Tag Archives: FDA

New pharmaceutical product to prevent heroin deaths

A new, lifesaving product aimed at reducing the death toll from heroin abuse — developed by a professor at the University of Kentucky College of Pharmacy — is in its final round of clinical trials and has received Fast Track designation by the Food and Drug Administration.

The product, a nasal spray application of the anti-opioid drug naloxone, was developed by Daniel Wermeling, UK professor of pharmacy practice and science, through his startup company AntiOp Inc.

Naloxone is the standard treatment for suspected opioid overdose, already in use by emergency rooms and emergency medical technicians across the country. Opioids are the class of pain-killing drugs that are related to morphine, including prescription drugs such as hydrocodone and oxycodone, as well as illegal drugs such as heroin.
Currently, naloxone is administered by injection. The nasal spray eliminates the need for needles, with a ready-to-use, single-use delivery device inserted into the nose of an overdose victim. The product delivers a consistent dose, absorbed across the nasal membranes even if the patient is not breathing.

“The goal is to make the medication available to patients at high risk of opioid overdose, and to caregivers, including family members, who may lack specialized medical training,” Wermeling said. “The treatment could be given in anticipation of EMS arrival, advancing the continuum of care and ultimately saving lives.”

Nationwide, deaths from opioid overdose are on the rise, according to data from the Centers for Disease Control and Prevention. Kentucky, long troubled by widespread abuse of prescription opioids, has seen a dramatic rise in deaths from heroin overdose in recent years. In autopsies from 2013, the state medical examiner attributed 230 deaths to heroin overdose, an increase of more than 60 percent from the previous year.

UK President Eli Capilouto congratulated Wermeling on his success with AntiOp, saying that it reflects the core values of the university.

“Too many Kentucky families have experienced the tragedy of seeing a loved one’s life cut short by a drug overdose,” Capilouto said. “The epidemic of opioid abuse in our state presents an enormous and urgent challenge, not only for health care providers and law enforcement, but also for us here at the University of Kentucky. Dr. Wermeling’s project is putting a powerful new tool into the hands of those on the front line of the fight against heroin, both here in Kentucky and beyond. This type of innovation embodies the three main components of the university’s mission — education, research and, above all, service.”

UK College of Pharmacy Dean Timothy S. Tracy said Wermeling’s work also provides an illustration of “bench-to-bedside” research in action. “Dr. Wermeling’s project is a great example of how UK College of Pharmacy faculty are working each and every day to create healthier Kentucky communities,” Tracy said. “Dr. Wermeling and his collaborative team of research colleagues saw a problem facing families in Kentucky and across the nation and developed an innovative solution. That type of translational approach is important to our college, this university, and, of course, the future of our Commonwealth.”

Wermeling’s research was supported by a three-year, $3 million grant from the National Institutes of Health through the National Institute on Drug Abuse with additional funding from the Kentucky Science and Technology Corporation. In May, AntiOp partnered with Reckitt Benckiser Pharmaceuticals to accelerate production and worldwide marketing of intranasal naloxone.

The Fast Track program of the FDA is designed to expedite the development and review of new drugs that are intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs. Fast Track-designated drugs ordinarily qualify for priority review, thereby expediting the FDA review process.
“As an educator, pharmacist, researcher and entrepreneur, being able to work on this naloxone project has been a dream come true,” Wermeling said. “I often tell my students and colleagues that this project has allowed me to use all of the skills I have learned over the years. It has been the ultimate problem-solving project, requiring me to utilize my pharmacological skills, my drug delivery knowledge, my business and marketing skills — all at the same time.

“At the end of the day, however, this project has always been about people. It has always been about utilizing the knowledge and skills that we have to improve patient care.”

A video featuring Dr. Wermeling discussing this work may be viewed online at https://www.youtube.com/watch?v=pgjIH5KkH0k

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New ‘Abuse Resistant’ Painkiller May Torpedo Zohydro

The news of Purdue Pharma’s intention to rival Zohydro has caused the drug’s maker, Zogenix, to see its stock drop by more than 20 percent.

