 May-June 2008; Issue 15
This edition of News/Research Updates was researched/compiled by Winnie Dawson, MA, RN, BSN [WD], and edited by Stewart B. Leavitt, MA, PhD [SBL]. Medical reviewers were: James D. Toombs, MD; Lee A. Kral, PharmD, BCPS; Seth I. Kaufman, MD. Posting Date: June 23, 2008.
Where noted, product brand names are for informational purposes only and are registered trademarks of their respective manufacturers. In some cases, additional brands may be available for specific products.
 Access to all external URL links was checked prior to posting; however, some may change or become obsolete over time and will no longer function. This is beyond our control.
 A comprehensive evidence-based review from Pain Treatment Topics examines the influence of inadequate vitamin D intake on chronic pain and fatigue syndromes and provides guidance for practitioners. According to clinical research examining adult patients of all ages, inadequacies of vitamin D have been linked to chronic musculoskeletal pain of various types, muscle weakness or fatigue, fibromyalgia syndrome, rheumatic disorders, osteoarthritis, hyperesthesia, migraine headaches, and other somatic complaints. It also has been implicated in the mood disturbances of chronic fatigue syndrome and seasonal affective disorder.
Current best evidence demonstrates that supplemental vitamin D can help to resolve or alleviate chronic pain and fatigue syndromes in many patients who have been unresponsive to other therapies. Vitamin D therapy is easy for patients to self-administer, well-tolerated, available over-the-counter, and very economical.
Several peer-reviewed documents on this subject are available for healthcare providers and their patients from Pain-Topics.org. These include: 1) Full Report, 50 pages, providing a comprehensive literature review responding to questions practitioners may have regarding why, when, how, and for whom to recommend vitamin D supplementation, 2) Practitioner Briefing providing a 7-page summary of the full Report, and 3) Patient Brochure, 6 pages, explaining in simple language how vitamin D works and how it might help offer relief for chronic musculoskeletal pain and fatigue conditions.
 All 3 documents are available at: http://pain-topics.org/VitaminD
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Methylnaltrexone Relieves Opioid-Induced Constipation
Researchers at a San Diego, CA, palliative care center evaluated the efficacy of methylnaltrexone – a peripheral opioid-receptor antagonist – to relieve constipation induced by opioid therapy. Opioid-treated patients (n=133) with advanced illness and unresolved opioid-induced constipation were randomized to receive subcutaneous methylnaltrexone or placebo every second day for 2 weeks. Patients who completed the first phase of treatment on a dosage of 0.15 mg per kilogram of body weight were eligible to enter a 3-month open-label extension study.
One primary outcome – laxation within 4 hours after the first dose – was met by 48% of methylnaltrexone patients, compared with 15% in the placebo group (p < 0.001). A second outcome – laxation within 4 hours after 2 or more of the first 4 doses – was met by 52% of the treatment group, compared with 8% of the placebo-treated patients (p < 0.001). This response rate was consistent through the study’s extension period. The most common adverse events in the methylnaltrexone group were mild-to-moderate abdominal pain and flatulence but, overall, the incidence of adverse events was similar in treatment and placebo groups.
Clinical Implications: While the authors expressed disappointment that methylnaltrexone only provided laxation in about half of participants, they concluded that methylnaltrexone offers the therapeutic potential to reverse the constipation side effect of opioids without interfering with pain relief or precipitating opioid withdrawal symptoms. They recommend future studies with larger numbers of patients in this vulnerable end-stage population.
References: Thomas J, Karver S, Cooney GA et al. Methylnaltrexone for opioid-induced constipation in advanced illness. N Engl J Med. 2008(May 29);358(22):2332-2343.
[Commentary: Also see the “Drug Approval and Announcement” section below for the FDA-approval press release and prescribing information on Relistor™. At the present time, only the subcutaneous formulation of methylnaltrexone has been approved; however, clinical trials are underway leading toward approval of an oral formulation that would be useful for outpatients. – SBL]
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Frequent Opioid Use May Increase Risk of Chronic Migraine
Medication overuse headache is a clinically important concern for migraineurs who use medications for acute symptomatic relief. Results of a longitudinal population study exploring potential medication overuse as a risk factor for chronic migraine attacks were reported at the American Academy of Neurology annual meeting in April 2008. A migraine headache on fewer than 15 days per month was classified as episodic, whereas 15 or more migraine days each month was considered chronic.
