Addiction Medicine

During an opioid-addiction epidemic, can any new opioid pain drug meet prevailing safety demands to gain regulatory approval?

On Jan. 14 and 15, a Food and Drug Administration advisory committee voted virtually unanimously against two new opioid formulations and evenly split for and against a third; the 2 days of data and discussion showed how high a bar new opioids face these days for getting onto the U.S. market.

The bar’s height is very understandable given how many Americans have become addicted to opioids over the past decade, more often than not by accident while using pain medications as they believed they had been directed, said experts during the sessions held on the FDA’s campus in White Oak, Md.

Among the many upshots of the opioid crisis, the meetings held to discuss these three contender opioids highlighted the bitter irony confronting attempts to bring new, safer opioids to the U.S. market: While less abusable pain-relief medications that still harness the potent analgesic power of mu opioid receptor agonists are desperately desired, new agents in this space now receive withering scrutiny over their safeguards against misuse and abuse, and over whether they add anything meaningfully new to what’s already available. While these demands seem reasonable, perhaps even essential, it’s unclear whether any new opioid-based pain drugs will ever fully meet the safety that researchers, clinicians, and the public now seek.

A special FDA advisory committee that combined the Anesthetic and Analgesic Drug Products Advisory Committee with members of the Drug Safety and Risk Management Advisory Committee considered the application for three different opioid drugs from three separate companies. None received a clear endorsement. Oxycodegol, a new type of orally delivered opioid molecule engineered to slow brain entry and thereby delay an abuser’s high, got voted down without any votes in favor and 27 votes against agency approval. Aximris XR, an extended-release oxycodone formulation that successfully deterred intravenous abuse but had no deterrence efficacy for intranasal or oral abuse failed by a 2-24 vote against. The third agent, CTC, a novel formulation of the schedule IV opioid tramadol with the NSAID celecoxib designed to be analgesic but with limited opioid-abuse appeal, came the closest to meaningful support with a tied 13-13 vote from advisory committee members for and against agency approval. FDA staff takes advisory committee opinions and votes into account when making their final decisions about drug marketing approvals.

In each case, the committee members, mostly the same roster assembled for each of the three agents, identified specific concerns with the data purported to show each drug’s safety and efficacy. But the gathered experts and consumer representatives also consistently cited holistic challenges to approving new opioids and the stiffer criteria these agents face amid a continuing wave of opioid misuse and abuse.

“In the context of the public health issues, we don’t want to be perceived in any way of taking shortcuts,” said Linda S. Tyler, PharmD,, an advisory committee member and professor of pharmacy and chief pharmacy officer at the University of Utah in Salt Lake City. “There is no question that for a new product to come to market in this space it needs to add to what’s on the market, meet a high bar, and provide advantages compared with what’s already on the market,” she said.

Tramadol plus celecoxib gains some support

The proposed combined formulation of tramadol and celecoxib came closest to meeting that bar, as far as the advisory committee was concerned, coming away with 13 votes favoring approval to match 13 votes against. The premise behind this agent, know as CTC (cocrystal of tramadol and celecoxib), was that it combined a modest dose (44 mg) of the schedule IV opioid tramadol with a 56-mg dose of celecoxib in a twice-daily pill. Eugene R. Viscusi, MD, professor of anesthesiology and director of acute pain management at Thomas Jefferson University in Philadelphia and a speaker at the session on behalf of the applicant company, spelled out the rationale behind CTC: “We are caught in a dilemma. We need to reduce opioid use, but we also need to treat pain. We have an urgent need to have pain treatment options that are effective but have low potential for abuse and dependence. We are looking at multimodal analgesia, that uses combination of agents, recognizing that postoperative pain is a mixed pain syndrome. Multimodal pain treatments are now considered standard care. We want to minimize opioids to the lowest dose possible to produce safe analgesia. Tramadol is the least-preferred opioid for abuse,” and is rated as schedule IV, the U.S. designation for drugs considered to have a low level of potential for causing abuse or dependence. “Opioids used as stand-alone agents have contributed to the current opioid crisis,” Dr. Viscusi told the committee.

In contrast to tramadol’s schedule IV status, the mainstays of recent opioid pain therapy have been hydrocodone and oxycodone, schedule II opioids rated as having a “high potential for abuse.”

Several advisory committee members agreed that CTC minimized patient exposure to an opioid. “This drug isn’t even tramadol; it’s tramadol light. It has about as low a dose [of an opioid] as you can have and still have a drug,” said member Lee A. Hoffer, PhD, a medical anthropologist at Case Western Reserve University, Cleveland, who studies substance use disorders. “All opioids are dangerous, even at a low dose, but there is a linear relationship based on potency, so if we want to have an opioid for acute pain, I’d like it to have the lowest morphine milligram equivalent possible. The ideal is no opioids, but that is not what happens,” he said. The CTC formulation delivers 17.6 morphine milligram equivalents (MME) per pill, the manufacturer’s representatives said. The Centers for Disease Control and Prevention defines a “relatively low” daily opioid dose as 20-50 MME.

Some committee members hailed the CTC formulation as a meaningful step toward cutting opioid consumption.

“We may be very nervous about abuse of scheduled opioids, but a schedule IV opioid in an opioid-sparing formulation is as good as it gets in 2020,” said committee member Kevin L. Zacharoff, MD, a pain medicine specialist at the State University of New York at Stony Brook. “Any opioid has potential for abuse, but this is a safer alternative to the schedule II drugs. There is less public health risk with this,” said committee member Sherif Zaafran, MD, a Houston anesthesiologist. “This represents an incremental but important approach to addressing the opioid crisis, especially if used to replace schedule II opioids,” said Brandon D.L. Marshall, PhD, an epidemiologist and substance abuse researcher at Brown University in Providence, R.I.

But despite agreement that CTC represented a new low in the MME of an opioid given to patients, several committee members still saw the formulation as problematic by introducing any opioid, no matter how small the dose.

“The landscape of tramadol use and prescribing is evolving. There’s been an exponential upturn in tramadol prescribing. It’s perceived [as] safer, but it’s not completely safe. Will this change tramadol abuse and open the door to abuse of other opioids? This is what got us into trouble with opioids in the first place. Patients start with a prescription opioid that they perceive is safe. Patients don’t start with oxycodone or heroin. They start with drugs that are believed to be safe. I feel this combination has less risk for abuse, but I’m worried that it would produce a false sense of security for tolerability and safety,” said committee member Maryann E. Amirshahi, MD, a medical toxicologist at Georgetown University and MedStar Health in Washington.

Several other committee members returned to this point throughout the 2 days of discussions: The majority of Americans who have become hooked on opioids reached that point by taking an opioid pain medication for a legitimate medical reason and using the drug the way they had understood they should.

“I’m most concerned about unintentional misuse leading to addiction and abuse. Most people with an opioid addiction got it inadvertently, misusing it by mistake,” said committee member Suzanne B. Robotti, a consumer representative and executive director of DES Action USA. “I’m concerned about approving an opioid, even an opioid with a low abuse history, without a clearer picture of the human abuse potential data and what would happen if this drug were abused,” she added, referring to the proposed CTC formulation.

“All the patients I work with started [their opioid addiction] as pain patients,” Dr. Hoffer said.

“The most common use and abuse of opioids is orally. We need to avoid having patients who use the drug as prescribed and still end up addicted,” said committee member Friedhelm Sandbrink, MD, a neurologist and director of pain management at the Veterans Affairs (VA) Medical Center in Washington.

What this means, said several panelists, is functionally clamping down a class-wide lid on new opioids. “The way to reduce deaths from abuse is to reduce addiction, and to have an impact you need to reduce opioid exposure.” said committee member Sonia Hernandez-Diaz, MD, professor of epidemiology at the Harvard School of Public Health in Boston.

“In this opioid crisis, we ask for data that we wouldn’t ordinarily ask for. I feel there are unanswered questions about the abuse potential [of CTC]. We have seen a recent reduction in oxycodone use, which is great, but also an increase in tramadol use. We should not be fooled. Tramadol is an opioid, even if it’s schedule IV,” Dr. Tyler said.

Two other opioids faced greater opposition

The other two agents that the committee considered received much less support and sharper skepticism. The application for Aximris XR, an extended release form of oxycodone with a purported abuse-deterrent formulation (ADF) that relies on being difficult to extract for intravenous use as well as possibly having effective deterrence mechanisms for other forms of abuse. But FDA staffers reported that the only effective deterrence they could document was against manipulation for intravenous use, making Aximris XR the first opioid seeking ADF labeling based on deterrence to a single delivery route. This led several committee members, as well as the FDA, to comment on the clinical meaningfulness of ADF for one route. So far, the FDA approved ADF labeling for seven opioids, most notably OxyContin, an extended-release oxycodone with the biggest share of the U.S. market for opioids with ADF labeling.

“For ADF, we label based on what we expect from the premarket data. We don’t really know how that translates into what happens once the drug is on the market. Every company with an ADF in their label is required to do postmarketing studies on the abuse routes that are supposed to be deterred. We see shifts to other routes. Assessment of ADF is incredibly challenging, both scientifically and logistically, because there has not been a lot of uptake of these products, for a variety of reasons,” said Judy Staffa, PhD, associate director for Public Health Initiatives in the Office of Surveillance & Epidemiology in the FDA’s Center for Drug Evaluation and Research. The company that markets OxyContin has been the first to submit to the FDA all of its required postmarketing data on ADF efficacy, and the agency is now reviewing this filing, Dr. Staffa said.

The data presented for Aximris XR appeared to generally fail to convince committee members that it provided a meaningful addition to the range of opioids with ADF designations already available, which meant that their decision mostly came down to whether they felt it made sense to bring a me-too opioid to the U.S. market. Their answer was mostly no.

“In the end, it’s another opioid, and I’m not sure we need another opioid,” said committee member Lonnie K. Zeltzer, MD, professor of pediatrics, anesthesiology, psychiatry, and biobehavioral sciences and director of pediatric pain at the University of California, Los Angeles “There are so many options for patients and for people who abuse these drug. I don’t see this formulation as having a profound impact, but I’m very concerned about adding more prescription opioids,” said Martin Garcia-Bunuel, MD, deputy chief of staff for the VA Maryland Health Care System in Baltimore. Another concern of some committee members was that ADF remains a designation with an uncertain meaning, pending the FDA’s analysis of the OxyContin data.

“At the end of the day, we don’t know whether any of the [ADF] stuff makes a difference,” noted Steve B. Meisel, PharmD, system director of medication safety for M Health Fairview in Minneapolis and a committee member,

The third agent, oxycodegol, a molecule designed to pass more slowly across the blood-brain barrier because of an attached polyethylene glycol chain that’s supposed to prevent a rapid high after ingestion and hence cut abuse potential. It received unanimous committee rejection, primarily because its safety and efficacy evidence had so many holes, but the shadow of opioid abuse permeated the committee’s discussion.

“One dogma in the abuse world is that slowing entry into the brain reduces abuse potential, but the opioid crisis showed that this is not the only factor. Some people have become addicted to slow-acting drugs. The abuse potential of this drug, oxycodegol, needs to be considered given where we’ve been with the opioid crisis,” said Jane B. Acri, PhD, chief of the Medications Discovery and Toxicology Branch of the National Institute on Drug Abuse.

“During the opioid epidemic, do we want to approve more opioids? If the [pain] efficacy is about the same as oxycodone, is better safety or abuse potential a reason to approve it? We need guidance [from the FDA] about what is ‘better enough.’ No opioid will ever be perfect; there will always be abuse and misuse. But what is good enough to justify bringing another opioid onto the market? What is a good enough improvement? I don’t have an answer,” Dr. Hernandez-Diaz said.

Adviser comments showed that the continued threat of widespread opioid addiction has cooled prospects for new opioid approvals by making FDA advisers skittish over how to properly score the incremental value of a new opioid.

“Do we need to go back to the drawing board on how we make decisions on exposing the American public to these kinds of agents?” Dr. Garcia-Bunuel asked. “I don’t think we have the tools to make these decisions.”

mzoler@mdedge.com

During an opioid-addiction epidemic, can any new opioid pain drug meet prevailing safety demands to gain regulatory approval?

On Jan. 14 and 15, a Food and Drug Administration advisory committee voted virtually unanimously against two new opioid formulations and evenly split for and against a third; the 2 days of data and discussion showed how high a bar new opioids face these days for getting onto the U.S. market.

The bar’s height is very understandable given how many Americans have become addicted to opioids over the past decade, more often than not by accident while using pain medications as they believed they had been directed, said experts during the sessions held on the FDA’s campus in White Oak, Md.

Among the many upshots of the opioid crisis, the meetings held to discuss these three contender opioids highlighted the bitter irony confronting attempts to bring new, safer opioids to the U.S. market: While less abusable pain-relief medications that still harness the potent analgesic power of mu opioid receptor agonists are desperately desired, new agents in this space now receive withering scrutiny over their safeguards against misuse and abuse, and over whether they add anything meaningfully new to what’s already available. While these demands seem reasonable, perhaps even essential, it’s unclear whether any new opioid-based pain drugs will ever fully meet the safety that researchers, clinicians, and the public now seek.

A special FDA advisory committee that combined the Anesthetic and Analgesic Drug Products Advisory Committee with members of the Drug Safety and Risk Management Advisory Committee considered the application for three different opioid drugs from three separate companies. None received a clear endorsement. Oxycodegol, a new type of orally delivered opioid molecule engineered to slow brain entry and thereby delay an abuser’s high, got voted down without any votes in favor and 27 votes against agency approval. Aximris XR, an extended-release oxycodone formulation that successfully deterred intravenous abuse but had no deterrence efficacy for intranasal or oral abuse failed by a 2-24 vote against. The third agent, CTC, a novel formulation of the schedule IV opioid tramadol with the NSAID celecoxib designed to be analgesic but with limited opioid-abuse appeal, came the closest to meaningful support with a tied 13-13 vote from advisory committee members for and against agency approval. FDA staff takes advisory committee opinions and votes into account when making their final decisions about drug marketing approvals.

In each case, the committee members, mostly the same roster assembled for each of the three agents, identified specific concerns with the data purported to show each drug’s safety and efficacy. But the gathered experts and consumer representatives also consistently cited holistic challenges to approving new opioids and the stiffer criteria these agents face amid a continuing wave of opioid misuse and abuse.

“In the context of the public health issues, we don’t want to be perceived in any way of taking shortcuts,” said Linda S. Tyler, PharmD,, an advisory committee member and professor of pharmacy and chief pharmacy officer at the University of Utah in Salt Lake City. “There is no question that for a new product to come to market in this space it needs to add to what’s on the market, meet a high bar, and provide advantages compared with what’s already on the market,” she said.

Tramadol plus celecoxib gains some support

The proposed combined formulation of tramadol and celecoxib came closest to meeting that bar, as far as the advisory committee was concerned, coming away with 13 votes favoring approval to match 13 votes against. The premise behind this agent, know as CTC (cocrystal of tramadol and celecoxib), was that it combined a modest dose (44 mg) of the schedule IV opioid tramadol with a 56-mg dose of celecoxib in a twice-daily pill. Eugene R. Viscusi, MD, professor of anesthesiology and director of acute pain management at Thomas Jefferson University in Philadelphia and a speaker at the session on behalf of the applicant company, spelled out the rationale behind CTC: “We are caught in a dilemma. We need to reduce opioid use, but we also need to treat pain. We have an urgent need to have pain treatment options that are effective but have low potential for abuse and dependence. We are looking at multimodal analgesia, that uses combination of agents, recognizing that postoperative pain is a mixed pain syndrome. Multimodal pain treatments are now considered standard care. We want to minimize opioids to the lowest dose possible to produce safe analgesia. Tramadol is the least-preferred opioid for abuse,” and is rated as schedule IV, the U.S. designation for drugs considered to have a low level of potential for causing abuse or dependence. “Opioids used as stand-alone agents have contributed to the current opioid crisis,” Dr. Viscusi told the committee.

In contrast to tramadol’s schedule IV status, the mainstays of recent opioid pain therapy have been hydrocodone and oxycodone, schedule II opioids rated as having a “high potential for abuse.”

Several advisory committee members agreed that CTC minimized patient exposure to an opioid. “This drug isn’t even tramadol; it’s tramadol light. It has about as low a dose [of an opioid] as you can have and still have a drug,” said member Lee A. Hoffer, PhD, a medical anthropologist at Case Western Reserve University, Cleveland, who studies substance use disorders. “All opioids are dangerous, even at a low dose, but there is a linear relationship based on potency, so if we want to have an opioid for acute pain, I’d like it to have the lowest morphine milligram equivalent possible. The ideal is no opioids, but that is not what happens,” he said. The CTC formulation delivers 17.6 morphine milligram equivalents (MME) per pill, the manufacturer’s representatives said. The Centers for Disease Control and Prevention defines a “relatively low” daily opioid dose as 20-50 MME.

