New OxyContin Formulation Designed to Discourage Abuse of the Drug

The U.S. Food and Drug Administration today approved a new formulation of the controlled-release drug OxyContin that has been designed to help discourage misuse and abuse of the medication.

OxyContin is made to slowly release the potent opioid oxycodone to treat patients who require a continuous, around-the-clock opioid analgesic for management of their moderate to severe pain for an extended period of time. Because of its controlled-release properties, each OxyContin tablet contains a large quantity of oxycodone, which allows patients to take their drug less often. However, people intent on abusing the previous formulation have been able to release high levels of oxycodone all at once, which can result in a fatal overdose and contributes to high rates of OxyContin abuse.

The reformulated OxyContin is intended to prevent the opioid medication from being cut, broken, chewed, crushed or dissolved to release more medication. The new formulation may be an improvement that may result in less risk of overdose due to tampering, and will likely result in less abuse by snorting or injection; but it still can be abused or misused by simply ingesting larger doses than are recommended.

“Although this new formulation of OxyContin may provide only an incremental advantage over the current version of the drug, it is still a step in the right direction,” said Bob Rappaport, M.D., director of the Division of Anesthesia and Analgesia Products in the FDA’s Center for Drug Evaluation and Research.

“As with all opioids, safety is an important consideration,” he said. “Prescribers and patients need to know that its tamper-resistant properties are limited and need to carefully weigh the benefits and risks of using this medication to treat pain.”

According to the U.S. Substance Abuse and Mental Health Services Administration’s National Survey on Drug Use and Health, approximately half a million people used OxyContin non-medically for the first time in 2008.

The manufacturer of OxyContin, Purdue Pharma L.P., will be required to conduct a postmarket study to collect data on the extent to which the new formulation reduces abuse and misuse of this opioid. The FDA is also requiring a REMS (Risk Evaluation and Mitigation Strategy) that will include the issuance of a Medication Guide to patients and a requirement for prescriber education regarding the appropriate use of opioid analgesics in the treatment of pain.

Purdue Pharma is based in Stamford, Conn.

Knee and Hip Replacement Pain: A New Approach to Pain Management

Patients undergoing knee or hip replacements recover more quickly when treated with targeted pain-blocking medications that may eliminate the need for general anesthesia during surgery and intravenous narcotics drugs after surgery.

A decade ago, patients undergoing hip or knee replacements were almost exclusively given general anesthesia during surgery and intravenous narcotic pain medications afterward. This approach works for most people and still is commonly practiced. But both general anesthesia and intravenous narcotic drugs can cause nausea, vomiting, grogginess, decreased bowel function and other side effects.

In the early 2000s, Mayo Clinic anesthesiologists began developing new anesthesia protocols for joint replacement surgery that used known anesthetic and pain relief techniques in new combinations. Their goal was to eliminate the need for general anesthesia and intravenous narcotics and the resulting side effects.

The new procedures may vary but typically involve:

A choice: Even with the new protocols, patients may choose regional anesthesia, where the lower half of the body is numbed, or general anesthesia.

Oral pain medications early on: A combination of oral narcotic pain medications are given prior to surgery. Oral narcotics have fewer side effects than narcotics given intravenously. This technique is helpful for recovery whether general or regional anesthesia is used.

Sedation: Sedative drugs given before surgery help patients using regional anesthesia nap during the procedure, but not lose consciousness.

Nerve blocks: Through a catheter, a continuous infusion of numbing medicine is pumped near the surgery site for 48 hours. Nerve blocks are performed in conjunction with general or regional anesthesia.

Oral pain medications after surgery: For more than 95 percent of patients, pain that occurs after the nerve blocks are removed can be managed with oral pain medications such as acetaminophen (Tylenol, others), tramadol (Ultram, others) or oxycodone. Intravenous narcotic medications are used as a last resort.

Patients who receive regional anesthesia report significantly less pain after surgery than those receiving general anesthesia and intravenous narcotics. These patients are out of bed sooner, begin physical therapy sooner and leave the hospital one to two days before patients who were given general anesthesia and intravenous narcotics. With the newer protocols, patients may still experience typical side effects including nausea and vomiting, but to a lesser degree than with the older anesthesia methods.

