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Doubling of prescriptions over 10 years is cause for concern, study says

By Robert Preidt

Friday, December 2, 2011

FRIDAY, Dec. 2 (HealthDay News) --

Prescriptions for opioid painkillers to treat chronic abdominal pain more than doubled in the United States between 1997 and 2008, according to a new study.

This large increase of prescriptions written at outpatient clinics is concerning for several reasons, said lead author Dr. Spencer Dorn, an assistant professor of medicine at the University of North Carolina Medical School at Chapel Hill, and colleagues.

Very little evidence exists to support the use of opioids to treat chronic pain that isn't cancer related, and opioids are frequently misused and sometimes abused, Dorn said.

Extended use of opioids can trigger other gastrointestinal symptoms such as nausea, vomiting and constipation, and may even worsen abdominal pain, he added.

The study appears in the December issue of the journal Clinical Gastroenterology and Hepatology.

Chronic abdominal pain is a common problem but is often incurable, which can make it challenging for doctors to help patients, the researchers said.

"Writing a prescription for a painkiller may be the path of least resistance; doing so may satisfy the patient's demand for relief and mitigate the clinician's possible feelings of inadequacy," Dorn said in a journal news release.

Numerous factors have likely contributed to the sharp rise in the use of opioids to treat chronic abdominal pain, the researchers said. These include a tendency to generalize recommendations for opioids' use in treating pain and widespread direct-to-consumer advertising.

SOURCE: Clinical Gastroenterology and Hepatology, news release, Nov. 29, 2011

Copyright (c) 2011 HealthDay. All rights reserved.

http://www.nlm.nih.gov/medlineplus/news/ fullstory_119324.html

By Cole Petrochko, Associate Staff Writer, MedPage Today

Published: January 09, 2012

The FDA has issued a warning that pills, tablets, or caplets of Percocet and eight other opioid products packaged by Novartis for Endo Pharmaceuticals may have been mixed up, with one drug being packaged as another.

The other products include Opana ER CII, Opana CII, Percodan CII, Oxymorphone hydrochloride CII, Endocet CII, Endodan CII, Morphine sulfate ER CII, and Zydone CIII.

A listing on the FDA website is augumented by a more complete list of strength and a guide to colors, shapes, and markings of the affected products on the Endo website.

The affected products were packaged at the Lincoln, Neb., plant involved in a recall of over-the-counter products manufactured by Novartis, including Excedrin and NoDoz.

The error is likely the result of improperly cleared packaging machinery, which may have caused pills from one product to be carried over into containers of another product, according to Edward Cox, MD, director of the FDA's Office of Antiviral Product, Office of New Drugs, and the Center for Drug Evaluation of Research.

The odds of a patient being affected by the drug mix-up are low and no adverse event reports related to incorrect product dosing have been filed, Cox said during a press conference.

Patients should be wary of any pills that are different in size, shape, color, or markings from their standard medication or are different from others in the container. Patients should return prescriptions that contain mixed drugs to their pharmacy.

The FDA has instructed pharmacists to visually inspect the opioid drugs that may be affected by the packaging error to prevent the spread of improperly packaged medications.

Cox noted that, although the FDA considered issuing a recall of the products, the low likelihood of a mix-up combined with the need for the opioid analgesics. Visual inspection by pharmacists and patients should further mitigate the risk to patients and potential product shortage as the result of the shutdown of the Nebraska facility during its inspection.

It is not known if there are any opioid drugs that have cross-contaminated the over-the-counter products recalled by Novartis at the same facility, Cox said during the press conference.

http://www.medpagetoday.com/ProductAlert/Prescriptions/ 30559?utm_medium=email&utm_campaign=DailyHeadlines&utm_source=

Linda, RN - Jan 09, 2012

Your article re: mix-up of opiods does not mention the potential danger of an allergic reaction to an ingredient present in one drug that is not present in another.

Andrew Borth - Jan 09, 2012

on one hand, it appears that this is a breakdown of QC controls, but on the other hand it also underlines the strength of having a systematic, multiple layer approach for drug regulation.

In this era of 'smaller government is always better', the FDA is one of my poster children for saying that we have regulations for a REASON. Yes, sometimes there are problems, but this is better than the alternative.

Consider:

1) this was only a mix-up in opioids with each other, NOT with something of vastly different action.