The makers of OxyContin have delivered a potentially devastating blow to the controversial new drug Zohydro – which produces an effect five to 10 times stronger than Vicodin – by revealing that they plan to submit an “abuse-resistant” painkiller to the Food and Drug Administration.

Purdue Pharma, which created MS Contin in 1984 and OxyContin in 1996, completed testing on a version of hydrocodone that cannot be crushed so abusers can snort or inject the drug. The new painkiller will be submitted to the FDA later this year, but it has already had a negative impact on Zohydro and its maker, Zogenix, which experienced a drop in shares by more than 20 percent following Purdue’s announcement.

The news is the latest in a series of public condemnations from the medical community directed toward Zohydro, a pure form of hydrocodone which was approved by the FDA in 2013 despite a lack of an abuse-deterrent formulation – an additive like naloxone or niacin which would cause an adverse effect if ingested by injection or snorting, but would remain inactive if consumed orally and absorbed into the gastrointestinal tract. The agency even ignored an 11-2 vote against approving the drug by their own scientific advisory panel.

The decision spurred a letter of protest from more than 40 doctors, addiction specialists, and lawmakers urging the FDA to reconsider its decision, given the recent overwhelming rate of painkiller addiction across the United States and elsewhere, as well as the inherent dangers of the drug. In the letter, the authors said that Zohydro is powerful enough to cause a fatal overdose in a person unaccustomed to taking opioids with just two capsules.

One of the letter’s signatories, Andrew Kolodny, president of Physicians for Responsible Opioid Prescribing, summed up the drug’s potential by stating, “It will kill people as soon as it’s released.” In response, Zogenix has posted a warning about the drug’s potential side effects on its site and established an external safe-use board to oversee “appropriate use” of Zohydro.

FDA approves a powerful new opioid painkiller

Addiction experts protested loudly when the Food and Drug Administration approved a powerful new opioid painkiller last month, saying that it would set off a wave of abuse much as OxyContin did when it first appeared. An F.D.A. panel had earlier voted, 11 to 2, against approval of the drug, Zohydro, in part because unlike current versions of OxyContin, it is not made in a formulation designed to deter abuse.

Now a new issue is being raised about Zohydro. The drug will be manufactured by the same company, Alkermes, that makes a popular medication called Vivitrol, used to treat patients addicted to painkillers or alcohol. In addition, the company provides financial support to a leading professional group that represents substance abuse experts, the American Society of Addiction Medicine.

For some critics, the company’s multiple roles in the world of painkillers is troubling.

Dr. Gregory L. Jones, an addiction specialist in Louisville, Ky., said he had long been concerned about financial links between the group and the drug industry, adding that the Zohydro situation amplified those potential conflicts.

Dr. Stuart Gitlow, the current president of the American Society of Addiction Medicine, said he had been unaware until now of Alkermes’s involvement with Zohydro. Dr. Gitlow, who is affiliated with Mount Sinai Hospital in New York City, said that the group would seek more information from Alkermes about the situation and then decide what, if anything, to do next.

Officials of Alkermes appear to recognize the issue they face. In recent years, the company has been trying to increase sales of Vivitrol, a form of a drug called naltrexone, that is used to treat both alcoholism and opioid addiction.

In a statement, Rebecca Peterson, a spokeswoman for Alkermes, said the company was “evaluating its role with respect to Zohydro” as a result of the drug’s approval. She declined to elaborate.

The tie between Alkermes and Zohydro had not drawn attention because the company did not initially own the drug, nor was it apparently involved in the efforts to get it approved in the United States.

A small California-based company called Zogenix purchased the right to market Zohydro in the United States from another drug maker, Elan. Then a year later, in 2011, Alkermes bought a unit of Elan that included Zohydro, among other products, and inherited the existing agreement with Zogenix.