Another benefit is that regional anesthesia protocols make surgery an option for older adults with more complicated conditions. A decade ago, older adults often were not considered candidates for surgery because they would have fared poorly with older anesthesia techniques.

Doctors report few downsides to these newer pain management approaches. Nerve injury is a rare potential complication. For most people, the regional anesthesia protocols are a change for the better, resulting in less pain, fewer complications and a quicker recovery.

Source: Mayo Clinic (2/10/2010)

Addiction to Prescription Pain Killers Among Patients and Physicians

Chemical dependency and recovery in patients and physicians are closely examined in a series of articles and editorials in the July 2009 issue of Mayo Clinic Proceedings. The subject is especially timely. As the immense challenges, including potential tragedies, of prescription chemical addiction and abuse are being discussed, these articles offer crucial overview, direction and optimism.

Addiction to and abuse of prescription opioid drugs are prevalent, and they exact an immense toll on patients, physicians and society, according to Steven Passik, Ph.D., Department of Psychiatry and Behavioral Sciences, Memorial Sloan-Kettering Cancer Center, New York, in “Issues in Long-Term Opioid Therapy: Unmet Needs, Risks, and Solutions.”

Opioid drugs have been used by humans for thousands of years and are the longest continuously used class of medications, explains William Lanier, M.D., editor-in-chief of Mayo Clinic Proceedings. Dr. Lanier and Evan Kharasch, M.D., Ph.D., Department of Anesthesiology, Washington University in St. Louis, authored the editorial “Contemporary Clinical Opioid Use: Opportunities and Challenges.” It summarizes the recent increased interest in this drug category.

Opioid medications are chemicals that work by binding to specific receptors, particularly in the nervous system and gastrointestinal tract; decrease perception of pain and reaction to pain; and increase pain tolerance. Side effects include sedation, respiratory depression and constipation. When opioid consumption is ongoing, physical dependence can and will develop. This, in turn, can lead to problematic withdrawal upon abrupt discontinuation of medication. Dependence, coupled with the feeling of euphoria these drugs can produce, leads to abuse.

According to Dr. Lanier, the recent growing interest in opioids stems from five sources: advances in the design of these drugs; expansion and innovation in methods of drug delivery; increased public awareness of pain management options and the appropriateness of aggressively treating pain as the “fifth vital sign” and pain relief as a fundamental human right; growing recognition of the serious consequences of opioid misuse, misadventure and addiction; and medicolegal aspects of practitioners’ prescribing practices and legal consequences for under- or overprescribing.

In addition to individuals who have chronic pain, both cancer and non-cancer related, anesthesiologists have the greatest risk of opioid dependence and abuse among health care providers. Also in the high-risk group for health care providers are nurse anesthetists and sedation nurses. Challenges specific to these groups are discussed by Michael Oreskovich, M.D., Washington Physicians Health Program in Seattle, and Ryan Caldeiro, M.D., Department of Psychiatry and Behavioral Sciences at the University of Washington, Seattle, in “Anesthesiologists Recovering From Chemical Dependency: Can They Safely Return to the Operating Room?”

Severe chronic pain includes that produced by cancer and such non-cancer conditions as back injury and surgery. Opioids are a cornerstone of pain management for individuals in these categories, according to Howard Smith, M.D., Department of Anesthesiology, Albany Medical College, N.Y. In “Opioid Metabolism,” he writes that approximately 10 percent to 20 percent of physicians will develop a substance abuse problem during their career, a rate similar to or exceeding the general population. For anesthesiologists, according to Drs. Oreskovich and Caldeiro, the increased risk is cited as an occupational hazard because of the highly addictive medications they administer to patients daily.

Health care professionals helping patients with chronic pain must balance aggressive treatment with the need to minimize the risks of misuse and abuse, according to Dr. Passik. In “A Comparison of Long- and Short-Acting Opioids for the Treatment of Chronic Noncancer Pain,” Charles Argoff, M.D., and Daniel Silvershein, M.D., both from the Department of Neurology, Albany Medical College, N.Y., write that management of chronic non-cancer pain, for example, requires comprehensive assessment of each patient; the establishment of a structured treatment regimen or program; ongoing reassessment of the pain condition and the response to therapy; and a continual appraisal of the patient’s adherence to the treatment. Their colleague, Dr. Smith, stresses the importance of understanding the metabolism of opioids in individual patients.

