Trump Administration Proposes More Rx Opioid Cuts

By Pat Anson, Editor

For the third year in a row, the U.S. Drug Enforcement Administration is proposing another round of cuts in the supply of opioid pain medication – a 10% reduction in manufacturing quotas in 2019 for several widely used opioids.  The Trump Administration says the pain relievers are “frequently misused” and reducing their supply will help prevent addiction and abuse.

The DEA proposal involves six opioids classified as Schedule II controlled substances:  oxycodone, hydrocodone, oxymorphone, hydromorphone, morphine, and fentanyl. Some of the medications are already in short supply, forcing some hospitals to use other pain relievers to treat surgery and trauma patients.

“President Trump has set the ambitious goal of reducing opioid prescription rates by one-third in three years. We embrace that goal and are resolutely committed to reaching it,” Attorney General Jeff Sessions said in a statement. “We have already made significant progress in reducing prescription rates over the past year. Cutting opioid production quotas by an average of ten percent next year will help us continue that progress and make it harder to divert these drugs for abuse.”

The DEA has already made substantial cuts in opioid production quotas, reducing them by 25 percent in 2017, followed by another 20 percent cut in 2018.  

The production cuts have had no effect on reducing the nation’s soaring overdose rate. According to a preliminary report released this week by the CDC, over 72,000 Americans died of drug overdoses last year, a 6 percent increase from 2016. The rising death toll is primarily attributed to illicit fentanyl, heroin and cocaine. Overdoses involving prescription opioids appear to have leveled off.

pills-1885550_640.jpg

The DEA’s latest round of production cuts is in line with President Trump’s “Safe Prescribing Plan” which seeks to reduce "the over-prescription of opioids” by cutting nationwide opioid prescription fills by one-third within three years.

“We’ve lost too many lives to the opioid epidemic and families and communities suffer tragic consequences every day,” said DEA Acting Administrator Uttam Dhillon. “This significant drop in prescriptions by doctors and DEA’s production quota adjustment will continue to reduce the amount of drugs available for illicit diversion and abuse while ensuring that patients will continue to have access to proper medicine.”

‘Serious Consequences’ for Patients

But legitimate patients are losing access to opioids.  Many hospitals and hospices now face a chronic shortage of three intravenous or injectable opioids --  morphine, hydromorphone and fentanyl -- which are used to treat patients recovering from surgery or trauma. Shortages of these "parenteral" drugs have been primarily blamed on manufacturing problems, although some critics say it has been worsened by the DEA production cuts.

“The shortage has serious consequences for patients and physicians. Parenteral opioids provide fast and reliable analgesia for patients admitted to the hospital with poorly controlled pain, patients who have undergone painful procedures such as major surgery, and those who were previously on oral opioid regimens but are unable to continue treatment by mouth,” Edward Bruera, MD, an oncologist at The University of Texas MD Anderson Cancer Center, wrote in an op/ed published this week in The New England Journal of Medicine.

“Shortages of the three best-known parenteral opioids may increase the risk for medication errors when it becomes necessary to switch a patient to a less familiar drug or to use opioid-sparing drug combinations. Opioids are already among the drugs most frequently involved in medication errors in hospitals. There are also increased risks of delayed time to analgesia and of side effects resulting in unnecessary patient suffering and delayed hospital discharge.”

Although opioid prescribing guidelines are only intended for physicians treating patients with “chronic non-cancer pain,” Bruera says some cancer patients are being affected by opioid shortages and over-zealous enforcement of prescribing guidelines.

“Most hospitalized patients and almost all patients with cancer need opioids, either on a temporary basis after surgery or painful treatments such as stem-cell transplantation, or longer for cancer-related pain or dyspnea,” he wrote. “It is impossible to appropriately treat such a large number of patients unless most physicians are able and willing to prescribe opioids. There were not enough palliative care and pain specialists to meet patient needs before the shortages began, and universal referral of patients who need parenteral opioids will therefore only result in more undertreated pain.”

The rationale behind the DEA’s production cuts defy some of the agency’s own analysis. Less than one percent of legally prescribed opioids are diverted, according to a 2017 DEA report, which also found that admissions for painkiller abuse to publicly funded addiction treatment facilities have declined significantly since 2011, the same year that opioid prescriptions began dropping.