In their presentation to the F.D.A., officials of Zogenix said they would closely monitor the drug’s use for signs that it was being abused and quickly move to stop such problems. Agency officials said they had approved the drug to give doctors another long-acting opioid to use when treating patients with chronic pain. A few days after the drug’s approval, Zogenix announced that it had signed an agreement with another company, Altus Formulation, under which Altus would develop a formulation of Zohydro that was less vulnerable to abuse than the one just approved.

The development of drug formulations that are less prone to abuse can take years and are not always successful. Currently, drugs like OxyContin are designed so their consistency changes when they are crushed, making them difficult to inject or snort.

Zogenix began running a clinical trial of Zohydro in 2010. In a statement, the company’s president, Dr. Stephen J. Farr, said that the F.D.A. only recently laid out guidelines for the types of features it would like to see in opioid formulations that deter abuse. “Zogenix is fully engaged in efforts to bring an abuse-deterrent-form formulation of Zohydro,” to market, he said.

Dr. Andrew J. Kolodny, the chief medical officer of Phoenix House, which runs drug and alcohol treatment centers in 10 states, said he believed that the American Society of Addiction Medicine should not take money from a company whose product would most likely worsen this country’s drug abuse problem. In addition, Dr. Kolodny, who is a member of the group, said that while Phoenix House will continue to use Vivitrol when appropriate to treat patients, Alkermes officials will find the door closed. “Representative of Alkermes are not welcome,” he said.

Narcotic painkillers fail to improve pain control

A new study finds that despite a decade of extensive prescription opioid use, the identification and treatment of pain has failed to improve.

Experts say use of prescription opioid analgesics has reached epidemic levels with the benefit of the prescriptions questionable. “There is an epidemic of prescription opioid addiction and abuse in the United States,” said G. Caleb Alexander, M.D., M.S., co-director of the Johns Hopkins Center for Drug Safety and Effectiveness. “We felt it was important to examine whether or not this epidemic has coincided with improved identification and treatment of pain.”

Alexander and his fellow researchers used the National Ambulatory Medical Care Survey, designed to analyze trends from 2000 to 2010 associated with patients seeking medical treatment for non-cancer pain. They found no significant change in the proportion of pain visits — approximately one-half – treated with pain relievers.

During this time, non-opioid (analgesic) prescriptions remained stable, consisting of 26-29 percent of pain visits. However, opioid (morphine-related) prescriptions nearly doubled, from 11 percent in 2000 to 19 percent in 2010. Of approximately 164 million pain visits in 2010, roughly half were treated with some kind of pain relieving drug: 20 percent with an opioid and 27 percent with a non-opioid pain reliever.

Alexander and colleagues also examined visits for new-onset musculoskeletal pain, and in spite of similar increases in opioid prescribing, the results showed a significant decrease in non-opioid analgesics prescriptions.

Researchers found a 38 to 29 percent drop between 2000 and 2010, despite a lack of evidence showing opioids are more effective or safer than non-opioid treatments for such pain. Chronic pain affects nearly 100 million U.S. adults and carries major costs in terms of health care and lost productivity.

Initiatives designed to increase patient and provider awareness of pain have come with unintended consequences. Prescription opioid abuse has been increasingly documented in emergency department visits and deaths.

“By 2008, the annual number of fatal drug poisonings surpassed those of motor vehicle deaths and overdose deaths attributable to prescription drugs exceeded those of cocaine and heroin combined,” Alexander and colleagues noted.

The new study is one of the first to focus on trends in pain treatment in ambulatory care—that is, office and clinic visits. Experts say the results highlight the importance of balancing the risks and benefits of analgesics prescribed in the primary care setting.

“The majority of pain medications are prescribed by primary care physicians, who treat over half of the chronic pain in the United States,” said Matthew Daubresse, M.H.S., lead author of the report. “Pain specialists only treat a fraction of these patients.”

