FDA Stands By Approval of OxyContin
FDA has repeatedly reviewed the approval process for OxyContin over the last quarter-century. FDA stands by its prior approval of OxyContin and the continued use of the medication.
FDA Repeatedly & Consistently Stands By Approval of OxyContin
1995
FDA approves OxyContin as “safe and effective” for patients with moderate to severe chronic pain following six clinical trials by Purdue. (OxyContin was never indicated for short-term pain such as from broken bones or immediately after surgery.)
2001
Purdue works with FDA to add Black Box Warning and notify physicians of label changes
2002
FDA says “benefits of OxyContin outweigh its risks”[1]
2008
FDA denies “citizen petition” for Purdue to revise OxyContin label[2]
2010
FDA approves abuse-deterrent formulation of OxyContin in comprehensive review of medication
2013
FDA confirms that reformulated OxyContin has abuse-deterrent properties and rejects request to implement maximum daily dose for physicians to prescribe[3]
JANUARY 2020
FDA Director of Center for Drug Evaluation and Research (now FDA Acting Commissioner) Janet Woodcock sends letter to U.S. Senate asserting propriety of OxyContin approval process[4]
MARCH 2021
FDA again confirms its approval of OxyContin[5]
False claims of misconduct in connection with FDA approval of OxyContin investigated multiple times by DOJ – with no action taken
Purdue Acted Properly & Provided Extensive Data During FDA Approval Process
- Purdue’s submissions to the FDA for OxyContin’s approval were comprehensive and in compliance with all rules and regulations.
- The Department of Justice twice investigated the circumstances of OxyContin’s approval and did not take any action.
- Purdue developed OxyContin for several years, with clinical trials beginning years prior to approval.
- FDA commented that Purdue’s application for OxyContin was “unusually robust.”[6]
- FDA approval of OxyContin’s New Drug Application (NDA) was based on six controlled clinical trials that showed the medicine is “safe and effective” – significantly more than the industry standard of two clinical trials.
- Three of the six clinical trials were for cancer pain; the others were for conditions such as osteoarthritis, low back pain and post-operative pain. (More than 700 patients participated in the trials.)
- FDA constantly monitors and evaluates the safety of OxyContin based on available science.
Purdue’s clinical trials for OxyContin were later used internally at the FDA to train new medical officers on the proper design and conduct of analgesic clinical trials.
Purdue’s trials were described as the “gold standard.”[6]
1995-Today OxyContin’s Label Has Always Disclosed Risk of Addiction
FDA-approved OxyContin label has always disclosed risks of abuse and addiction:
- All opioids have been known to have the risk of addiction for hundreds of years.
- Risks of abuse, addiction and death have consistently been disclosed.
- The label has repeatedly been updated to reflect advances in scientific knowledge.
- A Black Box Warning has been prominently displayed since 2001.
- Purdue communicated warnings and label revisions clearly to healthcare providers.
Original 1995 Label
WARNING: May be Habit Forming
OxyContin is a mu-agonist with an abuse liability similar to morphine, and is a Schedule II controlled substance.
Oxycodone products are common targets for both drug abusers and addicts.
Patients should be advised that OxyContin is a potential drug of abuse. They should protect it from theft, and it should never be given to anyone other than the individual for whom it was prescribed.
Physicians should be aware that psychological dependence may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true psychological dependence and is characterized by misuse for non-medical purposes.
OxyContin … TABLETS ARE TO BE SWALLOWED WHOLE, AND ARE NOT TO BE BROKEN, CHEWED OR CRUSHED. TAKING BROKEN, CHEWED OR CRUSHED OxyContin TABLETS COULD LEAD TO … A POTENTIALLY TOXIC DOSE OF OXYCODONE.
… care should be taken to prevent diversion or abuse by proper handling.
2001 Prescription Opioids, & OxyContin in Particular, Are Subjected to an Intense National Health Review
The need to preserve OxyContin’s important role in pain management was established, understood and stressed.
