ADDRESSING THE OPIOID CRISIS

Strong Track Record

Our Strong Track Record of Helping to Address the Opioid Addiction Crisis

The nation’s opioid addiction crisis is a significant and urgent public health challenge, and Purdue Pharma is deeply concerned about the toll it is having on communities. Here are some of the steps we have taken to address the crisis:

PUBLIC-PRIVATE PARTNERSHIPS

We participate in public-private partnerships to advance collaborative solutions, including:

  • The National Institutes of Health’s (NIH) public-private working groups to help end the opioid crisis including Helping to End Addiction Long-term (HEAL), an initiative focused on accelerating the development of treatments for opioid use disorder and non-opioid, non-addictive pain medications.
  • The Prescription Drug Safety Network (the “Network”) created by EVERFI, a leading prevention education innovator. Through this public-private coalition, Purdue underwrites efforts to bring prevention education regarding prescription drug misuse and abuse to high school students across the country. In August 2018, we reported results from the Network’s inaugural year which included a national 49% knowledge gain across six different learning modules and we expanded our initial support to include a statewide education program in Connecticut and a collaboration with the Connecticut Prevention Network.
  • The Governor’s Prevention Partnership of Connecticut, a public-private organization focusing on education about youth issues, including substance abuse, to sponsor educational initiatives including public service announcements (PSAs).

REDUCING DIVERSION OF PRESCRIPTION OPIOID MEDICATIONS

We advocate and support efforts to reduce prescription drug diversion such as the use of Prescription Drug Monitoring Programs (PDMPs) by healthcare professionals, safe storage and disposal initiatives, and supporting pharmacists to address safety and security.

  • Provided $3.1 million toward a public-private partnership with the Commonwealth of Virginia to integrate PDMP data and analysis into the electronic health record workflow of 18,000 doctors and nurses and 300 pharmacies. Data from an observational study presented in September 2018 at the PAINWeek® Annual Conference found a 91% increase in the average monthly number of unique individuals interacting with the Virginia PDMP (from 7,959 to 15,175 within one year).
  • We provided $1 million in funding to the National Association of Boards of Pharmacy (NABP) to enable states to connect at no cost to the NABP’s PMPInterConnect® platform and share prescription drug monitoring data with each other. It is now used by more than 40 states.
  • We partnered with Safe Kids North Carolina, Project Lazarus, and others to support state-wide medicine disposal activities and conduct systematic research to evaluate the impact of community-based prevention programs on opioid-related overdoses, abuse, and diversion.
  • We developed the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS®) System to measure rates of abuse, misuse, and diversion across the nation. RADARS® now operates as an independent, nonprofit operation of the Rocky Mountain Poison and Drug Center (RMPDC), a division of the Denver Health and Hospital Authority (DHHA). It contributes to the understanding of trends, aids in the development of effective interventions, and assists pharmaceutical companies in fulfillment of their regulatory obligation such as risk evaluation and mitigation strategies (REMS).
  • We created RxPATROL® (Pattern Analysis Tracking Robberies and Other Losses), the first national database to track, analyze, and provide information on pharmacy theft and loss to law enforcement and the retail pharmacy network. First developed in 2003, today RxPATROL®has more than 13,600 registered users and helps law enforcement solve pharmacy crimes and educate retail pharmacy leaders on how they can protect themselves, their businesses, and their customers.