2) Differences are identifiable visually because the appearance of each pill is specifically published and available to pharmacists.

3) There is a central authority to respond to these errors and take appropriate action to head off any rumors and/or panic regarding medications of ALL types. Regulation is good. Remember your history... http://en.wikipedia.org/wiki/Biologics_Control_Act

KWightman, ND - Jan 09, 2012

One wonders if the FDA is going to send in their armed agents to knock down the doors to the drug producer's facility to confiscate all suspected materials, computers, business records, and destroy everything else like they did when they flexed their big, strong FDA muscles to raid a producer of raw, organic milk?

william strinden - Jan 09, 2012

I am pleased that we have regulators and a mechanism to quickly send out information such as this. I am happy that we all agree to restrict our freedoms and only drive on the right side of the road in this country.

In the final analysis, what makes America work well is the intelligence and integrity of its people.

I will bet that the good people working at Novartis are horrified by their mistake.

Tyco, Enron,Bernie Madoff and too many examples to list all had SEC, auditors (some complicit), and layer after layer of stock analysts and bean counters to regulate them. Only the goodness within provides true regulation.

Beverly Richards-Smith, PhD - Jan 10, 2012

I have no doubt Novartis brought this to the attention of FDA. The agency must have little time or manpower to identify and deal with such potentially dangerous issues on its own, as it's so busy bullying producers of dietary supplements and walnuts (almost certainly at the behest of the pharmaceutical companies).

© 2012 Everyday Health, Inc. All rights reserved.

By George Lundberg, MD, Editor-at-Large, MedPage Today, with Maria Sullivan, MD, PhD

Published: June 11, 2012

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Hello and Welcome. I'm Dr. George Lundberg speaking for myself and co-author Dr. Maria Sullivan of Columbia University, and this is At Large at MedPage Today.

Acute and chronic pain is bad. Proper pain management is essential and has been strongly emphasized by the American medical establishment for the past nearly two decades.

Simultaneously, during these years, both the quantity of opioids prescribed by physicians and dentists has increased dramatically and prescription opioid abuse has escalated at an alarming rate among chronic pain patients and the general population.

Opioid analgesics now result in more American overdose deaths than cocaine and heroin combined.

What should physicians do? For treatment of chronic pain, non-opioid analgesics should be the first-line agents.

Physicians and nurses must discuss with patients common opioid side effects such as constipation and sedation, other risks such as addiction and overdose, and potential long-term risks such as hyperalgesia and sexual dysfunction.

Short-acting opioids such as Dilaudid (hydromorphone) and Vicodin (hydrocodone/paracetamol) may be helpful for initial pain relief, but longer-term dosing can lead to breakthrough pain and withdrawal, and these agents carry a relatively high abuse potential.

Oxycontin (oxycodone CR) is also widely abused, especially in rural areas; its elevated dosage means it is highly addictable, and coverage by insurance makes it cheaper than heroin.

Longer-acting opioid analgesics such as Suboxone (buprenorphine), methadone, and fentanyl have a much lower abuse liability.

However, methadone is found in more overdose deaths than any other prescription opioid and should not be prescribed for opioid-naive patients.

Because analgesic effects of methadone are of shorter duration (6 to 9 hours) than its half-life (36 hours), levels may accumulate, leading to respiratory suppression or cardiac events.

Patients should be instructed to keep controlled substances safe in a locked location to prevent use or sale by others.

If a physician intends to prescribe opioids for chronic pain, a narcotic protocol – medication contract, psychological evaluation, and urine toxicology – should be considered.

Monitoring both urine toxicology and aberrant behaviors will detect more opioid abuse than either strategy alone.

Combining a clinical interview and the SOAPP (Screening and Opioid Assessment for Patients with Pain) yields the highest sensitivity (.90) for abuse detection.

A "universal precautions" approach to minimizing risk includes asking patients about history of substance abuse, written informed consent, and ongoing reassessment of the benefits of opioid therapy. Clinicians can thus triage patients to low-, medium-, and high-risk addiction potential.

Treatment agreements should delineate rules such as having no early refills and requiring urine toxicology.

For patients who develop opioid addiction, substitution with buprenorphine or another abuse-deterrent formulation and adherence monitoring can be implemented.

The medical establishment should develop and use effective analgesics with lower abuse potential. Current research efforts to identify better methods to detect patients at heightened risk for developing addiction should be supported.