“Concerns of addiction should not prevent patients with appropriate pain conditions from using OxyContin or other narcotics for pain relief.”
OxyContin Q&A, JULY 26, 2001[7]
2001 Language Strengthened Further & Black Box Warning Added to Label
Removed statements:
- “Delayed absorption, as provided by OxyContin tablets, is believed to reduce the abuse liability of a drug”
- “Iatrogenic ‘addiction’ to opioids legitimately used in the management of pain is very rare.”
Revised Label:
- Black Box Warning, the highest level of warning to physicians, added to OxyContin’s label.
- “Misuse, Abuse and Diversion of Opioids”
- Oxycodone is an opioid agonist of the morphine-type. Such drugs are sought by drug abusers and people with addiction disorders and are subject to criminal diversion.
- Oxycodone can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing OxyContin in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion.
- OxyContin has been reported as being abused by crushing, chewing, snorting, or injecting the dissolved product. These practices will result in the uncontrolled delivery of the opioid and pose a significant risk to the abuser that could result in overdose and death (see WARNINGS and DRUG ABUSE AND ADDICTION).
July 2001
2001 Purdue Letter to Prescribers Alerting Them to Label Changes
In 2001, Purdue sent “Dear Doctor” letters to 800,000 physicians[8] nationwide informing them about the new label.
July 18, 2001
“FDA worked with Purdue to develop ‘Dear Health Care Professional’ letters, which the company distributed widely to health care professionals to alert them that the package insert had been revised to clarify the indication and strengthen the warnings related to misuse, abuse, and diversion.”
[9]
December 2003
2002 FDA Says “Benefits of OxyContin Outweigh its Risks”
“FDA continues to believe that the benefits of OxyContin outweigh its risks when the drug is used according to the approved labeling.”
Dr. John Jenkins, Director of FDA Office of New Drugs, Center for Drug Evaluation and Research – February 12, 2002[1]
2008 FDA Denies Connecticut AG’s “Citizen Petition” for Purdue to Revise OxyContin Label
- In 2004, Connecticut Attorney General Richard Blumenthal submitted a citizen petition to the FDA, seeking to revise the OxyContin label with additional warnings about the risk of taking the medication at more frequent intervals.
- FDA denied the petition in 2008,[2] concluding it “failed to provide sufficient information to demonstrate an association between dosing OxyContin more frequently than q12h and an increased risk of developing side effects and potentially serious adverse reactions.”
“Since 1995 when OxyContin was approved, the FDA has monitored and evaluated the safety concerns associated with OxyContin and has held meetings with Purdue, Congress, other agencies, and convened Advisory Committees regarding such issues. We will continue to closely monitor the safety of OxyContin and take actions as we believe appropriate.”
Janet Woodcock, M.D., Director, Center for Drug Evaluation & Research at FDA, SEPTEMBER 9, 2008[2]
September 9, 2008
2010 FDA Approves Abuse-Deterrent Formulation of OxyContin Following Comprehensive Review
Early 2000s
Purdue begins investing in research to create an abuse-deterrent formulation of OxyContin
2010
FDA approves abuse-deterrent formulation that makes tablets difficult to crush and Purdue begins to replace original formulation
2011
Purdue replaces all tablets sold in the U.S. with the abuse-deterrent formulation
2013
FDA approves abuse-deterrent labeling for reformulated OxyContin after extensive review of studies created after the introduction of the ADF[3]
2020
FDA review team finds reformulated OxyContin reduced abuse by non-oral routes[11]
2021
FDA continues to encourage the development of abuse-deterrent opioids[10]
“These postmarketing studies demonstrate that the abuse-deterrent properties of OxyContin have had the predicted effects on abuse and provide an incremental improvement over the original formulation that did not have these properties.”
