September-October 2006; Issue 5

Physicians Lacking Knowledge of Opioid Prescribing
Extended-Release Opioids for Chronic Pain Reviewed
Opioids for Chronic Non-Cancer Pain: Effectiveness Questioned
Plantar Fascia Tissue-Stretching Reduces Pain
Migraine With Aura Increases Cardiovascular Risk
Rizatriptan Provides Faster Migraine Relief
Physical Therapy & Exercise Help Long-Term Whiplash Pain
Arthritis Self-Management Program Shows Minimal Benefits
Pain Not Diminished in Patients With Alzheimer’s Disease
Tramadol Effective For Neuropathic Pain
Music Reduces Postsurgical Pain & Confusion in Older Adults
Magnets Ineffective for Postsurgical Pain
Cartoons Reduce the Pain of a Pediatric Blood Draw
EMLA® Topical Cream Reduces Intramuscular Injection Pain
Two JAMA Reviews Examine Cox-2 Risks
Recent Drug Approvals and Announcements

This edition of News/Research Updates was researched/compiled by Winnie Dawson, MA, RN, BSN, and edited by Stewart B. Leavitt, MA, PhD. Medical reviewers were: James D. Toombs, MD; Paul W. Lofholm, PharmD, FACA. Posting Date: October 26, 2006.

Physicians Lacking Knowledge of Opioid Prescribing

More than half (57%) of surveyed physicians rated their knowledge of opioid analgesics as either poor or fair; only 8% believed their knowledge was excellent. Furthermore, a quarter of the 216 physicians participating in the survey by Marla Zimbal and colleagues at the University of Wisconsin School of Medicine and Public Health said they had received no formal training in pain management, and only 7.5% of all respondents had received such education in medical school.

Although prescription of opioid analgesics is often first line treatment for moderate to severe chronic noncancer pain, only about half (53%) of physicians recognized that this is sanctioned by national guidelines and is lawful practice. Additionally, only about 12% thought is was legal and acceptable to prescribe opioids in patients with a history of substance abuse, although federal law allows this practice and experts note that such patients can be successfully treated with opioids when appropriate safeguards are in place. More than 4 in 10 reported they did not know that methadone could be legally prescribed by them for pain.

Clinical Concepts: Among those survey respondents who did prescribe opioids, concerns regarding regulatory scrutiny played an important role in their prescribing decisions, which might also have incurred inadequate analgesia. About 1 in 5 (21%) noted they at least occasionally prescribed a lower opioid dose and 39% said they prescribed a lower-schedule, less potent drug than they otherwise would due to fears of potential censor. Results from this survey are similar to previous investigations of this topic, and suggest that many physicians need better education regarding pain management and acceptable prescribing practices, as well as more awareness of current regulations governing opioid analgesic prescribing.

Reference: Reported by Crespi-Lofton J. Many physicians remain uninformed about opioids. Pharmacy Today. 2006;12(9):31.

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Extended-Release Opioids for Chronic Pain Reviewed

A thorough review examined the clinical pharmacology of investigational and currently marketed oral extended-release (ER) opioids. Current ER opioids include morphine and oxycodone, one was removed from the market (ER hydromorphone), and the development of new ER preparations are underway for codeine, oxymorphone, and tramadol.

Data from well-controlled clinical trials employing a variety of ER opioids demonstrate their efficacy in patients with a variety of chronic painful states, including osteoarthritis, chronic lower back pain, and postherpetic neuralgia. Diabetic neuropathy and other painful neuropathic conditions, previously thought to be resistant to opioid therapy, have been successfully treated with chronic ER opioids.

Recent experience with oxycodone ER suggests that such formulations have the potential to be abused. Also, when the timed-release mechanism of such formulations is defeated, the entire 12- or 24-hr dose of the opioid may be released, which presents increased risks. Recreational drug users are probably the most vulnerable population, as they are likely to be opioid naive and, therefore, more prone to life-threatening opioid toxicity.