Some committee members hailed the CTC formulation as a meaningful step toward cutting opioid consumption.

“We may be very nervous about abuse of scheduled opioids, but a schedule IV opioid in an opioid-sparing formulation is as good as it gets in 2020,” said committee member Kevin L. Zacharoff, MD, a pain medicine specialist at the State University of New York at Stony Brook. “Any opioid has potential for abuse, but this is a safer alternative to the schedule II drugs. There is less public health risk with this,” said committee member Sherif Zaafran, MD, a Houston anesthesiologist. “This represents an incremental but important approach to addressing the opioid crisis, especially if used to replace schedule II opioids,” said Brandon D.L. Marshall, PhD, an epidemiologist and substance abuse researcher at Brown University in Providence, R.I.

But despite agreement that CTC represented a new low in the MME of an opioid given to patients, several committee members still saw the formulation as problematic by introducing any opioid, no matter how small the dose.

“The landscape of tramadol use and prescribing is evolving. There’s been an exponential upturn in tramadol prescribing. It’s perceived [as] safer, but it’s not completely safe. Will this change tramadol abuse and open the door to abuse of other opioids? This is what got us into trouble with opioids in the first place. Patients start with a prescription opioid that they perceive is safe. Patients don’t start with oxycodone or heroin. They start with drugs that are believed to be safe. I feel this combination has less risk for abuse, but I’m worried that it would produce a false sense of security for tolerability and safety,” said committee member Maryann E. Amirshahi, MD, a medical toxicologist at Georgetown University and MedStar Health in Washington.

Several other committee members returned to this point throughout the 2 days of discussions: The majority of Americans who have become hooked on opioids reached that point by taking an opioid pain medication for a legitimate medical reason and using the drug the way they had understood they should.

“I’m most concerned about unintentional misuse leading to addiction and abuse. Most people with an opioid addiction got it inadvertently, misusing it by mistake,” said committee member Suzanne B. Robotti, a consumer representative and executive director of DES Action USA. “I’m concerned about approving an opioid, even an opioid with a low abuse history, without a clearer picture of the human abuse potential data and what would happen if this drug were abused,” she added, referring to the proposed CTC formulation.

“All the patients I work with started [their opioid addiction] as pain patients,” Dr. Hoffer said.

“The most common use and abuse of opioids is orally. We need to avoid having patients who use the drug as prescribed and still end up addicted,” said committee member Friedhelm Sandbrink, MD, a neurologist and director of pain management at the Veterans Affairs (VA) Medical Center in Washington.

What this means, said several panelists, is functionally clamping down a class-wide lid on new opioids. “The way to reduce deaths from abuse is to reduce addiction, and to have an impact you need to reduce opioid exposure.” said committee member Sonia Hernandez-Diaz, MD, professor of epidemiology at the Harvard School of Public Health in Boston.

“In this opioid crisis, we ask for data that we wouldn’t ordinarily ask for. I feel there are unanswered questions about the abuse potential [of CTC]. We have seen a recent reduction in oxycodone use, which is great, but also an increase in tramadol use. We should not be fooled. Tramadol is an opioid, even if it’s schedule IV,” Dr. Tyler said.

Two other opioids faced greater opposition

The other two agents that the committee considered received much less support and sharper skepticism. The application for Aximris XR, an extended release form of oxycodone with a purported abuse-deterrent formulation (ADF) that relies on being difficult to extract for intravenous use as well as possibly having effective deterrence mechanisms for other forms of abuse. But FDA staffers reported that the only effective deterrence they could document was against manipulation for intravenous use, making Aximris XR the first opioid seeking ADF labeling based on deterrence to a single delivery route. This led several committee members, as well as the FDA, to comment on the clinical meaningfulness of ADF for one route. So far, the FDA approved ADF labeling for seven opioids, most notably OxyContin, an extended-release oxycodone with the biggest share of the U.S. market for opioids with ADF labeling.

“For ADF, we label based on what we expect from the premarket data. We don’t really know how that translates into what happens once the drug is on the market. Every company with an ADF in their label is required to do postmarketing studies on the abuse routes that are supposed to be deterred. We see shifts to other routes. Assessment of ADF is incredibly challenging, both scientifically and logistically, because there has not been a lot of uptake of these products, for a variety of reasons,” said Judy Staffa, PhD, associate director for Public Health Initiatives in the Office of Surveillance & Epidemiology in the FDA’s Center for Drug Evaluation and Research. The company that markets OxyContin has been the first to submit to the FDA all of its required postmarketing data on ADF efficacy, and the agency is now reviewing this filing, Dr. Staffa said.

The data presented for Aximris XR appeared to generally fail to convince committee members that it provided a meaningful addition to the range of opioids with ADF designations already available, which meant that their decision mostly came down to whether they felt it made sense to bring a me-too opioid to the U.S. market. Their answer was mostly no.

“In the end, it’s another opioid, and I’m not sure we need another opioid,” said committee member Lonnie K. Zeltzer, MD, professor of pediatrics, anesthesiology, psychiatry, and biobehavioral sciences and director of pediatric pain at the University of California, Los Angeles “There are so many options for patients and for people who abuse these drug. I don’t see this formulation as having a profound impact, but I’m very concerned about adding more prescription opioids,” said Martin Garcia-Bunuel, MD, deputy chief of staff for the VA Maryland Health Care System in Baltimore. Another concern of some committee members was that ADF remains a designation with an uncertain meaning, pending the FDA’s analysis of the OxyContin data.

“At the end of the day, we don’t know whether any of the [ADF] stuff makes a difference,” noted Steve B. Meisel, PharmD, system director of medication safety for M Health Fairview in Minneapolis and a committee member,

The third agent, oxycodegol, a molecule designed to pass more slowly across the blood-brain barrier because of an attached polyethylene glycol chain that’s supposed to prevent a rapid high after ingestion and hence cut abuse potential. It received unanimous committee rejection, primarily because its safety and efficacy evidence had so many holes, but the shadow of opioid abuse permeated the committee’s discussion.

“One dogma in the abuse world is that slowing entry into the brain reduces abuse potential, but the opioid crisis showed that this is not the only factor. Some people have become addicted to slow-acting drugs. The abuse potential of this drug, oxycodegol, needs to be considered given where we’ve been with the opioid crisis,” said Jane B. Acri, PhD, chief of the Medications Discovery and Toxicology Branch of the National Institute on Drug Abuse.

“During the opioid epidemic, do we want to approve more opioids? If the [pain] efficacy is about the same as oxycodone, is better safety or abuse potential a reason to approve it? We need guidance [from the FDA] about what is ‘better enough.’ No opioid will ever be perfect; there will always be abuse and misuse. But what is good enough to justify bringing another opioid onto the market? What is a good enough improvement? I don’t have an answer,” Dr. Hernandez-Diaz said.

Adviser comments showed that the continued threat of widespread opioid addiction has cooled prospects for new opioid approvals by making FDA advisers skittish over how to properly score the incremental value of a new opioid.

“Do we need to go back to the drawing board on how we make decisions on exposing the American public to these kinds of agents?” Dr. Garcia-Bunuel asked. “I don’t think we have the tools to make these decisions.”

mzoler@mdedge.com

During an opioid-addiction epidemic, can any new opioid pain drug meet prevailing safety demands to gain regulatory approval?

On Jan. 14 and 15, a Food and Drug Administration advisory committee voted virtually unanimously against two new opioid formulations and evenly split for and against a third; the 2 days of data and discussion showed how high a bar new opioids face these days for getting onto the U.S. market.

The bar’s height is very understandable given how many Americans have become addicted to opioids over the past decade, more often than not by accident while using pain medications as they believed they had been directed, said experts during the sessions held on the FDA’s campus in White Oak, Md.

Among the many upshots of the opioid crisis, the meetings held to discuss these three contender opioids highlighted the bitter irony confronting attempts to bring new, safer opioids to the U.S. market: While less abusable pain-relief medications that still harness the potent analgesic power of mu opioid receptor agonists are desperately desired, new agents in this space now receive withering scrutiny over their safeguards against misuse and abuse, and over whether they add anything meaningfully new to what’s already available. While these demands seem reasonable, perhaps even essential, it’s unclear whether any new opioid-based pain drugs will ever fully meet the safety that researchers, clinicians, and the public now seek.

A special FDA advisory committee that combined the Anesthetic and Analgesic Drug Products Advisory Committee with members of the Drug Safety and Risk Management Advisory Committee considered the application for three different opioid drugs from three separate companies. None received a clear endorsement. Oxycodegol, a new type of orally delivered opioid molecule engineered to slow brain entry and thereby delay an abuser’s high, got voted down without any votes in favor and 27 votes against agency approval. Aximris XR, an extended-release oxycodone formulation that successfully deterred intravenous abuse but had no deterrence efficacy for intranasal or oral abuse failed by a 2-24 vote against. The third agent, CTC, a novel formulation of the schedule IV opioid tramadol with the NSAID celecoxib designed to be analgesic but with limited opioid-abuse appeal, came the closest to meaningful support with a tied 13-13 vote from advisory committee members for and against agency approval. FDA staff takes advisory committee opinions and votes into account when making their final decisions about drug marketing approvals.

In each case, the committee members, mostly the same roster assembled for each of the three agents, identified specific concerns with the data purported to show each drug’s safety and efficacy. But the gathered experts and consumer representatives also consistently cited holistic challenges to approving new opioids and the stiffer criteria these agents face amid a continuing wave of opioid misuse and abuse.

“In the context of the public health issues, we don’t want to be perceived in any way of taking shortcuts,” said Linda S. Tyler, PharmD,, an advisory committee member and professor of pharmacy and chief pharmacy officer at the University of Utah in Salt Lake City. “There is no question that for a new product to come to market in this space it needs to add to what’s on the market, meet a high bar, and provide advantages compared with what’s already on the market,” she said.

Tramadol plus celecoxib gains some support

The proposed combined formulation of tramadol and celecoxib came closest to meeting that bar, as far as the advisory committee was concerned, coming away with 13 votes favoring approval to match 13 votes against. The premise behind this agent, know as CTC (cocrystal of tramadol and celecoxib), was that it combined a modest dose (44 mg) of the schedule IV opioid tramadol with a 56-mg dose of celecoxib in a twice-daily pill. Eugene R. Viscusi, MD, professor of anesthesiology and director of acute pain management at Thomas Jefferson University in Philadelphia and a speaker at the session on behalf of the applicant company, spelled out the rationale behind CTC: “We are caught in a dilemma. We need to reduce opioid use, but we also need to treat pain. We have an urgent need to have pain treatment options that are effective but have low potential for abuse and dependence. We are looking at multimodal analgesia, that uses combination of agents, recognizing that postoperative pain is a mixed pain syndrome. Multimodal pain treatments are now considered standard care. We want to minimize opioids to the lowest dose possible to produce safe analgesia. Tramadol is the least-preferred opioid for abuse,” and is rated as schedule IV, the U.S. designation for drugs considered to have a low level of potential for causing abuse or dependence. “Opioids used as stand-alone agents have contributed to the current opioid crisis,” Dr. Viscusi told the committee.

In contrast to tramadol’s schedule IV status, the mainstays of recent opioid pain therapy have been hydrocodone and oxycodone, schedule II opioids rated as having a “high potential for abuse.”

Several advisory committee members agreed that CTC minimized patient exposure to an opioid. “This drug isn’t even tramadol; it’s tramadol light. It has about as low a dose [of an opioid] as you can have and still have a drug,” said member Lee A. Hoffer, PhD, a medical anthropologist at Case Western Reserve University, Cleveland, who studies substance use disorders. “All opioids are dangerous, even at a low dose, but there is a linear relationship based on potency, so if we want to have an opioid for acute pain, I’d like it to have the lowest morphine milligram equivalent possible. The ideal is no opioids, but that is not what happens,” he said. The CTC formulation delivers 17.6 morphine milligram equivalents (MME) per pill, the manufacturer’s representatives said. The Centers for Disease Control and Prevention defines a “relatively low” daily opioid dose as 20-50 MME.

Some committee members hailed the CTC formulation as a meaningful step toward cutting opioid consumption.

“We may be very nervous about abuse of scheduled opioids, but a schedule IV opioid in an opioid-sparing formulation is as good as it gets in 2020,” said committee member Kevin L. Zacharoff, MD, a pain medicine specialist at the State University of New York at Stony Brook. “Any opioid has potential for abuse, but this is a safer alternative to the schedule II drugs. There is less public health risk with this,” said committee member Sherif Zaafran, MD, a Houston anesthesiologist. “This represents an incremental but important approach to addressing the opioid crisis, especially if used to replace schedule II opioids,” said Brandon D.L. Marshall, PhD, an epidemiologist and substance abuse researcher at Brown University in Providence, R.I.

But despite agreement that CTC represented a new low in the MME of an opioid given to patients, several committee members still saw the formulation as problematic by introducing any opioid, no matter how small the dose.

“The landscape of tramadol use and prescribing is evolving. There’s been an exponential upturn in tramadol prescribing. It’s perceived [as] safer, but it’s not completely safe. Will this change tramadol abuse and open the door to abuse of other opioids? This is what got us into trouble with opioids in the first place. Patients start with a prescription opioid that they perceive is safe. Patients don’t start with oxycodone or heroin. They start with drugs that are believed to be safe. I feel this combination has less risk for abuse, but I’m worried that it would produce a false sense of security for tolerability and safety,” said committee member Maryann E. Amirshahi, MD, a medical toxicologist at Georgetown University and MedStar Health in Washington.

Several other committee members returned to this point throughout the 2 days of discussions: The majority of Americans who have become hooked on opioids reached that point by taking an opioid pain medication for a legitimate medical reason and using the drug the way they had understood they should.

“I’m most concerned about unintentional misuse leading to addiction and abuse. Most people with an opioid addiction got it inadvertently, misusing it by mistake,” said committee member Suzanne B. Robotti, a consumer representative and executive director of DES Action USA. “I’m concerned about approving an opioid, even an opioid with a low abuse history, without a clearer picture of the human abuse potential data and what would happen if this drug were abused,” she added, referring to the proposed CTC formulation.

“All the patients I work with started [their opioid addiction] as pain patients,” Dr. Hoffer said.

“The most common use and abuse of opioids is orally. We need to avoid having patients who use the drug as prescribed and still end up addicted,” said committee member Friedhelm Sandbrink, MD, a neurologist and director of pain management at the Veterans Affairs (VA) Medical Center in Washington.

What this means, said several panelists, is functionally clamping down a class-wide lid on new opioids. “The way to reduce deaths from abuse is to reduce addiction, and to have an impact you need to reduce opioid exposure.” said committee member Sonia Hernandez-Diaz, MD, professor of epidemiology at the Harvard School of Public Health in Boston.

“In this opioid crisis, we ask for data that we wouldn’t ordinarily ask for. I feel there are unanswered questions about the abuse potential [of CTC]. We have seen a recent reduction in oxycodone use, which is great, but also an increase in tramadol use. We should not be fooled. Tramadol is an opioid, even if it’s schedule IV,” Dr. Tyler said.

Two other opioids faced greater opposition

The other two agents that the committee considered received much less support and sharper skepticism. The application for Aximris XR, an extended release form of oxycodone with a purported abuse-deterrent formulation (ADF) that relies on being difficult to extract for intravenous use as well as possibly having effective deterrence mechanisms for other forms of abuse. But FDA staffers reported that the only effective deterrence they could document was against manipulation for intravenous use, making Aximris XR the first opioid seeking ADF labeling based on deterrence to a single delivery route. This led several committee members, as well as the FDA, to comment on the clinical meaningfulness of ADF for one route. So far, the FDA approved ADF labeling for seven opioids, most notably OxyContin, an extended-release oxycodone with the biggest share of the U.S. market for opioids with ADF labeling.

“For ADF, we label based on what we expect from the premarket data. We don’t really know how that translates into what happens once the drug is on the market. Every company with an ADF in their label is required to do postmarketing studies on the abuse routes that are supposed to be deterred. We see shifts to other routes. Assessment of ADF is incredibly challenging, both scientifically and logistically, because there has not been a lot of uptake of these products, for a variety of reasons,” said Judy Staffa, PhD, associate director for Public Health Initiatives in the Office of Surveillance & Epidemiology in the FDA’s Center for Drug Evaluation and Research. The company that markets OxyContin has been the first to submit to the FDA all of its required postmarketing data on ADF efficacy, and the agency is now reviewing this filing, Dr. Staffa said.