Purdue pharma postmarketing requirement briefing document, September 2020[11]
2013 Government Officials Praise Purdue’s Abuse-Deterrent Formulation
Forty-two Attorneys General Signed Letter to FDA, Thanking the Organization For its Efforts to Combat Opioid Abuse
“The State Attorneys General want to thank you for your recent efforts to ensure branded opioid drugs have abuse-deterrent formulations. But we must go further. Ensuring generic opioids, like their branded counterparts, have abuse-deterrent properties is a commonsense improvement that provides yet another important tool in the fight against our nation’s prescription drug epidemic.”
Letter from AGs to FDA, December 16, 2013[12]
Connecticut Gov. Dannel Malloy Said Reformulated OxyContin Deterred Abuse
“I encourage the FDA to consider seriously the public health and safety benefits of abuse deterrent formulations of opioids. These studies make a strong case that certain abuse-deterrent features make it harder to abuse OxyContin.”
Letter from D. Malloy, February 27, 2013[13]
2013 FDA Determined Reformulated OxyContin Has Abuse Deterrent Properties & Continues to Encourage Development of Abuse-Deterrent Opioids
FDA Press Release Announcing Approval of Abuse-Deterrent Labeling
“The FDA has determined that the reformulated product has abuse deterrent properties. The tablet is more difficult to crush, break, or dissolve. It also forms a viscous hydrogel and cannot be easily prepared for injection.”
April 16, 2013[3]
Current FDA website
“The FDA is encouraging the development of prescription opioids with abuse-deterrent formulations (ADFs) to help combat the opioid crisis. The agency recognizes that abuse-deterrent opioids are not abuse- or addiction-proof but are a step toward products that may help reduce abuse.”
As of March 8, 2021[10]
2013 FDA Rejected PROP Petition Asking for Maximum Daily Dose
Physicians for Responsible Opioid Prescribing (“PROP”) Petition asked the FDA:
“Add a maximum daily dose, equivalent to 100 milligrams of morphine for non-cancer pain . . . [because t]hree large observational studies published in 2010 and 2011 found dose-related overdose risk in CNCP patients on [chronic opioid therapy].”
September 2013[14]
FDA refused because:
“… the scientific literature does not support establishing a maximum recommended daily dose of 100 mg MED.”
September 2013
2020 (January) Letter to Senate from FDA Director of Center for Drug Evaluation & Research (now FDA Acting Commissioner) Janet Woodcock Asserting Propriety of OxyContin Approval Process:
- “FDA has examined the original 1995 approval of OxyContin, the approvals of the supplemental applications for the 80-mg and 160-mg strengths, and the approval of the 2001 safety labeling change. All applicable statutes and regulations were followed.”
- “Approval was based on efficacy findings from six controlled studies.”
- “… when OxyContin was approved in 1995 it was not limited to the treatment of acute pain or otherwise limited in its duration of use. Chronic or long-term use (in appropriate situations), with no maximum duration, was always part of the approved use of OxyContin.”
- “The disturbing reality that there are individuals who will intentionally prescribe and dispense opioids inappropriately for financial gain underscores the complex factors that contribute to the opioid crisis.”
- “OxyContin is not appropriate for ‘as-needed dosing’ (PRN), or in the immediate post-operative period if pain is mild or not expected to persist for an extended period of time.”
- “FDA also recently funded a research project to study the effect of opioid analgesic deprescribing (i.e., tapering and/or discontinuing) on patient outcomes, including suicidality, completed suicide, and overdose…”
Estimated Number of Prescriptions Dispensed for Opioid Analgesics vs. Oxycodone Extended-Release from U.S. Outpatient Pharmacies[4]
2021 (March) FDA Approves OxyContin (Again) for Patients with Severe Pain
“OxyContin is an opioid agonist 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 in adults. ”
March 2021 OxyContin Label[5]
Neither FDA Nor Purdue Anticipated Level of Abuse That Occurred
FDA and Purdue expected that any abuse of OxyContin would be similar to the experience with Purdue’s long-acting morphine medication, MS Contin. To this day, the FDA stands by this fact.