Keen awareness by family and friends of potential addiction is crucial for physicians and other health care providers, not to mention the general public, who might be at risk, according to “Chemical Dependency and the Physician” by Keith Berge, M.D., Department of Anesthesiology, Mayo Clinic; Marvin Seppala, M.D., Hazelden Foundation, Center City, Minn.; and Agnes Schipper, J.D., Mayo Clinic Legal Department. Especially important is that family, friends and co-workers of health care providers confront any suspected addiction and abuse because of the potential harm that might befall the individual and his or her patients. Health care facilities should have written policies and procedures in place to assist when these highly emotionally charged situations involving health care providers occur, Dr. Berge and his colleagues write. Long-term recovery and sobriety can be achieved with appropriate treatment, aftercare and monitoring, they add.

New opioid formulas designed to minimize abuse are now in late-stage development and could help, Dr. Passik says. These drugs are chemically designed to diminish euphoric effects, thus possibly reducing problematic use. For now, responsibility coupled with expertise, insight, diligence and compassion are among the components that can meet the challenges of opioid use in pain management, the authors agree.

Source: Mayo Clinic, July 7, 2009

One Quarter of All Americans Experience Daily Pain

More than a quarter of the entire population in the United States experiences some form of pain every day. Americans spent between $2 and $6 billion on non prescription painkillers in 2007, while the cost of productivity loss attributable to pain-related conditions is estimated at $60 billion a year.

"Although much is known about the pain experienced by those with chronic illnesses, until now relatively little was known about pain in the entire U.S. population," says Arthur A. Stone, Ph.D., a Professor in the Department of Psychiatry and Behavioral Science at Stony Brook University.

"Our assessment approach allowed us to get accurate information about pain at several carefully selected times from the previous day," explains Dr. Stone, which enabled the researchers to address several new questions about pain, daily activities, and respondents’ personal characteristics.

Ten thousand people were contacted via random-digit dialing, and a total of 3,982 people were actually interviewed. To make the study results representative of the U.S. population, the data were adjusted with sample weights developed by the Gallup Organization. 29% of men and 27% of women said they experienced pain at sampled times.

The researchers also found a correlation between pain and lower income and less education: "Those with lower income or less education spent a higher proportion of time in pain and reported higher average pain than did those with higher income or more education," they wrote.

Additionally, the report found that the average pain rating increased with age, although it reached a plateau between ages of about 45 years and 75 years, with little difference between men and women.

According to Dr. Stone, "The study results expand our understanding of pain in the United States and supplement more traditional assessment approaches with a very detailed perspective on the pain people experience on a daily basis. This suggests new avenues of research that may ultimately lead to improved treatment of pain."

Study authors: Arthur A. Stone, Ph.D., Distinguished Professor and Vice Chair, Department of Psychiatry and Behavioral Science at Stony Brook University, and Alan Krueger, Ph.D., Professor, Department of Economics and the Woodrow Wilson School at Princeton University

Source: The Lancet, May 3, 2008

Vertebroplasty Shows Promise for Vertebral Compression Fracture Treatment

Vertebroplasty, an interventional radiology treatment for vertebral compression fractures, provides patients with significant pain relief and lasting benefit, according to a 5-year follow-up study of 884 osteoporosis patients.

The procedure calls for the injection of medical-grade bone cement into a fractured vertebra, and acts like an internal cast on the fracture. It is particularly effective for painful vertebral compression fractures that do not respond to analgesics or intolerable narcotics. The average pre-treatment pain score on the 11-point Visual Analog Scale was 7.9 +/- 1.5, and it dropped significantly to an average of 1.3 +/- 1.8 after the vertebroplasty treatment.

The Oswestry Disability Questionnaire (ODQ), which measures a patient’s ability to manage everyday life, was completed by patients before, and one month after vertebroplasty, and showed greatly improved mobility—from an average of 69.3 percent +/- 13.5 to 18.8 percent +/- 6.9.

"These data provide good news for physicians and osteoporosis patients. Many osteoporosis patients with compression fractures are in terrible pain and have a greatly diminished ability to perform basic daily activities, such as dressing themselves," said Giovanni C. Anselmetti, M.D., interventional radiologist at the Institute for Cancer Research and Treatment in Turin, Italy. While vertebroplasty can improve a patient’s quality of life, the procedure is generally reserved for people for whom conventional medical management was ineffective.