DEA Adopts Rule to Further Limit Opioid Production

Pat Anson, Editor

The U.S. Justice Department has finalized a new rule that will allow the Drug Enforcement Administration to reduce the amount of opioid pain medication a drug maker can produce if it finds the opioid is being diverted or misused.

The controversial change in the opioid production quota system was adopted despite warnings from patients, doctors and drug makers that it targets the wrong the problem and could worsen shortages of some pain medications.

The DEA maintains the rule change will “encourage vigilance” on the part of opioid manufacturers to prevent their drugs from being abused.

“These common-sense actions directly respond to the national opioid epidemic by allowing DEA to use drug diversion as a basis to evaluate whether a drug’s production should be reduced,” said DEA Acting Administrator Uttam Dhillon in a statement. “This also opens the door for increased communication and better information sharing between DEA and individual states, as we work together to address the opioid problem plaguing our country.”

The final rule greatly enhances the roles played by states and other federal agencies in setting opioid production quotas. It requires DEA to share proposed quotas with state attorneys general, who could object to a quota and demand a hearing.

The rule also allows DEA to consider “relevant information” from all 50 states, the Department of Health and Human Services, Food and Drug Administration, the Centers for Disease Control, and the Centers for Medicare and Medicaid Services, before setting a quota.

"DEA must make sure that we prevent diversion and abuse of prescription opioids. Today's new rule, by taking diversion of these opioids into account, will allow the DEA to be more responsive to the facts on the ground. More importantly, it will help us stop and even prevent diversion from taking place,” said Attorney General Jeff Sessions.

DEA badge.jpg

Sessions announced the proposed rule changes in April, and DEA received over 1,500 public comments during an unusually short comment period. A clear majority opposed the new rule.

“This does nothing to stop addiction or overdose deaths. Addicts will find a high anywhere and where they find it now is street drugs! Illicit drugs are what’s killing, not doctor prescribed opioids filled at a pharmacy. The reporting you all are using is inaccurate and false,” wrote Amy Vallejo.

“By creating quotas, and thereby shortages, you are committing torture,” said Kimberley Comfort, who lives with arachnoiditis, a chronic spinal disease. “There is no reason why people having surgeries, people who suffer from incurable diseases, should be left to suffer when we are a nation that has the ability to take care of its citizens. The DEA does not have a clear understanding of the so-called opioid crisis and therefore needs to cease and desist making opiates harder to get.”

“Again, we have the DEA making laws and quotas on something they should not be. Let them worry about the drugs coming in from China, Mexico etc. which are illegal,” said Sarah Yerxa. “By cutting the quotas all they are doing is sending needy pain patients to the streets, which will just raise the addiction... and overdose problem.”

Opioid Shortages

The DEA has already made substantial cuts in opioid production quotas, reducing them by 25 percent in 2017, followed by another 20 percent cut in 2018. This year’s cuts were ordered despite warnings from drug makers that reduced supplies of opioids “were insufficient to provide for the estimated medical, scientific, research and industrial needs of the United States.”

Many hospitals and hospices now face a chronic shortage of intravenous and injectable opioids, which are used to treat patients recovering from surgery or trauma. The shortage has been primarily blamed on manufacturing problems, although some critics say it has been worsened by the DEA production cuts.

“I believe Attorney General Jeff Sessions needs to sit down and talk to some of these physicians who are pain specialists and understand that what he’s doing is going to put the chronic pain patient, the post-operative patient, and the patient that comes to the emergency room in serious jeopardy,” Tony Mack, CEO and chairman of Virpax Pharmaceuticals, told PNN in an earlier interview.

“I think that Jeff Sessions is not educated well. I think he is picking on something that sounds good politically but doesn’t make sense socially. It’s socially irresponsible.”

In a public notice announcing the rule change, the DEA said it was not responsible for “perceived shortages” of injectable drugs and blamed the “manufacturer induced shortages” on “internal business decisions.”

The agency also deflected criticism that it was targeting the wrong problem. Recent studies indicate that overdoses involving illicit fentanyl, heroin and other street drugs now outnumber deaths linked to prescription opioids.   

