Recent developments toward the safer use of opioids, with a focus on hydrocodone

Summary

Opioids have become a mainstay of treatment for pain in the United States, with over 250 million prescription issued in 2012 alone. The increased prescribing of these medications has also contributed to the unintended consequence of a widening prevalence of abuse and misuse, and therefore safety has become a top agenda item for both government and health care providers alike. The move toward new abuse-deterrent formulation technologies, enhanced regulatory requirements from the Food and Drug Administration (FDA) and Drug Enforcement Administration (DEA), and developments in national/state policies have worked together to target a goal of promoting safer clinician prescribing, pharmacy dispensing and patient use of opioids. Hydrocodone in particular, as the most widely prescribed opioid product, has recently been subject to a myriad of changes, both through the federal rescheduling of hydrocodone-combination products (HCPs) to Schedule II, as well as the introduction of two new extended-release formulations to the USA market. These efforts represent a first step toward tackling the opioid harms epidemic, although continuing follow-up through research and policy implementation is needed to see any measureable impact on safety in the future.

Introduction

Chronic pain has been estimated to affect approximately 100 million Americans with an annual national economic cost of $560–635 billion, equating to nearly $2000 for each person living in the United States (USA).¹ As anticipated, pain is one of the most common issues encountered in clinical care, reported by 20–50% of primary care encounters.2, 3 The use of opioid analgesics, a mainstay of pain treatment, has increased dramatically in recent years. In the USA, the rates of opioid prescribing nearly doubled among pain visits during 2000–2010 from 11.3% to 19.6% in one national analysis, without accompanying increases in non-opioid analgesics or the proportion of patients receiving pharmacologic treatment.⁴ Deaths associated with prescription analgesic overdoses have also increased over three-fold from 1998 to 2008, and nearly 500,000 emergency visits to hospitals in 2009 alone were associated with abuse/misuse of prescription analgesics.⁵

Hydrocodone in particular has been touted as a primary driver behind opioid-related abuse and misuse due to its widespread availability and use. Since the approval of the first product in 1943, hydrocodone has gained increasing popularity as a ‘middle-level’ opioid. In 2012, over 135 million prescriptions were issued for hydrocodone/acetaminophen products (e.g. Vicodin^®, Lortab^®), making it the most widely dispensed prescription medication in the USA market, at nearly 25% and 50% higher volume than next top-ranked medications levothyroxine and lisinopril, respectively.⁶ An observational study of opioid prescriptions issued at clinic visits to older adults from 1999 to 2010 found that the percentage of visits where an opioid was used increased from 4.1% to 9.0% over the study period; hydrocodone was the largest contributor, increasing from 1.1% to 3.5% alone.⁷ This increased use has been accompanied by concerning safety issues; in 2011, approximately 97,000 drug-related emergency room visits for abuse/misuse involved hydrocodone products, a 96% relative increase from 2004.⁸

In response to these trends, there have been several recent regulatory developments affecting opioids, and more specifically, hydrocodone. Most recently on August 22 2014, the Drug Enforcement Administration (DEA) published a final rule announcing the federal rescheduling of hydrocodone-combination products (HCPs) from Schedule III to Schedule II, which went into effect on October 6 2014.⁹ Additionally, two new single-agent extended-release (ER) hydrocodone products were recently approved by the Food and Drug Administration (FDA): Zohydro™ ER and Hysingla™ ER, in October 2013 and November 2014, respectively. These developments have been preceded by several years of debate, public and professional consultation, and split opinions due to the increasing number of safety issues associated with opioids balanced with the need for access to effective pain management. An understanding of this history is key to promoting future improvements in the safe use of opioids. Therefore, the objective of this commentary is to examine recent regulatory/policy developments regarding opioid safety in the USA, with a special focus on hydrocodone and opportunities for improving the future safe use of these medications.