Clinical concerns arose with encapsulated spheroid formulations of ER opioids being ingested with alcohol, which resulted in potentially harmful ‘dose dumping’ (rapidly excessive release of opioid). Palladone® (ER hydromorphone) capsules, introduced in the U.S. in 2004, were removed from marketing in 2005. Similar other formulations may be vulnerable, and Avinza® (ER morphine) is currently under examination in this regard, according to the authors.

[Clinical Comment: Fairly recently, extended-release formulations of oxymorphone (Opana®) and tramadol were FDA-approved for marketing. It is critical that healthcare providers regularly monitor their patients taking ER opioids for signs of adequate pain relief, adverse effects, and any suggestion of opioid misuse or abuse. Furthermore, as a general rule, patients should be cautioned against alcohol consumption while taking these medications. – SB Leavitt, MA, PhD.]

Reference: Sloan P, Babul N. Extended-release opioids for the management of chronic non-malignant pain. Expert Opin Drug Deliv. 2006(Jul);3(4):489-497.

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Opioids for Chronic Non-Cancer Pain: Effectiveness Questioned

Researchers in Copenhagen, Denmark evaluated the long-term effects of opioids on pain relief, quality of life, and functional capacity in patients with chronic non-cancer pain. The study of was based on data from the 2000 Danish Health and Morbidity Survey and included 10,066 persons (cancer patients were excluded).

An interview and self-administered questionnaire included questions on chronic/long-lasting pain (>6 months duration), health-related quality of life, use of the health care system, functional capabilities, satisfaction with medical pain treatment, and regular or continuous use of medications. Participants reporting pain were divided into opioid and non-opioid users. The analyses were adjusted for age, gender, concomitant use of anxiolytics and antidepressants, and pain intensity.

Chronic pain was significantly associated with female gender, age >45 years, living alone (being divorced, separated, or widowed), lower educational level, and poor self-perceived health. Opioid usage was significantly correlated with the reporting of moderate/severe or very severe pain, poor self-rated health, being unemployed, higher use of the health care system, and a negative influence on quality of life.

The researchers were surprised to find that opioid treatment of long-term/chronic non-cancer pain did not appear to achieve key outcome goals of pain management: pain relief, improved quality of life, and improved functional capacity. However, they did not report on alternate approaches used by those persons with chronic pain who avoided opioids. In those who did use opioids, they did not assess the types of chronic pain involved, or the specific opioids prescribed and the adequacy of their dosage.

[Clinical Comments: The researchers stressed that, because of the cross-sectional nature of their epidemiological study and the various limitations, causative relationships cannot be ascertained. That is, it cannot be assumed that prescribed opioid use itself was responsible for the lack of expected improvements. At the same time, this study might serve as a reminder that chronic pain can be multifactorial and may require multimodal therapies for its management. The administration of opioid medications as monotherapy may be insufficient in many cases to achieve desired or expected gains in pain relief, quality of life, and functionality. – SB Leavitt, MA, PhD.]

Reference: Eriksen J, Sjogren P, Bruera E, Ekholm O, Rasmussen NK. Critical issues on opioids in chronic non-cancer pain: an epidemiological study. Pain. 2006;125:172-179.

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Plantar Fascia Tissue-Stretching Reduces Pain

Plantar fasciitis, a common cause of foot pain, is an inflammation of the flat band of tissue that supports the arch and connects the heel bone to the toes. A 2-year study published in the August issue of the Journal of Bone and Joint Surgery evaluated long-term outcomes of a fascia-stretching protocol to decrease the pain and disability of plantar fasciitis.

A special exercise technique designed to stretch the affected plantar fascia (see Figure) was compared with a previous Achilles tendon-stretching protocol. Patients were instructed to perform the plantar fascia-stretching exercises 3 times each day for 8 weeks and as pain demanded thereafter, and were also encouraged to use shoe insoles that had previously been provided.