The study, funded by the National Headache Foundation, included a nationwide cohort of 24,000 headache sufferers who were evaluated by means of annual questionnaires. Participants with episodic migraine in 2005 were isolated and followed the next year for migraine-medication use.
Year 2006 results showed that 209 participants (2.5%) developed chronic migraine and that taking barbiturates and opioids for as few as 7 days per month doubled the likelihood of developing chronic migraine when compared with people taking other medications. Those taking triptans or nonsteroidal anti-inflammatory drugs (NSAIDs including aspirin, naproxen, or ibuprofen) were not found to be at increased risk of progressing from episodic to chronic migraine.
Clinical Implications: The authors concluded that frequent use of opioids and barbiturates appeared to be a risk factor for chronic migraine. Based on the results of this study and other evidence that shows medication overuse headache is one of the most common causes of a chronic migraine-like syndrome, healthcare providers should discuss treatment options with patients in advance of starting therapy.
Reference: Bigal M, Reed M, Serrano D, et al. Excessive use of barbiturates and opioids as risk factors for chronic migraine – a population study. American Academy of Neurology 60th Annual Meeting. Chicago, IL. April 12-19, 2008. Abstract #S46.007
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Transdermal Fentanyl Provides Osteoarthritis Pain Relief
When first-line analgesic drugs do not relieve osteoarthritis (OA) pain, current treatment guidelines recommend opioid administration. In an 8-week, open-label, multicenter Canadian trial researchers evaluated transdermal fentanyl (TDF) as a therapeutic option for 81 patients with OA of the hip or knee. TDF therapy was initiated at 25 mcg/hour and titrated until optimal pain control was achieved; patients were allowed rescue acetaminophen up to 4 g/day. The primary endpoint was improvement in pain control.
At the first endpoint of 2 weeks, 62 patients were eligible for evaluation, and 36 patients completed the full 8-week trial. Significant improvements were reported by more than half of evaluable patients at all study time points. For example, improvements in pain control ratings were reported by 74% and 65% of evaluable patients at 2 weeks and at study completion, respectively. There also were significant improvements in functionality and highly significant reductions in total WOMAC (Western Ontario and McMaster University Osteoarthritis Index) scores at study’s end. The mean daily dose was 44 mcg/hour (range=25-147 mcg/h). One serious adverse event – chest pain with obstructive sleep apnea – was reported.
Clinical Implications: Although opioid side effects were reportedly of mild to moderate intensity, 40% of originally-enrolled participants discontinued the study. The authors reported that patient education regarding adverse effects improved as the study progressed, and they also stated that it was noteworthy that 60% the evaluable patients who were 65 years and older (n=24) completed the full 8-week treatment period. Additionally, reductions in constipation in this TDF treatment group were statistically significant when compared to a pooled analysis of published studies of patients taking sustained-release morphine. The authors conclude that these results support the current treatment recommendations that include the use of TDF as a sustained-delivery opioid in a sub-population of patients with OA whose pain has been inadequately controlled on weak opioids.
References: Choquette D, McCarthy TG, Rodrigues JFN, et al. Transdermal fentanyl improves pain control and functionality in patients with osteoarthritis: an open-label Canadian trial. Clin Rheumatol. 2008 (May);27(5):587-595.
 Caution: The fentanyl patch (Duragesic® and generic products) carries an FDA ‘black box’ warning about the potential for life-threatening adverse events in patients who may be misusing the product. The warning reminds consumers and healthcare providers that the drug should only be used for patients who are tolerant to opioid drugs and who are suffering from moderate to severe chronic pain. Safety for fentanyl and Duragesic pain patches has not been established in children less than two years old, suggesting potentially dangerous complications when used by young children. Additionally, life threatening breathing problems can occur in certain situations among patients of any age. – WD.
