Purdue Pharma Statement on FDA Approval of New Label for Reformulated OxyContin and FDA Decision Regarding Withdrawal of Original Formulation Due to Safety
Professional Prescribing Information Now Includes Language Describing Abuse-Deterrence Studies Conducted with the Reformulated Tablets
April 16, 2013 – STAMFORD, Conn. – Purdue Pharma L.P. today announced that the U.S. Food and Drug Administration (FDA) has approved new language for the product label for OxyContin® (oxycodone hydrochloride controlled-release) Tablets CII that describes abuse-deterrence studies conducted with the reformulated tablets. Additionally, Purdue is gratified that the FDA has determined that the original OxyContin extended release tablets were withdrawn from sale for reasons of safety or effectiveness. FDA will not accept or approve any abbreviated new drug applications (generics) that rely upon the approval of original OxyContin.
The new labeling information is reflected in the product label’s Section 9.2 titled Abuse. The updates include:
Change of language in the subsection titled Risks Specific to Abuse of OxyContin
Addition of a new subsection entitled Abuse Deterrence Studies, which includes:
In Vitro Testing Description
Clinical Studies Descriptions featuring a Table and Figure
Table 2: Summary of Maximum Drug Liking (Emax) Data Following Intranasal Administration
Figure 1: Percent Reduction Profiles for Emax of Drug Liking VAS for OxyContin vs. oxycodone HCl, N=27 Following Intranasal Administration
Inclusion of a Summary of the study results
Full prescribing information for OxyContin® is available at www.PurduePharma.com/OxyContinPI. Also, read the boxed warning and additional safety information below.
“Purdue Pharma is pleased with the FDA’s approval of this new language for the OxyContin label, which will provide important information to healthcare professionals,” said Gary L. Stiles, MD, Senior Vice President of Research and Development at Purdue Pharma L.P. “While the data from the abuse-deterrence studies have been included in the product label, OxyContin remains a Schedule II controlled substance and healthcare professionals should continue to exercise care in selecting and monitoring patients when prescribing OxyContin.”
“Prescriber and patient education remains critically important to ensuring the proper use of opioid analgesics,” said Dr. Stiles. “We strongly encourage prescribers to take advantage of the professional education resources developed as part of the Risk Evaluation and Mitigation Strategy (REMS) for extended-release and long-acting opioids.”
In August of 2010, Purdue introduced the reformulated version of OxyContin in an effort to make the tablet more difficult to manipulate for the purpose of misuse and abuse by various routes of administration, e.g., snorting and intravenous (iv) injection. The reformulated tablet has properties intended to prevent it from being easily cut, broken, crushed or dissolved to release more medication. The physical and chemical properties of the reformulated tablet would not, however, be expected to have any impact on misuse or abuse by persons who swallow intact tablets in doses larger than are recommended or without legitimate purpose. Even intact tablets can lead to overdose and death when abused, as they are designed to release the medicine when swallowed.
Purdue has completed laboratory manipulation and extraction testing, pharmacokinetic and abuse “liking” studies for the reformulation of OxyContin. Additionally, Purdue has undertaken a series of epidemiological studies to evaluate in real world settings whether the changes made to OxyContin’s formulation are resulting in a decrease in misuse and abuse and their consequences: addiction, overdose and death. Results from these studies are being reported to the FDA on an ongoing basis and have also been presented at scientific meetings and/or published in peer-reviewed medical journals.
Purdue recognizes that abuse of prescription opioid analgesics is a persistent and significant public health problem. In addition to the risks abusers face, their actions also threaten access to these medicines by patients with legitimate medical need. For these reasons, Purdue is working to incorporate abuse-deterrence technologies into its portfolio of oral, solid-dosage form opioid analgesic products. Amongst multiple ongoing development projects intended to provide abuse deterrence are additional formulations of oxycodone, morphine and a once-daily formulation of hydrocodone bitartrate, which is in the final stages of clinical development and incorporates the same abuse-deterrence technology as reformulated OxyContin.