The data presented for Aximris XR appeared to generally fail to convince committee members that it provided a meaningful addition to the range of opioids with ADF designations already available, which meant that their decision mostly came down to whether they felt it made sense to bring a me-too opioid to the U.S. market. Their answer was mostly no.

“In the end, it’s another opioid, and I’m not sure we need another opioid,” said committee member Lonnie K. Zeltzer, MD, professor of pediatrics, anesthesiology, psychiatry, and biobehavioral sciences and director of pediatric pain at the University of California, Los Angeles “There are so many options for patients and for people who abuse these drug. I don’t see this formulation as having a profound impact, but I’m very concerned about adding more prescription opioids,” said Martin Garcia-Bunuel, MD, deputy chief of staff for the VA Maryland Health Care System in Baltimore. Another concern of some committee members was that ADF remains a designation with an uncertain meaning, pending the FDA’s analysis of the OxyContin data.

“At the end of the day, we don’t know whether any of the [ADF] stuff makes a difference,” noted Steve B. Meisel, PharmD, system director of medication safety for M Health Fairview in Minneapolis and a committee member,

The third agent, oxycodegol, a molecule designed to pass more slowly across the blood-brain barrier because of an attached polyethylene glycol chain that’s supposed to prevent a rapid high after ingestion and hence cut abuse potential. It received unanimous committee rejection, primarily because its safety and efficacy evidence had so many holes, but the shadow of opioid abuse permeated the committee’s discussion.

“One dogma in the abuse world is that slowing entry into the brain reduces abuse potential, but the opioid crisis showed that this is not the only factor. Some people have become addicted to slow-acting drugs. The abuse potential of this drug, oxycodegol, needs to be considered given where we’ve been with the opioid crisis,” said Jane B. Acri, PhD, chief of the Medications Discovery and Toxicology Branch of the National Institute on Drug Abuse.

“During the opioid epidemic, do we want to approve more opioids? If the [pain] efficacy is about the same as oxycodone, is better safety or abuse potential a reason to approve it? We need guidance [from the FDA] about what is ‘better enough.’ No opioid will ever be perfect; there will always be abuse and misuse. But what is good enough to justify bringing another opioid onto the market? What is a good enough improvement? I don’t have an answer,” Dr. Hernandez-Diaz said.

Adviser comments showed that the continued threat of widespread opioid addiction has cooled prospects for new opioid approvals by making FDA advisers skittish over how to properly score the incremental value of a new opioid.

“Do we need to go back to the drawing board on how we make decisions on exposing the American public to these kinds of agents?” Dr. Garcia-Bunuel asked. “I don’t think we have the tools to make these decisions.”

mzoler@mdedge.com

The opioid crisis has hit the American Indian and Alaska Native (AI/AN) communities particularly hard, and “[i]nfants born withdrawing from opioids represent one of the most heartbreaking aspects,” says US Department of Health and Human Services Secretary Alex Azar.

Intrauterine exposure to opioids can induce symptoms that may result in spontaneous abortion, placental injury, and reduced nutrients for the fetus. Moreover, as many as 55% to 94% of infants prenatally exposed to opioids develop neonatal opioid withdrawal syndrome (NOWS), which can vary in severity from mild to life-threatening.

AI/AN women face significant barriers to obtaining appropriate care for substance use disorders, which may delay early interventions for the newborn’s health, said Shaquita Bell, MD, FAAP, chair of the American Academy of Pediatrics (AAP) Committee on Native American Child Health. The Indian Health Service (IHS) and the AAP have recently released clinical recommendations on NOWS for IHS, tribal, and urban Indian organization health care facilities.

The recommendations describe supportive, culturally appropriate standards of care for screening, diagnosing, and treating pregnant mothers and infants affected by prenatal opioid exposure. Management of NOWS begins with identifying women at risk, says the multidisciplinary panel responsible for the recommendations. Among other things, the experts advise screening a pregnant woman at the initial presentation for risk of substance use disorder, as well as for prescription opioid use for treatment of pain, and other risk factors for NOWS.

The panel notes that early application of nonpharmacologic treatment and support can reduce the need for pharmacologic treatment and transfer. Patient education should be a “key component of every prenatal care visit,” the panel says, provided in a nonjudgmental, culturally competent way to increase engagement, involving the partner and other family members if possible. Discussion topics may include the physical effects of continued substance use on both the woman and her infant, but also may include social and legal consequences of continued use.

The recommendations are also a companion guide to clinical recommendations for improving care of AI/AN pregnant women and women of childbearing age with opioid use disorder, which were announced by IHS and the American College of Obstetricians and Gynecologists in March 2019.

The opioid crisis has hit the American Indian and Alaska Native (AI/AN) communities particularly hard, and “[i]nfants born withdrawing from opioids represent one of the most heartbreaking aspects,” says US Department of Health and Human Services Secretary Alex Azar.

Intrauterine exposure to opioids can induce symptoms that may result in spontaneous abortion, placental injury, and reduced nutrients for the fetus. Moreover, as many as 55% to 94% of infants prenatally exposed to opioids develop neonatal opioid withdrawal syndrome (NOWS), which can vary in severity from mild to life-threatening.

AI/AN women face significant barriers to obtaining appropriate care for substance use disorders, which may delay early interventions for the newborn’s health, said Shaquita Bell, MD, FAAP, chair of the American Academy of Pediatrics (AAP) Committee on Native American Child Health. The Indian Health Service (IHS) and the AAP have recently released clinical recommendations on NOWS for IHS, tribal, and urban Indian organization health care facilities.

The recommendations describe supportive, culturally appropriate standards of care for screening, diagnosing, and treating pregnant mothers and infants affected by prenatal opioid exposure. Management of NOWS begins with identifying women at risk, says the multidisciplinary panel responsible for the recommendations. Among other things, the experts advise screening a pregnant woman at the initial presentation for risk of substance use disorder, as well as for prescription opioid use for treatment of pain, and other risk factors for NOWS.

The panel notes that early application of nonpharmacologic treatment and support can reduce the need for pharmacologic treatment and transfer. Patient education should be a “key component of every prenatal care visit,” the panel says, provided in a nonjudgmental, culturally competent way to increase engagement, involving the partner and other family members if possible. Discussion topics may include the physical effects of continued substance use on both the woman and her infant, but also may include social and legal consequences of continued use.

The recommendations are also a companion guide to clinical recommendations for improving care of AI/AN pregnant women and women of childbearing age with opioid use disorder, which were announced by IHS and the American College of Obstetricians and Gynecologists in March 2019.

The opioid crisis has hit the American Indian and Alaska Native (AI/AN) communities particularly hard, and “[i]nfants born withdrawing from opioids represent one of the most heartbreaking aspects,” says US Department of Health and Human Services Secretary Alex Azar.

Intrauterine exposure to opioids can induce symptoms that may result in spontaneous abortion, placental injury, and reduced nutrients for the fetus. Moreover, as many as 55% to 94% of infants prenatally exposed to opioids develop neonatal opioid withdrawal syndrome (NOWS), which can vary in severity from mild to life-threatening.

AI/AN women face significant barriers to obtaining appropriate care for substance use disorders, which may delay early interventions for the newborn’s health, said Shaquita Bell, MD, FAAP, chair of the American Academy of Pediatrics (AAP) Committee on Native American Child Health. The Indian Health Service (IHS) and the AAP have recently released clinical recommendations on NOWS for IHS, tribal, and urban Indian organization health care facilities.

The recommendations describe supportive, culturally appropriate standards of care for screening, diagnosing, and treating pregnant mothers and infants affected by prenatal opioid exposure. Management of NOWS begins with identifying women at risk, says the multidisciplinary panel responsible for the recommendations. Among other things, the experts advise screening a pregnant woman at the initial presentation for risk of substance use disorder, as well as for prescription opioid use for treatment of pain, and other risk factors for NOWS.

The panel notes that early application of nonpharmacologic treatment and support can reduce the need for pharmacologic treatment and transfer. Patient education should be a “key component of every prenatal care visit,” the panel says, provided in a nonjudgmental, culturally competent way to increase engagement, involving the partner and other family members if possible. Discussion topics may include the physical effects of continued substance use on both the woman and her infant, but also may include social and legal consequences of continued use.

The recommendations are also a companion guide to clinical recommendations for improving care of AI/AN pregnant women and women of childbearing age with opioid use disorder, which were announced by IHS and the American College of Obstetricians and Gynecologists in March 2019.

Cigarette smokers who also use cannabis appear to face higher hurdles to quit smoking, a large national survey has found.

Scott Harms/iStockphoto

“Over the past decade, there has been an increase in the use of cannabis among cigarette smokers and prevalence of cigarettes and cannabis co-use, suggesting that the negative consequences of cigarette–cannabis co-use may also become more prevalent over time,” wrote Andrea H. Weinberger, PhD, of Yeshiva University, New York, and colleagues. They noted that the prevalence of cigarette smoking is nearly three times higher among persons who use cannabis and have cannabis use disorders relative to those who do not.

The 2019 National Survey of Drug Use and Health estimated that 15.9% of Americans aged 12 years or older used cannabis in the past year. This number has been rising throughout the 2000s.

In that same report, cannabis use disorder (or marijuana use disorder) was defined as when an individual experiences clinically significant impairment caused by the recurrent use of marijuana, including health problems, persistent or increasing use, and failure to meet major responsibilities at work, school, or home. The report stated that approximately 1.6% of Americans aged 12 or older in 2018 had marijuana use disorder.

In the study published in Tobacco Control, the researchers used the National Survey on Drug Use and Health data to analyze cigarette smoking quit ratios among U.S. adults with and without cannabis use and cannabis use disorders. “Quit ratio was calculated as the proportion of former smokers among lifetime smokers and is considered a measure of total cessation in a population,” the researchers said.

In 2016, the quit ratios for adults with a history of cannabis use or cannabis use disorders were 23% and 15%, respectively, compared with 51% and 48%, respectively, in those with no cannabis use or cannabis use disorders.

Overall, quit ratios did not change significantly from 2002 to 2016 for individuals with cannabis use disorders after controlling for multiple demographic factors and other substance use disorders. However, during the same time period, quit ratios showed a nonlinear increase in cannabis users, nonusers, and individuals without cannabis use disorders.

The study findings were limited by several factors including the inability to generalize results to youth or individuals living outside the United States, the use of DSM-IV criteria to identify cannabis use disorder, the use of self-reports, and the inability to examine the timing of cannabis use as related to attempts to quit smoking, the researchers noted. However, the results highlight the need to consider offering smoking cessation treatment to individuals being treated for cannabis use disorders, and to include cannabis users in smoking cessation programs, the researchers noted.

“Based on our results, both public health and clinical efforts to improve cigarette quit outcomes may benefit from including those with any cannabis use,” they said. More research is needed to determine whether trends in the quit ratio change over time for cannabis users or those with cannabis use disorder, they added.

The study was funded by the National Institute on Drug Abuse. The researchers had no financial conflicts to disclose.

SOURCE: Weinberger AH et al. Tob Control. 2020;29(1):74-80. doi: 10.1136/tobaccocontrol-2018-054590.

Cigarette smokers who also use cannabis appear to face higher hurdles to quit smoking, a large national survey has found.

Scott Harms/iStockphoto

“Over the past decade, there has been an increase in the use of cannabis among cigarette smokers and prevalence of cigarettes and cannabis co-use, suggesting that the negative consequences of cigarette–cannabis co-use may also become more prevalent over time,” wrote Andrea H. Weinberger, PhD, of Yeshiva University, New York, and colleagues. They noted that the prevalence of cigarette smoking is nearly three times higher among persons who use cannabis and have cannabis use disorders relative to those who do not.

The 2019 National Survey of Drug Use and Health estimated that 15.9% of Americans aged 12 years or older used cannabis in the past year. This number has been rising throughout the 2000s.

In that same report, cannabis use disorder (or marijuana use disorder) was defined as when an individual experiences clinically significant impairment caused by the recurrent use of marijuana, including health problems, persistent or increasing use, and failure to meet major responsibilities at work, school, or home. The report stated that approximately 1.6% of Americans aged 12 or older in 2018 had marijuana use disorder.

In the study published in Tobacco Control, the researchers used the National Survey on Drug Use and Health data to analyze cigarette smoking quit ratios among U.S. adults with and without cannabis use and cannabis use disorders. “Quit ratio was calculated as the proportion of former smokers among lifetime smokers and is considered a measure of total cessation in a population,” the researchers said.

In 2016, the quit ratios for adults with a history of cannabis use or cannabis use disorders were 23% and 15%, respectively, compared with 51% and 48%, respectively, in those with no cannabis use or cannabis use disorders.

Overall, quit ratios did not change significantly from 2002 to 2016 for individuals with cannabis use disorders after controlling for multiple demographic factors and other substance use disorders. However, during the same time period, quit ratios showed a nonlinear increase in cannabis users, nonusers, and individuals without cannabis use disorders.

The study findings were limited by several factors including the inability to generalize results to youth or individuals living outside the United States, the use of DSM-IV criteria to identify cannabis use disorder, the use of self-reports, and the inability to examine the timing of cannabis use as related to attempts to quit smoking, the researchers noted. However, the results highlight the need to consider offering smoking cessation treatment to individuals being treated for cannabis use disorders, and to include cannabis users in smoking cessation programs, the researchers noted.

“Based on our results, both public health and clinical efforts to improve cigarette quit outcomes may benefit from including those with any cannabis use,” they said. More research is needed to determine whether trends in the quit ratio change over time for cannabis users or those with cannabis use disorder, they added.

The study was funded by the National Institute on Drug Abuse. The researchers had no financial conflicts to disclose.

SOURCE: Weinberger AH et al. Tob Control. 2020;29(1):74-80. doi: 10.1136/tobaccocontrol-2018-054590.

Cigarette smokers who also use cannabis appear to face higher hurdles to quit smoking, a large national survey has found.

Scott Harms/iStockphoto

“Over the past decade, there has been an increase in the use of cannabis among cigarette smokers and prevalence of cigarettes and cannabis co-use, suggesting that the negative consequences of cigarette–cannabis co-use may also become more prevalent over time,” wrote Andrea H. Weinberger, PhD, of Yeshiva University, New York, and colleagues. They noted that the prevalence of cigarette smoking is nearly three times higher among persons who use cannabis and have cannabis use disorders relative to those who do not.

The 2019 National Survey of Drug Use and Health estimated that 15.9% of Americans aged 12 years or older used cannabis in the past year. This number has been rising throughout the 2000s.

In that same report, cannabis use disorder (or marijuana use disorder) was defined as when an individual experiences clinically significant impairment caused by the recurrent use of marijuana, including health problems, persistent or increasing use, and failure to meet major responsibilities at work, school, or home. The report stated that approximately 1.6% of Americans aged 12 or older in 2018 had marijuana use disorder.

In the study published in Tobacco Control, the researchers used the National Survey on Drug Use and Health data to analyze cigarette smoking quit ratios among U.S. adults with and without cannabis use and cannabis use disorders. “Quit ratio was calculated as the proportion of former smokers among lifetime smokers and is considered a measure of total cessation in a population,” the researchers said.

In 2016, the quit ratios for adults with a history of cannabis use or cannabis use disorders were 23% and 15%, respectively, compared with 51% and 48%, respectively, in those with no cannabis use or cannabis use disorders.

Overall, quit ratios did not change significantly from 2002 to 2016 for individuals with cannabis use disorders after controlling for multiple demographic factors and other substance use disorders. However, during the same time period, quit ratios showed a nonlinear increase in cannabis users, nonusers, and individuals without cannabis use disorders.

The study findings were limited by several factors including the inability to generalize results to youth or individuals living outside the United States, the use of DSM-IV criteria to identify cannabis use disorder, the use of self-reports, and the inability to examine the timing of cannabis use as related to attempts to quit smoking, the researchers noted. However, the results highlight the need to consider offering smoking cessation treatment to individuals being treated for cannabis use disorders, and to include cannabis users in smoking cessation programs, the researchers noted.

“Based on our results, both public health and clinical efforts to improve cigarette quit outcomes may benefit from including those with any cannabis use,” they said. More research is needed to determine whether trends in the quit ratio change over time for cannabis users or those with cannabis use disorder, they added.