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Opioid Pain-Relief Benefits Outweigh Risks of Abuse
In a press release from the American Pain Society and a presentation at their annual meeting in May 2008, it was reported that research shows that less than 3% of patients without prior history of drug abuse who are prescribed opioids for chronic pain will show signs of possible drug abuse or addiction. Srinivasa Raja, MD, from Johns Hopkins University School of Medicine, emphasized this fact in his plenary session address and encouraged clinicians and policymakers “not to allow the small percentage of abused pain prescriptions to prevent legitimate pain patients from getting [adequate] care.”
He recommended that physicians continue to provide effective chronic pain management by:
- communicating with patients about the benefits and risks of opioid pain-relief,
- screening for drug-seeking behavior and signs of potential abuse, and
- using a multi-faceted approach to treatment (including physical and cognitive-behavior therapies).
Raja further suggests that collaborations including healthcare providers, regulatory agencies, law enforcement agencies, and the pharmaceutical industry should be able to effectively attack the problem of prescription drug abuse. He suggested that media accusations that increased pain medication abuse was due to increased opioid prescribing for chronic pain management were unfounded, and added that progress has been evident in increased teen drug awareness programs and improved identification of illicit drug sources like unregulated Internet pharmacies.
Reference: Raja S. From poppies to pill popping: Is there a middle way? American Pain Society Annual Meeting Plenary Session, May 10, 2008, Tampa, Florida.
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Deep Heat and Exercise Improve Frozen Shoulder
Physiotherapists at Our Lady of Maryknoll Hospital in Hong Kong evaluated the effects of superficial and deep heat therapy (heat applied directly to injured tissues using the energy of ultrasound, high frequency currents, or electromagnetic radiation) on pain relief in patients with a frozen shoulder (also called adhesive capsulitis, and characterized by pain and loss of motion or stiffness in the shoulder). Patients (n=30) in the stiffness phase of frozen shoulder were randomized to one of 3 study groups: 1) deep heat plus stretching, 2) superficial heat plus stretching, or 3) stretching exercises alone. All subjects received their respective treatments 3 times each week for 4 weeks. Evaluations were performed using the American Shoulder and Elbow Surgeons assessment form at baseline, sessions 6 and 12, and at a 4-week follow-up appointment.
All groups showed significant improvements in all outcome measures, except for range of shoulder flexion. Improvements in shoulder range of motion were significantly better in the deep heating group than in the superficial heating or stretching-only groups.
Clinical Implications: While this study did not explore multiple phases of frozen shoulder, the addition of deep heat to stretching exercises during the stiffness phase did produce improvements in pain relief, daily activity performance, and range of motion when compared with superficial heat therapy. Deep heat therapy could be an additional treatment option for appropriately-selected patients who suffer from long-term pain and stiffness of frozen shoulder. However, any of the 3 therapies might be of some benefit if applied consistently and properly.
Reference: Leung MS, Cheing GL. Effects of deep and superficial heating in the management of frozen shoulder. J Rehabil Med. 2008(Feb);40(2):145-150.
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Recent Research Recommends Tai Chi for Arthritis
Tai Chi, a mind-body practice originating in China as a martial art, is now commonly practiced as a sequence of movements used to move vital energy throughout the body. Because the movements are gentle in nature, Tai Chi is gaining popularity as a complementary therapy for the treatment of a wide variety of disorders in the elderly. Two recent small pilot studies have shown positive benefits for the improvement of physical function and pain relief in patients with arthritis.
- A prospective, pretest-posttest clinical trial evaluated the effects of Tai Chi exercise on gait kinematics, physical function, pain, and pain self-efficacy in 40 elderly men and women with knee osteoarthritis. Participants practiced Tai Chi techniques for 6 weeks during two 1-hour sessions per week. All 4 evaluation measures were assessed at baseline and the conclusion of the intervention. Physical function was significantly improved (p < 0.001), knee pain was significantly decreased (p = 0.002), and increases were demonstrated in all 3 measures of gait kinematics. No change was observed in pain self-efficacy (ie, personal feelings of being able to cope with pain).
