Purdue Pharma Highlights Research from Multiple Studies at AMCP Managed Care & Specialty Pharma Annual Meeting 2017
STAMFORD, Conn., Mar. 28, 2017 – Purdue Pharma L.P. announced today the presentation of results from six clinical and non-clinical research studies at the Academy of Managed Care Pharmacy (AMCP) Managed Care & Specialty Pharmacy Annual Meeting 2017 in Denver, Mar. 27-30, 2017
The selected posters include:
|Wearable Health Technologies to Treat Chronic Pain: Establishing Baseline Treatment Effects in a Multidisciplinary Pain Program
||Graham J, Alfieri T, Baylor K, Robishaw S, Bond C, Mayne T, Han J
|Epidemiology of Opioid Use in a NC State Medicaid Program
||Pham TT, Skrepnek GH, Bond C, Alfieri T, Cothran TJ, Keast SL
|Impact of Oxycodone HCl Extended-release Formulary Restrictions on Extended-release Opioid Market Share, Healthcare Costs in Commercial and Medicare Plans
||Howard J, Chen C, De AP, Wade RL
|Assessing the Impact of a Community-based Overdose Prevention in Rural North Carolina
||Brason F, Alfieri T, Mayne T
|Prescription Opioid Deaths in a NC State Medicaid Population, 2012-2014
||Pham TT, Skrepnek GH, Bond C, Alfieri T, Cothran TJ, Keast SL
|Understanding Factors that Contribute to Opioid Misuse and Diversion
||Bond TC, Howard JC, Mayne T
“We are pleased to present results from several studies that show our commitment to the pain community while addressing the opioid crisis and encouraging responsible prescribing, storage and disposal,” said Gail Cawkwell, M.D., Ph.D., Vice President, Chief Medical Officer, Purdue Pharma L.P. “Through continued research, we aim to improve care for millions of patients suffering from chronic pain in the U.S. and are committed to continuously improving the future design of disposal and take-back programs that aim to improve public health outcomes by reducing the amount of medicine available for misuse and diversion.”
The posters will be available for viewing on Tues., Mar. 28, from 5:45 – 7:30 p.m. MT, where authors will be available to address questions. The posters will also be displayed on Wed., Mar. 29, from 11:45 a.m. – 2:45 p.m. MT.
The AMCP meeting abstracts can be assessed online here.
In addition, the AMCP Exhibit Hall will be open from Tuesday to Thursday, March 28-30. The Purdue Pharma booth is #413.
A map of the AMCP Exhibit Hall can be accessed here:
ABOUT THE STUDIES
“Wearable Health Technologies to Treat Chronic Pain: Establishing Baseline Treatment Effects in a Multidisciplinary Pain Program,” highlights research conducted in collaboration with the Geisinger Multidisciplinary Pain Program (MPP), which takes a bio-psycho-social approach to improve function and quality of life for chronic pain patients. The program includes a three-day educational seminar, 12 months of comprehensive follow-up, care coordination with primary care, and measurable goal development. The goal of the study was to establish current baseline treatment effects of the MPP so the incremental value and impact of wearable health technologies (WHT) could be measured in the future.
The study compared outcomes from electronic health records from the first 91 MPP patients to those of chronic pain patients treated in a primary care setting. MPP patients showed moderately greater improvement in pain and depression than controls. With mean scores and level of improvement suggesting no clear ceiling effect, there is a potential for further improvement with WHT use. A prospective study integrating WHT into MPP is planned to provide real-time feedback, support physical activity and medication adherence, and integrate treatment data into new patient and provider dashboards.
Although this study was conducted at a well-established multidisciplinary pain program that had robust electronic data available (including pain and depression scores), there is a limited sample size of pain program patients to date. In addition, missing data at 6 and 12 month follow-up times limits the ability to draw effect size inferences.
“Epidemiology of Opioid Use in a State Medicaid Program,” describes the demographics, medical utilization, opioid utilization patterns, and clinical characteristics of Medicaid members who used opioids or were diagnosed with opioid-related disorders during the study period. Medicaid populations are especially vulnerable to opioid-related disorders1,2; however, limited data exist on the characteristics and underlying treatment patterns for Medicaid sub-populations.
State Medicaid pharmacy and medical claims data spanning January 2011 to June 2016 were analyzed. Those with opioid overdose or opioid abuse/dependence exhibited higher medical and pharmacy utilization and more frequent use of opioids and benzodiazepines at the same time compared to those with any opioid use. Further research is planned to determine whether these patterns are predictive of opioid-related complications.
Coding misclassification, errors, and non-documentation may be present in administrative claims data, especially with complex substance use disorders. In addition, service and drug utilization outside of Medicaid coverage was unable to be analyzed. A single state Medicaid population may also not be directly generalizable to other state Medicaid populations.
“Impact of Oxycodone HCl Extended-release Formulary Restrictions on Extended-release Opioid Market Share and Healthcare Costs in Commercial and Medicare Plans,” highlights results from a study that evaluated the ER opioid market share and healthcare costs following prior authorizations, non-formulary and step therapy restrictions for branded oxycodone hydrochloride extended release (OER) in national and regional commercial/Medicare plans.
This retrospective, longitudinal case-control study analyzed pharmacy and medical claims data (2012 to 2015) for adult patients with chronic ER opioid use from U.S. plans that instituted formulary restrictions for OER. The results of this study found that formulary restrictions reduced the market share of OER, but did not result in significant net cost savings to the plan. This effect appears to be consistent across most types of formulary restriction and across national and regional commercial/Medicare plans.
