On July 9, 2012, the FDA announced the approval of a REMS for extended release (ER) and long-acting (LA) opioids. As Dr. Hamburg, the FDA commissioner, indicated: “The FDA’s goal with this REMS approval is to ensure that healthcare professionals are educated on how to safely prescribe opioids and that patients know how to safely use these drugs.” The REMS contains a prominent patient education component, consisting primarily of a patient counseling document (PCD) and standardized medication guide. The question arises whether this provides adequate information for patients about ER and LA opioids.


Since the Food and Drug Administration Amendments Act of 2007, the FDA has had the authority to require drug manufacturers to develop REMS as a means to ensure that the risks of a drug do not outweigh its benefits. There are currently 74 FDA-approved REMS: 70 for individual drugs and four for drug classes. The recently approved ER/LA opioids REMS is a class-wide REMS. It was developed because of increasing prescription opioid abuse, misuse, and inappropriate prescribing in the United States. It applies to all FDA-approved ER and LA opioids: 35 drugs at present.

Although the ER/LA opioids REMS encourages prescribers to consider other publicly-available educational material, its patient education component centers around the PCD and standardized medication guide. Both documents are one page in length and contain similar information. The PCD is identical for all ER/LA opioids, although it contains a blank area where prescribers can add comments/instructions. The FDA strongly encourages it to be discussed with and given to patients whenever ER/LA opioids are prescribed. The standardized medication guide is a template, which is minimally modified for each drug. The 1998 Prescription Drug Product Labeling: Medication Guide Requirements Final Rule gives the FDA the authority to require pharmacies to give patients a medication guide each time they dispense certain drugs, such as opioids.


Does the ER/LA opioids REMS provide adequate information for patients?


The ER/LA opioids REMS provides adequate information for patients if the PCD and standardized medication guide fulfill the following criteria:

1. they contain information about all important risks of the drugs

2. they are read by every patient receiving the drug


The PCD and standardized medication guide contain information about all important drug risks

Potential Risks: Addiction, Overdose, Interactions


Neither the PCD nor medication guide mentions the risk of addiction, which is an important risk of all opioids. A 2007 study reported that up to 50% of patients with chronic non-malignant pain displayed evidence of opioid addiction. The FDA clearly recognizes the risk of addiction, as the Full Prescribing Information for all ER/LA opioids includes a boxed warning that patients should be monitored for signs of addiction (eg, OxyContin, Duragesic). Likewise, the Patient Counseling section of the OxyContin Package Insert specifically states that “there is a risk of abuse or addiction with narcotic painkillers.”


The PCD does not warn against cutting the drug, which is especially important for transdermal fentanyl and buprenorphine. Cutting these patches destroys the controlled-release delivery system and leads to the risk of overdose due to excessive drug release. Although the prescriber can add this to the PCD’s blank area, it is unlikely that this will always happen.


The PCD and medication guide also do not warn against combining ER/LA opioids with other drugs that can cause sedation. Although these documents mention avoiding alcohol, sedating drugs can also interact with opioids to increase the risk of serious side effects, including depressed breathing, excessive sedation, coma, or death. The importance of this risk is exemplified by the statement in the Full Prescribing Information of many, if not all, ER/LA opioids to “instruct patients not to use … other CNS depressants (eg. sleep medications, tranquilizers) while using” the drug (eg, OxyContin, Duragesic). Thus, the PCD and standardized medication guide omit important information regarding risks of these drugs.

The PCD and standardized medication guide are read by every patient receiving the drugs


Although the ER/LA opioids REMS specifies that a PCD and standardized medication guide should be given to patients receiving the drugs, this may not always occur. No regulations mandate that patients be given PCDs, so it is likely that there will be instances when they do not receive one. The PCD is not attached to the prescription form, so distributing it requires an additional action by the prescriber (obtaining the PCD), which increases the possibility that this will not happen. Although pharmacies are required to provide patients with a standardized medication guide each time they fill a prescription, this is difficult to enforce. A 2008 continuing education program from the University of Florida indicated that “pharmacist compliance with providing medication guides to patients may be very low.” A 2007 study of 24 pharmacies reported that zero of 85 ibuprofen prescriptions included medication guides with the dispensed drugs. The same year, an unpublished investigation reported that only one of 20 pharmacies provided medication guides when dispensing celecoxib. The situation has hopefully improved in recent years, but without aggressive enforcement of regulations, it is unlikely that patients always receive medication guides.


Even if patients receive a PCD and medication guide, they will not necessarily read them. No regulations require patients to do this, so reading depends, amongst other things, on whether patients think the documents are important. Studies of other medication guides (many of which are several pages) indicate that they are not commonly read by patients. A 2006 study found that only 23% of 251 patients reported ever looking at medication guides or other information provided with their medications. Limiting the PCD and standardized medication guide to one page will hopefully encourage patients to read them, yet it is unlikely that they will be read by all patients until they are convinced of the documents’ importance.


The ER/LA opioids REMS does not provide adequate information for patients because the PCD and standardized medication guide do not contain information about all important risks of the drugs and because it is unlikely that they are read by every patient receiving these drugs.

For more information on this issue, contact the Kulkarni Law Firm.