- Researchers at Tufts-New England Medical Center, Boston, MA, conducted a controlled pilot study to evaluate the effects of Tai Chi on muscle strength and ‘mind-body’ interactions in patients with functional class I or II rheumatoid arthritis. Patients (n=20) were randomized to twice-weekly sessions of either Tai Chi exercises or lectures on wellness and stretching (control group) for 12 weeks. At study conclusion, half of the Tai Chi patients achieved an ACR-20 response* compared with none in the control group (p = 0.03). Tai Chi also showed greater improvement in measures of disability, vitality, depression, disease activity, functional capacity, and health-related quality of life. There were no adverse events and no patient withdrawals from the study.
[*American College of Rheumatology (ACR) criteria require that a patient have a 20% reduction in the number of swollen and tender joints and improvements in 3 additional symptom parameters.]
Sources:
Shen CL, James CR, Chyu MC, et al. Effects of tai chi on gait kinematics, physical function, and pain in elderly with knee osteoarthritis – a pilot study. Am J Chin Med. 2008;36(2):219-232.
Wang C. Tai chi improves pain and functional status in adults with rheumatoid arthritis: results of a pilot single-blinded randomized controlled trial. Med Sport Sci. 2008;52:218-229.
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Associations of Daily Chronic Pain & Diabetes Studied
Researchers at Kuopio University Hospital, Kuopio, Finland, investigated how plasma glucose levels and diabetes mellitus (DM) are associated with daily chronic pain (DCP) in the adult population. They conducted a structured interview and health examination of 480 participants aged 30-65 years. DCP was defined as pain of at least 3 months duration and occurring every day or continuously. Plasma glucose was defined as elevated if it was 6.1 mmol/L, and a DM diagnosis was based on self-report, reimbursed medications, or a health examination with laboratory tests.
The prevalence of daily chronic pain in the total sample was 21%, elevated plasma glucose was found in 19%, and diabetes in 11%. Subjects with DCP were 2.37 times more likely to have an elevated plasma glucose level (95% CI, 1.26–4.49) and 2.53 times more likely to have DM (95% CI, 1.12–5.72).
Practice Perspective: : The investigators concluded that elevated plasma glucose level and diabetes mellitus are strongly associated with daily chronic pain in adults. While this sort of investigation does not confirm a cause-effect relationship, it should be of concern to practitioners who treat patients with chronic pain conditions. Furthermore, in those patients with diabetes, related neuropathies should be considered in the differential diagnosis of pain.
Reference: Mäntyselkä P, Miettola J, Niskanen L, Kumpusalo E. Chronic pain, impaired glucose tolerance and diabetes: A community-based study. Pain. 2008(June);137(1):34-40.
[Commentary: Elevated plasma glucose levels and/or diabetes might be added to a growing list of potential physical and physiologic markers associated with chronic pain syndromes. In a recent article for Pain-Topics.org, Forest Tennant, MD, DrPH, describes an extensive list of objective indicators of chronic pain, including abnormal vital signs due to sympathetic discharge, as well as signs relating to how patients seek positional relief, sensory avoidance, and pain distraction. For more information see, “Using Objective Signs of Severe Pain to Guide Opioid Prescribing” at: http://pain-topics.org/clinical_concepts/comments.php#Tennant2 – SBL]
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Local Infiltration Analgesia For Postoperative Knee Pain
Investigators at the Joint Orthopaedic Centre, Australia, developed a multimodal “local infiltration analgesia” (LIA) technique for controlling postoperative pain following knee and hip surgery. Tissues surrounding the surgical field were infiltrated (intraarticular injection via catheter) with a mixture of ropivacaine, ketorolac, and adrenaline to achieve satisfactory pain control with minimal physiological disturbance. A nonrandomized case series of 325 surgical patients during a 2-year period had elective hip resurfacing, total hip replacement, or total knee replacement arthroplasty. Pain scores, mobilization times, and morphine usage were recorded for all patients.
