Purdue Pharma L.P. Presented Results from a Post Hoc Analysis from a Long-Term Safety and Effectiveness Study of Hysingla® ER (hydrocodone bitartrate) Extended-Release Tablets Cll at PAINWeek® 2015 Annual Conference

Stamford, Conn., Sept. 11, 2015 – Purdue Pharma L.P. today presented results from a post hoc analysis in 24 patients 75 and older from an open-label, long-term (12-month) safety and effectiveness study of Hysingla® ER (hydrocodone bitartrate) at the 9th Annual PAINWeek® Conference in Las Vegas, Sept. 8-12. Hysingla ER is a once-daily, single-entity hydrocodone bitartrate tablet with abuse-deterrent properties for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment for which other treatment options are inadequate.

The open-label study assessed the long-term safety and effectiveness and outcomes of Hysingla ER (20, 40, 60, 80, 120 mg/day) treatment in opioid-naïve and opioid-experienced patients aged 18 and over with chronic pain severe enough to require around-the-clock opioid therapy. This analysis assessed a subpopulation of patients aged 75 years and older. After completing a 45-day dose titration period, a total of 20 elderly patients entered the 12-month maintenance period. The mean “average pain over the last 24 hours” score decreased from 6.1 at baseline to 3.9 by the end of a 45-day dose titration period, and the reduction in mean pain score was maintained throughout the 12-month treatment period with a final mean pain score of 3.6 at 52 weeks.

“Given the prevalence of chronic pain among patients 75 and older and the challenges healthcare providers can face when treating this population due to safety and tolerability concerns, such as co-morbidities, it was important to analyze the long-term safety and efficacy within this specific subpopulation,” said lead author of the poster Kathleen Broglio, DNP, Columbia University Medical Center, New York, NY.”

The mean daily Hysingla ER dose increased during the titration period from 24.2 mg at the beginning of the titration period to 40.8 mg at the end of the dose titration period, and remained relatively stable during the maintenance period with a mean daily dose at 12 months of 49.6 mg. The use of nonstudy opioid drugs decreased during the dose titration period from 7.9 mg at the beginning of the dose titration period to 1.9 at the end of the dose titration period and remained low throughout the maintenance period, with patients taking no nonstudy opioid drugs by the end of the study.

Among elderly patients in the study, 17 (71%) experienced a treatment-emergent adverse event (TEAE).
The most common TEAE observed in the study were gastrointestinal disorders, including constipation (54%), nausea (17%), vomiting (8%) and dry mouth (4%). Overall, 7 (29%) discontinued treatment due to an adverse event during the study. Serious AEs were reported in five elderly patients (21%), all of which were related to patients’ prior history. There was no incidence of falls, fractures or deaths.

Hysingla ER is the first and only hydrocodone 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.

The 2015 accepted abstracts are available on the PAINWeek website.

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) and Clinical Pharmacology (12.3)].

Indications and Usage
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. Limitations of Use: Because of the risks of addiction, abuse and misuse with opioids, even at recommended doses, and because of the greater risk of overdose and death with extended-release opioid formulations, reserve Hysingla ER 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 (prn) analgesic.

Contraindications
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, hypersensitivity to any component of Hysingla ER or the active ingredient, hydrocodone bitartrate.

Important Safety Information

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 3A4 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.
Full Prescribing Information for Hysingla® ER, including Boxed Warning is available at http://www.purduepharma.com/HysinglaPI.

About PAINWeek®
PAINWeek is the largest U.S. pain conference for frontline practitioners with an interest in pain management. Convening at The Cosmopolitan of Las Vegas for its 9th year on Sept. 8-12, 2015, PAINWeek expects to welcome more than 2,100 physicians, nurses, pharmacists, and other healthcare professionals for a comprehensive program of course offerings, satellite events, and exhibits. Over 120 hours of continuing medical education activities will be presented. To learn more and register for PAINWeek 2015, visit www.painweek.org.

About Purdue Pharma L.P.
Purdue Pharma L.P. and associated U.S. companies are privately-held pharmaceutical companies known for pioneering research in chronic pain. Purdue Pharma is engaged in the research, development, production, and distribution of prescription and over-the-counter medicines, as well as hospital products. Purdue Pharma is committed to advancing the care of patients with quality products that make a positive impact on healthcare — and on lives. Purdue Pharma’s headquarters are located in Stamford, Conn. For more information about Purdue Pharma, please visit www.purduepharma.com. Follow Purdue Pharma on Twitter: @PurduePharma

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