The study was funded by the National Institute on Drug Abuse. The researchers had no financial conflicts to disclose.

SOURCE: Weinberger AH et al. Tob Control. 2020;29(1):74-80. doi: 10.1136/tobaccocontrol-2018-054590.

Binge drinking and misuse of opioids led to risky behavior during adolescence, two studies from the journal Pediatrics highlighted. And the binge drinking in high school may predict risky driving behaviors up to 4 years after high school.

wh1600/Getty Images

Federico E. Vaca, MD, of the developmental neurocognitive driving simulation research center at Yale University, New Haven, Conn., and colleagues examined the associations between risky driving behaviors and binge drinking of 2,785 adolescents in the nationally representative, longitudinal NEXT Generation Health Study. The researchers studied the effects of binge drinking on driving while impaired (DWI), riding with an impaired driver (RWI), blackouts, extreme binge drinking, and risky driving.

The adolescents were studied across seven waves, with Wave 1 beginning in the 2009-2010 school year (10th grade; mean age, 16 years), and data extended up to 4 years after high school. Of all adolescents enrolled, 91% completed Wave 1, 88% completed Wave 2, 86% completed Wave 3 (12th grade), 78% completed Wave 4, 79% completed Wave 5, 84% completed Wave 6, and 83% completed Wave 7 (4 years after leaving high school) of the study.

High school binge drinking predicts later risky behavior

About one-quarter of adolescents reported binge drinking in Waves 1-3, with an incidence of 27% in Wave 1, 24% in Wave 2, and 27% in Wave 3. Adolescents who reported binge drinking in Wave 3 had a higher likelihood of DWI in subsequent waves, with nearly six times higher odds in Wave 5 and more than twice as likely in Wave 7, researchers said. Binge drinking in Wave 3 also was associated with greater than four times higher odds of RWI in Wave 4, and more than two and a half times higher odds of RWI in Wave 7. Among adolescents who reported binge drinking across 3 years in high school, there was a higher likelihood of extreme binge drinking in Wave 7, and higher likelihood of risky driving after graduating.

Impact of parental knowledge of drinking

Parental knowledge of drinking and support for not drinking alcohol was associated with lower likelihood of DWI and RWI in some waves. Father monitoring knowledge of drinking in Waves 1-3 lowered the odds of DWI by 30% in Wave 5 and 20% in Wave 6, while also lowering the odds of RWI in Wave 4 and Wave 7 by 20%.

Mother knowledge of drinking in Waves 1-3 was associated with 60% lower odds of DWI in Wave 4, but did not lower odds in any wave for RWI.

Overall, parental support for not drinking lowered odds for DWI by 40% in Waves 4 and 5, and by 30% in Wave 7 while also lowering odds of RWI in Wave 4 by 20%.

The results are consistent with other studies examining risky driving behavior and binge drinking in adolescent populations, but researchers noted that “to an important but limited extent, parental practices while the teenager is in high school may protect against DWI, RWI, and blackouts as adolescents move into early adulthood.”

“Our findings are relevant to prevention programs that seek to incorporate alcohol screening with intentional inquiry about binge drinking. Moreover, our results may be instructive to programs that seek to leverage facets of parental practices to reduce health-risk contexts for youth,” Dr. Vaca and colleagues concluded. “Such prevention activities coupled with strengthening of policies and practices reducing adolescents’ access to alcohol could reduce later major alcohol-related health-risk behaviors and their consequences.”

Opioid misuse and risky behavior

In a second study, Devika Bhatia, MD, of the University of Colorado at Denver, Aurora, and colleagues examined opioid misuse in a nationally-representative sample of 14,765 adolescents from the Centers for Disease Control and Prevention’s 2017 Youth Risk Behavior Surveillance Survey. The researchers measured opioid misuse by categorizing adolescents into groups based on whether they had ever misused prescription opioids and whether they had engaged in risky driving behavior, violent behavior, risky sexual behavior, had a history of substance abuse, or attempted suicide.

Dr. Bhatia and colleagues found 14% of adolescents in the study reported misusing opioids, with an overrepresentation of 17-year-old and 18-year-old participants reporting opioid misuse (P less than .0001). there were no statistically significant difference between those who misused opioids and those who did not in terms of race, ethnicity, or sex.

Those adolescents who reported misusing opioids were 2.8 times more likely to not use a seatbelt; were 2.8 times more likely to have RWI; were 5.8 times more likely to have DWI; or 2.3 times more likely to have texted or emailed while driving. In each of these cases, P was less than .0001.

Adolescents who misused opioids also had significantly increased odds of engaging in risky sexual behaviors such as having sex before 13 years (3.9 times); having sex with four or more partners (4.8 times); using substances before sex (3.6 times); and not using a condom before sex (2.0 times). In each of these cases, P was less than .0001.

Additionally, adolescents in this category were between 5.4 times and 22.3 times more likely to use other substances (P less than .0001 for 10 variables); 4.9 times more likely to have attempted suicide (P less than .0001); or more likely to have engaged in violent behavior such as getting into physical fights (4.0 times), carrying a weapon (3.4 times) or a gun (5.1 times) within the last 30 days. In the four latter cases, P was less than .0001.

“With the ongoing opioid epidemic, pediatricians and child psychiatrists are likely to be more attuned to opioid misuse in their patients,” Dr. Bhatia and colleagues concluded. “If youth are screening positive for opioid misuse, pediatricians, nurses, social workers, child psychiatrists, and other providers assessing adolescents may have a new, broad range of other risky behaviors for which to screen regardless of the direction of the association.”

Substance use screening for treating substance use disorder traditionally has been is provided by a specialist, Jessica A. Kulak, PhD, MPH, said in an interview. “However, integration of care services may help to change societal norms around problematic substance use – both by decreasing stigma associated with substance use, as well as increasing clinicians’ preparedness, knowledge, and confidence in preventing and intervening on adolescents’ substance experimentation and use.” She recommended that clinicians in primary care improve their training by using the Substance Abuse and Mental Health Services Administration’s Screening, Brief Intervention, and Referral to Treatment program, which is available as a free online course.

Confidentiality is important in adolescent health, said Dr. Kulak, who is an assistant professor in the department of health, nutrition, and dietetics at State University of New York at Buffalo. “When discussing sensitive topics, such as binge drinking and opioid misuse, adolescents may fear that these or other risky activities may be disclosed to parents or law enforcement officials. Therefore, adolescent health providers should be aware of local, state, and federal laws pertaining to the confidentiality of minors.”

She added, “adolescents are often susceptible to others’ influences, so having open communication and support from a trusted adult – be it a parent or clinician – may also be protective against risky behaviors.”

The study by Vaca et al. was funded by the National Institutes of Health with support from the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development; the National Heart, Lung, and Blood Institute; the National Institute on Alcohol Abuse and Alcoholism; the National Institute on Drug Abuse; and the Maternal and Child Health Bureau of the Health Resources and Services Administration. The study by Bhatia et al. had no external funding. The authors from both studies reported no relevant financial disclosures. Dr. Kulak said she had no financial disclosures or other conflicts of interest.

pdnews@mdedge.com

SOURCE: Vaca FE et al. Pediatrics. 2020; doi: 10.1542/peds.2018-4095. Bhatia D et al. Pediatrics. 2020; doi: 10.1542/peds.2019-2470.

Binge drinking and misuse of opioids led to risky behavior during adolescence, two studies from the journal Pediatrics highlighted. And the binge drinking in high school may predict risky driving behaviors up to 4 years after high school.

wh1600/Getty Images

Federico E. Vaca, MD, of the developmental neurocognitive driving simulation research center at Yale University, New Haven, Conn., and colleagues examined the associations between risky driving behaviors and binge drinking of 2,785 adolescents in the nationally representative, longitudinal NEXT Generation Health Study. The researchers studied the effects of binge drinking on driving while impaired (DWI), riding with an impaired driver (RWI), blackouts, extreme binge drinking, and risky driving.

The adolescents were studied across seven waves, with Wave 1 beginning in the 2009-2010 school year (10th grade; mean age, 16 years), and data extended up to 4 years after high school. Of all adolescents enrolled, 91% completed Wave 1, 88% completed Wave 2, 86% completed Wave 3 (12th grade), 78% completed Wave 4, 79% completed Wave 5, 84% completed Wave 6, and 83% completed Wave 7 (4 years after leaving high school) of the study.

High school binge drinking predicts later risky behavior

About one-quarter of adolescents reported binge drinking in Waves 1-3, with an incidence of 27% in Wave 1, 24% in Wave 2, and 27% in Wave 3. Adolescents who reported binge drinking in Wave 3 had a higher likelihood of DWI in subsequent waves, with nearly six times higher odds in Wave 5 and more than twice as likely in Wave 7, researchers said. Binge drinking in Wave 3 also was associated with greater than four times higher odds of RWI in Wave 4, and more than two and a half times higher odds of RWI in Wave 7. Among adolescents who reported binge drinking across 3 years in high school, there was a higher likelihood of extreme binge drinking in Wave 7, and higher likelihood of risky driving after graduating.

Impact of parental knowledge of drinking

Parental knowledge of drinking and support for not drinking alcohol was associated with lower likelihood of DWI and RWI in some waves. Father monitoring knowledge of drinking in Waves 1-3 lowered the odds of DWI by 30% in Wave 5 and 20% in Wave 6, while also lowering the odds of RWI in Wave 4 and Wave 7 by 20%.

Mother knowledge of drinking in Waves 1-3 was associated with 60% lower odds of DWI in Wave 4, but did not lower odds in any wave for RWI.

Overall, parental support for not drinking lowered odds for DWI by 40% in Waves 4 and 5, and by 30% in Wave 7 while also lowering odds of RWI in Wave 4 by 20%.

The results are consistent with other studies examining risky driving behavior and binge drinking in adolescent populations, but researchers noted that “to an important but limited extent, parental practices while the teenager is in high school may protect against DWI, RWI, and blackouts as adolescents move into early adulthood.”

“Our findings are relevant to prevention programs that seek to incorporate alcohol screening with intentional inquiry about binge drinking. Moreover, our results may be instructive to programs that seek to leverage facets of parental practices to reduce health-risk contexts for youth,” Dr. Vaca and colleagues concluded. “Such prevention activities coupled with strengthening of policies and practices reducing adolescents’ access to alcohol could reduce later major alcohol-related health-risk behaviors and their consequences.”

Opioid misuse and risky behavior

In a second study, Devika Bhatia, MD, of the University of Colorado at Denver, Aurora, and colleagues examined opioid misuse in a nationally-representative sample of 14,765 adolescents from the Centers for Disease Control and Prevention’s 2017 Youth Risk Behavior Surveillance Survey. The researchers measured opioid misuse by categorizing adolescents into groups based on whether they had ever misused prescription opioids and whether they had engaged in risky driving behavior, violent behavior, risky sexual behavior, had a history of substance abuse, or attempted suicide.

Dr. Bhatia and colleagues found 14% of adolescents in the study reported misusing opioids, with an overrepresentation of 17-year-old and 18-year-old participants reporting opioid misuse (P less than .0001). there were no statistically significant difference between those who misused opioids and those who did not in terms of race, ethnicity, or sex.

Those adolescents who reported misusing opioids were 2.8 times more likely to not use a seatbelt; were 2.8 times more likely to have RWI; were 5.8 times more likely to have DWI; or 2.3 times more likely to have texted or emailed while driving. In each of these cases, P was less than .0001.

Adolescents who misused opioids also had significantly increased odds of engaging in risky sexual behaviors such as having sex before 13 years (3.9 times); having sex with four or more partners (4.8 times); using substances before sex (3.6 times); and not using a condom before sex (2.0 times). In each of these cases, P was less than .0001.

Additionally, adolescents in this category were between 5.4 times and 22.3 times more likely to use other substances (P less than .0001 for 10 variables); 4.9 times more likely to have attempted suicide (P less than .0001); or more likely to have engaged in violent behavior such as getting into physical fights (4.0 times), carrying a weapon (3.4 times) or a gun (5.1 times) within the last 30 days. In the four latter cases, P was less than .0001.

“With the ongoing opioid epidemic, pediatricians and child psychiatrists are likely to be more attuned to opioid misuse in their patients,” Dr. Bhatia and colleagues concluded. “If youth are screening positive for opioid misuse, pediatricians, nurses, social workers, child psychiatrists, and other providers assessing adolescents may have a new, broad range of other risky behaviors for which to screen regardless of the direction of the association.”

Substance use screening for treating substance use disorder traditionally has been is provided by a specialist, Jessica A. Kulak, PhD, MPH, said in an interview. “However, integration of care services may help to change societal norms around problematic substance use – both by decreasing stigma associated with substance use, as well as increasing clinicians’ preparedness, knowledge, and confidence in preventing and intervening on adolescents’ substance experimentation and use.” She recommended that clinicians in primary care improve their training by using the Substance Abuse and Mental Health Services Administration’s Screening, Brief Intervention, and Referral to Treatment program, which is available as a free online course.

Confidentiality is important in adolescent health, said Dr. Kulak, who is an assistant professor in the department of health, nutrition, and dietetics at State University of New York at Buffalo. “When discussing sensitive topics, such as binge drinking and opioid misuse, adolescents may fear that these or other risky activities may be disclosed to parents or law enforcement officials. Therefore, adolescent health providers should be aware of local, state, and federal laws pertaining to the confidentiality of minors.”

She added, “adolescents are often susceptible to others’ influences, so having open communication and support from a trusted adult – be it a parent or clinician – may also be protective against risky behaviors.”

The study by Vaca et al. was funded by the National Institutes of Health with support from the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development; the National Heart, Lung, and Blood Institute; the National Institute on Alcohol Abuse and Alcoholism; the National Institute on Drug Abuse; and the Maternal and Child Health Bureau of the Health Resources and Services Administration. The study by Bhatia et al. had no external funding. The authors from both studies reported no relevant financial disclosures. Dr. Kulak said she had no financial disclosures or other conflicts of interest.

pdnews@mdedge.com

SOURCE: Vaca FE et al. Pediatrics. 2020; doi: 10.1542/peds.2018-4095. Bhatia D et al. Pediatrics. 2020; doi: 10.1542/peds.2019-2470.

Binge drinking and misuse of opioids led to risky behavior during adolescence, two studies from the journal Pediatrics highlighted. And the binge drinking in high school may predict risky driving behaviors up to 4 years after high school.

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Federico E. Vaca, MD, of the developmental neurocognitive driving simulation research center at Yale University, New Haven, Conn., and colleagues examined the associations between risky driving behaviors and binge drinking of 2,785 adolescents in the nationally representative, longitudinal NEXT Generation Health Study. The researchers studied the effects of binge drinking on driving while impaired (DWI), riding with an impaired driver (RWI), blackouts, extreme binge drinking, and risky driving.

The adolescents were studied across seven waves, with Wave 1 beginning in the 2009-2010 school year (10th grade; mean age, 16 years), and data extended up to 4 years after high school. Of all adolescents enrolled, 91% completed Wave 1, 88% completed Wave 2, 86% completed Wave 3 (12th grade), 78% completed Wave 4, 79% completed Wave 5, 84% completed Wave 6, and 83% completed Wave 7 (4 years after leaving high school) of the study.

High school binge drinking predicts later risky behavior

About one-quarter of adolescents reported binge drinking in Waves 1-3, with an incidence of 27% in Wave 1, 24% in Wave 2, and 27% in Wave 3. Adolescents who reported binge drinking in Wave 3 had a higher likelihood of DWI in subsequent waves, with nearly six times higher odds in Wave 5 and more than twice as likely in Wave 7, researchers said. Binge drinking in Wave 3 also was associated with greater than four times higher odds of RWI in Wave 4, and more than two and a half times higher odds of RWI in Wave 7. Among adolescents who reported binge drinking across 3 years in high school, there was a higher likelihood of extreme binge drinking in Wave 7, and higher likelihood of risky driving after graduating.

Impact of parental knowledge of drinking

Parental knowledge of drinking and support for not drinking alcohol was associated with lower likelihood of DWI and RWI in some waves. Father monitoring knowledge of drinking in Waves 1-3 lowered the odds of DWI by 30% in Wave 5 and 20% in Wave 6, while also lowering the odds of RWI in Wave 4 and Wave 7 by 20%.

Mother knowledge of drinking in Waves 1-3 was associated with 60% lower odds of DWI in Wave 4, but did not lower odds in any wave for RWI.

Overall, parental support for not drinking lowered odds for DWI by 40% in Waves 4 and 5, and by 30% in Wave 7 while also lowering odds of RWI in Wave 4 by 20%.