“The DEA acknowledges that prescriptions for opioid drug products have decreased over the last several years due to the stepped up civil, criminal, and regulatory enforcement efforts of the agency. However, while there is a downward trend in prescribing, these Schedule II prescription opiates continue to have a high potential for abuse and dependence and require the annual assessment of quotas,” the DEA said.

The agency also claimed prescription opioids were “inextricably linked” to overdoses from heroin and illicit fentanyl, because many addicts start by taking pain medication from family medicine cabinets and then move on to street drugs.

The DEA statement defies some of its own analysis. Less than one percent of legally prescribed opioids are diverted, according to a 2017 DEA report, which also found that admissions for painkiller abuse to publicly funded addiction treatment facilities have declined significantly since 2011, the same year that opioid prescriptions began dropping.

FDA Uncovers Errors in Opioid Database

By Pat Anson, Editor

The U.S. Food and Drug Administration has identified potentially serious errors in a database of opioid sales maintained by IQVIA - a private company that provides data to the federal government on the volume of drugs sold by manufacturers and wholesalers to pharmacies and hospitals.

The FDA said the errors “raise serious questions” about the reliability of IQVIA’s database, which is used by the Drug Enforcement Administration to set opioid production quotas for drug makers. In the last two years, the DEA has reduced opioid production quotas by as much as 45 percent, claiming there was less demand for opioids and that the market was oversupplied with them.

“When we discover irregularities or inconsistencies in the data we use, we take such deficiencies very seriously,” the FDA said in a statement. "The FDA uses these data to assist the DEA in determining the medical and research needs for Schedule I and II controlled substances in the U.S. for the upcoming year."

The FDA believes the error was caused when IQVIA incorrectly converted into kilograms the amount of prescription fentanyl contained in transdermal skin patches and other fentanyl products. As a result, FDA researchers believe the company overestimated the amount of fentanyl sold in the U.S. in the last five years by over 20 percent.

“This error caused IQVIA to overestimate the total amount of fentanyl distributed into the marketplace,” the FDA said. “As a result of this work, we identified additional data quality issues related to several other controlled substances with similar weight-based conversion factors, including oxymorphone and hydrocodone. These additional errors raise serious concerns about systemic issues with IQVIA’s data and quality control procedures.”

bigstock-Pills-as-question-on-white-iso-53360449.jpg

Fentanyl is a potent synthetic opioid that is used to treat severe chronic pain and acute pain in patients recovering from surgery and trauma. There is currently a nationwide shortage of intravenous fentanyl and other opioids that has forced some hospitals to postpone surgeries or use other pain medications that are less effective.   

FDA Commissioner Scott Gottlieb, MD, called on IQVIA to immediately hire an independent, third party auditor to conduct a review of its database. Gottlieb said he would brief members of Congress about the data issues and their potential impact on public health.

IQVIA was formed in 2016 after the merger of IMS Health and Quintiles, two prominent healthcare research firms. The company released a statement saying it identified the problems in its opioid database last month and notified customers.  

“Recently, we made a correction to a kilogram conversion measurement in the United States IQVIA National Sales Perspective (NSP) market research service affecting reported measurements for transdermal patches in the opioid market,” the company said. “IQVIA’s internal processes had already identified the measurement conversion issue prior to the FDA’s notification. We notified our clients about this measurement conversion issue in April of this year. Ongoing steps have been undertaken to correct this measurement conversion issue.

“We stand behind our data methodologies. We value our long-standing relationship with the FDA. We take the FDA’s concerns seriously and will continue working with the FDA to resolve these concerns to its satisfaction.”

If confirmed, the database errors would be the second admission by federal agencies this year that their analysis of opioid prescriptions relied on faulty data. In March, four researchers in the CDC’s ironically named Division of Unintentional Injury Prevention acknowledged that many overdoses involving illicit fentanyl and other synthetic black market opioids were erroneously counted as prescription drug deaths.

Critics Say DEA Plan Could Worsen Opioid Shortages

By Pat Anson, Editor

Pain sufferers and patient advocates are overwhelming opposed to plans by the U.S. Drug Enforcement Administration to further restrict the supply of opioid medication to punish drug makers that allow too many of their painkillers to be diverted and abused. Health organizations also caution that the proposal could worsen an acute shortage of pain medication in the nation’s hospitals.

