Other drug companies began marketing their own narcotic painkillers for routine injuries. OxyContin accounted for a third of all sales revenue from painkillers that year, according to industry data. Rates of addiction and overdose have soared alongside the rise in prescriptions. News coverage of these problems in Appalachia and New England in the late s made OxyContin notorious.
Purdue dispatched representatives to Virginia, Maine and elsewhere to defend its drug. They blamed misuse of OxyContin and insisted their pill was a godsend for pain sufferers when taken as directed.
David Haddox, told a reporter in The U. Justice Dept. The company eventually rolled out a tamper-resistant version of the painkiller that was harder to crush and snort. Subscribe today for unlimited access to exclusive investigations, breaking news, features and more. But in all the scrutiny of Purdue and OxyContin, the problem of the drug wearing off early was not addressed. In reports to headquarters, they wrote that many physicians were prescribing it for three or even four doses a day.
Lawrence Robbins started prescribing OxyContin at his Chicago migraine clinic shortly after it hit the market. But insurance carriers often refused to cover the pharmacy bill for more than two pills a day, he said.
Over the years, he wrote insurance companies more than 25 times on behalf of patients who he believed needed OxyContin more frequently than every 12 hours, he said. In some cases, the insurers relented. When others did not, Robbins switched the patients to another drug. In this letter, a Purdue regional manager writes that he is concerned about doctors prescribing OxyContin at 8-hour intervals. Sales reps should visit those physicians and convince them to go back to hour dosing, he writes.
Data analyzed by company employees showed that one in five OxyContin prescriptions was for use every eight hours, or even more frequently. Purdue held closed-door meetings to retrain its sales force on the importance of hour dosing, according to training documents, some included in sealed court files and others described in FDA files. In a petition to the FDA, attorneys for the state of Connecticut described the alarm inside Purdue when some doctors began prescribing OxyContin at more frequent intervals.
There is no ceiling on the amount of OxyContin a patient can be prescribed, sales reps were to remind doctors, according to the presentation and other training materials.
After some physicians began prescribing OxyContin more frequently than every 12 hours, Purdue summoned its sales force to special seminars. As this presentation shows, company officials were concerned more frequent dosing would hurt business. Higher doses did mean more money for Purdue and its sales reps. Commissions and performance evaluations for the sales force were based in part on the proportion of sales from high-dose pills.
In this memo entitled "It's Bonus Time in the Neighborhood," a Purdue sales manager told her staff to talk up stronger doses of OxyContin in conversations with doctors. In the training materials reviewed by The Times, little was said about the effect of higher doses on patient health.
Those on higher doses of opioids are more likely to overdose, according to numerous research studies. An analysis of the medical records of more than 32, patients on OxyContin and other painkillers in Ontario, Canada, found that one in 32 patients on high doses fatally overdosed.
As a varsity athlete at the University of Central Florida and later a public school teacher, Burgess MacNamara was used to following rules. That changed in when he had knee surgery and his doctor put him on OxyContin. Your whole day revolves around that. Within a month, he was crushing and snorting the pills.
Within a year, he was forging prescriptions. He eventually tried heroin, which was cheaper, and other drugs. MacNamara was arrested for forging prescriptions, possession of controlled substances, stealing pills from a school clinic and other drug-fueled crimes. He lost his teaching career and spent 19 months behind bars. A separate study underwritten by a Purdue competitor, Janssen Pharmaceutica, reached a similar conclusion. In the real world practice of medicine, some doctors turned away from OxyContin entirely.
San Francisco public health clinics stopped dispensing the painkiller in , based in part on feedback from patients who said it wore off after eight hours. The clinics switched to generic morphine, which has a similar duration and costs a lot less.
Mitchell Katz, then head of the San Francisco public health department, said in an interview. One of the plaintiffs was a retired Alabama businessman named H.