“We found that not only have the rates of treated pain not improved, but in many cases, use of safer alternatives to opioids, such as medicines like ibuprofen and acetaminophen, have either stayed flat or declined,” said Alexander.

“This suggests that efforts to improve the identification and treatment of pain have backfired, due to an over-reliance on prescription opioids that have caused incredible morbidity and mortality among patients young and old alike.”

In response to the growing opioid epidemic, on September 10, the Food and Drug Administration announced new labeling changes and post-market study requirements for extended-release and long-acting opioid analgesics.

“These regulatory changes may help prescribers and patients to better appreciate the risks of these therapies,” Daubresse said. “Despite this, the ultimate impact of the FDA’s labeling change has yet to be seen.”

Pure but not so simple

At a party not long ago in Park Slope, Brooklyn, Kaitlin, a 22-year-old senior at Columbia University, was recalling the first time she was offered a drug called Molly, at the elegant Brooklyn home of a cultural figure she admired. “She was, like, 50, and she had been written about in the Talk of the Town,” said Kaitlin, who was wearing black skinny jeans and a tank top. “This woman was very smart and impressive.”

At one point, the hostess pulled Kaitlin aside and asked if she had ever tried the drug, which is said to be pure MDMA, the ingredient typically combined with other substances in Ecstasy pills. “She said that it wasn’t cut with anything and that I had nothing to worry about,” said Kaitlin, who declined to give her last name because she is applying for jobs and does not want her association with the drug to scare off potential employers. “And then everyone at the party took it.”

Since that first experience, Kaitlin has encountered Molly at a birthday celebration and at a dance party in Williamsburg. “It’s the only drug I can think of that I have to pay for,” she said. “It makes you really happy. It’s very loose. You just get very turned on — not even sexually, but you just feel really upbeat and want to dance or whatever.”

Molly is not new, exactly. MDMA, or 3,4-methylenedioxy-N-methylamphetamine, was patented by Merck pharmaceuticals in 1914 and did not make much news until the 1970s, when psychotherapists began giving it to patients to get them to open up. It arrived at New York nightclubs in the late 1980s, and by the early ’90s it became the preferred drug at raves at Limelight and Shelter, where a weekly party called NASA later served as a backdrop in Larry Clark’s movie “Kids.”

Known for inducing feelings of euphoria, closeness and diminished anxiety, Ecstasy was quickly embraced by Wall Street traders and Chelsea gallerinas. But as demand increased, so did the adulterants in each pill (caffeine, speed, ephedrine, ketamine, LSD, talcum powder and aspirin, to name a few), and by the new millennium, the drug’s reputation had soured.

Then, sometime in the last decade, it returned to clubs as Molly, a powder or crystalline form of MDMA that implied greater purity and safety: Ecstasy re-branded as a gentler, more approachable drug. And thanks in part to that new friendly moniker, MDMA has found a new following in a generation of conscientious professionals who have never been to a rave and who are known for making careful choices in regard to their food, coffee and clothing. Much as marijuana enthusiasts of an earlier generation sang the virtues of Mary Jane, they argue that Molly (the name is thought to derive from “molecule”) feels natural and basically harmless.

A 26-year-old New York woman named Elliot, who works in film, took Molly a few months ago at a friend’s apartment and headed to dinner at Souen, the popular “macrobiotic, natural organic” restaurant in the East Village, and then went dancing. “I’ve always been somewhat terrified of drugs,” she said. “But I’d been curious about Molly, which is sold as this pure, fun-loving drug. This is probably completely naïve, but I felt I wasn’t putting as many scary chemicals into my body.”

Robert Glatter, an emergency-room physician at Lenox Hill Hospital on the Upper East Side, might disagree. Dr. Glatter used to go months without hearing about Molly; now, he sees about four patients a month exhibiting its common side effects, which include teeth grinding, dehydration, anxiety, insomnia, fever and loss of appetite. (More dangerous ones include hyperthermia, uncontrollable seizures, high blood pressure and depression caused by a sudden drop in serotonin levels in the days after use, nicknamed Suicide Tuesdays.)