Over 1,500 people left public comments in the Federal Register on the DEA’s plan to change the rules governing opioid production quotas. Under the proposal, the DEA could arbitrarily reduce the amount of opioids a company can make -- even if it has no direct role in the diversion or abuse.

"It’s a common sense idea: the more a drug is diverted, the more its production should be limited," said Attorney General Jeff Sessions. 

But critics say the plan will not prevent opioid abuse and will likely harm patients.

“The DEA has no business deciding how much valid medicine can be produced. The doctors prescribing the medicine should dictate the amount. The DEA is going to cause a crisis,” wrote Tina Liles.

“Reducing opiate medication has done nothing to help the rate of overdose deaths in this country because opioid prescriptions are not the issue in this country it is illicit fentanyl and heroin,” said Nicole Garage.

“Limiting access to the only medication that helps to control severe, intractable pain will not stop the crisis; those who abuse or sell drugs illegally have not stopped due to current quotas and will not stop with any new quota reductions,” said James Loranc.

“The logic (behind) this DEA proposal is completely untested, unproven, and unsupportable. The shortages being seen in hospitals and by pain patients will only get worse with further DEA cutbacks, leading to more mistakes, waste, and higher costs, not to mention additional pain,” said Valerie Padgett Hawk, Director of a Coalition of 50 State Pain Advocacy Groups.  

Hospitals Rationing Opioids

bigstock-Prescription-Medication-1608757.jpg

The shortages mainly involve injectable opioids such as morphine, hydromorphone and fentanyl, which are used to treat acute pain in patients recovering from surgery or trauma. Hospitals have been forced to ration opioids or use other pain medications that are not as effective.

“With limited availability of some opioids, operations may have to be postponed or cancelled.  In some cases, this could prove life‐threatening to the patient,” wrote Janis Orlowski, MD, Chief Health Care Officer for the Association of American Medical Colleges. “We urge the DEA to remember that opioids are also an important part of treatment regimens for controlling acute and chronic pain in a variety of patients – including trauma, postoperative and patients with advanced stage cancer – and any limits on quotas should not negatively impact access for patients that have a legitimate and critical need for these medications.”  

“Please, I beg you, don't do this. My dear friend Sarah takes painkillers for her rheumatoid arthritis. Even with the medication it's terrible; without it, I have no doubt she'll kill herself. Her mental health is already fragile,” wrote Kelsey Hazzard. “This regulation will destroy her.”  

“For the love of God let the doctors and pharmacists handle prescribing and filling prescriptions and allow the patients and doctors to worry about how much opioid pain medication they need to take. This is none of the DEA’s concern!” wrote Brandon Tull, a disabled police officer who shared the tragic story of Jennifer Adams, a Montana pain patient who recently committed suicide.

“That suicide will probably be the first in a long line if you continue this attack upon innocent chronic pain sufferers!”

The public comment period on the DEA proposal ended May 4th. The public was given only 15 days to comment in the Federal Register on the rule change. Public comment periods are usually between 30 and 60 days long, with some taking up to 180 days. Agencies are allowed to use shorter comment periods "when that can be justified."

"This shortened period for public comment is necessary as an element in addressing the largest drug crisis in the nation's history," the DEA said.

The DEA has already made substantial cuts in opioid production quotas, reducing them by 25% in 2017, followed by a 20% cut in 2018. This year’s cuts were ordered despite warnings from drug makers that reduced supplies of opioids “were insufficient to provide for the estimated medical, scientific, research and industrial needs of the United States.”

Under the proposed rules, the DEA would be required to consult with states, Food and Drug Administration, Centers for Disease Control and Prevention, and the Department of Health and Human Services before setting opioid quotas. The rule change was triggered by a lawsuit filed against the DEA by West Virginia, alleging that the current quota system “unlawfully conflates market demand for dangerous narcotics” with the legitimate needs of pain patients.    

Although overdose deaths from heroin, illicit fentanyl and other street drugs now surpass those from pain medication, the DEA claims prescription opioids are gateway drugs to long-term substance abuse.

