1 provides specific recommendations for medication guide provision for various settings.

Table 1: Medication Guide Enforcement Discretion Policy Setting.³

Setting	Patient or patient's agent requests medication guide	Medication guide provided each time drug dispensed	Medication guide provided at time of first dispensing	Medication guide provided when medication guide materially changed	Drug is subject to an ETASU REMS that includes specific requirements for providing and reviewing a medication guide
Inpatient	Must provide medication guide	FDA intends to exercise enforcement discretion; medication guide need not be provided	FDA intends to exercise enforcement discretion; medication guide need not be provided	FDA intends to exercise enforcement discretion; medication guide need not be provided	Must provide medication guide as specified in REMS
Outpatient when drug dispensed to healthcare professional for administration to patient (e.g., clinic, infusion center, emergency department, outpatient surgery)	Must provide medication guide	FDA intends to exercise enforcement discretion; medication guide need not be provided	Must provide medication guide	Must provide medication guide	Must provide medication guide as specified in REMS
Outpatient when drug dispensed directly to patient or caregiver (e.g., retail pharmacy, hospital ambulatory pharmacy, patient samples)	Must provide medication guide	Must provide medication guide	Must provide medication guide	Must provide medication guide	Must provide medication guide as specified in REMS

ETASU=Elements to Assure Safe Use; FDA=Food and Drug Administration; REMS=Risk Evaluation Mitigation Strategy.

As previously stated, not all medication guides are part of REMS.³ The FDA will continue to evaluate medications and as risks associated with the use of a medication increase, the FDA may determine that a medication guide be required under REMS to ensure safe use and that the benefits of the drug outweigh the risks.

Conclusion

The guidance published on the distribution of medication guides required as part of a REMS represents the FDA's current stance on the topic. The guidance will not be legally enforced by the FDA and should be viewed as recommendations unless specific regulatory requirements are cited. Healthcare providers may use alternative approaches to implement the guidance. It is recommended that these be discussed with the Agency by contacting the FDA at 800-835-4709.

References

1. American Society of Health-Systems Pharmacists. REMS resource center. http://www.ashp.org/menu/PracticePolicy/ResourceCenters/REMS.aspx . Accessed December 21, 2011.

2. Goldman SA, Hoffman JM, Monroe CD, Stubbings J. Clinical considerations of Risk Evaluation and Mitigation Strategies in Health Care Systems. American Society of Health-Systems Pharmacists Advantage e-Newsletter. American Society of Health-Systems Pharmacists Website. http://www.remsupdates.org/docs/rems_e-newsletter_8-2011.pdf. August 2011. Accessed December 21, 2011.

3. Guidance medication guides - distribution requirements and inclusion in Risk Evaluation and Mitigation Strategies (REMS). Food and Drug Administration Website. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/ Guidances/UCM244570.pdf . November 2011. Accessed December 21, 2011.

4. Kishore R, Tabor E. Overview of the FDA Amendments Act of 2007: its effect on the drug development landscape. Drug Information Journal. 2010;44(4):469-475.