At the 2-year endpoint, a follow-up evaluation was completed by 66 patients. Almost 95% of patients reported a decrease in pain and more than 75% indicated that they did not have any limitation in recreational activities. Ninety-two percent of participants were generally satisfied with results of the plantar fascia tissue-stretching approach.

Clinical Implications: The authors note that the plantar fascia tissue-stretching exercise could be an important complement to the treatment of plantar fascia pain and disability. It is easy to teach, noninvasive, and appears to provide significant improvement in many patients as early as 8 weeks.

Source: DiGiovanni BF, Nawoczenski DA, Malay DP, et al. Plantar fascia-specific stretching exercise improves outcomes in patients with chronic plantar fasciitis. A prospective clinical trial with two-year follow-up. J Bone Joint Surg Am. 2006(Aug);88-A(8):1775-1781.

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Migraine With Aura Increases Cardiovascular Risk

Research has shown that an increased risk of stroke is linked to patients who have a history of migraine headache with aura. Aura symptoms with migraine are less common than migraine without aura, and include: visual disturbances like blurred vision, blind spots, and flashes or lines of light just before or during the migraine. Using data from the Women’s Health Study, which followed almost 28,000 women aged 45 years and older for 10 years, this study evaluated the prevalence of subsequent cardiovascular disease (CVD) in 5125 patients who had reported any history of migraine symptoms at baseline.

During the 10-year follow-up period, 580 major first-time cardiovascular events were reported; defined as nonfatal ischemic stroke, nonfatal myocardial infarction, or death caused by an ischemic cardiovascular cause. An additional 514 coronary revascularizations, including coronary artery bypass graft or percutaneous coronary angioplasty, were reported and there were 408 anginal events. When compared with women without a history of migraine, risks for women migraineurs with aura ranged from a 1.7-fold increase for coronary revascularization or angina to a 2.3-fold increase for death due to CVD.

The women who had reported migraine without aura at baseline did not show any increased risk of cardiovascular disease over women without a history of migraine.

[Clinical Perspectives: In an editorial published in the same issue of JAMA (noted below; p. 332), Richard Lipton, MD, suggests that one explanation for the increased risk of cardiovascular disease in migraineurs with aura may involve a genetic predisposition to moderately increased homocysteine levels, also associated with increased risks of CVD. He also recommends future studies to help identify preventive medications or therapy that could reduce the CVD risk. Healthcare providers should be vigilant for cardiovascular risk factors in patients with migraine with aura, and modifiable factors should be addressed with the patient. Migraineurs without aura might be reassured that their risk of cardiovascular disease may be roughly equal to patients with no history of migraine. – W Dawson, MA, RN, BSN.]

Source: Kurth T, Gaziano JM, Cook NR, et al. Migraine and risk of cardiovascular disease in women. JAMA. 2006(Jul);296(3):283-291.

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Rizatriptan Provides Faster Migraine Relief

Migraine headache pain is well-known for impairing work productivity and reducing quality of life for sufferers. Effective treatment includes rapid reduction in pain and, ultimately, freedom from pain. A recent multicenter open-label study, published in Clinical Therapeutics, evaluated the effectiveness of rizatriptan in 1489 patients during 2 consecutive migraine attacks. Participants were instructed to take 10 mg of rizatriptan or their usual-care medications in a crossover fashion beginning with their first migraine attack and were given a study kit containing procedural information, the study drug, and a stopwatch. The most common usual-care medications were other oral triptans (80%), while NSAIDs (5%), butalbital-containing compounds (4%), and isometheptene (3%) were used less often.

Compared with usual-care therapy, onset of pain relief was 22 minutes faster and pain freedom was achieved 76 minutes faster with rizatriptan. At the 2 hour point, rizatriptan users were twice as likely to be pain free. In addition, significant differences in pain relief were noted as early as 15 minutes after the initial rizatriptan dose. The need for rescue medications was lower with rizatriptan use (9%) than with the usual-care treatment (12%), and the number of patients using a single dose of rizatriptan was significantly greater than the number of patients who used a single dose of their usual-care medication. Overall satisfaction with rizatriptan was almost 65% compared with nearly 58% for patients using their usual-care treatments.

