Data on Long-Term Safety and Effectiveness of Hysingla® ER (hydrocodone bitartrate) Extended-Release Tablets CII Presented at American Pain Society Scientific Meeting

Stamford, Conn. – May 13, 2015 9:00 a.m. ET – Purdue Pharma today presented data from a long-term (76 week) safety and efficacy study of Hysingla ER, a once-daily, single-entity hydrocodone bitartrate tablet formulated with abuse-deterrent properties. Results of this and two other studies sponsored by Purdue are being presented at the 34th Annual American Pain Society Scientific Meeting in Palm Springs, California, May 13-16.

The research found that treatment with Hysingla ER resulted in improvements in and maintenance of chronic pain relief, as well as other outcome measures, throughout the 76-week treatment period in patients with chronic pain without the continual need for dose increase.

“These findings are consistent with data from other research evaluating the safety and effectiveness of long-term opioid therapy,” said Gail Cawkwell, MD, PhD, Purdue Pharma Vice President of Medical Affairs and Chief Medical Officer. “While this is an open label study, these data can be used to help inform the ongoing evaluation of the long-term use of opioids in patients with chronic pain.”

The long-term, open-label study with up to a 76-week maintenance period measured the safety, effectiveness and other outcomes of Hysingla ER (20, 40, 60, 80, 120 mg/day) treatment in patients with moderate-to-severe chronic pain. A total of 106 opioid-naïve and opioid-experienced patients participated in the study.

Treatment-emergent adverse events observed in the study were typical of those associated with mu opioid agonist treatments, the most common being constipation, nausea, upper respiratory tract infection, and fatigue. There was no incidence of abuse or diversion of study drug reported, and no apparent safety concerns were revealed from evaluations of audiologic, clinical laboratory, and ECGs assessments. Seven patients discontinued the treatment due to an adverse event.

Hysingla ER is the first and only hydrocodone product to be recognized by the U.S. Food & Drug Administration (FDA) as having abuse-deterrent properties that are expected to deter abuse via chewing, snorting and injection. However, abuse of Hysingla ER by the intravenous, intranasal and oral routes is still possible. With parenteral abuse, the inactive ingredients in Hysingla can result in death, local tissue necrosis, infection, pulmonary granulomas, and increased risk of endocarditis and valvular heart injury.

Other Hysingla ER posters being presented at the 34th Annual American Pain Society Meeting include:

  • Evaluation of Once-Daily Hydrocodone in Patient Subgroups: This post-hoc analysis evaluated the treatment effectiveness and tolerability of Hysingla ER in patient subgroups.
  • Safety and Effectiveness of Once-Daily Hydrocodone in Patients Switching from an Oral ER Morphine Regimen: This post-hoc analysis evaluated the treatment effectiveness and safety of Hysingla ER in individuals rotating from oral ER morphine to Hysingla ER during an open-label, long-term study with a 12-month maintenance period.

Information within the poster presentations is embargoed until May 13, 2015. Full abstracts will be available on the American Pain Society website following the conference.

The Full Prescribing Information for Hysingla ER contains the following Boxed Warning:

WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; AND CYTOCHROME P450 3A4 INTERACTION

Addiction, Abuse, and Misuse

Hysingla ER exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing Hysingla ER, and monitor all patients regularly for the development of these behaviors or conditions [see Warnings and Precautions (5.1)].

Life-Threatening Respiratory Depression

Serious, life-threatening, or fatal respiratory depression may occur with use of Hysingla ER. Monitor for respiratory depression, especially during initiation of Hysingla ER or following a dose increase. Instruct patients to swallow Hysingla ER tablets whole; crushing, chewing, or dissolving Hysingla ER tablets can cause rapid release and absorption of a potentially fatal dose of hydrocodone [see Warnings and Precautions (5.2)].

Accidental Ingestion

Accidental ingestion of even one dose of Hysingla ER, especially by children, can result in a fatal overdose of hydrocodone [see Warnings and Precautions (5.2)].

Neonatal Opioid Withdrawal Syndrome

Prolonged use of Hysingla ER during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see Warnings and Precautions (5.3)].

Cytochrome P450 3A4 Interaction

The concomitant use of Hysingla ER with all cytochrome P450 3A4 inhibitors may result in an increase in hydrocodone plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in hydrocodone plasma concentration. Monitor patients receiving Hysingla ER and any CYP3A4 inhibitor or inducer [see Warnings and Precautions (5.11), Drug Interactions (7.1), and Clinical Pharmacology (12.3)].

INDICATION AND USAGE AND CONTRAINDICATIONS

Hysingla ER is indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment in patients for whom 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

WARNINGS AND PRECAUTIONS

Addiction, Abuse, and Misuse
Hysingla ER contains hydrocodone, a Schedule II controlled substance. Hysingla ER exposes users to the risks of opioid addiction, abuse, and misuse. As extended-release products such as Hysingla ER deliver the opioid over an extended period of time, there is a greater risk for overdose and death due to the larger amount of hydrocodone present. Addiction can occur at recommended doses and if the drug is misused or abused. Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing Hysingla ER, and monitor all patients during therapy for the development of these behaviors or conditions. Abuse or misuse of Hysingla ER by crushing, chewing, snorting, or injecting the dissolved product will result in the uncontrolled delivery of the hydrocodone and can result in overdose and death.