Jerry Bodie. His doctor had Bodie on 30 milligrams of OxyContin every eight hours for chronic back pain. A Purdue sales rep persuaded him to switch Bodie to a higher dose every 12 hours, according to a judge's summary of the evidence. The doctor kept raising the dose, eventually putting Bodie on milligrams a day. Purdue got suits dismissed by asserting, among other defenses, a legal doctrine which shields drug companies from liability when their products are prescribed by trained physicians.
Purdue settled other lawsuits on confidential terms. In a federal suit, Alabama businessman H. Jerry Bodie accused Purdue of overstating the duration of OxyContin, among other complaints. The lawsuit was dismissed. In these legal battles, the company successfully petitioned courts to have evidence sealed, citing the need to protect trade secrets. In the fall of , in a remote courthouse in Appalachia, the hour dosing issue came close to a public airing.
In describing problems with OxyContin, many said the drug wore off hours early. All these efforts failed. April: On April 1, FDA issued a final guidance to assist industry in developing opioid drug products with potentially abuse-deterrent properties. July: On July , FDA, in collaboration with the National Institutes of Drug Abuse, the Centers for Disease Control and Prevention, the Substance Abuse and Mental Health Services Administration, and the Health Resources and Services Administration, held a scientific workshop to initiate a public discussion about issues surrounding the uptake of naloxone in certain medical settings — such as on ambulances and in association with prescriptions for opioids — as well as outside of conventional medical settings to reduce the incidence of opioid overdose fatalities.
Discussions focused on which populations are at risk for opioid overdose; how public health groups can work together to use naloxone to reduce the risk of overdose; and legal, regulatory, logistical and clinical aspects related to making naloxone more widely available. August: On August 13, FDA approved OxyContin for certain pediatric patients for pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.
This approval is limited to opioid-tolerant pediatric patients 11 and up who are already taking and tolerating a minimum daily dose of at least 20 mg oxycodone orally or its equivalent.
These patients can be expected to remain on treatment with an opioid for several weeks or more. October: On October 2, FDA approved MorphaBond morphine sulfate , an extended-release ER opioid analgesic to treat pain severe enough to require daily, around-the-clock, long-term opioid treatment for which alternative treatment options are inadequate. MorphaBond has properties that are expected to reduce, but not eliminate, abuse of the drug when crushed and snorted or injected. November: On November 18, FDA approved Narcan nasal spray , the first FDA-approved nasal spray version of naloxone hydrochloride, a life-saving medication that can temporarily stop or reverse the effects of an opioid overdose, including an overdose from heroin.
The plan will focus on policies aimed at reversing the epidemic, while still providing patients in pain access to effective relief. On February 4, FDA released five postmarketing PMR requirements announced on September 13, , and replaced them with 11 PMRs 10 postmarketing studies and one clinical trial because the 10 postmarketing observational studies and one clinical trial include refined measures for assessing the known serious risks of misuse, abuse, addiction, overdose, and death.
This joint meeting is scheduled for September 15 and 16, and during this meeting the FDA will be calling on a broad range of independent experts with real-world experience to provide recommendations on how to address the unique needs of children in pain. March: On March 1, the FDA convened the Science Board to hear about and discuss a range of pressing issues related to the current opioid epidemic, including: 1 the role of opioids in pain management; 2 scientific challenges facing FDA in supporting the development of pain medications 3 scientific challenges facing FDA in seeking to understand the real-world use of opioids to treat pain 4 the role that FDA plays as a part of a larger Federal, State and local response to the challenges of providing appropriate pain treatment while reducing opioid abuse; and 5 postmarket surveillance activities related to opioids.
On March 22, FDA announced required class-wide safety labeling changes for immediate-release IR opioid pain medications. Among the changes, the FDA is requiring a new boxed warning about the serious risks of misuse and abuse, which can lead to addiction, overdose and death.
The FDA is also requiring several additional safety labeling changes across all prescription opioid products to include additional information on the risk of these medications. April: On April 26, FDA approved Xtampza ER oxycodone , an extended-release ER opioid analgesic to treat pain severe enough to require daily, around-the-clock, long-term opioid treatment for which alternative treatment options are inadequate.