“(Opioid) users may be initiated into a life of substance abuse and dependency after first obtaining these drugs from their health care providers or without cost from the family medicine cabinet or from friends. Once ensnared, dependency on potent and dangerous street drugs may ensue,” the DEA said.

According to the National Institutes of Health (NIH), only about 5 percent of patients taking opioids as directed for a year end up with an addiction problem. And the DEA itself estimates that less than 1% of legally prescribed opioids are diverted.

Hospital Opioid Shortages Cause Pain & Medical Errors

By Pauline Bartolone, Kaiser Health News

Even as opioids flood American communities and fuel widespread addiction, hospitals are facing a dangerous shortage of the powerful painkillers needed by patients in acute pain, according to doctors, pharmacists and a coalition of health groups.

The shortage, though more significant in some places than others, has left many hospitals and surgical centers scrambling to find enough injectable morphine, Dilaudid and fentanyl — drugs given to patients undergoing surgery, fighting cancer or suffering traumatic injuries. The shortfall, which has intensified since last summer, was triggered by manufacturing setbacks and a government effort to reduce addiction by restricting drug production.

As a result, hospital pharmacists are working long hours to find alternatives, forcing nurses to administer second-choice drugs or deliver standard drugs differently. That raises the risk of mistakes — and already has led to at least a few instances in which patients received potentially harmful doses, according to the nonprofit Institute for Safe Medication Practices, which works with health care providers to promote patient safety.

In the institute’s survey of hospital pharmacists last year, one provider reported that a patient received five times the appropriate amount of morphine when a smaller-dose vial was out of stock. In another case, a patient was mistakenly given too much sufentanil, which can be up to 10 times more powerful than fentanyl, the ideal medication for that situation.

bigstock-Medical-Team-Working-On-Patien-55984199.jpg

In response to the shortages, doctors in states as far-flung as California, Illinois and Alabama are improvising the best they can.

Some patients are receiving less potent medications like acetaminophen or muscle relaxants as hospitals direct their scant supplies to higher-priority cases.

Other patients are languishing in pain because preferred, more powerful medications aren’t available, or because they have to wait for substitute oral drugs to kick in.

The American Society of Anesthesiologists confirmed that some elective surgeries, which can include gall bladder removal and hernia repair, have been postponed.

In a Feb. 27 letter to the U.S. Drug Enforcement Administration, a coalition of professional medical groups — including the American Hospital Association, the American Society of Clinical Oncology and the American Society of Health-System Pharmacists — said the shortages “increase the risk of medical errors” and are “potentially life-threatening.”

In addition, “having diminished supply of these critical drugs, or no supply at all, can cause suboptimal pain control or sedation for patients,” the group wrote.

The shortages involve prefilled syringes of these drugs, as well as small ampules and vials of liquid medication that can be added to bags of intravenous fluids.

Drug shortages are common, especially of certain injectable drugs, because few companies make them. But experts say opioid shortages carry a higher risk than other medications.

Small Mistakes Lead to Big Errors

Giving the wrong dose of morphine, for example, “can lead to severe harm or fatalities,” explained Mike Ganio, a medication safety expert at the American Society of Health-System Pharmacists.

Calculating dosages can be difficult and seemingly small mistakes by pharmacists, doctors or nurses can make a big difference, experts said.

Marchelle Bernell, a nurse at St. Louis University Hospital in Missouri, said it would be easy for medical mistakes to occur during a shortage. For instance, in a fast-paced environment, a nurse could forget to program an electronic pump for the appropriate dose when given a mix of intravenous fluids and medication to which she was unaccustomed.

“The system has been set up safely for the drugs and the care processes that we ordinarily use,” said Dr. Beverly Philip, a Harvard University professor of anesthesiology who practices at Brigham and Women’s Hospital in Boston. “You change those drugs, and you change those care processes, and the safety that we had built in is just not there anymore.”

Chicago-based Marti Smith, a nurse and spokeswoman for the National Nurses United union, offered an example.

“If your drug comes in a prefilled syringe and at 1 milligram, and you need to give 1 milligram, it’s easy,” she said. “But if you have to pull it out of a 25-milligram vial, you know, it’s not that we’re not smart enough to figure it out, it just adds another layer of possible error.”