The results are consistent with other studies examining risky driving behavior and binge drinking in adolescent populations, but researchers noted that “to an important but limited extent, parental practices while the teenager is in high school may protect against DWI, RWI, and blackouts as adolescents move into early adulthood.”

“Our findings are relevant to prevention programs that seek to incorporate alcohol screening with intentional inquiry about binge drinking. Moreover, our results may be instructive to programs that seek to leverage facets of parental practices to reduce health-risk contexts for youth,” Dr. Vaca and colleagues concluded. “Such prevention activities coupled with strengthening of policies and practices reducing adolescents’ access to alcohol could reduce later major alcohol-related health-risk behaviors and their consequences.”

Opioid misuse and risky behavior

In a second study, Devika Bhatia, MD, of the University of Colorado at Denver, Aurora, and colleagues examined opioid misuse in a nationally-representative sample of 14,765 adolescents from the Centers for Disease Control and Prevention’s 2017 Youth Risk Behavior Surveillance Survey. The researchers measured opioid misuse by categorizing adolescents into groups based on whether they had ever misused prescription opioids and whether they had engaged in risky driving behavior, violent behavior, risky sexual behavior, had a history of substance abuse, or attempted suicide.

Dr. Bhatia and colleagues found 14% of adolescents in the study reported misusing opioids, with an overrepresentation of 17-year-old and 18-year-old participants reporting opioid misuse (P less than .0001). there were no statistically significant difference between those who misused opioids and those who did not in terms of race, ethnicity, or sex.

Those adolescents who reported misusing opioids were 2.8 times more likely to not use a seatbelt; were 2.8 times more likely to have RWI; were 5.8 times more likely to have DWI; or 2.3 times more likely to have texted or emailed while driving. In each of these cases, P was less than .0001.

Adolescents who misused opioids also had significantly increased odds of engaging in risky sexual behaviors such as having sex before 13 years (3.9 times); having sex with four or more partners (4.8 times); using substances before sex (3.6 times); and not using a condom before sex (2.0 times). In each of these cases, P was less than .0001.

Additionally, adolescents in this category were between 5.4 times and 22.3 times more likely to use other substances (P less than .0001 for 10 variables); 4.9 times more likely to have attempted suicide (P less than .0001); or more likely to have engaged in violent behavior such as getting into physical fights (4.0 times), carrying a weapon (3.4 times) or a gun (5.1 times) within the last 30 days. In the four latter cases, P was less than .0001.

“With the ongoing opioid epidemic, pediatricians and child psychiatrists are likely to be more attuned to opioid misuse in their patients,” Dr. Bhatia and colleagues concluded. “If youth are screening positive for opioid misuse, pediatricians, nurses, social workers, child psychiatrists, and other providers assessing adolescents may have a new, broad range of other risky behaviors for which to screen regardless of the direction of the association.”

Substance use screening for treating substance use disorder traditionally has been is provided by a specialist, Jessica A. Kulak, PhD, MPH, said in an interview. “However, integration of care services may help to change societal norms around problematic substance use – both by decreasing stigma associated with substance use, as well as increasing clinicians’ preparedness, knowledge, and confidence in preventing and intervening on adolescents’ substance experimentation and use.” She recommended that clinicians in primary care improve their training by using the Substance Abuse and Mental Health Services Administration’s Screening, Brief Intervention, and Referral to Treatment program, which is available as a free online course.

Confidentiality is important in adolescent health, said Dr. Kulak, who is an assistant professor in the department of health, nutrition, and dietetics at State University of New York at Buffalo. “When discussing sensitive topics, such as binge drinking and opioid misuse, adolescents may fear that these or other risky activities may be disclosed to parents or law enforcement officials. Therefore, adolescent health providers should be aware of local, state, and federal laws pertaining to the confidentiality of minors.”

She added, “adolescents are often susceptible to others’ influences, so having open communication and support from a trusted adult – be it a parent or clinician – may also be protective against risky behaviors.”

The study by Vaca et al. was funded by the National Institutes of Health with support from the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development; the National Heart, Lung, and Blood Institute; the National Institute on Alcohol Abuse and Alcoholism; the National Institute on Drug Abuse; and the Maternal and Child Health Bureau of the Health Resources and Services Administration. The study by Bhatia et al. had no external funding. The authors from both studies reported no relevant financial disclosures. Dr. Kulak said she had no financial disclosures or other conflicts of interest.

pdnews@mdedge.com

SOURCE: Vaca FE et al. Pediatrics. 2020; doi: 10.1542/peds.2018-4095. Bhatia D et al. Pediatrics. 2020; doi: 10.1542/peds.2019-2470.

The Food and Drug Administration has taken steps to target the use of flavors in cartridge-based e-cigarette products among minors, but states it is not a “ban.”

librakv/Thinkstock

On Jan. 2, the agency issued enforcement guidance alerting companies that manufacture, distribute, and sell unauthorized flavored cartridge-based e-cigarettes within the next 30 days will risk FDA enforcement action.

FDA has had the authority to require premarket authorization of all e-cigarettes and other electronic nicotine delivery systems (ENDS) since August 2016, but thus far has exercised enforcement discretion regarding the need for premarket authorization for these types of products.

“By prioritizing enforcement against the products that are most widely used by children, our action today seeks to strike the right public health balance by maintaining e-cigarettes as a potential off-ramp for adults using combustible tobacco while ensuring these products don’t provide an on-ramp to nicotine addiction for our youth,” Department of Health & Human Services Secretary Alex Azar said in a statement.

The action comes in the wake of more than 2,500 vaping-related injuries being reported, including more than 50 deaths associated with vaping reported by the Centers for Disease Control and Prevention (although many are related to the use of tetrahydrocannabinol [THC] within vaping products) and a continued rise in youth use of e-cigarettes noted in government surveys.

The agency noted in a Jan. 2 statement announcing the enforcement action that, to date, no ENDS products have received a premarket authorization, “meaning that all ENDS products currently on the market are considered illegally marketed and are subject to enforcement, at any time, in the FDA’s discretion.”

FDA said it is prioritizing enforcement in 30 days against:

• Any flavored, cartridge-based ENDS product, other than those with a tobacco or menthol flavoring.
• All other ENDS products for which manufacturers are failing to take adequate measures to prevent access by minors.
• Any ENDS product that is targeted to minors or is likely to promote use by minors.

In the last category, this might include labeling or advertising resembling “kid-friendly food and drinks such as juice boxes or kid-friendly cereal; products marketed directly to minors by promoting ease of concealing the product or disguising it as another product; and products marketed with characters designed to appeal to youth,” according to the FDA statement.

As of May 12, FDA also will prioritize enforcement against any ENDS product for which the manufacturer has not submitted a premarket application. The agency will continue to exercise enforcement discretion for up to 1 year on these products if an application has been submitted, pending the review of that application.

“By not prioritizing enforcement against other flavored ENDS products in the same way as flavored cartridge-based ENDS products, the FDA has attempted to balance the public health concerns related to youth use of ENDS products with consideration regarding addicted adult cigarette smokers who may try to use ENDS products to transition away from combustible tobacco products,” the agency stated, adding that cartridge-based ENDS products are most commonly used among youth.

The FDA statement noted that the enforcement priorities outlined in the guidance document were not a “ban” on flavored or cartridge-based ENDS, noting the agency “has already accepted and begun review of several premarket applications for flavored ENDS products through the pathway that Congress established in the Tobacco Control Act. ... If a company can demonstrate to the FDA that a specific product meets the applicable standard set forth by Congress, including considering how the marketing of the product may affect youth initiation and use, then the FDA could authorize that product for sale.”

“Coupled with the recently signed legislation increasing the minimum age of sale of tobacco to 21, we believe this policy balances the urgency with which we must address the public health threat of youth use of e-cigarette products with the potential role that e-cigarettes may play in helping adult smokers transition completely away from combustible tobacco to a potentially less risky form of nicotine delivery,” FDA Commissioner Stephen Hahn, MD, said in a statement. “While we expect that responsible members of industry will comply with premarket requirements, we’re ready to take action against any unauthorized e-cigarette products as outlined in our priorities. We’ll also closely monitor the use rates of all e-cigarette products and take additional steps to address youth use as necessary.”

The American Medical Association criticized the action as not going far enough, even though it was a step in the right direction.

“The AMA is disappointed that menthol flavors, one of the most popular, will still be allowed, and that flavored e-liquids will remain on the market, leaving young people with easy access to alternative flavored e-cigarette products,” AMA President Patrice A. Harris, MD, said in a statement. “If we are serious about tackling this epidemic and keeping these harmful products out of the hands of young people, a total ban on all flavored e-cigarettes, in all forms and at all locations, is prudent and urgently needed. We are pleased the administration committed today to closely monitoring the situation and trends in e-cigarette use among young people, and to taking further action if needed.”

gtwachtman@mdedge.com

The Food and Drug Administration has taken steps to target the use of flavors in cartridge-based e-cigarette products among minors, but states it is not a “ban.”

librakv/Thinkstock

On Jan. 2, the agency issued enforcement guidance alerting companies that manufacture, distribute, and sell unauthorized flavored cartridge-based e-cigarettes within the next 30 days will risk FDA enforcement action.

FDA has had the authority to require premarket authorization of all e-cigarettes and other electronic nicotine delivery systems (ENDS) since August 2016, but thus far has exercised enforcement discretion regarding the need for premarket authorization for these types of products.

“By prioritizing enforcement against the products that are most widely used by children, our action today seeks to strike the right public health balance by maintaining e-cigarettes as a potential off-ramp for adults using combustible tobacco while ensuring these products don’t provide an on-ramp to nicotine addiction for our youth,” Department of Health & Human Services Secretary Alex Azar said in a statement.

The action comes in the wake of more than 2,500 vaping-related injuries being reported, including more than 50 deaths associated with vaping reported by the Centers for Disease Control and Prevention (although many are related to the use of tetrahydrocannabinol [THC] within vaping products) and a continued rise in youth use of e-cigarettes noted in government surveys.

The agency noted in a Jan. 2 statement announcing the enforcement action that, to date, no ENDS products have received a premarket authorization, “meaning that all ENDS products currently on the market are considered illegally marketed and are subject to enforcement, at any time, in the FDA’s discretion.”

FDA said it is prioritizing enforcement in 30 days against:

• Any flavored, cartridge-based ENDS product, other than those with a tobacco or menthol flavoring.
• All other ENDS products for which manufacturers are failing to take adequate measures to prevent access by minors.
• Any ENDS product that is targeted to minors or is likely to promote use by minors.

In the last category, this might include labeling or advertising resembling “kid-friendly food and drinks such as juice boxes or kid-friendly cereal; products marketed directly to minors by promoting ease of concealing the product or disguising it as another product; and products marketed with characters designed to appeal to youth,” according to the FDA statement.

As of May 12, FDA also will prioritize enforcement against any ENDS product for which the manufacturer has not submitted a premarket application. The agency will continue to exercise enforcement discretion for up to 1 year on these products if an application has been submitted, pending the review of that application.

“By not prioritizing enforcement against other flavored ENDS products in the same way as flavored cartridge-based ENDS products, the FDA has attempted to balance the public health concerns related to youth use of ENDS products with consideration regarding addicted adult cigarette smokers who may try to use ENDS products to transition away from combustible tobacco products,” the agency stated, adding that cartridge-based ENDS products are most commonly used among youth.

The FDA statement noted that the enforcement priorities outlined in the guidance document were not a “ban” on flavored or cartridge-based ENDS, noting the agency “has already accepted and begun review of several premarket applications for flavored ENDS products through the pathway that Congress established in the Tobacco Control Act. ... If a company can demonstrate to the FDA that a specific product meets the applicable standard set forth by Congress, including considering how the marketing of the product may affect youth initiation and use, then the FDA could authorize that product for sale.”

“Coupled with the recently signed legislation increasing the minimum age of sale of tobacco to 21, we believe this policy balances the urgency with which we must address the public health threat of youth use of e-cigarette products with the potential role that e-cigarettes may play in helping adult smokers transition completely away from combustible tobacco to a potentially less risky form of nicotine delivery,” FDA Commissioner Stephen Hahn, MD, said in a statement. “While we expect that responsible members of industry will comply with premarket requirements, we’re ready to take action against any unauthorized e-cigarette products as outlined in our priorities. We’ll also closely monitor the use rates of all e-cigarette products and take additional steps to address youth use as necessary.”

The American Medical Association criticized the action as not going far enough, even though it was a step in the right direction.

“The AMA is disappointed that menthol flavors, one of the most popular, will still be allowed, and that flavored e-liquids will remain on the market, leaving young people with easy access to alternative flavored e-cigarette products,” AMA President Patrice A. Harris, MD, said in a statement. “If we are serious about tackling this epidemic and keeping these harmful products out of the hands of young people, a total ban on all flavored e-cigarettes, in all forms and at all locations, is prudent and urgently needed. We are pleased the administration committed today to closely monitoring the situation and trends in e-cigarette use among young people, and to taking further action if needed.”

gtwachtman@mdedge.com

The Food and Drug Administration has taken steps to target the use of flavors in cartridge-based e-cigarette products among minors, but states it is not a “ban.”

librakv/Thinkstock

On Jan. 2, the agency issued enforcement guidance alerting companies that manufacture, distribute, and sell unauthorized flavored cartridge-based e-cigarettes within the next 30 days will risk FDA enforcement action.

FDA has had the authority to require premarket authorization of all e-cigarettes and other electronic nicotine delivery systems (ENDS) since August 2016, but thus far has exercised enforcement discretion regarding the need for premarket authorization for these types of products.

“By prioritizing enforcement against the products that are most widely used by children, our action today seeks to strike the right public health balance by maintaining e-cigarettes as a potential off-ramp for adults using combustible tobacco while ensuring these products don’t provide an on-ramp to nicotine addiction for our youth,” Department of Health & Human Services Secretary Alex Azar said in a statement.

The action comes in the wake of more than 2,500 vaping-related injuries being reported, including more than 50 deaths associated with vaping reported by the Centers for Disease Control and Prevention (although many are related to the use of tetrahydrocannabinol [THC] within vaping products) and a continued rise in youth use of e-cigarettes noted in government surveys.

The agency noted in a Jan. 2 statement announcing the enforcement action that, to date, no ENDS products have received a premarket authorization, “meaning that all ENDS products currently on the market are considered illegally marketed and are subject to enforcement, at any time, in the FDA’s discretion.”

FDA said it is prioritizing enforcement in 30 days against:

• Any flavored, cartridge-based ENDS product, other than those with a tobacco or menthol flavoring.
• All other ENDS products for which manufacturers are failing to take adequate measures to prevent access by minors.
• Any ENDS product that is targeted to minors or is likely to promote use by minors.

In the last category, this might include labeling or advertising resembling “kid-friendly food and drinks such as juice boxes or kid-friendly cereal; products marketed directly to minors by promoting ease of concealing the product or disguising it as another product; and products marketed with characters designed to appeal to youth,” according to the FDA statement.

As of May 12, FDA also will prioritize enforcement against any ENDS product for which the manufacturer has not submitted a premarket application. The agency will continue to exercise enforcement discretion for up to 1 year on these products if an application has been submitted, pending the review of that application.

“By not prioritizing enforcement against other flavored ENDS products in the same way as flavored cartridge-based ENDS products, the FDA has attempted to balance the public health concerns related to youth use of ENDS products with consideration regarding addicted adult cigarette smokers who may try to use ENDS products to transition away from combustible tobacco products,” the agency stated, adding that cartridge-based ENDS products are most commonly used among youth.

The FDA statement noted that the enforcement priorities outlined in the guidance document were not a “ban” on flavored or cartridge-based ENDS, noting the agency “has already accepted and begun review of several premarket applications for flavored ENDS products through the pathway that Congress established in the Tobacco Control Act. ... If a company can demonstrate to the FDA that a specific product meets the applicable standard set forth by Congress, including considering how the marketing of the product may affect youth initiation and use, then the FDA could authorize that product for sale.”

“Coupled with the recently signed legislation increasing the minimum age of sale of tobacco to 21, we believe this policy balances the urgency with which we must address the public health threat of youth use of e-cigarette products with the potential role that e-cigarettes may play in helping adult smokers transition completely away from combustible tobacco to a potentially less risky form of nicotine delivery,” FDA Commissioner Stephen Hahn, MD, said in a statement. “While we expect that responsible members of industry will comply with premarket requirements, we’re ready to take action against any unauthorized e-cigarette products as outlined in our priorities. We’ll also closely monitor the use rates of all e-cigarette products and take additional steps to address youth use as necessary.”