"Osteoporosis patients who have persistent spinal pain lasting more than three months should consult an interventional radiologist, and those who require constant narcotic pain relief should seek help immediately," noted Anselmetti. The treatment was completed in all patients without major complications and with good clinical results. The data add to the body of evidence in the United States for the minimally invasive treatment’s safety, effectiveness and low-complication rate. The treatment is widely available in the United States at all major institutions and many smaller institutions and is generally covered by health insurance.

The study also showed that vertebroplasty does not increase the risk of fracture in nearby vertebra. "Vertebroplasty is already known to be a safe and effective treatment for osteoporotic vertebral fractures. Osteoporosis patients remain susceptible to new fractures, which often occur in the contiguous vertebra to an existing fracture. Our large-scale study shows that vertebroplasty does not increase the risk of fracture in the level contiguous to previously treated vertebra and that these new fractures occur at the same rate as they would in osteoporosis patients who did not have vertebroplasty," added Anselmetti.

The research was presented at the Society of Interventional Radiology’s 33rd Annual Scientific Meeting.

What You Don’t Want for Christmas: Weight Gain and Back Pain

In a recent survey conducted by SpineUniverse, 69%
of people estimated that they typically gain up to 8 pounds during the
holiday season. Another 9% put their weight gain at over 8 pounds.

 Those extra pounds from sugar cookies and big family dinners don’t come
off easily, either: it takes 60% of the people surveyed up to 10 months
to lose their holiday weight. 11% said that they never lose the weight.
A study published in the New England Journal of Medicine agrees: most
people can’t shake their holiday weight until the next fall–just in
time for the Halloween candy.

 So year after year, people add on weight during the holidays, and in
the long-term, that holiday weight gain can add up–to back pain. Dr.
Steven Richeimer, a member of the SpineUniverse Editorial Board and
Chief of Pain Medicine at the University of Southern California, Keck
School of Medicine, explains, "If you’re overweight, your spine may be
overworked as it tries to carry that extra weight. This can produce
injury and back pain."

He continues, "When you’re overweight, you’re more likely to injure
your back, and it is more difficult to recover–the result can be
chronic back pain. Additionally, being overweight can exacerbate or
even lead to symptoms of degenerative disc disease, compression
fracture, osteoporosis, osteoarthritis, spinal stenosis, and
spondylolisthesis."

Thinking about back pain isn’t exactly full of holiday cheer. But
suffering excruciating back pain is even less cheerful. For some simple
steps to follow this holiday season to prevent the typical holiday
weight gain, visit Spine Universe.

Simple and Cost Effective Treatment of Calcific Shoulder Tendinitis

A simple and cost effective way of treating calcium tendinitis of the shoulder was revealed by Spanish researchers,led by Dr. Del Cura, publishing in the American Journal of Roentgenology.

Calcium tendinitis presents as small calcium deposits (1 – 2 cm) on the rotator cuff of the shoulder in individuals over 35 years old. Often painful, some resolve spontaneously, but others persist and become disabling.

Traditional treatment involves shockwave therapy to the shoulder, and in worst case scenarios, surgery.

Dr. del Cura’s treatments, in contrast to surgery, are relatively non-invasive, and involve percutaneous needle lavage (with lidocaine or saline solution) guided by sonography.

In a study of 67 shoulders, 91% were "substantially or completely improved." Of note is that "transitory" recurrences were observed 15 weeks after treatment in 44% of shoulders that had previously improved.

Source: American Journal of Roentgenology (AJR 2007; 189:W128-W134)

Lidocaine Derivative (QX-314) with Capasicin Key to Pain-Specific Local Anesthesia Technique

Researchers from Massachusetts General Hospital and Harvard Medical School have found a way to target only pain-sensing neurons when injecting a local anesthetic. The technique blocks pain without affecting motor function or sensitivity to non-pain stimulus.

While current local and general anesthetics work well for controlling pain, since they work by interfering with the excitability of all neurons and not just pain-sensing neurons, they produce dramatic side effects—loss of consciousness for general anesthetics, and loss of motor function for local anesthetics.

The experimental results were achieved in rats by combining a normally inactive lidocaine derivative (QX-314) with capasicin, the "hot" ingredient in chili peppers.