HARM REDUCTION

We’ve supported initiatives to improve access to opioid overdose reversal agents, including:

  • A $3.41 million grant to Harm Reduction Therapeutics, Inc. to support its effort to advance the development of a low-cost, over-the-counter (OTC) naloxone* nasal spray in the US. The grant, provided in September 2018, will help accelerate development by approximately 12 months. We’ve committed that Purdue will not see any revenue from this product.
  • Purdue has provided funding to the National Sherriff’s Association (NSA) for the purchase of naloxone* kits and training of law enforcement officers on overdose reversal. Since November 2015, the NSA estimates it has distributed nearly 3,500 naloxone doses to 21 states and trained more than 1,000 law enforcement officers on administering naloxone to victims of a drug overdose.
  • Working to bring forward nalmefene hydrochloride (HCl) injection, an investigational opioid antagonist for the emergency treatment of known or suspected opioid overdose. In 2019, U.S. Food & Drug Administration (FDA) granted Fast Track and Competitive Generic Therapy (CGT) designations to nalmefene which facilitate the development, and expedite the review, and timely market entry of new therapies that treat serious conditions and fulfill an unmet medical need. Because of the increasing number of deaths due to fentanyl and its even more potent analogues, we are focusing on a potentially more potent and longer-lasting rescue option specifically intended to work in those overdose situations. We have committed to not profit from any future sales of this drug.

*there is no guarantee that these investigational agents will successfully complete clinical development or gain FDA approval.

CONDUCTING AND SUPPORTING RESEARCH AND DEVELOPMENT

For many years, we have worked collaboratively with academia and industry to advance the science of pain treatment.

  • In 2010, Purdue received FDA approval for reformulated OxyContin® (oxycodone HCl) extended-release tablets after spending nearly a decade and hundreds of millions of dollars on its development. In 2013, based on laboratory and clinical data, the FDA granted OxyContin the first-ever label stating that the medication has abuse-deterrent properties that are expected to make it more difficult to abuse via injection and snorting. However, abuse by injection, intranasal and oral route is still possible, and all opioids, including those with FDA-recognized abuse-deterrent properties, carry risks of addiction, abuse, and misuse, which can lead to overdose and death. Today, the FDA continues to encourage the development of opioid pain medications that are harder to manipulate and abuse.
  • For more than two decades, Purdue has conducted non-opioid pain research. The data and conclusions from this research have been shared with the academic scientific community through peer-reviewed publications, presentations, and posters. Additional unpublished data were summarized and shared with the NIH as part of Project HEAL.

For additional information on Purdue Pharma’s strong record of helping to address prescription
drug abuse and diversion, please visit: www​.PurduePharma​.com

  • Purdue is currently working with partner companies to develop non-opioid pain therapies for the low back, eye and bladder as well as other types of chronic pain. These technologies have potential for development of additional non-opioids for pain throughout the body.
  • As part of our collaborative research program, we supported a research fellowship at the University of Oklahoma College of Pharmacy from 2016 to 2018. Through this program, the fellow worked with academic advisors to conduct epidemiologic research to evaluate factors influencing unintentional prescription opioid deaths and diagnosed opioid use disorder in the Oklahoma state Medicaid program. Findings from this program of research were published in Medical Care and presented at PainWeek and the Academy of Managed Care Pharmacy (AMCP) conferences. Additional findings generated during the fellowship program are being submitted for publication.
  • As part of our commitment to research non-opioid pain treatments and addiction, we have supported a scholarship for three graduate students per year, for three years, at the University of Nebraska Medical Center. We also donated an estimated $1 million in lab equipment and consumables to the University of Nebraska Medical Center in July 2017.
  • In 2017, we joined in a clinical study with Geisinger to assess the effect of wearable health technology on patient health outcomes. An interim analysis from this observational work was presented in September 2018 at the PAINWeek® Annual Conference.
  • In 2017, we donated a nuclear magnetic resonance spectrometer to the New Jersey Institute of Technology. The instrument, valued at approximately $500,000, is used by chemists to identify and characterize new molecules with the potential to become new therapies. The instrument was installed in a facility that is dedicated to facilitating cross-departmental collaborative research including pain, addiction, and other fields.

IMPORTANT SAFETY INFORMATION

WARNING: ADDICTION, ABUSE AND MISUSE; RISK EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; CYTOCHROME P450 3A4 INTERACTION; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS

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 and conditions [see Warnings and Precautions (5.1)].

Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)
To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a REMS for these products [see Warnings and Precautions (5.2)]. Under the requirements of REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to

  • complete a REMS-compliant education program,
  • counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products,
  • emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and
  • consider other tools to improve patient, household, and community safety.

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 (5.3)].

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 (5.3)].

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 (5.4)].

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 (5.5), Drug Interactions (7), Clinical Pharmacology (12.3)].

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants
Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death [see Warnings and Precautions (5.6), Drug Interactions (7)].

  • Reserve concomitant prescribing of OXYCONTIN and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.
  • Limit dosages and durations to the minimum required.
  • Follow patients for signs and symptoms of respiratory depression and sedation.
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CONTRAINDICATIONS
OxyContin 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 gastrointestinal obstruction, including paralytic ileus
  • Hypersensitivity (e.g., anaphylaxis) to oxycodone.

WARNINGS AND PRECAUTIONS
Addiction, Abuse, and Misuse

  • OxyContin contains oxycodone, a Schedule II controlled substance. OxyContin exposes users to the risks of opioid addiction, abuse, and misuse. Because extended-release products such as OxyContin deliver the opioid over an extended period of time, there is a greater risk for overdose and death due to the larger amount of oxycodone present.
  • Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed OxyContin. 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 OxyContin, and monitor all patients receiving OxyContin for the development of these behaviors and conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids such as OxyContin, but use in such patients necessitates intensive counseling about the risks and proper use of OxyContin along with intensive monitoring for signs of addiction, abuse, and misuse.
  • Abuse or misuse of OxyContin by crushing, chewing, snorting, or injecting the dissolved product will result in the uncontrolled delivery of oxycodone and can result in overdose and death.
  • Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing OxyContin. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug.

Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)

  • To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to do all of the following:
    • complete a REMS-compliant education program,
    • counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products,
    • emphasize to patients and their caregivers the importance of reading the Medication Guide that they will receive from their pharmacist every time an opioid analgesic is dispensed to them
    • consider other tools to improve patient, household, and community safety.
  • To obtain further information on the opioid analgesic REMS and for a list of accredited REMS CME/CE, call 1-800-503-0784, or log on to www​.opioidanalgesicrems​.com. The FDA Blueprint can be found at www​.fda​.gov/​O​p​i​o​i​d​A​n​a​l​g​e​s​i​c​R​E​M​S​B​l​u​e​print

Life-Threatening Respiratory Depression

  • Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended, and if not immediately recognized and treated, may lead to respiratory arrest and death.
  • While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of OxyContin, the risk is greatest during the initiation of therapy or following a dosage increase. Closely monitor patients for respiratory depression, especially within the first 24-72 hours of initiating therapy with and following dosage increases of OxyContin.
  • To reduce the risk of respiratory depression, proper dosing and titration of OxyContin are essential. Overestimating the OxyContin dosage when converting patients from another opioid product can result in a 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.

Neonatal Opioid Withdrawal Syndrome

  • Prolonged use of OxyContin during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.

Risks of Concomitant Use or Discontinuation of Cytochrome P450 3A4 Inhibitors and Inducers

  • Concomitant use with a CYP3A4 inhibitor, such as macrolide antibiotics, azole-antifungal agents, and protease inhibitors, particularly when an inhibitor is added after a stable dose of OxyContin is achieved, and discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, may increase plasma concentrations of oxycodone and prolong opioid adverse reactions, which may cause potentially fatal respiratory depression. Monitor patients closely at frequent intervals and consider dosage reduction of OxyContin until stable drug effects are achieved. Concomitant use of OxyContin with CYP3A4 inducers or discontinuation of a CYP3A4 inhibitor could decrease oxycodone plasma concentrations, decrease opioid efficacy or, possibly, lead to a withdrawal syndrome in a patient who had developed physical dependence to oxycodone. Monitor patients closely at frequent intervals and consider increasing the opioid dosage if needed to maintain adequate analgesia or if symptoms of opioid withdrawal occur.

Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants

  • Profound sedation, respiratory depression, coma, and death may result from the concomitant use of OxyContin with benzodiazepines or CNS depressants (e.g., non-benzodiazepines sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.
  • If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. Follow patients closely for signs and symptoms of respiratory depression and sedation.
  • Advise both patients and caregivers about the risks of respiratory depression and sedation when OxyContin is used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs). Advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine or other CNS depressant have been determined. Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs.

Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients

  • The use of OxyContin in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.
  • OxyContin-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of OxyContin.
  • Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients.
  • Monitor such patients closely, particularly when initiating and titrating OxyContin and when OxyContin is given concomitantly with other drugs that depress respiration. Alternatively, consider the use of non-opioid analgesics in these patients.

Adrenal Insufficiency

  • Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers.

Severe Hypotension

  • OxyContin may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is an increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressants drugs (eg, phenothiazines or general anesthetics). Monitor these patients for signs of hypotension after initiating or titrating the dosage of OxyContin. In patients with circulatory shock, OxyContin may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of OxyContin in patients with circulatory shock.

Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness

  • In patients who may be susceptible to the intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), OxyContin may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Monitor those patients for signs of sedation and respiratory depression, particularly when initiating therapy with OxyContin. Opioids may obscure the clinical course in a patient with a head injury. Avoid the use of OxyContin in patients with impaired consciousness or coma.

Difficulty in Swallowing and Risk for Obstruction in Patients at Risk for a Small Gastrointestinal Lumen

  • There have been post-marketing reports of difficulty swallowing OxyContin tablets. These reports include choking, gagging, regurgitation, and tablets stuck in the throat. Instruct patients not to pre-soak, lick or otherwise wet OxyContin tablets prior to placing in the mouth, and to take one tablet at a time with enough water to ensure complete swallowing immediately after placing in the mouth.
  • There have been rare post-marketing reports of cases of intestinal obstruction, and exacerbation of diverticulitis, some of which have required medical intervention to remove the tablet. Patients with underlying GI disorders such as esophageal cancer or colon cancer with a small gastrointestinal lumen are at greater risk of developing these complications. Consider use of an alternative analgesic in patients who have difficulty swallowing and patients at risk for underlying GI disorders resulting in a small gastrointestinal lumen.

Risks of Use in Patients with Gastrointestinal Conditions

  • OxyContin is contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus. The oxycodone in OxyContin may cause spasm of the sphincter of Oddi. Opioids may cause increases in the serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis.

Increased Risk of Seizures in Patients with Seizure Disorders

  • The oxycodone in OxyContin may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures. Monitor patients with a history of seizure disorders for worsened seizure control during OxyContin therapy.

Withdrawal

  • Avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic, including OxyContin. In these patients, mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or may precipitate withdrawal symptoms. When discontinuing OxyContin, gradually taper the dosage. Do not abruptly discontinue OxyContin.

Risks of Driving and Operating Machinery

  • OxyContin may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of OxyContin and know how they will react to the medication.

Laboratory Monitoring

  • Not every urine drug test for “opioids” or “opiates” detects oxycodone reliably, especially those designed for in-office use. Further, many laboratories will report urine drug concentrations below a specified “cut-off” value as “negative.” Therefore, if urine testing for oxycodone is considered in the clinical management of an individual patient, ensure that the sensitivity and specificity of the assay is appropriate, and consider the limitations of the testing used when interpreting results.

ADVERSE REACTIONS

  • OxyContin may increase the risk of serious adverse reactions such as those observed with other opioid analgesics, including respiratory depression, apnea, respiratory arrest, circulatory depression, hypotension, or shock.
  • The most common adverse reactions (≥5%) reported by adult patients in clinical trials comparing OxyContin with placebo are constipation, nausea, somnolence, dizziness, pruritus, vomiting, headache, dry mouth, asthenia, and sweating.

Please read Full Prescribing Information, including Boxed Warning.