The American Medical Association criticized the action as not going far enough, even though it was a step in the right direction.

“The AMA is disappointed that menthol flavors, one of the most popular, will still be allowed, and that flavored e-liquids will remain on the market, leaving young people with easy access to alternative flavored e-cigarette products,” AMA President Patrice A. Harris, MD, said in a statement. “If we are serious about tackling this epidemic and keeping these harmful products out of the hands of young people, a total ban on all flavored e-cigarettes, in all forms and at all locations, is prudent and urgently needed. We are pleased the administration committed today to closely monitoring the situation and trends in e-cigarette use among young people, and to taking further action if needed.”

gtwachtman@mdedge.com

Opioid use disorder (OUD) and deaths by opioid overdose are a major public health concern, especially with the advent of synthetic opioids such as fentanyl.¹ Enrolling patients with OUD into substance abuse treatment programs can be a difficult hurdle to cross because patients do not want to experience withdrawal. The fear of withdrawal leads many individuals to refuse appropriate interventions. For these patients, consider the alpha-2 agonist lofexidine, which was FDA-approved in 2018 to help diminish the signs and symptoms of opioid withdrawal.^1-3 Use of lofexidine might encourage more patients with OUD to accept substance abuse treatment.^1,4,5

How to prescribe lofexidine

For decades, clinicians in Britain have prescribed lofexidine to attenuate opioid withdrawal.¹An analog of clonidine, lofexidine is reportedly less likely than clonidine to induce hypotension.^1,4 While this agent does not diminish drug toxicity, it can provide symptomatic relief for patients undergoing opioid withdrawal, and is efficacious as a supplement to and/or replacement for methadone, buprenorphine, clonidine, or other symptomatic pharmacotherapies.^1,4,5

Lofexidine is available in 0.18-mg tablets. For patients experiencing overt symptoms of opioid withdrawal, initially prescribe 3 0.18-mg tablets, 4 times a day.³ The recommended maximum dosage is 2.88 mg/d, and each dose generally should not exceed 0.72 mg/d. Lofexidine may be continued for up to 14 days, with dosing guided by symptoms. Initiate a taper once the patient no longer experiences withdrawal symptoms.³

Adverse effects. Lofexidine’s efficacy and safety were evaluated in 3 randomized, double-blind, placebo-controlled trials that included 935 participants dependent on short-acting opioids who were experiencing abrupt opioid withdrawal and received lofexidine, 2.16 or 2.88 mg/d, or placebo.³ The most common adverse effects of lofexidine were insomnia, orthostatic hypotension, bradycardia, hypotension, dizziness, somnolence, sedation, and dry mouth.³ In the 3 trials, these effects were reported by ≥10% of patients receiving lofexidine, and occurred more frequently compared with placebo (Table³).

Take precautions when prescribing lofexidine because it can cause QT prolongation and CNS depression, especially when co-administered with sedative agents.³ It also can result in rebound hypertension once discontinued. This may be minimized by gradually reducing the dosage.³

A pathway to OUD treatment

Lofexidine can help relieve symptoms of opioid withdrawal, such as stomach cramps, muscle spasms or twitching, feeling cold, muscular tension, and aches and pains.^1-5 This new option might help clinicians encourage more patients with OUD to fully engage in substance abuse treatment.

Opioid use disorder (OUD) and deaths by opioid overdose are a major public health concern, especially with the advent of synthetic opioids such as fentanyl.¹ Enrolling patients with OUD into substance abuse treatment programs can be a difficult hurdle to cross because patients do not want to experience withdrawal. The fear of withdrawal leads many individuals to refuse appropriate interventions. For these patients, consider the alpha-2 agonist lofexidine, which was FDA-approved in 2018 to help diminish the signs and symptoms of opioid withdrawal.^1-3 Use of lofexidine might encourage more patients with OUD to accept substance abuse treatment.^1,4,5

How to prescribe lofexidine

For decades, clinicians in Britain have prescribed lofexidine to attenuate opioid withdrawal.¹An analog of clonidine, lofexidine is reportedly less likely than clonidine to induce hypotension.^1,4 While this agent does not diminish drug toxicity, it can provide symptomatic relief for patients undergoing opioid withdrawal, and is efficacious as a supplement to and/or replacement for methadone, buprenorphine, clonidine, or other symptomatic pharmacotherapies.^1,4,5

Lofexidine is available in 0.18-mg tablets. For patients experiencing overt symptoms of opioid withdrawal, initially prescribe 3 0.18-mg tablets, 4 times a day.³ The recommended maximum dosage is 2.88 mg/d, and each dose generally should not exceed 0.72 mg/d. Lofexidine may be continued for up to 14 days, with dosing guided by symptoms. Initiate a taper once the patient no longer experiences withdrawal symptoms.³

Adverse effects. Lofexidine’s efficacy and safety were evaluated in 3 randomized, double-blind, placebo-controlled trials that included 935 participants dependent on short-acting opioids who were experiencing abrupt opioid withdrawal and received lofexidine, 2.16 or 2.88 mg/d, or placebo.³ The most common adverse effects of lofexidine were insomnia, orthostatic hypotension, bradycardia, hypotension, dizziness, somnolence, sedation, and dry mouth.³ In the 3 trials, these effects were reported by ≥10% of patients receiving lofexidine, and occurred more frequently compared with placebo (Table³).

Take precautions when prescribing lofexidine because it can cause QT prolongation and CNS depression, especially when co-administered with sedative agents.³ It also can result in rebound hypertension once discontinued. This may be minimized by gradually reducing the dosage.³

A pathway to OUD treatment

Lofexidine can help relieve symptoms of opioid withdrawal, such as stomach cramps, muscle spasms or twitching, feeling cold, muscular tension, and aches and pains.^1-5 This new option might help clinicians encourage more patients with OUD to fully engage in substance abuse treatment.

Opioid use disorder (OUD) and deaths by opioid overdose are a major public health concern, especially with the advent of synthetic opioids such as fentanyl.¹ Enrolling patients with OUD into substance abuse treatment programs can be a difficult hurdle to cross because patients do not want to experience withdrawal. The fear of withdrawal leads many individuals to refuse appropriate interventions. For these patients, consider the alpha-2 agonist lofexidine, which was FDA-approved in 2018 to help diminish the signs and symptoms of opioid withdrawal.^1-3 Use of lofexidine might encourage more patients with OUD to accept substance abuse treatment.^1,4,5

How to prescribe lofexidine

For decades, clinicians in Britain have prescribed lofexidine to attenuate opioid withdrawal.¹An analog of clonidine, lofexidine is reportedly less likely than clonidine to induce hypotension.^1,4 While this agent does not diminish drug toxicity, it can provide symptomatic relief for patients undergoing opioid withdrawal, and is efficacious as a supplement to and/or replacement for methadone, buprenorphine, clonidine, or other symptomatic pharmacotherapies.^1,4,5

Lofexidine is available in 0.18-mg tablets. For patients experiencing overt symptoms of opioid withdrawal, initially prescribe 3 0.18-mg tablets, 4 times a day.³ The recommended maximum dosage is 2.88 mg/d, and each dose generally should not exceed 0.72 mg/d. Lofexidine may be continued for up to 14 days, with dosing guided by symptoms. Initiate a taper once the patient no longer experiences withdrawal symptoms.³

Adverse effects. Lofexidine’s efficacy and safety were evaluated in 3 randomized, double-blind, placebo-controlled trials that included 935 participants dependent on short-acting opioids who were experiencing abrupt opioid withdrawal and received lofexidine, 2.16 or 2.88 mg/d, or placebo.³ The most common adverse effects of lofexidine were insomnia, orthostatic hypotension, bradycardia, hypotension, dizziness, somnolence, sedation, and dry mouth.³ In the 3 trials, these effects were reported by ≥10% of patients receiving lofexidine, and occurred more frequently compared with placebo (Table³).

Take precautions when prescribing lofexidine because it can cause QT prolongation and CNS depression, especially when co-administered with sedative agents.³ It also can result in rebound hypertension once discontinued. This may be minimized by gradually reducing the dosage.³

A pathway to OUD treatment

Lofexidine can help relieve symptoms of opioid withdrawal, such as stomach cramps, muscle spasms or twitching, feeling cold, muscular tension, and aches and pains.^1-5 This new option might help clinicians encourage more patients with OUD to fully engage in substance abuse treatment.

E-cigarette use is significantly and independently associated with an increased risk of respiratory disease, according to recent longitudinal analysis published in the American Journal of Preventive Medicine.

E-cigarettes have been promoted as a safer alternative to combustible tobacco, and until recently, there has been little and conflicting evidence by which to test this hypothesis. This study conducted by Dharma N. Bhatta, PhD, and Stanton A. Glantz, PhD, of the Center for Tobacco Control Research and Education at the University of California, San Francisco, is one of the first longitudinal examinations of e-cigarette use and controlling for combustible tobacco use.

Dr. Bhatta and Dr. Glantz performed a multivariable, logistic regression analysis of adults enrolled in the nationally representative, population-based, longitudinal Population Assessment of Tobacco and Health study. The researchers analyzed the tobacco use of adults in the study in three waves, following them through wave 1 (September 2013 to December 2014), wave 2 (October 2014 to October 2015), and wave 3 (October 2015 to October 2016), analyzing the data between 2018 and 2019. Overall, wave 1 began with 32,320 participants, and 15.1% of adults reported respiratory disease at baseline.

Lung or respiratory disease was assessed by asking participants whether they had been told by a health professional that they had chronic obstructive pulmonary disease, chronic bronchitis, emphysema, or asthma. The researchers defined e-cigarette and combustible tobacco use as participants who never, currently, or formerly used e-cigarettes or smoked combustible tobacco. Participants who indicated they used e-cigarettes or combustible tobacco frequently or infrequently were placed in the current-user group, while past users were those participants who said they used to, but no longer use e-cigarettes or combustible tobacco.

The results showed former e-cigarette use (adjusted odds ratio, 1.34; 95% confidence interval, 1.23-1.46) and current e-cigarette use (aOR, 1.32; 95% CI, 1.17-1.49) were associated with an increased risk of having incident respiratory disease.

The data showed a not unexpected statistically significant association between former combustible tobacco use (aOR, 1.29; 95% CI, 1.14-1.47) as well as current combustible tobacco use (aOR, 1.61; 95% CI, 1.42-1.82) and incident respiratory disease risk.

There was a statistically significant association between respiratory disease and former or current e-cigarette use for adults who did not have respiratory disease at baseline, after adjusting for factors such as current combustible tobacco use, clinical variables, and demographic differences. Participants in wave 1 who reported former (aOR, 1.31; 95% CI, 1.07-1.60) or current e-cigarette use (aOR, 1.29; 95% CI, 1.03-1.61) had a significantly higher risk of developing incident respiratory disease in subsequent waves. There was also a statistically significant association between use of combustible tobacco and subsequent respiratory disease in later waves of the study (aOR, 2.56; 95% CI, 1.92-3.41), which the researchers noted was independent of the usual risks associated with combustible tobacco.

The investigators also looked at the link between dual use of e-cigarettes and combustible tobacco and respiratory disease risk. “The much more common pattern is dual use, in which an e-cigarette user continues to smoke combusted tobacco products at the same time (93.7% of e-cigarette users at wave 2 and 91.2% at wave 3 also used combustible tobacco; 73.3% of e-cigarette users at wave 2 and 64.9% at wave 3 also smoked cigarettes),” they wrote.

The odds of developing respiratory disease for participants who used both e-cigarettes and combustible tobacco were 3.30, compared with a participant who never used e-cigarettes, with similar results seen when comparing e-cigarettes and cigarettes.

“Although switching from combustible tobacco, including cigarettes, to e-cigarettes theoretically could reduce the risk of developing respiratory disease, current evidence indicates a high prevalence of dual use, which is associated with in-creased risk beyond combustible tobacco use,” the investigators wrote.

Harold J. Farber, MD, FCCP, professor of pediatrics in the pulmonary section at Baylor College of Medicine and Texas Children’s Hospital, both in Houston, said in an interview that the increased respiratory risk among dual users, who are likely using e-cigarettes and combustible tobacco together as a way to quit smoking, is particularly concerning.

“There is substantial reason to be concerned about efficacy of electronic cigarette products. Real-world observational studies have shown that, on average, tobacco smokers who use electronic cigarettes are less likely to stop smoking than those who do not use electronic cigarettes,” he said. “People who have stopped tobacco smoking but use electronic cigarettes are more likely to relapse to tobacco smoking than those who do not use electronic cigarettes.”

Dr. Farber noted that there are other Food and Drug Administration–approved medications for treating tobacco addiction. In addition, the World Health Organization, American Medical Association, Centers for Disease Control and Prevention, and FDA have all advised that e-cigarettes should not be used as smoking cessation aids, he said, especially in light of current outbreak of life-threatening e-cigarette and vaping lung injuries currently being investigated by the CDC and FDA.

“These study results suggest that the CDC reports of e-cigarette, or vaping, product use–associated lung injury are likely to be just the tip of the iceberg,” he said. “Although the CDC has identified vitamin E acetate–containing products as an important culprit, it is unlikely to be the only one. There are many substances in the emissions of e-cigarettes that have known irritant and/or toxic effects on the airways.”

Dr. Bhatta and Dr. Glantz acknowledged several limitations in their analysis, including the possibility of recall bias, not distinguishing between nondaily and daily e-cigarette or combustible tobacco use, and combining respiratory conditions together to achieve adequate power. The study shows an association, but the mechanism by which e-cigarettes may contribute to the development of lung disease remains under investigation.

This study was supported by grants from the National Institute on Drug Abuse; the National Cancer Institute; the FDA Center for Tobacco Products; the National Heart, Lung, and Blood Institute; and the University of California, San Francisco Helen Diller Family Comprehensive Cancer Center Global Cancer Program. Dr. Bhatta and Dr. Glantz reported no relevant conflicts of interest.

SOURCE: Bhatta DN, Glantz SA. Am J Prev Med. 2019 Dec 16. doi: 10.1016/j.amepre.2019.07.028.

E-cigarette use is significantly and independently associated with an increased risk of respiratory disease, according to recent longitudinal analysis published in the American Journal of Preventive Medicine.

E-cigarettes have been promoted as a safer alternative to combustible tobacco, and until recently, there has been little and conflicting evidence by which to test this hypothesis. This study conducted by Dharma N. Bhatta, PhD, and Stanton A. Glantz, PhD, of the Center for Tobacco Control Research and Education at the University of California, San Francisco, is one of the first longitudinal examinations of e-cigarette use and controlling for combustible tobacco use.

Dr. Bhatta and Dr. Glantz performed a multivariable, logistic regression analysis of adults enrolled in the nationally representative, population-based, longitudinal Population Assessment of Tobacco and Health study. The researchers analyzed the tobacco use of adults in the study in three waves, following them through wave 1 (September 2013 to December 2014), wave 2 (October 2014 to October 2015), and wave 3 (October 2015 to October 2016), analyzing the data between 2018 and 2019. Overall, wave 1 began with 32,320 participants, and 15.1% of adults reported respiratory disease at baseline.

Lung or respiratory disease was assessed by asking participants whether they had been told by a health professional that they had chronic obstructive pulmonary disease, chronic bronchitis, emphysema, or asthma. The researchers defined e-cigarette and combustible tobacco use as participants who never, currently, or formerly used e-cigarettes or smoked combustible tobacco. Participants who indicated they used e-cigarettes or combustible tobacco frequently or infrequently were placed in the current-user group, while past users were those participants who said they used to, but no longer use e-cigarettes or combustible tobacco.

The results showed former e-cigarette use (adjusted odds ratio, 1.34; 95% confidence interval, 1.23-1.46) and current e-cigarette use (aOR, 1.32; 95% CI, 1.17-1.49) were associated with an increased risk of having incident respiratory disease.

The data showed a not unexpected statistically significant association between former combustible tobacco use (aOR, 1.29; 95% CI, 1.14-1.47) as well as current combustible tobacco use (aOR, 1.61; 95% CI, 1.42-1.82) and incident respiratory disease risk.

There was a statistically significant association between respiratory disease and former or current e-cigarette use for adults who did not have respiratory disease at baseline, after adjusting for factors such as current combustible tobacco use, clinical variables, and demographic differences. Participants in wave 1 who reported former (aOR, 1.31; 95% CI, 1.07-1.60) or current e-cigarette use (aOR, 1.29; 95% CI, 1.03-1.61) had a significantly higher risk of developing incident respiratory disease in subsequent waves. There was also a statistically significant association between use of combustible tobacco and subsequent respiratory disease in later waves of the study (aOR, 2.56; 95% CI, 1.92-3.41), which the researchers noted was independent of the usual risks associated with combustible tobacco.