Xtampza ER has properties that are expected to reduce, but not eliminate, abuse of the drug when crushed and snorted or injected. The committees provided comments as to whether this REMS with Elements to Assure Safe Use ETASU assures safe use, is not unduly burdensome to patient access to the drugs, and to the extent practicable, minimizes the burden to the healthcare delivery system.
On May 26, FDA announced required safety labeling changes for methadone and buprenorphine products when used by pregnant women for medication-assisted treatment MAT of opioid use disorder to ensure providers have complete information about the benefits and risks of these products.
On May 26, FDA approved Probuphine , the first buprenorphine implant for the maintenance treatment of opioid dependence.
Probuphine, an implant designed to provide a constant, low level of buprenorphine for six months, should be used in patients who are already stable on low-to-moderate doses of other forms of buprenorphine and as part of a complete treatment program that includes counseling and psychosocial support. August: On August 19, FDA approved Troxyca ER oxycodone hydrochloride and naltrexone hydrochloride extended-release capsules , an extended-release ER opioid analgesic to treat pain severe enough to require daily, around-the-clock, long-term opioid treatment for which alternative treatment options are inadequate.
Troxyca ER has properties that are expected to reduce, but not eliminate, abuse of the drug when crushed and then taken orally, snorted, or injected. On August 31, FDA announced required class-wide changes to drug labeling to help inform health care providers and patients of the serious risks associated with the combined use of certain opioid medications and a class of central nervous system depressant drugs called benzodiazepines.
Among the changes, the FDA is requiring boxed warnings and Medication Guides for prescription opioid analgesics, opioid-containing cough products, and benzodiazepines with information about the serious risks, including extreme sleepiness, respiratory depression, coma and death, associated with using these medications at the same time. September: On September , the FDA convened a joint meeting of the Anesthetic and Analgesic Drug Products Advisory Committee, the Drug Safety and Risk Management Advisory Committee, and the Pediatric Advisory Committee to discuss the appropriate development plans for establishing the safety and efficacy of prescription opioid analgesics for pediatric patients, including obtaining pharmacokinetic data and the use of extrapolation.
October: On October 5, the FDA convened a joint meeting of the Anesthetic and Analgesic Drug Products Advisory Committee and the Drug Safety and Risk Management to discuss naloxone products intended for use in the community, specifically the most appropriate dose or doses of naloxone to reverse the effects of life-threatening opioid overdose in all ages, and the role of having multiple doses available in this setting.
The committees also discussed the criteria prescribers will use to select the most appropriate dose in advance of an opioid overdose event and the labeling to inform this decision, if multiple doses are available.
On October 31 — November 1, the FDA held a public meeting, Pre-Market Evaluation of Abuse-Deterrent Properties of Opioid Drug Products , to discuss scientific and technical issues relating to formulation development and pre-market evaluation of opioid drug products with abuse-deterrent properties. December : On December 16, the FDA approved several safety labeling changes SLCs about the serious risks of prescription opioid analgesics and opioids approved for medication assisted treatment MAT of opioid addiction including class-wide SLCs for immediate-release IR opioid pain medications , SLCs for methadone and buprenorphine products , and class-wide SLCs about the serious risks associated with the combined use of certain opioid medications with benzodiazepines or other central nervous system CNS depressants.
January: On January 9, FDA approved Arymo ER morphine sulfate extended-release tablets , an extended-release ER opioid analgesic to treat pain severe enough to require daily, around-the-clock, long-term opioid treatment for which alternative treatment options are inadequate. Arymo ER is formulated to give it physicochemical properties expected to make abuse by injection difficult. On January 17, FDA approved Vantrela ER hydrocodone bitartrate extended-release tablets , an extended-release ER opioid analgesic to treat pain severe enough to require daily, around-the-clock, long-term opioid treatment for which alternative treatment options are inadequate.