Costs might be underestimated as out-of-network and inpatient hospital encounters were unavailable. In addition, six-month post-restriction period may not be sufficient to fully capture the long-term formulary restriction effects. Rebates, restriction-related member and provider disruption and formulary restrictions of other opioids were not considered. In this study, safety and costs due to market share shifts from products with abuse-deterrent properties to products without abuse deterrence were also not evaluated.
Please see OxyContin® (oxycodone HCl) extended-release tablets Boxed Warning below.
“Assessing the Impact of a Community-based Overdose Prevention in Rural North Carolina,” assesses the impact of Project Lazarus (PL), a community-based prevention program that started in 2008 in Wilkes County, North Carolina, in response to an epidemic of unintentional prescription opioid poisoning deaths. The goals of PL are to decrease opioid-related overdose deaths, promote and present appropriate care for pain patients, and enhance engagement within the community.
The PL initiative may have had a positive impact on both hospitalization and death rates. The prescription opioid poisoning hospitalization rate per 100,000 persons in Wilkes County declined from 36.1 in 2009 to 18.7 in 2010. The prescription opioid poisoning death rate per 100,000 persons in Wilkes County was 42.1 in 2009, which was 4 times that of the state. The death rate declined to 20.2 in 2010 and 13.0 in 2011. The most recent data, from 2015, shows the opioid poisoning death rate in Wilkes County climbed to 33.6 per 100,000.
There is considerable variation in coding hospital overdose-related encounters and limited specificity in identifying opioids. In addition, the early impacts of PL on public health outcomes in Wilkes County are encouraging but may not be permanent. Further research on borderline retrenchment rates and drug take back programs are recommended to help communities design statewide initiatives. In addition, more robust data collection, evaluation measures, and recording system would allow characterization of the program’s overall impact on public health.
“Prescription Opioid Deaths in a State Medicaid Population, 2012-2014,” analyzed the cause of death, medical utilization, opioid use, and demographic and clinical characteristics of a state’s Medicaid unintentional opioid prescription drug overdose deaths from 2012 to 2014. This cross-sectional study combined medical examiner data from a state’s Fatal Unintentional Poisoning Surveillance System with the state’s Medicaid pharmacy and medical claims data. Among current or recent Medicaid enrollees, opioid death rates were highest among those aged 35-64 years. Based on these study results, an opportunity exists to identify members at risk of overdose death and apply early intervention strategies based on member characteristics and utilization patterns.
Patterns of pharmacy and medical utilization outside Medicaid claims were not available to be analyzed.Medical examiner data do not contain information on source of drugs, and thus, the study was unable to determine whether the decedent’s medication was obtained legally or from diversion. In addition, provider coding practices may underestimate prevalence of comorbidities, especially among substance use disorders.
“Understanding Factors that Contribute to Opioid Misuse and Diversion,” highlights results from a study that conducted interviews with 152 chronic pain patients prescribed opioid medicines in the past two years. Patients in the study were asked about their behaviors, beliefs and motivations regarding disposal of unused medication, to better understand the conditions contributing to opioid misuse and potential diversion. The objective of the study is to inform the future design of disposal and take-back programs. Each incident case of opioid abuse incurs approximately $14,000 in cost for commercial health plans.3,4 Prior research has shown that two-third of opioids diverted for non-medical use come from family members and friends, including intentional and unintentional diversion.5
Around two-thirds of patients do not dispose of unused prescription opioids, according to the study. When healthcare providers discuss the importance of disposal of unused prescription opioids, patients are 2.5 times more likely to properly dispose of their unused opioids. Patients prefer disposal methods involving kiosks and drug take-back programs. These results reinforce the need to educate patients about the importance of disposing unused opioid medications, and for providing easy access to disposal methods through kiosks and drug take-back programs.
Although these results match previous reports, these 152 patients cannot be assumed to represent all pain patients.
The professional product labeling for OxyContin contains the following Boxed Warning:
|WARNING: ADDICTION, ABUSE AND MISUSE; 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)].
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 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 (5.4), 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 (5.5), 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.
ADULT INDICATIONS AND USAGE
OXYCONTIN 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 risks of overdose and death with extended-release opioid formulations, reserve OXYCONTIN 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.
- OXYCONTIN is not indicated as an as-needed (prn) analgesic.
- 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
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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 after concurrent administration of certain CNS depressant drugs (e.g., 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.
- 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.
- 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 exacerbations 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Full Prescribing Information for OxyContin® (oxycodone HCl) extended-release tablets, including Boxed Warning, is available at http://app.purduepharma.com/xmlpublishing/pi.aspx?id=o.
The Academy of Managed Care Pharmacy (AMCP) is the nation’s leading professional association dedicated to increasing patient access to affordable medicines, improving health outcomes and ensuring the wise use of health care dollars. Through evidence- and value-based strategies and practices, the Academy’s 8,000 pharmacists, physicians, nurses and other practitioners manage medication therapies for the 270 million Americans served by health plans, pharmacy benefit management firms, emerging care models and government. www.amcp.org
ABOUT PURDUE PHARMA L.P.
Purdue Pharma is a privately-held pharmaceutical company and is part of a global network of independent associated companies that is known for pioneering research in chronic pain and opioids with abuse deterrent properties. The company’s leadership and employees are committed to providing healthcare professionals, patients and caregivers quality products and educational resources to support their proper use. Purdue Pharma is engaged in the development, production and distribution of both prescription and over-the-counter medicines and hospital products. With Purdue Pharma’s expertise in drug development, commercialization and life-cycle management, the company is diversifying in high-need areas to expand through strategic acquisitions and creative partnerships. For more information, please visit www.purduepharma.com.
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Purdue Pharma L.P.
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