The investigators also looked at the link between dual use of e-cigarettes and combustible tobacco and respiratory disease risk. “The much more common pattern is dual use, in which an e-cigarette user continues to smoke combusted tobacco products at the same time (93.7% of e-cigarette users at wave 2 and 91.2% at wave 3 also used combustible tobacco; 73.3% of e-cigarette users at wave 2 and 64.9% at wave 3 also smoked cigarettes),” they wrote.

The odds of developing respiratory disease for participants who used both e-cigarettes and combustible tobacco were 3.30, compared with a participant who never used e-cigarettes, with similar results seen when comparing e-cigarettes and cigarettes.

“Although switching from combustible tobacco, including cigarettes, to e-cigarettes theoretically could reduce the risk of developing respiratory disease, current evidence indicates a high prevalence of dual use, which is associated with in-creased risk beyond combustible tobacco use,” the investigators wrote.

Harold J. Farber, MD, FCCP, professor of pediatrics in the pulmonary section at Baylor College of Medicine and Texas Children’s Hospital, both in Houston, said in an interview that the increased respiratory risk among dual users, who are likely using e-cigarettes and combustible tobacco together as a way to quit smoking, is particularly concerning.

“There is substantial reason to be concerned about efficacy of electronic cigarette products. Real-world observational studies have shown that, on average, tobacco smokers who use electronic cigarettes are less likely to stop smoking than those who do not use electronic cigarettes,” he said. “People who have stopped tobacco smoking but use electronic cigarettes are more likely to relapse to tobacco smoking than those who do not use electronic cigarettes.”

Dr. Farber noted that there are other Food and Drug Administration–approved medications for treating tobacco addiction. In addition, the World Health Organization, American Medical Association, Centers for Disease Control and Prevention, and FDA have all advised that e-cigarettes should not be used as smoking cessation aids, he said, especially in light of current outbreak of life-threatening e-cigarette and vaping lung injuries currently being investigated by the CDC and FDA.

“These study results suggest that the CDC reports of e-cigarette, or vaping, product use–associated lung injury are likely to be just the tip of the iceberg,” he said. “Although the CDC has identified vitamin E acetate–containing products as an important culprit, it is unlikely to be the only one. There are many substances in the emissions of e-cigarettes that have known irritant and/or toxic effects on the airways.”

Dr. Bhatta and Dr. Glantz acknowledged several limitations in their analysis, including the possibility of recall bias, not distinguishing between nondaily and daily e-cigarette or combustible tobacco use, and combining respiratory conditions together to achieve adequate power. The study shows an association, but the mechanism by which e-cigarettes may contribute to the development of lung disease remains under investigation.

This study was supported by grants from the National Institute on Drug Abuse; the National Cancer Institute; the FDA Center for Tobacco Products; the National Heart, Lung, and Blood Institute; and the University of California, San Francisco Helen Diller Family Comprehensive Cancer Center Global Cancer Program. Dr. Bhatta and Dr. Glantz reported no relevant conflicts of interest.

SOURCE: Bhatta DN, Glantz SA. Am J Prev Med. 2019 Dec 16. doi: 10.1016/j.amepre.2019.07.028.

E-cigarette use is significantly and independently associated with an increased risk of respiratory disease, according to recent longitudinal analysis published in the American Journal of Preventive Medicine.

E-cigarettes have been promoted as a safer alternative to combustible tobacco, and until recently, there has been little and conflicting evidence by which to test this hypothesis. This study conducted by Dharma N. Bhatta, PhD, and Stanton A. Glantz, PhD, of the Center for Tobacco Control Research and Education at the University of California, San Francisco, is one of the first longitudinal examinations of e-cigarette use and controlling for combustible tobacco use.

Dr. Bhatta and Dr. Glantz performed a multivariable, logistic regression analysis of adults enrolled in the nationally representative, population-based, longitudinal Population Assessment of Tobacco and Health study. The researchers analyzed the tobacco use of adults in the study in three waves, following them through wave 1 (September 2013 to December 2014), wave 2 (October 2014 to October 2015), and wave 3 (October 2015 to October 2016), analyzing the data between 2018 and 2019. Overall, wave 1 began with 32,320 participants, and 15.1% of adults reported respiratory disease at baseline.

Lung or respiratory disease was assessed by asking participants whether they had been told by a health professional that they had chronic obstructive pulmonary disease, chronic bronchitis, emphysema, or asthma. The researchers defined e-cigarette and combustible tobacco use as participants who never, currently, or formerly used e-cigarettes or smoked combustible tobacco. Participants who indicated they used e-cigarettes or combustible tobacco frequently or infrequently were placed in the current-user group, while past users were those participants who said they used to, but no longer use e-cigarettes or combustible tobacco.

The results showed former e-cigarette use (adjusted odds ratio, 1.34; 95% confidence interval, 1.23-1.46) and current e-cigarette use (aOR, 1.32; 95% CI, 1.17-1.49) were associated with an increased risk of having incident respiratory disease.

The data showed a not unexpected statistically significant association between former combustible tobacco use (aOR, 1.29; 95% CI, 1.14-1.47) as well as current combustible tobacco use (aOR, 1.61; 95% CI, 1.42-1.82) and incident respiratory disease risk.

There was a statistically significant association between respiratory disease and former or current e-cigarette use for adults who did not have respiratory disease at baseline, after adjusting for factors such as current combustible tobacco use, clinical variables, and demographic differences. Participants in wave 1 who reported former (aOR, 1.31; 95% CI, 1.07-1.60) or current e-cigarette use (aOR, 1.29; 95% CI, 1.03-1.61) had a significantly higher risk of developing incident respiratory disease in subsequent waves. There was also a statistically significant association between use of combustible tobacco and subsequent respiratory disease in later waves of the study (aOR, 2.56; 95% CI, 1.92-3.41), which the researchers noted was independent of the usual risks associated with combustible tobacco.

The investigators also looked at the link between dual use of e-cigarettes and combustible tobacco and respiratory disease risk. “The much more common pattern is dual use, in which an e-cigarette user continues to smoke combusted tobacco products at the same time (93.7% of e-cigarette users at wave 2 and 91.2% at wave 3 also used combustible tobacco; 73.3% of e-cigarette users at wave 2 and 64.9% at wave 3 also smoked cigarettes),” they wrote.

The odds of developing respiratory disease for participants who used both e-cigarettes and combustible tobacco were 3.30, compared with a participant who never used e-cigarettes, with similar results seen when comparing e-cigarettes and cigarettes.

“Although switching from combustible tobacco, including cigarettes, to e-cigarettes theoretically could reduce the risk of developing respiratory disease, current evidence indicates a high prevalence of dual use, which is associated with in-creased risk beyond combustible tobacco use,” the investigators wrote.

Harold J. Farber, MD, FCCP, professor of pediatrics in the pulmonary section at Baylor College of Medicine and Texas Children’s Hospital, both in Houston, said in an interview that the increased respiratory risk among dual users, who are likely using e-cigarettes and combustible tobacco together as a way to quit smoking, is particularly concerning.

“There is substantial reason to be concerned about efficacy of electronic cigarette products. Real-world observational studies have shown that, on average, tobacco smokers who use electronic cigarettes are less likely to stop smoking than those who do not use electronic cigarettes,” he said. “People who have stopped tobacco smoking but use electronic cigarettes are more likely to relapse to tobacco smoking than those who do not use electronic cigarettes.”

Dr. Farber noted that there are other Food and Drug Administration–approved medications for treating tobacco addiction. In addition, the World Health Organization, American Medical Association, Centers for Disease Control and Prevention, and FDA have all advised that e-cigarettes should not be used as smoking cessation aids, he said, especially in light of current outbreak of life-threatening e-cigarette and vaping lung injuries currently being investigated by the CDC and FDA.

“These study results suggest that the CDC reports of e-cigarette, or vaping, product use–associated lung injury are likely to be just the tip of the iceberg,” he said. “Although the CDC has identified vitamin E acetate–containing products as an important culprit, it is unlikely to be the only one. There are many substances in the emissions of e-cigarettes that have known irritant and/or toxic effects on the airways.”

Dr. Bhatta and Dr. Glantz acknowledged several limitations in their analysis, including the possibility of recall bias, not distinguishing between nondaily and daily e-cigarette or combustible tobacco use, and combining respiratory conditions together to achieve adequate power. The study shows an association, but the mechanism by which e-cigarettes may contribute to the development of lung disease remains under investigation.

This study was supported by grants from the National Institute on Drug Abuse; the National Cancer Institute; the FDA Center for Tobacco Products; the National Heart, Lung, and Blood Institute; and the University of California, San Francisco Helen Diller Family Comprehensive Cancer Center Global Cancer Program. Dr. Bhatta and Dr. Glantz reported no relevant conflicts of interest.

SOURCE: Bhatta DN, Glantz SA. Am J Prev Med. 2019 Dec 16. doi: 10.1016/j.amepre.2019.07.028.

Vaping has expanded as a popular method of drug delivery for U.S. teenagers, and one in five students in grades 10 and 12 reported vaping marijuana in the past year, according to results of the 2019 Monitoring the Future survey conducted by the National Institute on Drug Abuse (NIDA).

licsiren/iStock/Getty Images

This year’s findings, announced Dec. 18, continue to illustrate “a clear shift in the pattern of drug taking among teenagers,” said NIDA Director Nora D. Volkow, MD, in a teleconference held to review the results.

Use of alcohol and drugs – including opioids and stimulants – continues to decline among teens, but vaping continues its significant rise, with a surge in marijuana vaping this year.

The increase in past-month marijuana vaping among 12th graders, from 7.5% in 2018 to 14% in 2019, represents the second-largest 1-year jump tracked for any substance in the survey’s history, Dr. Volkow said. The largest jump was the increase in past-month nicotine vaping among 12th-graders from 2017-2018.

Past-year marijuana vaping has more than doubled in the past 2 years, with rates this year of 20.8% among 12th-graders, 19.4% among 10th-graders, and 7.0% among 8th-graders.

“It is very unfortunate that we are seeing the steep rise in the use of vaping devices” because the devices deliver drugs in very high concentration, Dr. Volkow said. The growing popularity of vaping “threatens to undo years of progress protecting the health of adolescents in the U.S.,” Dr. Volkow said in a statement. The Monitoring the Future survey began including vaping questions in 2017.

Monitoring the Future is a national tool to assess drug and alcohol use and related attitudes among adolescent students across the United States. This year’s self-reported survey included 42,531 in grades 8, 10, and 12 from 396 public and private schools.

Nicotine vaping increased from 2018 to 2019 across all three grades; past-month nicotine use equated to 1 in 4, 1 in 5, and 1 in 10 (26%, 20%, and 10%) among 12th, 10th, and 8th graders, respectively, according to the survey. Daily nicotine vaping, measured for the first time this year because of public health concerns, was approximately 12% for 12th graders, 7% for 10th graders, and 2% for 8th graders. Daily marijuana vaping, also measured for the first time this year, was approximately 4%, 3%, and 1% among 12th, 10th, and 8th graders, respectively. Additional findings on the rise of vaping by U.S. teenagers were released Dec. 17 in a research letter published online in JAMA (doi: 10.1001/jama.2019.20185).

Meanwhile, positive trends in this year’s survey included a reduction in the misuse of prescription drugs, including OxyContin, Vicodin, and Adderall, and in the use of traditional cigarettes and other tobacco products, as well as alcohol, noted Richard A. Miech, PhD, MPH, of the University of Michigan, Ann Arbor, principal investigator for Monitoring the Future. However, the challenge of preventing and reducing vaping in teens remains “a whole new uncharted territory,” in part because the design of the vaping devices facilitates discreet use at home and at school, he said.

Physicians and parents have important roles to play in screening for vaping among teens, Dr. Volkow said in a question and answer session. Health care clinicians, including pediatricians and family physicians, “are in a unique position to communicate with their young patients” by educating them about the dangers of vaping, encouraging them to stop if they have started using these devices, and referring them for further treatment if they are showing signs of addiction, she said.

Monitoring the Future was funded by NIDA. The researchers had no disclosures.

Vaping has expanded as a popular method of drug delivery for U.S. teenagers, and one in five students in grades 10 and 12 reported vaping marijuana in the past year, according to results of the 2019 Monitoring the Future survey conducted by the National Institute on Drug Abuse (NIDA).

licsiren/iStock/Getty Images

This year’s findings, announced Dec. 18, continue to illustrate “a clear shift in the pattern of drug taking among teenagers,” said NIDA Director Nora D. Volkow, MD, in a teleconference held to review the results.

Use of alcohol and drugs – including opioids and stimulants – continues to decline among teens, but vaping continues its significant rise, with a surge in marijuana vaping this year.

The increase in past-month marijuana vaping among 12th graders, from 7.5% in 2018 to 14% in 2019, represents the second-largest 1-year jump tracked for any substance in the survey’s history, Dr. Volkow said. The largest jump was the increase in past-month nicotine vaping among 12th-graders from 2017-2018.

Past-year marijuana vaping has more than doubled in the past 2 years, with rates this year of 20.8% among 12th-graders, 19.4% among 10th-graders, and 7.0% among 8th-graders.

“It is very unfortunate that we are seeing the steep rise in the use of vaping devices” because the devices deliver drugs in very high concentration, Dr. Volkow said. The growing popularity of vaping “threatens to undo years of progress protecting the health of adolescents in the U.S.,” Dr. Volkow said in a statement. The Monitoring the Future survey began including vaping questions in 2017.

Monitoring the Future is a national tool to assess drug and alcohol use and related attitudes among adolescent students across the United States. This year’s self-reported survey included 42,531 in grades 8, 10, and 12 from 396 public and private schools.

Nicotine vaping increased from 2018 to 2019 across all three grades; past-month nicotine use equated to 1 in 4, 1 in 5, and 1 in 10 (26%, 20%, and 10%) among 12th, 10th, and 8th graders, respectively, according to the survey. Daily nicotine vaping, measured for the first time this year because of public health concerns, was approximately 12% for 12th graders, 7% for 10th graders, and 2% for 8th graders. Daily marijuana vaping, also measured for the first time this year, was approximately 4%, 3%, and 1% among 12th, 10th, and 8th graders, respectively. Additional findings on the rise of vaping by U.S. teenagers were released Dec. 17 in a research letter published online in JAMA (doi: 10.1001/jama.2019.20185).

Meanwhile, positive trends in this year’s survey included a reduction in the misuse of prescription drugs, including OxyContin, Vicodin, and Adderall, and in the use of traditional cigarettes and other tobacco products, as well as alcohol, noted Richard A. Miech, PhD, MPH, of the University of Michigan, Ann Arbor, principal investigator for Monitoring the Future. However, the challenge of preventing and reducing vaping in teens remains “a whole new uncharted territory,” in part because the design of the vaping devices facilitates discreet use at home and at school, he said.

Physicians and parents have important roles to play in screening for vaping among teens, Dr. Volkow said in a question and answer session. Health care clinicians, including pediatricians and family physicians, “are in a unique position to communicate with their young patients” by educating them about the dangers of vaping, encouraging them to stop if they have started using these devices, and referring them for further treatment if they are showing signs of addiction, she said.

Monitoring the Future was funded by NIDA. The researchers had no disclosures.

Vaping has expanded as a popular method of drug delivery for U.S. teenagers, and one in five students in grades 10 and 12 reported vaping marijuana in the past year, according to results of the 2019 Monitoring the Future survey conducted by the National Institute on Drug Abuse (NIDA).

licsiren/iStock/Getty Images

This year’s findings, announced Dec. 18, continue to illustrate “a clear shift in the pattern of drug taking among teenagers,” said NIDA Director Nora D. Volkow, MD, in a teleconference held to review the results.

Use of alcohol and drugs – including opioids and stimulants – continues to decline among teens, but vaping continues its significant rise, with a surge in marijuana vaping this year.

The increase in past-month marijuana vaping among 12th graders, from 7.5% in 2018 to 14% in 2019, represents the second-largest 1-year jump tracked for any substance in the survey’s history, Dr. Volkow said. The largest jump was the increase in past-month nicotine vaping among 12th-graders from 2017-2018.

Past-year marijuana vaping has more than doubled in the past 2 years, with rates this year of 20.8% among 12th-graders, 19.4% among 10th-graders, and 7.0% among 8th-graders.