“Typically in the past we’d see rave kids, but now we’re seeing more people into their 30s and 40s experimenting with it,” Dr. Glatter said. “MDMA use has increased dramatically. It’s really a global phenomenon now.”

Nationally, the Drug Abuse Warning Network reports that the number of MDMA-related emergency-room visits have doubled since 2004. It is possible to overdose on MDMA, though when taken by itself, the drug rarely leads to death, Dr. Glatter said. (Official mortality figures are not available, but a study by New York City’s deputy chief medical examiner determined that from 1997 to 2000, two people died solely because of MDMA.)

According to the United States Customs and Border Protection, there were 2,670 confiscations of MDMA in 2012, up from 186 in 2008.

“Oh, we’re very aware of it,” said Rusty Payne, an agent at the Drug Enforcement Agency’s national office. Mr. Payne had not heard of Molly before 2008. Since then, the agency has used the term to document arrests in Syracuse and Jackson, Miss. “Molly has been very much glamorized in pop culture, which is obviously a problem,” he said.

Indeed, many attribute MDMA’s resurgence to the return of Electronic Dance Music (or E.D.M.), the pulsating Euro beat that has infiltrated the sound of pop radio acts like Rihanna, Kesha and Katy Perry. At the Ultra Music Festival in Miami last year, Madonna was criticized for asking her audience, “How many people in this crowd have seen Molly?” (She later said that she was referring to a friend’s song, not the drug.)

In the last year, rappers have also embraced Molly, with references to the drug appearing in lyrics by Gucci Mane, Kanye West and Lil Wayne, who raps, “Pop a Molly, smoke a blunt, that mean I’m a high roller,” on Nicki Minaj’s 2012 hit “Roman Reloaded.” Rick Ross was recently dropped as a Reebok spokesman after he rapped about spiking a woman’s Champagne with Molly. And Miley Cyrus has a new single called “We Can’t Stop,” in which she sings what sounds like, “We like to party, dancing with Molly.” (Her producer has said the lyric is “dancing with Miley.”)

People who like Molly, which can cost $20 to $50 a dose, say it is a more socially acceptable drug than cocaine, because it is not physically addictive. Cat Marnell, 30, the former beauty director at xoJane.com who recently sold a memoir about drug addiction to Simon & Schuster for a reported $500,000, has noticed that many of her friends who sell Molly like to pack the powder into clear capsules that they buy from LifeThyme Market, the health food store next to C. O. Bigelow in the West Village. “Molly is the big thing now,” Ms. Marnell said. “Coke is sort of grimy and passé. Weed smells too much and is also sort of low rent and junior high.”

But Ms. Marnell scoffed at MDMA’s reformed image. “People think Molly is this flower-child drug,” she said recalling photos from the 2011 Coachella music festival showing the former Disney star Vanessa Hudgens, wearing a floppy ’70s hat and American Indian-inspired jewelry, dipping into a white powder that the gossip blogs ruled to be Molly. (Her publicist said it was white chocolate.) “It’s true that it’s not like cocaine in that it doesn’t make you bloated and it doesn’t make your nose raw, but sometimes you take it and you can’t sleep or you get really sick. It’s still a hard-core drug.”

MDMA was first classified as an illegal substance in 1985. By the early 2000s, public officials nicknamed Ecstasy “Agony,” and warned that MDMA use could lead to Parkinson’s disease, a lifetime of depression and “holes in your brain.”

Those claims have since been disproved, according to Dr. John Halpern, a psychiatrist at Harvard who has conducted several MDMA studies. In recent years, the Food and Drug Administration has approved studies looking into whether MDMA can be used to treat post-traumatic stress disorder and anxiety in terminal cancer patients. And Dr. Halpern has found no evidence that the drug impairs cognitive performance. “A drug that actually does kill brain cells — which MDMA doesn’t — is alcohol,” he said.