1995
OxyContin’s original 1995 label disclosed risk of addiction: “Delayed absorption as provided by OxyContin tablets, is believed to reduce the abuse liability of a drug.”
2002
FDA’s John K. Jenkins testified before U.S. Senate: “At the time of approval, FDA also considered the abuse potential of OxyContin and determined that its abuse potential was similar to that of other Schedule II narcotics and we did not foresee the widespread abuse and misuse of OxyContin that has been reported in the past few years. Despite these troubling reports, however, FDA continues to believe that the benefits of OxyContin outweigh its risks when the drug is used according to the approved labeling.”[1]
2002
FDA’s John K. Jenkins testified before U.S. Senate: “In part, FDA based its judgment of the abuse potential for OxyContin on the prior marketing history of a similar product, MS-Contin, a controlled-release formulation of morphine that had been marketed in the U.S. by Purdue Pharma without significant reports of abuse and misuse for many years.”[1]
2019
FDA said: “There was no evidence to suggest at the time that crushing the controlled-release capsule followed by oral ingestion or snorting would become widespread and lead to a high level of abuse.”[16]
2020
FDA continues to recognize opioid analgesics taken as prescribed rarely cause addiction: “According to the National Institutes of Health, studies have shown that properly managed medical use of opioid analgesic compounds (taken exactly as prescribed) is safe, can manage pain effectively, and rarely causes addiction.”[17]
False Claims of Misconduct During FDA Approval Process Were Investigated by DOJ Twice – No Action Was Taken
FDA first approved OxyContin in 1995. The Department of Justice has twice investigated the approval process of OxyContin, in 2006–2007 and a decade later in 2016–2018, including specifically regarding statements in the original label and launch materials, the underlying clinical studies, and the independence of the approval process.
False Claim
Purdue defrauded the FDA by not making the FDA aware of a change in the package insert of a competitor’s drug.
Fact
Information about the competitor’s product, which was used as a comparative tool in Purdue’s clinical studies, was publicly known and immaterial to the FDA’s review of OxyContin. Regardless, Purdue brought the information to the FDA’s attention before it began marketing OxyContin.
False Claim
FDA official was improperly involved in the extensive approval process that determined OxyContin is safe and effective.
Fact
- Dr. Curtis Wright had an impeccable service record with the FDA and received several awards, including for Distinguished Service.
- FDA’s team consisted of at least three medical review representatives – as well as additional experts in the areas of biopharmaceutics, pharmacology and toxicology, chemistry, statistics and consumer safety.
- All of Purdue’s interactions with FDA, including formal and informal interactions with Dr. Wright, were logged in contact reports – and summaries were submitted to the FDA on a regular basis.
- During sworn testimony, Dr. Wright explained the process that eventually led to him being hired at Purdue.[18]
- Purdue’s hiring of Dr. Wright was legal, proper and transparent and consistent with industry norms.
FDA Finds “No Clear Evidence” Reformulated OxyContin Led to New Heroin Users, as Media Falsely Suggests
False Narrative
“… after the reconstituted form of OxyContin went on the market in 2010, that balance changed. Prescription opioid death rates began to slow, but overdoses involving heroin more than quintupled.”
February 2019[19]
Fact
However, FDA review team did not find that OxyContin’s abuse-deterrent formulation led to new heroin users.
“There was not clear evidence that OxyContin’s reformulation caused heroin-naïve individuals to initiate use, and the shifts from OxyContin to heroin and other opioids may have often occurred in the setting of pre-existing polysubstance abuse including these drugs.”
Briefing Document, OxyContin Abuse-Deterrent Formulation (ADF), September 2020[21]
Additionally, the National Survey on Drug Use and Abuse found less than 4% of people who abused prescription opioids started using heroin within five years[20].