[Clinical Comment: This study highlights differences in treatment results and can be useful in guiding treatment decisions for patients who experience significant periods of disability. Because some patients failed to be pain-free at the 24 hour endpoint (3.8% for rizatriptan vs 5.9% for usual-care treatments), the authors suggest that patients with intractable headaches may require a different treatment strategy. – W Dawson, MA, RN, BSN.]

Reference: Bell CF, Foley KA, Barlas S, et al. Time to pain freedom and onset of pain relief with rizatriptan 10 mg and prescription usual-care oral medications in the acute treatment of migraine headaches: a multicenter, prospective, open-label, two-attack, crossover study. Clinical Therapeutics. 2006(Jun);28(6):872-880.

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Physical Therapy & Exercise Help Long-Term Whiplash Pain

The pain of whiplash-associated disorders is a challenge to clinicians and patients alike. Frequently, patients are treated with a conservative regimen of analgesics, such as non-steroidal anti-inflammatory medications, muscle relaxants, and a soft cervical collar for up to 3 weeks (NINDS). Recent studies, such as the 2 below, demonstrate the positive long-term effects of active exercise:

• Patients with whiplash injury (n = 200) were seen in the trauma department of a major European hospital and assigned to one of two treatment groups in a prospective randomized controlled study (Vassiliou et al, 2006). Participants in the standard group were given 2 treatment medications and a soft collar to wear continuously for 7 days. The physical therapy group patients received 10 physical therapy appointments within the first 14 days of program enrollment, which included heat application, lymph drainage, neck massage, and instructions for performing active exercises with resistance bands. While differences in mean pain intensity were insignificant at the 7-day evaluation point, the physical therapy group scored significantly lower in pain intensity score compared with the standard group at the 6-week point. At 6 months, the physical therapy group’s mean pain intensity score was approximately half that of the standard group.
• A Swedish study of 102 consecutive patients with whiplash trauma who presented to 29 healthcare facilities were randomized to 1 of 4 interventions: a) active involvement within 96 hours, b) standard intervention within 96 hours, c) active involvement with a 14-day delay, and d) standard intervention with a 14-day delay (Rosenfeld et al, 2006). The active-involvement intervention included an initial phase of postural control and neck exercises, then progressed to an active exercise protocol based on the McKenzie System for patients whose symptoms were unresolved in the first phase. The standard intervention consisted of patient education and postural correction. Results demonstrated a significant reduction in pain and cost-benefit ratio for the active involvement group when compared with standard interventions even though the cost of healthcare alone was higher in the active involvement group.

Clinical Perspective: Investigators in the Vassiliou et al. study speculated that active exercises and physical therapy reduce pathophysiological postures following injury and facilitate the restoration of the normal functional cervical spine.

For information, see:

NINDS Whiplash Information Page. Available at: http://www.ninds.nih.gov/disorders/whiplash/whiplash.htm.  Access checked 10/10/06.

Rosenfeld M, Seferiadis A, Gunnarsson R. Active involvement and intervention in patients exposed to whiplash trauma in automobile crashes reduces costs: a randomized, controlled clinical trial and health economic evaluation. Spine. 2006(Jul);31(16):1799-1804.

Vassiliou T, Kaluza G, Putzke C, et al. Physical therapy and active exercises—an adequate treatment for prevention of late whiplash syndrome? Randomized controlled trial in 200 patients. Pain. 2006(Sep);124(1-2):69-76.

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Arthritis Self-Management Program Shows Minimal Benefits

Osteoarthritis is a common disease that can lead to chronic disability, pain, and reduced quality of life. A randomized, controlled study was designed to evaluate the effectiveness of a self-management program in patients being treated in a primary care environment. Patients 50 years of age and older (n = 812) were randomized to an intervention that included 6 sessions of an arthritis self-management course and an educational booklet, or to a control group that received only the educational booklet.