Pain control was rated as satisfactory (range 0-3 on a 0-10 numerical rating scale) and two-thirds of the patients did not require morphine for postoperative pain control. Most patients walked with assistance within 5-6 hours following surgery and independent mobility was accomplished 13-22 hours postoperatively. More than 70% of patients were discharged directly home after a single overnight hospital stay. Adverse effects of orthostatic hypotension, nausea, and vomiting were usually associated only with the first attempt to walk; other side effects were unremarkable, according to the researchers.
Clinical Implications: The researchers stated that a short-acting spinal anesthetic was used intraoperatively and the postoperative “local infiltration analgesia” technique was designed to manage acute postoperative pain lasting about 36 hours overall. They added that the technique was safe and practical, allowing nearly immediate mobilization following surgery and earlier discharge from the hospital. Limitations of the study include the fact that the patient population was drawn from a single private practice with biases toward specific surgical procedures.
Reference: Kerr DR, Kohan L. Local infiltration analgesia: a technique for the control of acute postoperative pain following knee and hip surgery: a case study of 325 patients. Acta Orthop. 2008(Apr);79(2):174-183.
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SPINE Supplement Devoted to Neck Pain Research
Results of research from the Bone and Joint Decade 2000-2010 Task Force on Neck Pain are reported in a February 2008 supplement of the journal, Spine. Healthcare professionals from 9 countries, 19 specialty disciplines, and multiple research and professional organizations were represented in the task force. The 220-page supplement is devoted entirely to neck pain and includes a synthesis of existing documentation on epidemiology, diagnosis, and treatment after a systematic review of the literature and best available evidence. The Executive Summary provides a synopsis of key findings including the following points:
- The 12-month prevalence of neck pain in the general population ranges from 12% to about 71%; however, the prevalence of neck-related disability is much lower at a range of about 2%-12%.
- Annually, 11% to 14% of workers report functional limitations due to neck pain.
- The incidence of whiplash-associated disorders has increased in the past 3 decades.
- Risk factors and prognosis for neck pain are both multifactorial and included age, gender, physiological health, psychological health, and exposure to tobacco.
- Most people do not experience full relief from neck pain symptoms and it is estimated that between 50%-85% of patients with neck pain will report subsequent symptoms within 1-5 years.
- Treatment evidence includes education, noninvasive interventions (exercise, low-level laser therapy, acupuncture), injections, and surgical treatment.
- The Task Force recommended a 4-grade classification system for neck-pain severity and proposed a new conceptual model that outlines the options available for people with neck pain and those at risk for neck pain.
Reference: Haldeman S, Carroll L, Cassidy JD, et al. The Bone and Joint Decade 2000-2010 Task Force on Neck Pain and its associated disorders: executive summary. Spine. 2008(Feb);33(4 Suppl):S5-S7.
 Download the full text PDF of the Executive Summary at:
http://www.spinejournal.com/pt/re/spine/pdfhandler.00007632-200802151-00004.pdf;jsessionid=LQqpKGhn244vQsnmRSZwMWzJVFFhnF2hfJnpyTvmz6t61LLSRX48!-1809387994!181195628!8091!-1 (access checked 6/13/08).
The complete Spine supplement table of contents can be reviewed at (subscription required to access full articles):
http://www.spinejournal.com/pt/re/spine/toc.00007632-200802151-00000.htm;jsessionid=LQqpKGhn244vQsnmRSZwMWzJVFFhnF2hfJnpyTvmz6t61LLSRX48!-1809387994!181195628!8091!-1 (access checked 6/13/08).
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Pregabalin Offers Long-Term Relief of Painful Neuropathy
Researchers from Beth Israel Deaconess Medical Center, Boston, MA, reporting at the 2008 American Diabetes Association Scientific Sessions, presented the results of 7 long-term open-label studies of pregabalin (Lyrica®) in patients with painful diabetic neuropathy. Patients (n=1426) were allowed to adjust the pregabalin dose between 150 mg/day and 600 mg/day based on response to treatment and drug tolerability. Pain levels were evaluated quarterly on a 100-mm visual analogue scale (VAS). At baseline, the mean pain VAS (patients = 1321) was 60.5.