During the last major opioid shortage in 2010, two patients died from overdoses when a more powerful opioid was mistakenly prescribed, according to the institute. Other patients had to be revived after receiving inaccurate doses.

Pfizer Manufacturing Problems

The shortage of the three medications, which is being tracked by the FDA, became critical last year as a result of manufacturing problems at Pfizer, which controls at least 60 percent of the market of injectable opioids, said Erin Fox, a drug shortage expert at the University of Utah.

A Pfizer spokesman, Steve Danehy, said its shortage started in June 2017 when the company cut back production while upgrading its plant in McPherson, Kansas. 

The company is not currently distributing prefilled syringes “to ensure patient safety,” it said, because of problems with a third-party supplier it declined to name.

Pfizer.png

That followed a February 2017 report by the U.S. Food and Drug Administration that found significant violations at the McPherson plant. The agency cited “visible particulates” floating in the liquid medications and a “significant loss of control in your manufacturing process [that] represents a severe risk of harm to patients.” Pfizer said, however, that the FDA report wasn’t the impetus for the factory upgrades.

Other liquid-opioid manufacturers, including West-Ward Pharmaceuticals and Fresenius Kabi, are deluged with back orders, Fox said. Importing these heavily regulated narcotics from other countries is unprecedented and unlikely, she added, in part because it would require federal approval.

DEA Reduced Opioid Supply

At the same time, in an attempt to reduce the misuse of opioid painkillers, the Drug Enforcement Administration called for a 25 percent reduction of all opioid manufacturing last year, and an additional 20 percent this year.

“DEA must balance the production of what is needed for legitimate use against the production of an excessive amount of these potentially harmful substances,” the agency said in August.

When the coalition of health groups penned its letter to the DEA last month, it asked the agency to loosen the restrictions for liquid opioids to ease the strain on hospitals.

The shortages are not being felt evenly across all hospitals. Dr. Melissa Dillmon, medical oncologist at the Harbin Clinic in Rome, Ga., said that by shopping around for other suppliers and using pill forms of the painkillers, her cancer patients are getting the pain relief they need.

Dr. Shalini Shah, the head of pain medicine at the University of California-Irvine health system, pulled together a team of 20 people in January to figure out how to meet patients’ needs. The group meets for an hour twice a week.

The group has established workarounds, such as giving tablet forms of the opioids to patients who can swallow, using local anesthetics like nerve blocks and substituting opiates with acetaminophen, ketamine and muscle relaxants.

“We essentially have to ration to patients that are most vulnerable,” Shah said.

Two other California hospital systems, Kaiser Permanente and Dignity Health in Sacramento, confirmed they’re experiencing shortages, and that staff are being judicious with their supplies and using alternative medications when necessary.

At Helen Keller Hospital’s emergency department in Sheffield, Ala., earlier this month, a 20-year-old showed up with second-degree burns. Dr. Hamad Husainy said he didn’t have what he needed to keep her out of pain.

Sometime in January, the hospital ran out of Dilaudid, a drug seven times more potent than morphine, and has been low on other injectable opioids, he said.

Because Husainy’s patient was a former opioid user, she had a higher tolerance to the drugs. She needed something strong like Dilaudid to keep her out of pain during a two-hour ride to a burn center, he said.

“It really posed a problem,” said Husainy, who was certain she was in pain even after giving her several doses of the less potent morphine. “We did what we could, the best that we could,” he said.

Bernell, the St. Louis nurse, said some trauma patients have had to wait 30 minutes before getting pain relief because of the shortages.

“That’s too long,” said Bernell, a former intensive care nurse who now works in radiology.

Dr. Howie Mell, an emergency physician in Chicago, said his large hospital system, which he declined to name, hasn’t had Dilaudid since January. Morphine is being set aside for patients who need surgery, he said, and the facility has about a week’s supply of fentanyl.

Mell, who is also a spokesman for the American College of Emergency Physicians, said some emergency departments are considering using nitrous oxide, or “laughing gas,” to manage patient pain, he said.

When Mell first heard about the shortage six months ago, he thought a nationwide scarcity of the widely used drugs would force policymakers to “come up with a solution” before it became dire.

“But they didn’t,” he said.

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of the Kaiser Family Foundation, which is not affiliated with Kaiser Permanente.