But a greater worry for doctors and law enforcement officials is the many substances that people might be ingesting unknowingly when they take Molly. “Anyone can call something Molly to try to make sound less harmful,” said Mr. Payne of the D.E.A. “But it can be anything.”

According to Dr. Halpern, many of the powders sold as Molly contain no MDMA whatsoever; others are synthetic concoctions designed to mimic the drug’s effects, Mr. Payne said. Despite promises of greater purity and potency, Molly, as its popularity had grown, is now thought to be as contaminated as Ecstasy once was.

“You’re fooling yourself if you think it’s somehow safer because it’s sold in powdered form,” Dr. Halpern said.

But to some users, Molly still feels like a more respectable substance than others.

“I think people are much more aware of where coke comes from and what it does in those countries,” said Sarah Nicole Prickett, 27, a writer for Vice and The New Inquiry, a culture and commentary site, who called cocaine a “blood drug.” “Molly, if it’s pure, it feels good and fun.” (Much of it comes from Canada and the Netherlands, Mr. Payne said.)

Ms. Prickett, who moved to New York from Toronto last year, added that she could see why the drug might be taking hold in her new habitat.

“My impression of New York was that everyone just did drugs for work, that everyone was on speed,” she said. “Molly makes you feel unplanned, and that’s not a common feeling in New York, where everyone knows where they’re going all the time and they’re going very, very fast.”

Rick Doblin, the founder of the Multidisciplinary Association for Psychedelic Studies, which has helped finance MDMA studies since the drug first entered the club scene, put Molly in the context of past drug trends: in the 1960s, he suggested, people searched for deeper spirituality and found LSD; in the ’70s, as hippie culture became mainstream, marijuana entered the suburban household; in the ’80s, cocaine complemented the extravagance and selfishness of the greed decade; and by the early ’90s, youths dropped out of reality, dancing all night on Ecstasy or slumping in the corner on heroin. MDMA, which in addition to acting as a stimulant also promotes feelings of bonding and human connection, just might be what people are looking for right now.

“As we move more and more electronic, people are extremely hungry for the opposite: human interaction on a deeper level where you’re not rushing around,” Mr. Doblin said. “The rise of Molly is in tune with how people are feeling emotionally.”

A step to curb painkiller abuse

Consumers will be less apt to overdose on prescription painkillers — but still less safe than they should be — under new labeling rules announced by the Food and Drug Administration on Tuesday for a class of drugs known as opioid analgesics.

Fatal overdoses from these painkillers more than quintupled among women and more than tripled among men from 1999 to 2010, when they killed more than 16,000 people and led many other users into addiction. Federal officials have called the misuse and abuse of prescription painkillers an epidemic.

The new requirements will change the wording on the labels for “extended release” and “long-acting” painkillers, like OxyContin, which release the opioid slowly to treat chronic pain and are sometimes taken for months on end. Current labels say the drugs should be used for “moderate to severe pain.” The new labels will drop “moderate” and say the pain must be “severe enough” to require round-the-clock treatment in patients who have no other options.

That’s good as far as it goes. But Physicians for Responsible Opioid Prescribing, an advocacy group in New York whose petition spurred the F.D.A. action, had also asked the agency to set a maximum daily dose and a maximum duration of 90 days for use in treating pain, an important request the agency declined to grant. That will leave drug makers free to imply in their advertising that long-term use and high doses are acceptable.

The agency also declined to grant the petition’s request that it rein in all opioid analgesics, including immediate-release forms like Vicodin and Percocet, which are typically taken for shorter periods to treat acute pain, such as that caused by surgery or severe injuries. The F.D.A. considers these painkillers to be less risky, although other experts believe they are potentially lethal in their own right.

Dr. Thomas Farley, New York City’s health commissioner, who had signed the petition to the agency, said the F.D.A. had taken only a limited step in the right direction. He rightly observed that the agency missed an opportunity to move more aggressively to reduce overdoses.