The US Food and Drug Administration (FDA) has approved Purdue Pharma's Hysingla ER (hydrocodone bitartrate) extended-release tablets CII, a once-daily, single-entity medication formulated using Purdue’s proprietary extended-release solid oral platform, Resistec. It is the first and only hydrocodone product to be recognized by the FDA as having abuse-deterrent properties that are expected to deter misuse and abuse via chewing, snorting and injection. However, abuse of Hysingla ER by the intravenous, intranasal, and oral routes is still possible.
Hysingla ER does not contain acetaminophen, the overuse of which has been reported to be a leading cause of acute liver failure in the United States. Prescription products containing hydrocodone and acetaminophen are both the most prescribed and among the most widely abused (nonmedical use) medications in the United States.
“The burden of chronic pain and the abuse of prescription medications are both pressing societal problems,” said Charles E. Argoff, MD, Professor of Neurology at Albany Medical College and Director of the Comprehensive Pain Center at Albany Medical Center in New York. “Opioids are an essential tool in our arsenal of medical treatments options, so greater availability and use of opioid analgesics with abuse-deterrent properties has the potential to help alleviate suffering among people with chronic pain while reducing the abuse of these medications. Furthermore, this product gives treatment providers the option to use hydrocodone without acetaminophen if they are concerned that their patients may be taking too much acetaminophen on a daily basis.”
“We are proud to offer healthcare professionals and chronic pain patients another treatment option,” said Mark Timney, CEO of Purdue Pharma L.P. “Hysingla ER is the third product in our pain management portfolio to receive an FDA label describing its abuse-deterrent characteristics. These innovations are an important step forward in helping meet patients’ needs while also working to deter misuse and abuse.”
Purdue expects to launch Hysingla ER in the United States in early 2015 in dosage strengths of 20 mg, 30 mg, 40 mg, 60 mg, 80 mg, 100 mg and 120 mg to be taken once every 24 hours.
Hysingla ER is indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. Hysingla ER has the following Limitations of Use: Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, Hysingla ER should be reserved for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. Hysingla ER is not indicated as an as-needed analgesic. Hysingla ER is contraindicated in patients with significant respiratory depression, acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment, known or suspected paralytic ileus and gastrointestinal obstruction, and hypersensitivity to any component of Hysingla ER or the active ingredient, hydrocodone bitartrate.
Purdue conducted laboratory manipulation and extraction studies, and clinical abuse potential studies with Hysingla ER, in accordance with the FDA’s 2013 Draft Guidance on Abuse-Deterrent Opioids: Evaluation and Labeling. Based on the results of these studies, Hysingla ER is recognized by the FDA as having abuse-deterrent properties that are expected to deter misuse and abuse via chewing, snorting and injection, resulting in Tier 1 and 3 abuse-deterrence labeling. However, abuse of Hysingla ER by the intravenous, intranasal, and oral routes is still possible. The methodology and results of these studies are summarized in section 9.2 of the product’s label.1 Additional data, including epidemiological data, when available, may provide further information on the impact of Hysingla ER on the abuse liability of the drug. Accordingly, section 9.2 may be updated in the future as appropriate.
Tier 1 labeling means that a product is formulated with physico-chemical barriers to abuse. To gain Tier 1 labeling, data from laboratory manipulation and extraction studies that assess how the abuse-deterrent properties of a formulation can be defeated or compromised are provided to the FDA. Tier 3 labeling means that the product is expected to result in a meaningful reduction in abuse. To gain Tier 3 labeling, data from clinical abuse potential studies are provided that assess the impact of a formulation’s abuse-deterrent properties on measures that predict how probable it is that the formulation will be attractive to, or “liked” by, abusers. For Tier 4 labeling, the product must demonstrate reduced abuse in the community. Purdue will conduct post-marketing surveillance studies to assess this impact of the drug on reducing abuse and diversion in a real-world setting.
Resistec is Purdue Pharma’s proprietary extended-release solid oral dosage formulation platform. Resistec uses a unique combination of polymer and processing that confers tablet hardness and imparts viscosity when dissolved in aqueous solutions.
The use of products containing acetaminophen in high doses over a long period of time can cause severe liver injury, with reports of up to 63 per cent of unintentional acetaminophen overdoses associated with the use of opioid-acetaminophen combination products. In January 2014, the FDA issued a statement that combination prescription pain relievers that contain more than 325 mg of acetaminophen per tablet, capsule, or other dosage unit should no longer be prescribed or dispensed because of a risk of liver damage if taken in doses exceeding the maximum recommended dose. According to the FDA statement, cases of severe liver injury have been reported in patients who took more than the prescribed dose of an acetaminophen-containing product in a 24-hour period, took two or more acetaminophen-containing products simultaneously, or combined alcohol with acetaminophen.
Purdue Pharma L.P. and its associated US companies are privately-held pharmaceutical companies known for pioneering research on chronic pain.