New Data Examining Effects of OxyContin® (oxycodone HCI extended-release tablets) CII Reformulation at PAINWeek

Purdue to present data showing decline in abuse, addiction or poisoning, as well as three-year trend in reduction of abuse, diversion of OxyContin after it was reformulated

 

Stamford, Conn. – Sept. 4, 2014 –Purdue Pharma is presenting results from two epidemiological studies evaluating the reformulation of OxyContin®, which occurred in 2010, that showed a marked decrease in rates of abuse, addiction and poisoning in the first year after the product was introduced to the marketplace with physicochemcial properties intended to decrease abuse, misuse and diversion by various routes of administration (e.g., snorting and intravenous injection). These studies also show that declines in abuse and diversion have persisted three years since the introduction. These data are being presented at the PAINWeek national conference Sept. 2 – 6 in Las Vegas.

Purdue Pharma’s OxyContin is an extended-release oxycodone product that was originally approved by the FDA in 1995 and reformulated with abuse deterrent properties to make the tablet more difficult to manipulate for misuse and abuse. Approved in April 2010 the product was shipped in August 2010 when shipments of the original formulation ceased. OxyContin has physicochemical properties expected to make abuse via injection and intranasal route difficult. However, abuse of OxyContin by these routes, as well as by the oral route is still possible.

Highlights of the results of two among several posters are as follows:

  • One study, titled “Decrease in diagnosed opioid abuse, addiction, or poisoning after OxyContin with abuse-deterrent characteristics was introduced in commercial insurance population,” used MarketScan commercial data to assess the effect of reformulating OxyContin with abuse-deterrent characteristics on diagnosed opioid abuse, addiction and poisoning in a commercially insured population. The retrospective study cohort included patients 18 years or older who were incident or prevalent users of, either, OxyContin or three comparator opioids – immediate-release single-entity oxycodone, extended release oxymorphone or extended-release morphine and found that from the year before to the year after reformulation:
    • Among all patients prescribed OxyContin, diagnoses for opioid abuse, addiction or poisoning decreased by -12 percent (95 percent CI -17 percent to -7 percent). In comparison, rates of abuse, addiction or poisoning for the three opioid comparator groups
    • Among patients prescribed a single opioid, rates of abuse, addiction or poisoning for OxyContin decreased -29 percent (95 percent CI-38 percent to -18 percent, p<.0001), from 4.3 percent to 3.1 percent, which was significantly greater than changes for IR SE oxycodone, ER oxymorphone and for ER morphine as rates of abuse, addiction or poisoning in the three comparator groups
    • Among patients prescribed multiple opioids that included OxyContin, rates of abuse, addiction or poisoning decreased -10 percent (95 percent CI-16 percent to -5 percent, p=.0005), from 11.1 percent to 9.9 percent. In comparison, rates of abuse, addiction or poisoning for the three comparator groups
  • The second study, titled “Trends in abuse and diversion in multiple surveillance systems three years after introduction of reformulated OxyContin” examined the abuse and diversion of reformulated OxyContin three years after being introduced on the market via quarterly data from four ongoing major surveillance systems and found that in all surveillance systems, reductions in rates of abuse were observed for both oral and non-oral routes of administration although the magnitude of decline was larger for abuse through non-oral routes.
    • o In two of the surveillance systems – the RADARS Poison Center program and the National Poison Data System, population-adjusted rates of intentional abuse exposures for OxyContin reported declined steadily in the three-year post-reformulation period relative to the one-year period prior to reformulation.
      • For each of these systems, rates declined approximately 20 percent in the first quarter in the post-reformulation period (1Q 2011), to more than a 70 percent decline by the end of the 3-year follow-up (4Q 2013).
      • On average, intentional abuse exposures declined 55 percent, in both the RADARS PC and NPDS , in the three years after reformulation compared to the year prior to reformulation.
    • o Among opioid abusers assessed in the NAVIPPRO ASI-NV system, rates of abuse of reformulated OxyContin were 48 percent lower in the post- relative to the pre-reformulation period. OxyContin drug diversion rates declined more than 70 percent in the third year after compared to the year before reformulation.

OxyContin contains oxycodone, an opioid agonist and Schedule II controlled substance with an abuse liability similar to other opioid agonists, legal and illicit, including fentanyl, hydromorphone, methadone, morphine, and oxymorphone. OxyContin can be abused and is subject to misuse, addiction, and criminal diversion . The high drug content in extended-release formulations adds to the risk of adverse outcomes from abuse and misuse.

