FDA approves final ER/LA opioid analgesic REMS

Pharmacists to dispense one-page MedGuides

FDA announced its approval of a final Risk Evaluation and Mitigation Strategy (REMS) for extended-release and long-acting opioids (ER/LA opioid analgesic REMS) on July 9.

Affecting nearly 20 companies and more than 30 brand-name and generic products (see Table 1), the class-wide REMS includes voluntary prescriber continuing education for which financial support by manufacturers is mandatory, a patient education document for prescribers to go over with the patient, a one-page Medication Guide (MedGuide) for pharmacists to dispense with the medication, and knowledge assessment and independent third-party audits of the continuing education content.

While it is not clear when the new, printed MedGuides will be distributed to pharmacies, the new MedGuide for each product is available at www.fda.gov/drugs/drugsafety/ucm085729.htm. The prescriber continuing education programs are expected to be up and running by March 1, 2013.

“FDA’s goal with this REMS approval is to ensure that health care professionals have the educational information they need to safely prescribe opioids and patients have the know-how to safely use these drugs,” FDA Commissioner Margaret Hamburg, MD, told reporters in a teleconference that day. She added that FDA had developed the REMS with input from stakeholders including pharmacists.

“The opioid REMS discussion has served as a valuable vehicle for APhA to discuss with FDA, manufacturers, and other stakeholders the need to improve and standardize REMS programs to make them less burdensome on pharmacists and more effective for patients,” said Marcie Bough, PharmD, APhA Senior Director of Government Affairs.

These new, one-page MedGuides are simplified and consumer friendly, serving as a starting point for FDA’s work to improve all MedGuides, Bough added.

Big picture

The components to be included in the ER/LA opioid analgesic REMS program were announced in April 2011 as part of the Obama administration’s plan to reduce prescription drug abuse, a coordinated effort involving the White House Office of National Drug Control Policy (ONDCP), the U.S. Department of Health & Human Services, FDA, and DEA that focuses on four areas: education (the REMS), monitoring, proper medication disposal, and enforcement.

“The problem of prescription drug abuse and misuse is very real,” Hamburg said. “Nevertheless, patients in pain must have continued and appropriate access to these medications.”

The finalized REMS program was years in the making. FDA first notified manufacturers of ER/LA opioids that their products would require a REMS in February 2009. In July 2010, two FDA advisory committees voted not to recommend the then-proposed class-wide REMS. Members of the committees wanted training for prescribers to be mandatory, rather than voluntary, as FDA had proposed.

Voluntary prescriber training is an important step, “but we can’t stop there,” Gil Kerlikowske, MA, ONDCP Director, said during the teleconference. He cited several pending pieces of legislation and the support of the administration for mandatory training.

“We are still working with Congress to explore a way of mandating training as part of DEA registration,” Hamburg said.

In the meantime, FDA hopes to see at least 60% of the nation’s 320,000 prescribers of ER/LA opioids having completed the voluntary training within 3 years. A list of all REMS-compliant training activities by accredited continuing education providers—supported by independent grants from the REMS Program Committee of manufacturers—will be posted at www.ER-LA-opioidREMS.com when available.

Role of pharmacists

Along with dispensing the MedGuide, pharmacists may be interested in using the prescribers’ patient counseling document with the MedGuide when talking with patients and participating in continuing education programming, Bough said.

“While the REMS specifically calls out prescribers, pharmacists are in an excellent position to work alongside the prescribing community in efforts to mitigate risk and ensure patients have access to medication,” said Peter VanPelt, BSPharm, APhA Associate Director of Corporate Alliances.

“There are plenty of opportunities for APhA to continue its role in sharing REMS updates, communications, and education with the broader pharmacy audience,” VanPelt continued. “APhA will continue efforts to educate pharmacists in … pain management as well as abuse, misuse, and diversion.”

Resources on ER/LA opioid analgesic REMS are available at www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm163647.htm, including a set of questions and answers, the FDA blueprint containing the core messages for prescriber training, a news release, a consumer update, the REMS, the MedGuide template, and the MedGuides, as well as approval letters for the brand-name products and background and historical information on the class-wide REMS.

For additional resources on REMS, APhA’s 2009 and 2011 REMS white papers are available at www.japha.org.

Table 1. Extended-release and long-acting opioid products with required opioid REMS

Generic drugs

Brand-name products (manufacturer)

Generic alternatives and manufacturers

Morphine sulfate extended-release capsules

Avinza (Pfizer)


Buprenorphine transdermal system

Butrans (Purdue Pharma)


Methadone hydrochloride tablets and liquid alternatives

Dolophine (Roxane)

Liquid concentrate (Roxane); tablets (Pharmanetwork, Mallinckrodt, Sandoz); oral solution (Roxane, Vistapharm)

Fentanyl transdermal system

Duragesic (Janssen Pharmaceuticals)

Actavis, Lavipharm Labs, Mallincrkodt, Mylan Technologies, Noven, Aveva, Watson

Morphine sulfate and naltrexone extended-release capsules

Embeda (Pfizer)a


Hydromorphone hydrochloride extended-release capsules

Exalgo (Mallinckrodt)


Morphine sulfate extended-release capsules

Kadian (Actavis)

Capsules (Watson); tablets (Endo, Mallinckrodt, Mylan, Nesher, Ranbaxy, Rhodes, Watson Labs)

Morphine sulfate controlled-release tablets

MS Contin (Purdue Pharma)


Tapentadol extended-release oral tablets

Nucynta ER (Janssen Pharmaceuticals)


Oxymorphone hydrochloride extended-release tablets

Opana ER (Endo Pharmaceuticals)

Impax, Actavis

Oxycodone hydrochloride controlled-release tablets

OxyContin (Purdue Pharma)


Hydromorphone hydrochloride extended-release capsules

Palladone (Purdue Pharma)b


a Not currently available or marketed due to a voluntary recall, but still approved

b No longer marketed, but still approved

Source: FDA. List of extended-release and long-acting opioid products required to have an opioid REMS. Accessed at www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm251735.htm, July 17, 2012.