Using an ‘arthritis self-efficacy scale’ assessment, results showed a significant benefit for the intervention group in sub-scores of anxiety, pain, and ‘other.’ However, the two groups were similar on all other measures and the intervention did not result in any differences in the number of visits to healthcare practitioners during the study period.

[Clinical Comment: This study demonstrated some temporary patient benefits in the areas of depression and ‘other’ self-efficacy, and longer-term benefits for anxiety and pain. Primarily, however, the study reinforces the potential of self-study programs to improve a patient’s internal locus of control and the perception that some personal resources are available for pain control. Healthcare providers can look for opportunities to educate patients with arthritis about individual choices that can make a difference in their pain management. For additional information on self-directed education for arthritis patients, see ‘How to Encourage Exercise in Arthritis Sufferers’ in Pain-Topics.org News/Research Updates (July-August 2006; Vol. 1, No. 4). – W Dawson, MA, RN, BSN.]

Source: Buszewicz M, Rait G, Griffin M, et al. Self management of arthritis in primary care: randomised controlled trial. BMJ. 2006(Oct);[epub ahead of print]: doi:10.1136/bmj.38965.375718.80.

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Pain Not Diminished in Patients With Alzheimer’s Disease

Prior research has proposed that people with Alzheimer’s disease experience less pain because of impaired brain function. This study published in the September issue of Brain compared 14 Alzheimer’s patients with 15 control participants to compare responses to pain. The brain responses of each participant were measured by functional MRI while receiving enough pressure stimulus to the thumbnail to elicit weak to moderate pain.

Results showed that pain perception is not diminished for patients with Alzheimer’s disease; conversely, MRI evidence demonstrated greater pain amplitude and duration in these patients when compared with controls. These results – which covered sensory, affective, and cognitive processing regions – were suggestive of a more sustained focus on the painful stimulus in patients with Alzheimer’s disease.

[Clinical Comment: Patients with Alzheimer’s disease are at a disadvantage when communicating their healthcare issues to clinicians. Such patients can be uncommunicative or appear confused, and the challenges of meeting their pain management needs can be complex. It is important to use appropriate assessment methods to identify the signs and symptoms of unrelieved pain to ensure effective analgesic treatment in this population. For an overview of pain assessment techniques in non-verbal patients, see ‘Pain Assessment in Non-verbal Patients,’ a position statement with clinical practice recommendations from the American Society for Pain Management Nursing, under the Pain-Topics.org Clinical Concepts tab at http://www.pain-topics.org/clinical_concepts/index.php.  Access checked 10/12/06. – W Dawson, MA, RN, BSN.]

Reference: Cole LJ, Farrell MJ, Duff EP, et al. Pain sensitivity and fMRI pain-related brain activity in Alzheimer’s disease. Brain. 2006(Sep);[epub ahead of print]: doi:10.1093/brain/awl228.

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Tramadol Effective For Neuropathic Pain

Neuropathic pain is a common cause of chronic noncancer pain and causes a dramatic reduction in quality of life for its victims. It can be difficult to treat and can cause symptoms of extreme numbness or tingling, burning or stabbing sensations, abnormal sensitivity to stimuli that would be typically painless, or an exaggerated pain response.

To assess the efficacy and safety of tramadol for the treatment of neuropathic pain, investigators conducted a Cochrane Systematic Review of the literature and identified 6 trials meeting inclusion criteria. Of these studies, 4 compared tramadol with placebo and the other 2 compared the drug with either clomipramine or morphine. However, the investigators failed to find sufficient data to provide valid results for the effectiveness of clomipramine or morphine.