All prescribers of opioids must actively manage pain control while aggressively and intelligently attempting to prevent opioid abuse.

That's our opinion. We are Dr. George Lundberg and co-author Dr. Maria Sullivan, At Large for MedPage Today.

Maria A. Sullivan, M.D., Ph.D. is an Associate Professor of Clinical Psychiatry in the Division on Substance Abuse at Columbia University and the New York State Psychiatric Institute.

She has served as Principal Investigator on several NIDA-funded clinical trials implementing novel treatments for opioid dependence.

She is board-certified in Psychiatry and has a sub-specialty diplomate in Addiction Psychiatry.

http://www.medpagetoday.com/Columns/At-Large/33215? utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=

© 2012 Everyday Health, Inc. All rights reserved.

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By Kristina Fiore, Staff Writer, MedPage Today

Published: June 21, 2012

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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The respiratory depression and nausea often experienced by patients on opioid therapy appears to have some genetic basis, a study has found.

Note that age was associated with greater respiratory depression, drug-induced slowing of cognitive speed, and greater drug disliking.

The respiratory depression and nausea often experienced by patients on opioid therapy appears to have some genetic component, researchers found.

In a twin study, genetic effects accounted for almost 60% of the response variance in nausea and 30% of the variance in respiratory depression, Martin Angst, MD, of Stanford University in Palo Alto, Calif., and colleagues reported online in Anesthesiology.

"Our findings strongly encourage the use of downstream molecular genetics to identify patients who are more likely or less likely to benefit from these drugs -- to help make decisions on how aggressive you want to be with treatment, how carefully you monitor patients, and whether certain patients are suitable candidates for prolonged treatment," Angst said in a statement.

Opioids are a mainstay of pain management, but they carry side effects such as respiratory depression, sedation, nausea, and pruritus, as well as addiction.

However, there have been few studies looking at the contributions of genetic and environmental factors to patient response to opioids.

So Angst and colleagues conducted a twin study of 114 monozygotic and dizygotic twin pairs who were given either an infusion of saline placebo or alfentanil (Alfenta) -- chosen for its quick onset and offset of action.

They found that there was significant heritability for both respiratory depression and nausea, with genetic effects accounting for 30% and 59% of variance in response, respectively.

Genetic factors also appeared to play a role in patients' dislike of the drugs, accounting for 36% of the variance, the researchers reported.

"Opioid disliking may constitute a useful and easily measurable index phenotype to assess the abuse potential of opioids in future research," they wrote.

There were other factors that weren't necessarily found to be inherited, but still had a strong familial effect, which is due to shared genetic and environmental factors, the researchers said.

These included sedation, pruritus, and dizziness, with familial effects accounting for up to 29%, 38%, and 39% of the variance in response, respectively.

There was also a significant familial effect for drug liking, which accounted for up to 26% of response variance, they reported, noting that a "failure to detect heritability per se does not preclude relevant genetic effects."

Angst and colleagues also found that covariates such as age, sex, race, ethnicity, education, mood, and depression affected sedation, pruritus, drug liking and disliking, and dizziness. In particular, age was associated with greater respiratory depression and drug-induced slowing of cognitive speed, they found.

Also, older age was associated with greater drug disliking, which is consistent with lower rates of opioid abuse in aging patients with chronic pain, they wrote.

They concluded that genetic, environmental, and demographic factors "work together to control adverse and reinforcing opioid responses, but contribute differently to specific responses."

The researchers reported no conflicts of interest.

Primary source: Anesthesiology

Source reference:

Angst MS, et al "Aversive and reinforcing opioid effects: A pharmacogenomic twin study" Anesthesiol 2012; 117: 22-37.

http://www.medpagetoday.com/PainManagement/PainManagement/ 33411?utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=

© 2012 Everyday Health, Inc. All rights reserved.

By John Fauber, Reporter, Milwaukee Journal Sentinel/MedPage Today

Published: July 25, 2012

Nearly 40 doctors, researchers, and public health officials Wednesday asked the Food and Drug Administration to change the labeling used on narcotic painkillers, a move that, if approved, would make it more difficult for drug companies to market the medications for chronic, noncancer pain.

Although many of the 37 who signed the petition are associated with the reform group known as Physicians for Responsible Opioid Prescribing, most are from other institutions, including the New York City Health Commissioner, the Cleveland Clinic, the Mayo Clinic, several universities, and the watchdog group, Public Citizen.

