University of Massachusetts-Amherst School of Public Health and Health Sciences associate professor of health policy and management Dr. Rosa Rodriguez-Monguio, with co-authors Dr. Enrique Seoane-Vazquez of the Massachusetts College of Pharmacy and Health Sciences and Dr. Richard Hansen of Auburn University, are raising safety concerns regarding the interchangeability, effectiveness, and safety of modified release opioid prescription drugs. Modified release drugs, which may provide clinical advantages compared to immediate-release forms and improve convenience to the patient and health outcomes, also raise concerns on lack of bioequivalence, reduced efficacy, and increased incidence of adverse events.
[Photo: Dr. Rosa Rodriguez-Monguio]
In a recent study titled “Interchangeability and safety of modified release formulation drugs in the US: The case of opioids and other nervous system drugs,” the authors assessed market trends and characteristics of all modified release forms approved by the United States Food and Drug Administration (FDA), safety concerns and FDA regulatory actions related with generic modified release products, their respective brand name drugs and generic drugs with different formulation design characteristics. They report their results in the journal Clinical Drug Investigation.
Modified release drugs, including extended, delayed and fast release formulations, may improve convenience and facilitate the administration of drugs. Conversely, modified release forms may increase drug toxicity associated with dose dumping and difficulty to stop the release once the drug is administered to the patient.
The number of FDA approved modified release drugs has increased significantly since 1980. Modified release forms represent an important part of the drugs approved by the FDA; over one in eight active ingredients and fixed-dose combinations approved by the FDA have at least one modified release form. Medicare Part D expenditures on modified released drugs amounted $16.0 billion (17% of total pharmaceutical expenditures) in 2013. Several modified release drugs were ranked in the top 10 drugs in the Medicare Part D program that year.
The FDA recommends the use of extended-release opioid formulations only for patients for whom alternative treatment options are ineffective, not tolerated, or inadequate to provide effective pain management. In 2012, the FDA identified safety problems related to the use of extended release formulations of opioid prescription drugs and required a risk evaluation and mitigation strategy (REMS) to ensure that the benefits of extended release opioids outweigh its risks associated with overdose and abuse.
Dr. Rodriguez-Monguio stated that misuse and abuse of opioid prescription drugs is a major public health concern potentially leading to overdoses and deaths. These problems may be even more prevalent in the case of modified release opioid formulations. Safety problems with modified release formulations occur when patients take more than the prescribed dose of an opioid believing that the release of the drug is immediate and not experiencing the appropriate effect. Patients may also cut, break, chew, crush, or dissolve the dose form causing rapid release and absorption of a potentially lethal dose intended to be released over an extended period of time.
Post-marketing studies are needed to evaluate usage and substitution patterns, safety and clinical outcomes of generic modified release products compared to their respective reference products and other therapeutic equivalent generic drugs with different formulation design characteristics. Opioid abuse and dependence is a prevalent and persistent public health problem in the U.S. Yet, little is known about opioid prescription and utilization patterns.