Category Archives: Opiates

Treating infants of mothers with opioid dependence

As more infants are born to mothers with dependence on prescription pain medications, the costs of treatment for babies with neonatal abstinence syndrome (NAS) have increased dramatically, suggests a report in the March/April issue of the Journal of Addiction Medicine, the official journal of the American Society of Addiction Medicine. The journal is published by Wolters Kluwer.

“At our institution, costs associated with treating infants with NAS are exponentially higher than the costs associated with infants not affected,” write Dr. Kay Roussos-Ross, Assistant Professor of Obstetrics and Gynecology, and colleagues of University of Florida College of Medicine, Gainesville. The researchers believe their findings support recent recommendations to screen or test for substance use in pregnant women.

Rising Treatment Costs for Neonatal Abstinence Syndrome

Nonmedical use of prescription opioid pain medications during pregnancy has increased fivefold since the late 1990s, according to a recent study. Some infants born to women with opioid use disorder will develop neonatal abstinence syndrome — symptoms and complications related to withdrawal from the opioid pain medication to which they were exposed in utero.

Dr. Roussos-Ross and coauthors analyzed cost trends for infants with NAS at one university-affiliated hospital between 2008 and 2011. They identified 160 opioid-exposed newborns: 40 in the first year of the study, 57 in the second year, and 63 in the third year.

Ninety-five of the infants were exposed to “opioid agonist” drugs — methadone or buprenorphine — given during pregnancy to treat the mother’s opioid use disorder. The rest were exposed to various “short-acting” prescription opioids taken illicitly by the mother.

In each year, about 50 to 60 percent of opioid-exposed infants developed symptoms of NAS. These infants remained in the hospital after birth for an average of 23 days, compared to the usual post birth stay of one or two days for a normal healthy newborn. For opioid-exposed infants who did not develop opioid withdrawal symptoms, the average hospital stay was about five days.

The total costs of treatment for NAS rose sharply: from about $1.1 million in the first year, to $1.5 million in the second year, to $1.8 million in the third year. These costs were 15 to 16 times higher than of healthy infants.

The rising rates and costs of NAS reflect the ongoing “opioid epidemic” in the United States. The results add to other recent studies showing high costs for treatment for babies born to women with opioid dependence. Those previous studies found that most of the costs are paid by state Medicaid programs.

Dr. Roussos-Ross and coauthors suggest some steps to help address the high financial and human costs associated with neonatal abstinence syndrome. They encourage doctors to be “proactive in screening for drug use, urging women who use chronic opioids to actively engage in family planning and contraception, and encouraging pregnant women who use opioids to seek substance treatment.”

The researchers note that although universal screening for drug use during pregnancy has been recommended by major specialty organizations, it is not yet standard practice. They also call for studies to improve the management of NAS and for follow up of evidence that buprenorphine may lead to better treatment outcomes, in comparison to methadone, in the treatment of pregnant women with opioid use disorder.

New pharmaceutical product to prevent heroin deaths

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

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

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

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

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

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

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

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

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

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

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

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

New ‘Abuse Resistant’ Painkiller May Torpedo Zohydro

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

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

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

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

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

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

FDA approves a powerful new opioid painkiller

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

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

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

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

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

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

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

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

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

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

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

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

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