The physical and chemical properties of Vantrela ER are expected to make intravenous injection abuse difficult and are expected to reduce, but not eliminate, abuse by nasal and oral routes. However, abuse of Vantrela ER by these routes is still possible. April: On April 20, FDA announced the restricted the use of codeine and tramadol medicines in children because these medicines carry serious risks, including slowed or difficult breathing and death, which appear to be a greater risk in children younger than 12 years, and should not be used in these children.
These medicines should also be limited in some older children. The FDA also recommended against the use of codeine and tramadol medicines in breastfeeding mothers due to possible harm to their infants. On April 20, the FDA approved RoxyBond oxycodone hydrochloride , an opioid analgesic indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.
Based on laboratory studies, RoxyBond tablets are resistant to certain forms of manipulation such as crushing, grinding, or otherwise extracting oxycodone from the tablet that are typically used to make opioids easier to abuse by the nasal and intravenous routes.
May: On May , FDA held a public meeting, Training Health Care Providers on Pain Management and Safe Use of Opioid Analgesics — Exploring the Path Forward , to obtain input on issues and challenges associated with Federal efforts to support training on pain management and the safe prescribing, dispensing, and patient use of opioids safe use of opioids for health care providers.
On May 10, FDA released the " FDA Education Blueprint for Health Care Providers Involved in the Management or Support of Patients with Pain" draft revisions to the Blueprint , which broadens the current Blueprint to include information on pain management, including the principles of acute and chronic pain management; non-pharmacologic treatments for pain; and pharmacologic treatments for pain both non-opioid analgesic and opioid analgesic.
June: On June 8, FDA requested that Endo Pharmaceuticals remove its opioid pain medication, reformulated Opana ER oxymorphone hydrochloride , from the market based on its concern that the benefits of the drug may no longer outweigh its risks. Scott Gottlieb and Dr. On July 13, the National Academies of Science, Engineering, and Medicine release the consensus report , commissioned by the FDA, which outline the state of the science regarding prescription opioid abuse and misuse, as well as the evolving role that opioids play in pain management.
September: On September 11, FDA held a Pediatric Advisory Committee meeting to discuss the use of prescription opioid products containing hydrocodone or codeine for the treatment of cough in pediatric patients. The discussion included current practice for the treatment of cough in children and benefit-risk considerations regarding the use of prescription opioid products in pediatric patients.
On September 20, FDA advised that the opioid addiction medications buprenorphine and methadone should not be withheld from patients taking benzodiazepines or other drugs that depress the central nervous system CNS.
The combined use of these drugs increases the risk of serious side effects; however, the harm caused by untreated opioid addiction can outweigh these risks. Careful medication management by health care professionals can reduce these risks. On November 30, FDA approved Sublocade , the first once-monthly injectable buprenorphine product for the treatment of moderate-to-severe opioid use disorder in adult patients who have initiated treatment with a transmucosal absorbed through mucus membrane buprenorphine-containing product.
It is indicated for patients that have been on a stable dose of buprenorphine treatment for a minimum of seven days. December: On December , FDA hosted a public workshop regarding the role of packaging, storage, and disposal options within the larger landscape of activities aimed at addressing abuse, misuse, or inappropriate access of prescription opioid drug products; guiding principles and considerations for the design of packaging, storage, and disposal options for opioids; integrating packaging, storage, and disposal options into existing health care and pharmacy systems, including both open and closed health care systems; data needs and how to address challenges in assessing the impact of packaging, storage, and disposal options in both the premarket and postmarket settings; and ways in which FDA could encourage the development and assessment of packaging, storage, and disposal options for opioids that have the potential to enhance opioid safety.
Part of the Roadmap is reducing misuse and abuse of opioid drugs. On January 11, FDA announced that it is requiring safety labeling changes for prescription cough and cold medicines containing codeine or hydrocodone to limit the use of these products to adults 18 years and older because the risks of these medicines outweigh their benefits in children younger than The agency is also requiring the addition of safety information about the risks of misuse, abuse, addiction, overdose, death, and slowed or difficult breathing to the Boxed Warning of the drug labels for prescription cough and cold medicines containing codeine or hydrocodone.