According to the researchers, the results of their new technique were achieved by taking advantage of a membrane-spanning protein called TRPV1, which is unique to pain-sensing neurons. TRPV1 forms a large channel, where molecules can enter and exit the cell. But a "gate" typically blocks this opening. In this case, that gate is opened when the cells are exposed to the heat of the capsaicin. Non-pain sensing neurons are unaffected because they do not possess TRPV1.

The lidocaine derivative QX-314 is not used clinically because it can’t penetrate cell membranes to block the excitability of the cell, so it typically remains outside the neurons. In this case, that property is a benefit to the new pain management technique. When pain-sensing neurons are exposed to capsaicin, however, QX-314 can enter the cells and shut them down. But the drug remains outside other types of neurons that do not contain these channels so they retain their ability to send and receive signals.

"We’re optimistic that this method will eventually be applied to humans and change our experience during procedures ranging from knee surgery to tooth extractions," says the study’s senior author, Professor Clifford Woolf of Massachusetts General Hospital. "Eventually this method could completely transform surgical and post-surgical analgesia, allowing patients to remain fully alert without experiencing pain or paralysis."

The study appears in the October 4, 2007 issue of Nature.

Source: Harvard Medical School

Deaths Linked to Cephalon’s Cancer Pain Drug, Fentora

After receiving reports of deaths and other serious side effects, FDA is alerting consumers and health care professionals to concerns about the use of Fentora (fentanyl buccal) tablets, a potent opioid pain medication.

Fentora is used only for treating breakthrough pain in cancer patients receiving opioid treatment and who have become tolerant to it—those who take a regular, daily, around-the-clock narcotic pain medicine. Breakthrough pain is intense increases in pain that occur rapidly, even when opioid pain-control medication is being used.

People who develop tolerance to narcotic pain medicines are more resistant to the dangerous side effects of these medications than those who take narcotic pain medication less frequently.

The deaths reported indicate that some cancer patients

  • should not have been prescribed this medicine
  • were prescribed the wrong Fentora dose
  • took too many Fentora doses
  • received Fentora as a substitute for another fentanyl-containing product that is not equal to Fentora

Important Safety Information

  • Ask your doctor if you are opioid-tolerant before taking Fentora. The drug should only be used for breakthrough pain in opioid-tolerant patients with cancer.
  • Fentora should not be used to treat any type of short-term pain, including headaches or migraines, pain after an operation, or pain due to injury.
  • People who only take narcotic pain medications occasionally should not use Fentora.
  • Do not substitute Fentora for other fentanyl medicines, including Actiq. The dosage strength of fentanyl in Fentora is NOT equal to the same dosage strength of fentanyl in other fentanyl-containing products. Using the same dose can result in a fatal overdose.
  • Read the Medication Guide that comes with Fentora,and follow the directions exactly.

Watch For These Signs

Get medical attention right away if you have any of these signs:

  • trouble breathing or shallow breathing
  • tiredness, extreme sleepiness, or sedation
  • inability to think, talk, or walk normally
  • feeling faint, dizzy, or confused

FDA Actions

  • requested the manufacturer, Cephalon Inc., strengthen warnings and improve the dosing instructions in the drug’s product labeling and Medication Guide for patients
  • requested the company improve their education plan for prescribers and pharmacists
  • published a Public Health Advisory and Health Care Professional Sheet warning health care professionals that it is critical to follow Fentora’s product labeling
  • monitoring the Fentora issue closely and reviewing available information, including adverse events
  • working with the manufacturer to ensure the safest use of the medicine
  • providing updates as new information is available

Adverse events related to Fentora should be reported to MedWatch, the FDA’s voluntary reporting program.

Source: FDA

Electronic Device to Eliminate Migraine Pain

A new type of electronic device is designed to provide relief for migraine pain. The device is called TMS, which has been designed to stop migraine pain even before it begins.

According to a recent study, TMS has been found to be effective in treating the pain when used at the onset of migraine.
Earlier, it was assumed that migraines were caused by vascular constriction that resultant in aura—commonly known as electrical storms in the brain, followed by vascular dilation that resulted in severe pain.

However, in the late 1990s, studies revealed that migraine pain is caused by to neuronal electrical hyperexcitability. TMS is based on this new understating of the migraine mechanism and works by interrupting the aura phase of the migraine.