About 40% of patients took 300-449 mg/day pregabalin and 32% took 600 mg/day. At 12 weeks, the mean pain VAS scores had dropped to 30.6 and remained stable until the 2-year endpoint. Therapy-related adverse effects were mild to moderate in intensity and consistent with previous reports in short-term studies.
Clinical Implications: Previous reports noted efficacy and safety data from trials that lasted from only 5 to 13 weeks, while the results of this study demonstrated sustained pain-relief throughout a period of 2 years. Additionally, in a related news story (Doctor’s Guide), the lead author Roy Freeman, MD, concludes that “pregabalin offers effective maintenance therapy without clinically meaningful dosage increases” and no clinically significant changes in hemoglobin A1C levels.
Reference: Freeman R, D’Urso-Decruz E, Murphy TK, et al. Long-term safety and efficacy of pregabalin as treatment of painful diabetic neuropathy (DPN): findings from open-label extension studies. American Diabetes Association 68th Scientific Sessions. June 6-10, 2008. San Francisco, CA. Abstract #507-P.
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Duloxetine Effective for OA Knee Pain; Research Report
New data presented at the annual congress of the European League Against Rheumatism in Paris reported that patients with osteoarthritis pain of the knee treated with 60 mg and 120 mg of duloxetine (Cymbalta®) once daily experienced significant pain reduction. In this randomized, controlled study, 111 patients received 60 mg per day of duloxetine and 120 received placebo. At week seven, those receiving active treatment were re- randomized to either 60 mg duloxetine or 120 mg duloxetine per day, and both dosage groups were combined in overall analyses.
Compared with placebo, patients taking duloxetine reported significant pain improvement within the first week of treatment that lasted throughout the 13-week trial. Treatment with duloxetine also was associated with improved patient outcomes compared with placebo as measured by the Patient Global Impressions of Improvement (PGI-I) and physical functioning as measured by the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) physical functioning subscale. A total of 22 patients (9.5%) discontinued the trial due to adverse events, most commonly nausea, fatigue, somnolence, dizziness, hypertension, constipation, and decreased libido.
Practice Pointer: According to Amy Chappell, M.D., lead author of the study, “these data are important because it's the first time duloxetine has been studied in a large, placebo-controlled trial in what's classified as an inflammatory disease state. Although the exact mechanism of action is unknown, this study may provide important insights into the treatment of pain in the central nervous system." Duloxetine is a serotonin and norepinephrine reuptake inhibitor currently approved for major depressive disorder and generalized anxiety disorder, and to manage diabetic peripheral neuropathic pain.
Source: Medical News Today, June 14, 2008.
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Gender Biases in Cancer-Pain Relief Found
Researchers in Tampa, Florida, evaluated gender differences in pain severity and adequacy of cancer pain management. In addition to a review of their patient records, 131 patients referred to a multidisciplinary cancer pain clinic were asked to complete a Brief Pain Inventory Short Form.
An analysis showed no differences in the previous week’s worst pain ratings between male and female patients. However, the records showed that women were less likely to have been prescribed high potency opioids by their primary oncology team. Additionally, they were significantly more likely to report inadequate pain management based on Pain Management Index scores.
Clinical Implications: The results of this study suggest a gender bias in the treatment of cancer pain, but there are many potential reasons for the differences. Additional studies could serve to substantiate these differences, further identify the prevalence rates, identify the underlying causes of such differences, and identify interventions that would reduce disparities.
Reference: Donovan KA, Taliaferro LA, Brock CW, et al. Sex differences in the adequacy of pain management among patients referred to a multidisciplinary cancer pain clinic. J Pain Symptom Manage. 2008 (Apr 3); Early online publication prior to print.
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Headache Sufferers May Need Evaluation for TMD
Headache is frequently one of the most debilitating symptoms of temporomandibular disorders (TMD). However, researchers at the University of Copenhagen, Denmark, evaluated the prevalence of TMD in patients referred to a single specialty headache practice. Patients (n=99) were classified according to the International Classification of Headache Disorders.
About 56% of patients in this headache population were diagnosed with TMD and, while there were no significant differences between headache groups, patients with combined migraine and tension-type headache demonstrated a higher prevalence of TMD. Psychosocial dysfunction caused by the TMD pain was evident in about 40% of patients and moderate to severe depression was experienced by almost 55%.