“It is very unfortunate that we are seeing the steep rise in the use of vaping devices” because the devices deliver drugs in very high concentration, Dr. Volkow said. The growing popularity of vaping “threatens to undo years of progress protecting the health of adolescents in the U.S.,” Dr. Volkow said in a statement. The Monitoring the Future survey began including vaping questions in 2017.

Monitoring the Future is a national tool to assess drug and alcohol use and related attitudes among adolescent students across the United States. This year’s self-reported survey included 42,531 in grades 8, 10, and 12 from 396 public and private schools.

Nicotine vaping increased from 2018 to 2019 across all three grades; past-month nicotine use equated to 1 in 4, 1 in 5, and 1 in 10 (26%, 20%, and 10%) among 12th, 10th, and 8th graders, respectively, according to the survey. Daily nicotine vaping, measured for the first time this year because of public health concerns, was approximately 12% for 12th graders, 7% for 10th graders, and 2% for 8th graders. Daily marijuana vaping, also measured for the first time this year, was approximately 4%, 3%, and 1% among 12th, 10th, and 8th graders, respectively. Additional findings on the rise of vaping by U.S. teenagers were released Dec. 17 in a research letter published online in JAMA (doi: 10.1001/jama.2019.20185).

Meanwhile, positive trends in this year’s survey included a reduction in the misuse of prescription drugs, including OxyContin, Vicodin, and Adderall, and in the use of traditional cigarettes and other tobacco products, as well as alcohol, noted Richard A. Miech, PhD, MPH, of the University of Michigan, Ann Arbor, principal investigator for Monitoring the Future. However, the challenge of preventing and reducing vaping in teens remains “a whole new uncharted territory,” in part because the design of the vaping devices facilitates discreet use at home and at school, he said.

Physicians and parents have important roles to play in screening for vaping among teens, Dr. Volkow said in a question and answer session. Health care clinicians, including pediatricians and family physicians, “are in a unique position to communicate with their young patients” by educating them about the dangers of vaping, encouraging them to stop if they have started using these devices, and referring them for further treatment if they are showing signs of addiction, she said.

Monitoring the Future was funded by NIDA. The researchers had no disclosures.

The first time I was sure I was witnessing someone vaping occurred when I saw an alarming cloud of smoke billowing from driver’s side window of the car in front of me. My initial concern was that vehicle was on fire. But none of the other drivers around me seemed concerned and as I pulled up next to the car I could see the driver ostentatiously inhaling deeply in preparation for releasing another monstrous cloud of vapor.

However, you probably have learned, as have I, that most vaping is done furtively. In fact, the pocketability of vaping devices is part of their appeal to teenagers. Hiding a lit cigarette in one’s pocket is something even the most risk-loving adolescent usually won’t attempt. I suspect that regardless of what is in the vapor, the high one can get by putting one over on the school administration by vaping in the school restroom or in the middle of history class is a temptation that many teenagers can’t resist.

Listening to educators, substance abuse counselors, and police officers who have first hand knowledge, it’s clear that vaping is an activity that’s very difficult to detect and police. Where there’s smoke there’s fire, but if it’s just a vapor it is easy to hide.

Part of the problem seems to be that vaping was flying under the radar and expanding rapidly long before educators, parents, and I fear physicians woke up to the severity and magnitude of the problem. And now everybody is playing catchup.

Of course the initial, and as yet unconfirmed, notion that e-cigarettes might provide a viable strategy for tobacco withdrawal has added confusion to the mix. It turns out that vaping can provide many orders of magnitude more nicotine in a small volume than cigarettes, which creates an outsized addiction potential for those more vulnerable users – even with a very short history of use. My experts tell me that this level of addiction has forced them to consider strategies and dosages far beyond those they are accustomed to using with patients whose addiction stems from standard cigarette use.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

The first time I was sure I was witnessing someone vaping occurred when I saw an alarming cloud of smoke billowing from driver’s side window of the car in front of me. My initial concern was that vehicle was on fire. But none of the other drivers around me seemed concerned and as I pulled up next to the car I could see the driver ostentatiously inhaling deeply in preparation for releasing another monstrous cloud of vapor.

However, you probably have learned, as have I, that most vaping is done furtively. In fact, the pocketability of vaping devices is part of their appeal to teenagers. Hiding a lit cigarette in one’s pocket is something even the most risk-loving adolescent usually won’t attempt. I suspect that regardless of what is in the vapor, the high one can get by putting one over on the school administration by vaping in the school restroom or in the middle of history class is a temptation that many teenagers can’t resist.

Listening to educators, substance abuse counselors, and police officers who have first hand knowledge, it’s clear that vaping is an activity that’s very difficult to detect and police. Where there’s smoke there’s fire, but if it’s just a vapor it is easy to hide.

Part of the problem seems to be that vaping was flying under the radar and expanding rapidly long before educators, parents, and I fear physicians woke up to the severity and magnitude of the problem. And now everybody is playing catchup.

Of course the initial, and as yet unconfirmed, notion that e-cigarettes might provide a viable strategy for tobacco withdrawal has added confusion to the mix. It turns out that vaping can provide many orders of magnitude more nicotine in a small volume than cigarettes, which creates an outsized addiction potential for those more vulnerable users – even with a very short history of use. My experts tell me that this level of addiction has forced them to consider strategies and dosages far beyond those they are accustomed to using with patients whose addiction stems from standard cigarette use.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

The first time I was sure I was witnessing someone vaping occurred when I saw an alarming cloud of smoke billowing from driver’s side window of the car in front of me. My initial concern was that vehicle was on fire. But none of the other drivers around me seemed concerned and as I pulled up next to the car I could see the driver ostentatiously inhaling deeply in preparation for releasing another monstrous cloud of vapor.

However, you probably have learned, as have I, that most vaping is done furtively. In fact, the pocketability of vaping devices is part of their appeal to teenagers. Hiding a lit cigarette in one’s pocket is something even the most risk-loving adolescent usually won’t attempt. I suspect that regardless of what is in the vapor, the high one can get by putting one over on the school administration by vaping in the school restroom or in the middle of history class is a temptation that many teenagers can’t resist.

Listening to educators, substance abuse counselors, and police officers who have first hand knowledge, it’s clear that vaping is an activity that’s very difficult to detect and police. Where there’s smoke there’s fire, but if it’s just a vapor it is easy to hide.

Part of the problem seems to be that vaping was flying under the radar and expanding rapidly long before educators, parents, and I fear physicians woke up to the severity and magnitude of the problem. And now everybody is playing catchup.

Of course the initial, and as yet unconfirmed, notion that e-cigarettes might provide a viable strategy for tobacco withdrawal has added confusion to the mix. It turns out that vaping can provide many orders of magnitude more nicotine in a small volume than cigarettes, which creates an outsized addiction potential for those more vulnerable users – even with a very short history of use. My experts tell me that this level of addiction has forced them to consider strategies and dosages far beyond those they are accustomed to using with patients whose addiction stems from standard cigarette use.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

SAN DIEGO – Emergency physicians can be persuaded to follow a recommended strategy to prescribe buprenorphine to patients with opioid addictions and to refer them to follow-up care, Kathryn F. Hawk, MD, said at the annual meeting of the American Academy of Addiction Psychiatry.

“People are willing to change their practices and evolve as long as they have the support to do so,” Dr. Hawk, assistant professor of emergency medicine at Yale University, New Haven, Conn., said at the meeting.

Dr. Hawk highlighted a landmark 2015 study led by Yale colleagues that compared three strategies to treating patients with opioid use disorder in the emergency department. Researchers randomly assigned 329 patients to 1) referral to treatment; 2) brief intervention and facilitated referral to community-based treatment services; and 3) emergency department-initiated treatment with buprenorphine/naloxone (Suboxone) plus referral to primary care for 10-week follow-up.

At 30 days, 78% of patients in the third group were in addiction treatment vs. 37% in the first group and 45% in the second group. (P less than .001). However, the percentage of patients in the groups who had negative urine screens for opioids were not statistically different (JAMA. 2015. Apr 28;313[16]:1636-44).

Both the American College of Emergency Physicians (ACEP) and the American College of Medical Toxicology have endorsed the use of buprenorphine in the ED “as a bridge to long-term addiction treatment,” said Dr. Hawk, who also is affiliated with Yale New Haven Hospital.

Emergency department physicians, however, have been reluctant to start prescribing buprenorphine and get more deeply involved in referrals to care, said E. Jennifer Edelman, MD, associate professor of general internal medicine at Yale. She described the results of a 2017-2019 survey of 268 medical professionals at urban emergency departments in Seattle, Cincinnati, New York City, and Baltimore. Only 20% of the survey respondents said they were “ready” to initiate the buprenorphine treatment protocol.

Researchers also held focus groups with 74 clinicians who offered insight into their hesitation. “That’s not something that we’re even really taught in medical school and certainly not in our training as emergency physicians,” one faculty member said. “It is this detox black box across the street, and that’s how it is in many places.”

Another faculty member expressed regret about the current system: “I feel like this is particularly vulnerable patient population [and] we’re just saying, ‘Here’s a sheet. Call some numbers. Good luck.’ That’s the way it feels when I discharge these folks.” And a resident said: “We can’t provide all of that care up front. It’s just too time-consuming, and there are other patients to see.”

But not all of the findings were grim.

“There was broad recognition that the status quo was unacceptable, and emergency medicine physicians were excited about an opportunity to do more,” Dr. Edelman said.

According to her, strategies aimed at boosting the Suboxone approach include establishing protocols, and providing leadership support and resources. Addiction psychiatrists also can be helpful, she said.

“Let’s think about partnering together to bridge that gap,” she said. One idea: Invite emergency physicians to observe a treatment initiation.

“Showing how you counsel patients to start medication at home would be really a wonderful way to facilitate practices in the emergency department,” she said.

Another idea, she said, is to “give them feedback on their patients.” If an emergency physician refers a patient and they walk in the door, “let them know how they did. That’s going to be really, really powerful.”

ACEP and the American Society of Addiction Medicine have created a tool aimed at helping facilitate the use of buprenorphine and naloxone in the emergency department.

Dr. Hawk and Dr. Edelman reported no relevant disclosures.

SAN DIEGO – Emergency physicians can be persuaded to follow a recommended strategy to prescribe buprenorphine to patients with opioid addictions and to refer them to follow-up care, Kathryn F. Hawk, MD, said at the annual meeting of the American Academy of Addiction Psychiatry.

“People are willing to change their practices and evolve as long as they have the support to do so,” Dr. Hawk, assistant professor of emergency medicine at Yale University, New Haven, Conn., said at the meeting.

Dr. Hawk highlighted a landmark 2015 study led by Yale colleagues that compared three strategies to treating patients with opioid use disorder in the emergency department. Researchers randomly assigned 329 patients to 1) referral to treatment; 2) brief intervention and facilitated referral to community-based treatment services; and 3) emergency department-initiated treatment with buprenorphine/naloxone (Suboxone) plus referral to primary care for 10-week follow-up.

At 30 days, 78% of patients in the third group were in addiction treatment vs. 37% in the first group and 45% in the second group. (P less than .001). However, the percentage of patients in the groups who had negative urine screens for opioids were not statistically different (JAMA. 2015. Apr 28;313[16]:1636-44).

Both the American College of Emergency Physicians (ACEP) and the American College of Medical Toxicology have endorsed the use of buprenorphine in the ED “as a bridge to long-term addiction treatment,” said Dr. Hawk, who also is affiliated with Yale New Haven Hospital.

Emergency department physicians, however, have been reluctant to start prescribing buprenorphine and get more deeply involved in referrals to care, said E. Jennifer Edelman, MD, associate professor of general internal medicine at Yale. She described the results of a 2017-2019 survey of 268 medical professionals at urban emergency departments in Seattle, Cincinnati, New York City, and Baltimore. Only 20% of the survey respondents said they were “ready” to initiate the buprenorphine treatment protocol.

Researchers also held focus groups with 74 clinicians who offered insight into their hesitation. “That’s not something that we’re even really taught in medical school and certainly not in our training as emergency physicians,” one faculty member said. “It is this detox black box across the street, and that’s how it is in many places.”

Another faculty member expressed regret about the current system: “I feel like this is particularly vulnerable patient population [and] we’re just saying, ‘Here’s a sheet. Call some numbers. Good luck.’ That’s the way it feels when I discharge these folks.” And a resident said: “We can’t provide all of that care up front. It’s just too time-consuming, and there are other patients to see.”

But not all of the findings were grim.

“There was broad recognition that the status quo was unacceptable, and emergency medicine physicians were excited about an opportunity to do more,” Dr. Edelman said.

According to her, strategies aimed at boosting the Suboxone approach include establishing protocols, and providing leadership support and resources. Addiction psychiatrists also can be helpful, she said.

“Let’s think about partnering together to bridge that gap,” she said. One idea: Invite emergency physicians to observe a treatment initiation.

“Showing how you counsel patients to start medication at home would be really a wonderful way to facilitate practices in the emergency department,” she said.

Another idea, she said, is to “give them feedback on their patients.” If an emergency physician refers a patient and they walk in the door, “let them know how they did. That’s going to be really, really powerful.”

ACEP and the American Society of Addiction Medicine have created a tool aimed at helping facilitate the use of buprenorphine and naloxone in the emergency department.

Dr. Hawk and Dr. Edelman reported no relevant disclosures.

SAN DIEGO – Emergency physicians can be persuaded to follow a recommended strategy to prescribe buprenorphine to patients with opioid addictions and to refer them to follow-up care, Kathryn F. Hawk, MD, said at the annual meeting of the American Academy of Addiction Psychiatry.

“People are willing to change their practices and evolve as long as they have the support to do so,” Dr. Hawk, assistant professor of emergency medicine at Yale University, New Haven, Conn., said at the meeting.

Dr. Hawk highlighted a landmark 2015 study led by Yale colleagues that compared three strategies to treating patients with opioid use disorder in the emergency department. Researchers randomly assigned 329 patients to 1) referral to treatment; 2) brief intervention and facilitated referral to community-based treatment services; and 3) emergency department-initiated treatment with buprenorphine/naloxone (Suboxone) plus referral to primary care for 10-week follow-up.

At 30 days, 78% of patients in the third group were in addiction treatment vs. 37% in the first group and 45% in the second group. (P less than .001). However, the percentage of patients in the groups who had negative urine screens for opioids were not statistically different (JAMA. 2015. Apr 28;313[16]:1636-44).

Both the American College of Emergency Physicians (ACEP) and the American College of Medical Toxicology have endorsed the use of buprenorphine in the ED “as a bridge to long-term addiction treatment,” said Dr. Hawk, who also is affiliated with Yale New Haven Hospital.

Emergency department physicians, however, have been reluctant to start prescribing buprenorphine and get more deeply involved in referrals to care, said E. Jennifer Edelman, MD, associate professor of general internal medicine at Yale. She described the results of a 2017-2019 survey of 268 medical professionals at urban emergency departments in Seattle, Cincinnati, New York City, and Baltimore. Only 20% of the survey respondents said they were “ready” to initiate the buprenorphine treatment protocol.

Researchers also held focus groups with 74 clinicians who offered insight into their hesitation. “That’s not something that we’re even really taught in medical school and certainly not in our training as emergency physicians,” one faculty member said. “It is this detox black box across the street, and that’s how it is in many places.”

Another faculty member expressed regret about the current system: “I feel like this is particularly vulnerable patient population [and] we’re just saying, ‘Here’s a sheet. Call some numbers. Good luck.’ That’s the way it feels when I discharge these folks.” And a resident said: “We can’t provide all of that care up front. It’s just too time-consuming, and there are other patients to see.”

But not all of the findings were grim.

“There was broad recognition that the status quo was unacceptable, and emergency medicine physicians were excited about an opportunity to do more,” Dr. Edelman said.

According to her, strategies aimed at boosting the Suboxone approach include establishing protocols, and providing leadership support and resources. Addiction psychiatrists also can be helpful, she said.

“Let’s think about partnering together to bridge that gap,” she said. One idea: Invite emergency physicians to observe a treatment initiation.

“Showing how you counsel patients to start medication at home would be really a wonderful way to facilitate practices in the emergency department,” she said.

Another idea, she said, is to “give them feedback on their patients.” If an emergency physician refers a patient and they walk in the door, “let them know how they did. That’s going to be really, really powerful.”

ACEP and the American Society of Addiction Medicine have created a tool aimed at helping facilitate the use of buprenorphine and naloxone in the emergency department.

Dr. Hawk and Dr. Edelman reported no relevant disclosures.