Hydrocodone Bitartrate Extended-release Tablets (Hysingla ER) CII
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
The FDA has approved the first abuse-deterrent, extended-release form of hydrocodone. The extended-release formulation provides similar bioavailability to the immediate-release formulation but with a lower maximum plasma concentration at steady state. This product is marketed by Purdue Pharma as Hysingla™ ER.
Hydrocodone extended-release tablets are indicated for the management of severe pain that requires around-the-clock, long-term opioid treatment and for which alternative options are inadequate.1
The recommended starting dose for opioid-naïve patients is 20 mg every 24 hours.1 Dose may be titrated every 3 to 5 days. To convert to hydrocodone ER tablets, a conversion factor is provided in the package insert. The total calculated hydrocodone daily dose is reduced by 25% for interpatient variability in relative potency of different opioids.1
Hydrocodone ER tablets are available as 20 mg, 30 mg, 40 mg, 60 mg, 80 mg, 100 mg, and 120 mg.
This formulation is designed to reduce abuse. The tablet is difficult to crush, break, or dissolve. It forms a viscous hydrogel when tampered with that makes it difficult to inject or inhale.
The drug should be used with caution in patients with difficulty swallowing.1 Most common side effects are constipation, nausea, vomiting, upper respiratory inections, dizziness, headache, and somnolence.1
Hydrocodone is formulated to resist crushing, breaking, and dissolution and still retain some extended-release properties.1 The approval of hydrocodone ER tablets was based both on its abuse-deterrent properties as well as its efficacy and safety.1 In a non-dependent opioid abuser, the median drug liking score was 56 for the manipulated hydrocodone ER tablets for intranasal use compared to 100 for hydrocodone powder. For oral (chewed), the median score was 66, compared to 100. The scores were similar for likeliness to take the drug again. The efficacy and safety were shown in subjects (both opioid-naïve and experienced) with chronic low back pain (n = 905) who were adequately treated with their prior analgesic treatment. These patients entered into an open-label dose titration phase with hydrocodone ER. Rescue oxycodone immediate-release tablets (up to 10 mg) were permitted. Sixty-five (65%) reached a stable dose of hydrocodone ER and were subsequently randomized to the stable dose or matching placebo with hydrocodone taper. Hydrocodone ER provided statistically significant improvement in (30% or 50%) pain management compared to placebo at 12 weeks. The wholesale cost for Hysingla ER is approximately $3 per 10 mg.
This is the first abuse-deterrant form of hydrocodone to be marketed. The FDA approved a non-abuse-deterrant, long-acting form of hydrocodone last year (Zohydro, Zogenix Inc), and the FDA was roundly criticized because of the potential for abuse of the drug. For the new abuse-deterrant form, the FDA is requiring post-marketing studies on the effect of the abuse-deterrant properties on the risk of abuse and "consequences of that abuse in the community."2 Drug abuse is a significant public health problem. As such, the FDA has encouraged manufacturers to produce abuse-deterrent opioid products.3 Abuse-deterrent can be categorized in several ways: 1) physical/chemical barriers that can prevent chewing, crushing, cutting, etc.; 2) agonist/antagonists combinations; 3) aversion (product unpleasant effects; 4) delivery systems; 5) prodrugs; and 6) combinations of the above methods. Currently, several opioid products on the market use the physical/chemical barriers. These include oxycodone (Oxycontin), oxymorphone (Opana ER), and hydromorphone (Exalgo). In a survey of opioid-dependent subjects, oxycodone and hydrocodone were regarded as abuse drugs of choice (75%), with preference favoring oxycodone over hydrocodone (45% vs 29%) because of a better high.4
- Hysingla ER Prescribing Information. Purdue Pharma. November 2011.
- http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm423977.htm. Accessed 12/6/14.http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm334743.pdf. Accessed 12/7/14.
- Cicero TJ, et al. Pain 2013;154:2639-2648.
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