On January 24, FDA and the Federal Trade Commission posted joint warning letters to the marketers and distributors of 12 opioid cessation products, for illegally marketing unapproved products with claims about their ability to help in the treatment of opioid addiction and withdrawal. It is important to note that the revised Blueprint will not be considered final until the Opioid Analgesic Risk Evaluation and Mitigation Strategy is approved.
The committees also discussed the abuse potential of this non-abuse-deterrent product and whether it should be approved.
March : On March 27, FDA held a meeting of the Psychopharmacologic Drugs Advisory Committee to discuss the new drug application for lofexidine hydrochloride , submitted by US WorldMeds, LLC, for mitigation of symptoms associated with opioid withdrawal and facilitation of completion of opioid discontinuation treatment. May : On May 16, FDA approved Lucemyra lofexidine hydrochloride , the first non-opioid treatment for the mitigation of withdrawal symptoms associated with abrupt discontinuation of opioids.
The committees will also be asked to discuss whether this product should be approved. June : On June 1, FDA sent safety labeling change notification letters to drug companies with approved opioid analgesic products intended for use in an outpatient setting, which require the companies to include new safety information regarding the Opioid Analgesic REMS in the Boxed Warning and Warnings and Precautions sections of prescribing information due to a general lack of awareness of the REMS among all opioid analgesic prescribers.
June: On June 5, FDA took action against 53 websites marketing unapproved opioids as part of a comprehensive effort to target illegal online sales. June: On June 26, FDA convened a joint meeting of the Anesthetic and Analgesic Drug Products Advisory Committee and the Drug Safety and Risk Management Advisory Committee to discuss the new drug application for oxycodone extended-release capsules , submitted by Pain Therapeutics, with the proposed indication of the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.
The product is intended to have abuse-deterrent properties based on its physicochemical properties. The committees will be asked to discuss whether the data submitted by the Applicant are sufficient to support labeling of the product with the properties expected to deter abuse.
June: On June 27, FDA convened internet stakeholders, government entities, academic researchers, and advocacy groups at a one-day Online Opioid Summit to discuss ways to collaboratively take stronger action in combatting the opioid crisis by reducing the availability of illicit opioids online. On August 22, FDA awarded a contract to the National Academies of Sciences, Engineering, and Medicine NASEM to help advance the development of evidence-based guidelines for appropriate opioid analgesic prescribing for acute pain resulting from specific conditions or procedures.
September : On September 7, FDA approved a new dosage strength of buprenorphine and naloxone sublingual film as maintenance treatment for opioid dependence. The committee also discussed the efficacy and safety data and benefit-risk considerations. But nine states and others had opposed it, largely because of the protections granted to the family. The attorneys general of Connecticut, the District of Columbia and Washington state immediately announced they will either appeal the ruling or explore the possibility of doing so.
Some families who lost loved ones to drugs also came out against the settlement, including Ed Bisch, of Westampton, New Jersey, whose year-old son died of an overdose nearly 20 years ago. But other families said they did not want to risk losing the money that will go toward treatment and prevention.
The bankruptcy judge, based in White Plains, New York, had urged the holdouts to work out an agreement for the same reason. Some of the opioid deaths over the past two decades have been attributed to OxyContin and other prescription painkillers, but most are from illicit forms of opioids such as heroin and illegally produced fentanyl.
Opioid-linked deaths in the U. The crisis devastated the reputation of the Sackler family, major philanthropists whose name was once emblazoned on the walls of museums and universities around the world.
With the settlement, family members who have owned the company will still be worth billions. Another branch of the Sackler family has had no involvement with Purdue for decades. Whether the deal holds the Sacklers sufficiently accountable was the most contentious question through the proceedings. David Sackler, a former Purdue board member, had testified that family members would not accept the agreement unless it protected them from lawsuits.
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