The move comes amid concerns that prescribing practices of doctors have contributed to an opioid epidemic in America.

"By implementing the label changes proposed in this petition, FDA has an opportunity to reduce harm caused to chronic pain patients as well as societal harm caused by diversion of prescribed opioids," the petition says.

Controversy has grown over the practice of prescribing powerful painkillers such as Oxycontin or fentanyl to treat long-term, noncancer pain.

Over a decade, prescriptions for opioids have increased four times, accompanied by big increases in opioid-related overdose deaths and in people seeking treatment for addiction.

Before the late 1990s, opioids had been used primarily to treat short-term pain, such as after surgery, and pain associated with cancer and end-of-life disease.

Morgan Liscinsky, an FDA spokesperson, said the agency will review the petition and provide a response directly to Public Citizen.

The issue involves labeling on most opioid analgesics.

Public Citizen says most of the labels are overly broad, stating simply that the drugs are approved for moderate to severe pain without any limit on the amount of time a patient should be taking the products.

The petition calls for changing the labels to eliminate the word "moderate," and to include a maximum of the equivalent of 100 mg a day of morphine and a time period of no more than 90 days when used to treat noncancer pain.

Such uses then would become off-label.

That, in turn, would prevent drug companies from promoting the drugs for the off-label uses such as in advertisements, dinner talks for physicians, and at medical meetings. It also would affect continuing medical education courses.

The changes would not affect a doctor's ability to prescribe off-label, just such promotion by drug companies, said Sydney Wolfe, MD, director of the health research group at Public Citizen.

The petition notes that many doctors are under the false impression that opioids have been proven safe and effective for long-term noncancer pain.

Typically, studies of opioids for treating noncancer pain last less than 12 weeks.

"In the absence of long-term studies demonstrating safety and effectiveness, we need limits on what drug companies can claim about opioids," Ed Covington, MD, director of the Neurological Center for Pain at the Cleveland Clinic, said in a statement.

Lewis Nelson, MD, an emergency physician and medical toxicologist at NYU Langone Medical Center, said doctors are wrong in assuming that the current "on-label" use of opioids is based on good scientific evidence.

"It's time to close the loophole on opioid labels," he said in a statement.

Both Covington and Nelson signed the petition.

Beginning in the late 1990s, Purdue Pharma and several other companies that market opioids funded activities that promoted use of the drugs for long-term, noncancer pain such as low-back pain and fibromyalgia.

"Over-prescribing of opioids is harming many chronic pain patients," Covington added. "The label change is a way for the FDA to let the medical community know that risks may outweigh benefits when used long term."

That is not to say that opioids don't help some chronic pain patients.

Doctors estimate that about 30% of such patients may benefit. Typically they get about a 30% reduction in pain.

But that uncertainty over who might benefit has to be weighed against serious risks such as addiction, overdosing, respiratory suppression, falls and fractures in the elderly, sleep apnea, and cognitive impairment.

The label change setting the maximum dose at the equivalent of 100 mg of morphine means that it would apply mainly to higher doses of the drugs, which also are the most dangerous, said Andrew Kolodny, MD, president of Physicians for Responsible Opioid Prescribing.

That's about equal to 14 tablets of Vicodin or 13 tablets of Percocet a day, said Kolodny, chairman of psychiatry at Maimonides Medical Center in Brooklyn. Someone taking twice-a-day, 80 mg of Oxycontin, which is made by Purdue, also would be over that limit, he said.

A Purdue spokesman, noting that opioid use and dosing has been on the FDA's radar over the past decade, said "FDA, its advisory committees, and numerous medical experts maintain that the current indications for long-acting opioids are appropriate.

We agree with the FDA that prescribing information for any medication should be subject to ongoing review and modification to the extent that compelling medical evidence emerges."

Public Citizen's Wolfe, said the next step is for the FDA to take action on the petition. He said they could simply grant the labeling changes or hold an advisory panel hearing on the issue.

"They can't just write this off," he said.

If the agency does not take action in a reasonable amount of time, Public Citizen could take it to court to force a response, he Wolfe said.

http://www.medpagetoday.com/PainManagement/PainManagement/ 33900?utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=

© 2012 Everyday Health, Inc. All rights reserved.