Evidence from the 4 trials comparing tramadol with placebo in 338 patients showed that dosages between 100 and 400 mg were effective in treating the symptoms of peripheral neuropathic pain. Compared with placebo, approximately 25% more patients treated with tramadol – or 1 in 4 – will achieve a 50% or greater reduction in neuropathic pain (NNT=3.8 [95% CI, 2.8 – 6.3]). Pain relief for all trials was recorded between 4 and 7 weeks. Adverse effects of tramadol can include nausea, constipation, dizziness, sedation, and dry mouth; 3 trials provided data that, when combined, showed that 1 in 8 people discontinued tramadol therapy due to side effects.

Clinical Implications: The investigators conclude that tramadol is effective for neuropathic pain and state that evidence of abuse is extremely low and potential side effects are reversible with discontinuation of the drug. They further state that the efficacy of tramadol compares favorably with antidepressants and anticonvulsants, but further research is needed to compare these agents with tramadol as an adjuvant treatment. [Comment: In September the FDA approved for marketing an extended release (ER) formulation of tramadol. – Editor.]

Reference: Hollingshead J, Duhmke RM, Cornblath DR. Tramadol for neuropathic pain. Cochrane Database Syst Rev. 2006(Jul);3:CD003726.

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Music Reduces Postsurgical Pain & Confusion in Older Adults

The older adult needs to participate in a rehabilitation program following hip or knee surgery, and a cooperative patient whose pain is controlled will enhance restoration of functionality, tissue healing, and the prevention of complications. In this regard, a randomized, controlled study evaluated the effects of music on postoperative pain, cognition, ambulation, and patient satisfaction. Patients (n = 124) aged 65 years and older who were alert and well-oriented were randomly assigned to a standard postoperative room with or without a CD player.

For patients in the music intervention rooms, the first music session was a lullaby collection; all subsequent music selections were made by the patient and played 4 times daily for one hour. The 20 CDs available to patients included easy-listening orchestral and vocal music, or sounds of nature.

Pain was assessed on a numerical rating scale and by measuring the amount of postoperative pain medication administered to each patient. Patient levels of orientation were assessed by systematic nursing notations and ‘readiness to ambulate’ was scored on several factors by each patient’s physical therapist.

Results showed that the mean pain levels on a 1-to-10 scale for the music intervention (experimental) group from days 1 through 3 (7.8, 6.2, 4.6 respectively) compared favorably against control group pain scores (8.9, 8.2, 7.4). The experimental group had higher ‘readiness-to-ambulate’ scores and significantly greater daily ambulation distances. The overall patient satisfaction score of the music group also was significantly higher than that of the control group.

Practice Pointers: The authors suggest that these results support music as a pain reduction intervention for older adults undergoing hip or knee surgery. Music is a safe, effective, and inexpensive intervention that allows patients an additional measure of self-empowerment by choosing music they enjoy. While reducing the patient’s level of pain and confusion, healthcare providers can enhance the healing environment with music at times that suit the inpatient facility and schedules.

Reference: McCaffrey R, Locsin R. The effect of music on pain and acute confusion in older adults undergoing hip and knee surgery. Holist Nurs Pract. 2006(Sep-Oct);20(5):218-224.

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Magnets Ineffective for Postsurgical Pain

Magnets failed to provide pain relief after surgery for patients in a new study at a hospital in Bogota, Colombia. The study, presented in Chicago at the American Society of Anesthesiologists’ annual meeting, was conducted by M. Soledad Cepeda, MD, PhD, and colleagues. Cepeda's team investigated 165 patients at least 12 years old with moderate to severe pain after unspecified surgical procedures.

The researchers randomly placed a magnetic device or a sham device containing no magnets on the patients' surgical wounds. During the next 2 hours, patients rated their pain every 10 minutes and also received morphine doses to bring their pain intensity down to a score of 4 or less (0-10 point scale). The results showed equivalent pain intensity ratings and morphine requirements in both groups.

Conclusion: The researchers asserted that magnetic therapy "lacks efficacy" in controlling postsurgical pain and “should not be recommended for pain relief in this setting.” The study did not address magnet use for other types of pain.