Full Prescribing Information for OxyContin 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
OXYCONTIN® 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 OXYCONTIN 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 OXYCONTIN. Monitor for respiratory depression, especially during initiation of OXYCONTIN or following a dose increase. Instruct patients to swallow OXYCONTIN tablets whole; crushing, chewing, or dissolving OXYCONTIN tablets can cause rapid release and absorption of a potentially fatal dose of oxycodone [see Warnings and Precautions (5.2)].

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

Neonatal Opioid Withdrawal Syndrome
Prolonged use of OXYCONTIN 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 OXYCONTIN with all cytochrome P450 3A4 inhibitors may result in an increase in oxycodone 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 oxycodone plasma concentration. Monitor patients receiving OXYCONTIN and any CYP3A4 inhibitor or inducer [see Warnings and Precautions (
5.14) and Clinical Pharmacology (12.3)].

Risks Specific to Abuse of OxyContin
OxyContin is for oral use only. Abuse of OxyContin poses a risk of overdose and death. The risk is increased with concurrent use of OxyContin with alcohol and other central nervous depressants. Taking cut broken, chewed, crushed, or dissolved OxyContin enhances drug release and increases the risk of overdose and death. All patients treated with opioids require careful monitoring for signs of abuse and addiction, since use of opioid analgesic products carries the risk of addiction even under appropriate medical use.

With parenteral abuse, the inactive ingredients in OxyContin can be expected to result in local tissue necrosis, infection, pulmonary granulomas, and increased risk of endocarditis and valvular heart injury. Parenteral drug abuse is commonly associated with transmission of infectious diseases, such as hepatitis and HIV.

Additional Important Safety Information
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 initiation of therapy or following a dose increase; therefore, closely monitor patients for respiratory depression. Proper dosing and titration of OxyContin are essential. Overestimating the OxyContin dose when converting patients from another opioid product can result in fatal overdose with the first dose.

Accidental ingestion of even one dose of OxyContin, especially by children, can result in respiratory depression and death due to an overdose of oxycodone.

Prolonged use of OxyContin 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.

Hypotension, profound sedation, coma, respiratory depression, or death may result if OxyContin is used concomitantly with other CNS depressants, including alcohol or illicit drugs that can cause CNS depression. Start with 1/3 to 1/2 the usual dose of OxyContin, monitor patients for signs of sedation and respiratory depression, and consider using a lower dose of the concomitant CNS depressant.

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

OxyContin may cause severe hypotension, including orthostatic hypotension and syncope in ambulatory patients. Monitor patients during dose initiation and titration. Avoid use of OxyContin in patients with circulatory shock. Monitor patients taking OxyContin who may be susceptible to the intracranial effects of CO2 retention for signs of sedation and respiratory depression. Avoid the use of OxyContin in patients with impaired consciousness or coma. OxyContin is contraindicated in patients with GI obstruction, including paralytic ileus. Use caution when prescribing OxyContin for patients who have difficulty swallowing, or have underlying GI disorders that may predispose them to obstruction. Consider use of an alternative analgesic in these patients.

OxyContin may cause spasm of the sphincter of Oddi. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.

OxyContin may aggravate convulsions in patients with convulsive disorders and may induce or aggravate seizures in some clinical settings. Monitor patients with a history of seizure disorders for worsened seizure control. Avoid the use of mixed agonist/antagonist or partial agonist analgesics in patients who have received or are receiving OxyContin, as they may reduce the analgesic effect and/or precipitate withdrawal. Do not abruptly discontinue OxyContin.

OxyContin may impair the mental and physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery.

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.

Full prescribing information for OxyContin, including the Medication Guide and Boxed Warning is available at:  www.purduepharma.com/oxycontinpi.

About Chronic Pain
Purdue is a leader in developing treatment options for the management of chronic pain, which is one of the most common reasons for visits to healthcare professionals. Chronic pain conditions affect more than 100 million U.S. adults and cost the American economy as much as $635 billion each year in direct healthcare expenses and lost productivity.

About Purdue Pharma L.P.
Purdue Pharma L.P. 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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Contact:
James Heins
Senior Director, Public Affairs
office: 203-588-8069
mobile: 203-856-2121
Email: james.heins@pharma.com
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Bob Josephson
Associate Director, Media Relations
office: 203-588-7114
mobile: 203-914-7741
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.

There is more to come – as we continue to work with partners and experts to deliver solutions. Below you will find additional information about our efforts.

Read our open letter about the opioid crisis.