Purdue Pharma Urges Accuracy in Communications
on Abuse-Deterrent Formulations of Opioids
STAMFORD, Conn. – September 24, 2018 – Marcelo E. Bigal MD, Ph.D. Chief Medical Officer, Purdue Pharma L.P., issued the following statement today:
The nation’s opioid crisis is a significant and urgent public health challenge, and Purdue Pharma is deeply concerned about the toll this crisis is having on communities. While we no longer market opioids to prescribing healthcare professionals through a sales team, we remain committed to patients who need this important therapy.
Recent public statements regarding opioid formulary coverage have incorrectly conveyed that OxyContin® (oxycodone HCL)1 is not approved as an abuse deterrent formulation by the FDA, and that certain other opioids with abuse-deterrent properties (ADP) are less likely to be abused. As the company that brought the first FDA-approved opioid medicine with ADP to the market, we believe it is important to correct this misinformation.
OxyContin® extended-release tablets were reformulated eight years ago with properties expected to deter intranasal and intravenous abuse. In 2010, after nearly a decade of research and development, Purdue received FDA-approval for reformulated OxyContin with abuse-deterrent properties. In 2013, FDA updated the label stating, ‘FDA has determined that the reformulated version of OxyContin has abuse-deterrent properties and has approved new labeling that indicates that the product has physical and chemical properties that are expected to make abuse by injection difficult and to reduce abuse via the intranasal route.’
Most importantly, different abuse-deterrent formulations use different methods to deter abuse. No formulation has been approved to claim based on human liking studies or real-world data that it is better or safer than another, and none are abuse-proof or less addictive. Instead, each abuse deterrent formulation offers different options for prescribers and patients. Inaccurate characterizations of these different formulations may lead to a false sense of security by patients and/or their health care providers. It is therefore incumbent upon healthcare plans, prescribers, and anyone publicly discussing these medicines to understand these facts and communicate them accurately.
Opioids with abuse-deterrent properties are not by themselves a solution. The currently available FDA-approved opioids with abuse-deterrent properties are expected to make certain routes of abuse more difficult, but each also has vulnerabilities. The FDA also recognizes that post marketing studies are needed in order to assess the real world impact of abuse deterrent formulations. Nonetheless, they are recognized by leading government agencies and elected officials as part of a multifaceted approach to addressing prescription opioid abuse.
All resources should be available and responsibly considered to help address this crisis and to help stem the tide of opioid-related deaths.
About Purdue Pharma
Purdue Pharma L.P. develops and provides prescription medicines that meet the evolving needs of healthcare professionals, patients, and caregivers. We were founded by physicians and we are currently led by a physician. Beyond our efforts to provide quality medications, Purdue is committed to supporting national, regional and local collaborations to drive innovations in patient care. Privately held, Purdue is pursuing a pipeline of new medications and technologies through internal research & development and strategic industry partnerships. For more information, please visit www.purduepharma.com.
- OxyContin [Full Prescribing Information]. Stamford, CT: Purdue Pharma LP, 2016.
- Seth P, Scholl L, Rudd RA, Bacon S. Overdose Deaths Involving Opioids, Cocaine, and Psychostimulants — United States, 2015–2016. MMWR Morb Mortal Wkly Rep 2018;67:349–358. DOI: http://dx.doi.org/10.15585/mmwr.mm6712a1.
See OxyContin® Full Prescribing Information and Boxed Warning below.
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.
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
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. Addiction can occur in patients appropriately prescribed OxyContin, 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 during therapy for the development of these behaviors and conditions.
Instruct patients to swallow the OxyContin tablets intact. Crushing, chewing, snorting, or injecting the dissolved product could result in overdose and death.
Serious, life-threatening, or fatal respiratory depression has been reported with 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 dosage increase; therefore, closely monitor patients for respiratory depression, especially within the first 24-72 hours of initiating therapy with and following dosage increases of OxyContin. Proper dosing and titration of OxyContin are essential. Overestimating the OxyContin dosage 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.
Concomitant use with a CYP3A4 inhibitor, particularly when an inhibitor is added after a stable dose of OxyContin is achieved, and discontinuation of a CYP3A4 inducer 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 other CNS depressants (e.g., non-benzodiazepine 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. Follow patients closely for signs and symptoms of respiratory depression and sedation.
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. Closely monitor elderly, cachectic, or debilitated patients, and patients with chronic obstructive pulmonary disease or cor pulmonale because of the increased risk of life-threatening respiratory depression. 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. Monitor patients during dosage initiation and titration. Avoid use of OxyContin in patients with circulatory shock.
Monitor patients closely who may be susceptible to the intracranial effects of CO2 retention 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.
OxyContin is contraindicated in patients with gastrointestinal 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. The oxycodone in OxyContin may cause spasm of the sphincter of Oddi. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening of symptoms.
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 or partial agonist analgesics in patients who are receiving OxyContin, as they may reduce the analgesic effect and/or precipitate withdrawal. 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.
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.
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