Developing abuse-deterrence formulations is just one of the initiatives Purdue is undertaking to help reduce the abuse and diversion of prescription medications. Purdue also supports prescriber and patient education as part of a comprehensive approach to address misuse, abuse and diversion of opioid pain medicines, while ensuring that these medications remain accessible for patients with moderate to severe, chronic pain when appropriate. Information on the shared REMS is available at www.ER-LA-opioidREMS.com.
For more information about Purdue’s efforts to prevent and reduce prescription drug abuse, go to www.rxsafetymatters.org.
The professional product labeling for OxyContin® Tablets contains the following boxed warning:
WARNING: ABUSE POTENTIAL, LIFE-THREATENING RESPIRATORY DEPRESSION, and ACCIDENTAL EXPOSURE
OxyContin® contains oxycodone, an opioid agonist and Schedule II controlled substance with an abuse liability similar to other opioid agonists, legal or illicit [see Warnings and Precautions (5.1)]. Assess each patient’s risk for opioid abuse or addiction prior to prescribing OxyContin. The risk for opioid abuse is 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 depressive disorder). Routinely monitor all patients receiving OxyContin for signs of misuse, abuse, and addiction during treatment [see Drug Abuse and Dependence (9)].
Life-Threatening Respiratory Depression
Respiratory depression, including fatal cases, may occur with use of OxyContin, even when the drug has been used as recommended and not misused or abused [see Warnings and Precautions (5.2)]. Proper dosing and titration are essential and OxyContin should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain. Monitor for respiratory depression, especially during initiation of OxyContin or following a dose increase. Instruct patients to swallow OxyContin tablets intact. Crushing, dissolving, or chewing the tablet can cause rapid release and absorption of a potentially fatal dose of oxycodone.
Accidental ingestion of OxyContin, especially in children, can result in a fatal overdose of oxycodone [see Warnings and Precautions (5.3)].
Indications and Usage
OxyContin is indicated for the management of moderate to severe pain when a continuous, around-the-clock opioid analgesic is needed for an extended period of time.
Limitations of Use
OxyContin is not for use:
As an as-needed (prn) analgesic
For pain that is mild or not expected to persist for an extended period of time
For acute pain
In the immediate postoperative period
For postoperative pain, unless the patient is already receiving chronic opioid therapy prior to surgery, or if the postoperative pain is expected to be moderate to severe and persist for an extended period of time
OxyContin 60 mg and 80 mg tablets, a single dose greater than 40 mg, or a total daily dose greater than 80 mg are only for patients in whom tolerance to an opioid of comparable potency is established. Patients considered opioid tolerant are those who are taking at least 60 mg oral morphine/day, 25 mcg transdermal fentanyl/hour, 30 mg oral oxycodone/day, 8 mg oral hydromorphone/day, 25 mg oral oxymorphone/day, or an equianalgesic dose of another opioid for one week or longer.
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 paralytic ileus and gastrointestinal obstruction
Hypersensitivity (e.g., anaphylaxis) to oxycodone
Additional Safety Information
Respiratory depression is the chief hazard of opioid agonists, including OxyContin. Respiratory depression is more likely to occur in elderly, cachectic, and debilitated patients, and patients with chronic pulmonary disease; therefore closely monitor these patients.
Hypotension, and profound sedation, coma or respiratory depression may result if OxyContin is used concomitantly with other CNS depressants (e.g., sedatives, anxiolytics, hypnotics, neuroleptics, muscle relaxants, other opioids). When considering the use of OxyContin in a patient taking a CNS depressant, assess the duration of use of the CNS depressant and the patient’s response, including the degree of tolerance that has developed to CNS depression. If OxyContin therapy is to be initiated in a patient taking a CNS depressant, start with a lower OxyContin dose than usual and monitor patients for signs of sedation and respiratory depression and consider using a lower dose of the concomitant CNS depressant.
Use caution when prescribing OxyContin for patients who have difficulty swallowing or have underlying GI disorders that may predispose them to obstruction. 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.
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 patients in clinical trials comparing OxyContin with placebo are: constipation, nausea, somnolence, dizziness, vomiting, pruritus, headache, dry mouth, asthenia, and sweating.
Full prescribing information for OxyContin® is available at www.purduepharma.com/OxyContinPI
Posted: April 2013