Clinical Implications: The researchers state that the results could suggest that combined migraine and tension-type headache may be a risk factor for TMD development. The overall findings highlight the need for a multidimensional approach in the examination of chronic headache patients. Patients with headache diagnosis may need a TMD evaluation and patients with co-existing headache and TMD may need depression screening and treatment.
Reference: Ballegaard V, Thede-Schmidt-Hansen P, Svensson P, et al. Are headaches and temporomandibular disorders related? A blinded study. Cephalalgia. 2008(May 21); Early online publication prior to print.
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What is Consumer Reports Telling Patients About Opioids?
A Consumer Reports® booklet on opioids in pain management (23-pages) was released in April 2008. A sampling of recommendations include:
- “Don't take an opioid painkiller to treat chronic pain until you have tried other, less risky, pain relievers – such as acetaminophen, a non-steroidal anti-inflammatory drug (NSAID), or salsalate.”
- “Talk with your doctor about non-drug treatments as single or combination treatments.”
- When a stronger medication is needed, Consumer Reports recommends the following generic drugs as “Best Buys” and advises against brand-name formulations: codeine plus acetaminophen; morphine extended release; oxycodone extended release; oxycodone with acetaminophen.
The booklet includes a section on “opioid problems” as well as a caution to consumers that “there are no hard and fast medical rules about the appropriate use of opioids in treating chronic pain.” Additional problems such as side effects, addiction, abuse, tolerance, and overdose are explained in easy-to-understand language. Helpful sections include: 1) an explanation of terms such as short-acting, long-acting, and fast-acting opioid formulations, 2) an extensive table of opioids that includes trade names, average daily dose, and costs, and 3) a chart that provides remedies for common types of pain.
[Commentary: Healthcare providers may want to review this publication as one example of the pain management advice that is being offered to consumers. Recommendations and cautions from consumer sources such as this could conflict with the advice and prescribed therapies of practitioners; hence, negatively affecting patient acceptance and compliance. Mention of this publication here does not imply approval or endorsement of it by Pain Treatment Topics. – SBL, WD]
Download Consumer Reports Best Buy Drugs™ – “Treating Chronic Pain: The Opioids” at: :
http://www.consumerreports.org/health/resources/pdf/best-buy-drugs/OpioidsFINAL-April2008.pdf (access checked 6/14/08).
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Recent Drug or Device Approvals and Announcements
Following are briefs on new pain-management drug or device approvals or announcements, as well as items related to safety concerns for existing products. If the FDA or DEA news websites posted a specific announcement, the link to it has been provided below. All brand names are registered trademarks of their respective manufacturers.
Additionally, the FDA Center for Drug Evaluation and Research website offers the option to search on any approved drug name or active ingredient at http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm, and safety information is posted by FDA’s MedWatch at http://www.fda.gov/medwatch/safety/2006/safety06.htm.
Relistor™ (methylnaltrexone bromide) – FDA Approval to Treat Constipation
In April, the FDA approved Relistor as the first drug for the treatment of opioid-induced constipation. Two phase 3 placebo-controlled clinical trials established the efficacy and safety profile of this medication that stops opioids from interfering with bowel movements without compromising pain relief. Relistor, administered by subcutaneous injection, will be beneficial to adult patients in palliative care who experience severe constipation associated with the continuous use of pain-relieving morphine or other opioids. The manufacturers, Wyeth Pharmaceuticals Inc. and Progenics Pharmaceuticals, are also developing the drug in oral and intravenous formulations.
For more information, see the FDA press release at:
http://www.fda.gov/bbs/topics/NEWS/2008/NEW01826.html (access checked 6/3/08).
Relistor prescribing information can be downloaded at:
http://www.wyeth.com/content/showlabeling.asp?id=499 (access checked 6/3/08).