Life‐Threatening Respiratory Depression
Serious, life-threatening, or fatal respiratory depression has been reported with modified-release opioids, even when used as recommended, and if not immediately recognized and treated, may lead to respiratory arrest and death. The risk of respiratory depression is greatest during the initiation of therapy or following a dose increase; therefore, closely monitor patients for respiratory depression. Proper dosing and titration of Hysingla ER are essential. Overestimating the Hysingla ER dose when converting patients from another opioid product can result in fatal overdose with the first dose. Accidental ingestion of even one dose of Hysingla ER, especially by children, can result in respiratory depression and death due to an overdose of hydrocodone.

Neonatal Opioid Withdrawal Syndrome
Prolonged use of Hysingla ER during pregnancy can result in neonatal opioid withdrawal syndrome which may be life-threatening to the neonate if not recognized and treated, and requires management according to protocols developed by neonatology experts.

Interactions with Central Nervous System Depressants
Hypotension, profound sedation, coma, respiratory depression, or death may result if Hysingla ER is used concomitantly with other CNS depressants, including alcohol or illicit drugs that can cause CNS depression. Start with a lower Hysingla ER dose than usual (i.e., 20-30% less), monitor patients for signs of sedation and respiratory depression, and consider using a lower dose of the concomitant CNS depressant.

Use in Elderly, Cachectic, and Debilitated Patients and Patients with Chronic Pulmonary Disease
Closely monitor elderly, cachectic, and debilitated patients, and patients with chronic obstructive pulmonary disease because of the increased risk of life-threatening respiratory depression. Consider the use of alternative non-opioid analgesics in patients with chronic obstructive pulmonary disease if possible.

Use in Patients with Head Injury and Increased Intracranial Pressure
Monitor patients closely who may be susceptible to the intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or impaired consciousness). Opioids may obscure the clinical course in a patient with a head injury. Avoid the use of Hysingla ER in patients with impaired consciousness or coma.

Hypotensive Effect
Hysingla ER may cause severe hypotension, including orthostatic hypotension and syncope in ambulatory patients. Monitor patients during dose initiation or titration. In patients with circulatory shock, Hysingla ER may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of Hysingla ER in patients with circulatory shock.

Gastrointestinal Obstruction, Dysphagia, and Choking
Use caution when prescribing Hysingla ER for patients who have difficulty swallowing, or have underlying gastrointestinal disorders that may predispose them to obstruction, dysphagia, or choking. Consider use of an alternative analgesic in these patients.

Decreased Bowel Motility
Hysingla ER is contraindicated in patients with gastrointestinal obstruction, including paralytic ileus. Monitor for decreased bowel motility in post-operative patients receiving opioids. The administration of Hysingla ER may obscure the diagnosis or clinical course in patients with acute abdominal conditions. Hydrocodone may cause spasm of the sphincter of Oddi. Monitor patients with biliary tract disease, including acute pancreatitis.

Cytochrome P450 CYP3A4 Inhibitors and Inducers
Concomitant use of CYP3A4 inhibitors may prolong opioid effects. Use with CYP3A4 inducers may cause lack of efficacy or development of withdrawal symptoms. If co-administration is necessary, evaluate patients frequently and consider dose adjustments until stable drug effects are achieved.

Driving and Operating Machinery
Hysingla ER may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery.

Interaction with Mixed Agonist/Antagonist Opioid Analgesics
Avoid the use of mixed agonist/antagonist analgesics in patients who have received or are receiving Hysingla ER, as they may reduce the analgesic effect and/or precipitate withdrawal.

QTc Interval Prolongation
QTc prolongation has been observed following daily doses of 160 mg of Hysingla ER. Avoid use in patients with congenital QTc syndrome. This observation should be considered in making clinical decisions regarding patient monitoring when prescribing Hysingla ER in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, or who are taking medications that are known to prolong QTc interval. In patients who develop QTc prolongation, consider reducing the dose.

ADVERSE REACTIONS
Most common treatment-emergent adverse reactions (≥5%) reported by patients treated with Hysingla ER in the clinical trials were constipation, nausea, vomiting, fatigue, upper respiratory tract infection, dizziness, headache, and somnolence.

The Full Prescribing Information for Hysingla ER, including the Boxed Warning and Medication Guide is available at http://www.purduepharma.com/HysinglaPI

About Purdue Pharma Purdue Pharma and its associated U.S. companies are privately-held pharmaceutical companies known for pioneering research on chronic pain. Headquartered in Stamford, CT, Purdue is engaged in the research, development, production, and distribution of both prescription and over-the-counter medicines and hospital products. Additional information about Purdue can be found at www.purduepharma.com.

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Email: james.heins@pharma.com

Bob Josephson
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email: robert.josephson@pharma.com

The prescription and illicit opioid abuse crisis is a multifaceted public health challenge, and as a manufacturer of prescription opioids, we have a responsibility to join the fight. At Purdue we are committed to lead our industry in helping address our nation's prescription and illicit opioid abuse crisis.

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