Treximet™ (sumatriptan and naproxen sodium) – Newly Approved Migraine Drug
The FDA granted an April 2008 approval of Treximet, a formulation containing 500 mg of the anti-inflammatory pain-reliever naproxen and 85 mg of the migraine medication sumatriptan (the active ingredient in Imitrex®). The approval came after 2900 migraineurs in 2 placebo-controlled trials experienced more pain relief at 2 and 4 hours post-therapy from the combination product than with either of the 2 drugs or placebo alone. Tablets will be available in 25 mg, 50 mg, and 100 mg strengths.
Treximet prescribing information can be downloaded at:
http://us.gsk.com/products/assets/us_treximet.pdf (access checked 6/4/08).
Morphine Sulfate 60 mg – Extended Release Tablets Recalled
Ethex Corporation has voluntarily recalled a single lot (# 91762) of morphine sulfate 60 mg extended-release tablets following a report of a double-thickness tablet. An oversized tablet may contain up to 2 times the active labeled dose and the consequences of an overdose of opioids, like morphine, can result in respiratory depression, low blood pressure, and other life-threatening events. It is important to note that many patients taking morphine for pain relief may be debilitated or otherwise unable to identify a change in the tablet’s size. Consumers should be encouraged to double-check their product and see their pharmacist or other healthcare provider with questions.
Read the FDA notice at:
http://www.fda.gov/oc/po/firmrecalls/ethex06_08.html (access checked 6/10/08).
Tumor Necrosis Factor (TNF) Blockers – Early Warning of Possible Cancer Association
In June 2008, The FDA issued an “Early Communication” about an ongoing safety review regarding a possible association between the use of TNF blockers and the development of lymphoma and other cancers in children and young adults. The Adverse Event Reporting System reported 30 cases of cancer during a 10-year period in children and young adults who began taking TNF blockers at age 18 or younger for the symptoms of juvenile idiopathic arthritis or Crohn’s disease. Long-term studies are needed to definitively determine whether TNF blockers increase the occurrence of cancers in children – half of reported cases were lymphomas, including Hodgkin’s and non-Hodgkin’s lymphomas.
For more information, see the FDA press release at:
http://www.fda.gov/cder/drug/early_comm/TNF_blockers.htm (access checked 6/4/08).
Amitiza® (lubiprostone) – Approved for Irritable Bowel Syndrome with Constipation
In April 2008, the FDA approved Amitiza, the first prescription drug therapy for irritable bowel syndrome with constipation (IBS-C) in adult women. IBS affects twice the number of women as men and can be a disabling disorder due to symptoms of severe cramping, abdominal pain, bloating, constipation, and diarrhea. The treatment does not yet have approval for men or children. Two efficacy and safety studies of 1154 patients diagnosed with IBS-C demonstrated that Amitiza relieved symptoms moderately or significantly during a 12-week treatment period in more treated patients than those receiving placebo. Amitiza dosing is 8 mcg taken twice daily with food and water. Patients should be assessed by healthcare professionals periodically to evaluated the need for continued treatment.
For more information, see the FDA press release at:
http://www.fda.gov/bbs/topics/NEWS/2008/NEW01828.html (access checked 6/12/08).
Amitiza prescribing information can be downloaded at:
http://www.sucampo.com/downloads/amitiza-pi-2007-06.pdf (access checked 6/12/08).
Orencia® (abatacept) – FDA Approval for Juvenile Idiopathic Arthritis
Orencia – a synthetic protein administered as a 30-minute intravenous infusion – was approved for pediatric patients in April 2008. The drug is specifically indicated for reducing the signs and symptoms of moderate to severe polyarticular juvenile idiopathic arthritis (JIA) in pediatric patients aged 6-17 years. Common symptoms include chronic pain, stiffness, and swelling of joints. The Orencia efficacy and safety profile in JIA was established in the 1-year, 3-part AWAKEN study. Dosing is based on the child’s weight and is designed to be administered at 2 and 4 weeks following an initial infusion, and subsequently every 4 weeks. The drug can be used as monotherapy or concomitantly with methotrexate, but should not be administered concomitantly with tumor necrosis factor (TNF) antagonists. Additionally, administration is not recommended with other types of biologic rheumatoid arthritis therapy, like anakinra.
Orencia information is available at:
http://www.orencia.com/ (access checked 6/14/08).
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