Source: Magnets May Not Reduce Post-Surgery Pain. Presented at: American Society of Anesthesiologists’ 2006 Annual Meeting, Chicago, Oct. 14-18, 2006. News release reported via WebMD (Miranda Hitti).

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Cartoons Reduce the Pain of a Pediatric Blood Draw

Results showed that the pain ratings by children watching the cartoons were significantly lower than ratings from the other 2 groups and, in addition, were lower than the rating levels scored by the mothers of the TV watchers. The TV-watching children rated their pain at 8.91, while the mothers rated it at 12.17.

For the children whose mothers provided a distraction, the mothers scored 23.04 and the children scored the pain at 17.39. These scores were not significantly lower than for children without any distraction: mother and child ratings were 21.30 and 23.04, respectively.

[Comment: In a news interview, one of the study authors, Carlo Bellieni, MD, stated that these results do not suggest that the parents presence is not needed, but rather that the influence of the cartoons created an added benefit. He also suggested that the pleasure generated by watching entertainment might also stimulate natural pain-killing endorphins. While concerns over the power of television could be an issue for some parents, it may be an acceptable pediatric analgesic for short-term procedures in the medical office. – W Dawson, MA, RN, BSN.]

Reference: Bellieni CV, Cordelli DM, Raffaelli M, et al. Analgesic effect of TV watching during venipuncture. Arch Dis Child. 2006(Aug);[epub ahead of print]: doi:10.1136/adc.2006.097246.

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EMLA® Topical Cream Reduces Intramuscular Injection Pain

Treatment for conditions such as multiple sclerosis often includes frequent injections of therapeutic agents. This study was initiated to identify the effectiveness of EMLA® cream – Eutectic Mixture of Local Anesthetics; a topical analgesic containing lidocaine (2.5%) and prilocaine (2.5%) – in reducing the fear and pain of injection as a way to maintain treatment compliance. Pretreatment with EMLA cream, has been shown to reduce the pain of skin puncture, and this study endeavored to identify efficacy for pain reduction in deeper intramuscular injections.

A single-blind, placebo-controlled, crossover study enrolled 18 patients with multiple sclerosis who were randomized to use of either the EMLA cream or a placebo cream for weekly injections of an immunomodulatory agent for the first 4 consecutive weeks and, subsequently, to use the alternate cream for the second 4 weeks.

Using a 10-point visual analog scale (VAS), the participants rated ‘fear of injection’ before each injection and ‘pain of injection’ after the procedure. Results showed a preinjection/postinjection reduction in mean scores of 6.4 for the EMLA injections and 2.3 for the placebo cream. Regardless of the cream applied, however, all participants reported less fear and pain by the end of the study.

[Comment: The mix of emotions in patients with chronic illness who must receive regular injections is complex, and even more intense for those with injection-phobia. Healthcare providers must be alert for effective ways to help patients improve treatment compliance when possible. While the results of this study show that all participants reported less pain by the eighth injection, the greater reduction in EMLA VAS scores suggests that this is a viable pretreatment analgesic that could help improve treatment acceptance and adherence. – W Dawson, MA, RN, BSN.]

Reference: Buhse M. Efficacy of EMLA cream to reduce fear and pain associated with interferon beta-1a injection in patients with multiple sclerosis. J Neurosci Nurs. 2006(Aug);38(4):222-226.

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Two Reviews Examine Cox-2 Risks

Since the withdrawal of the selective cyclooxygenase 2 (Cox-2) inhibitor rofecoxib (VIOXX®) in 2004, clinicians and patients have been confused about safety issues related to that class of drugs. The October 4, 2006 issue of the Journal of the American Medical Association (JAMA) contained 2 review articles that further evaluated the risks of Cox-2 inhibitor products.

• In a systematic review of 2 bibliographic databases, Medline and Embase, 114 randomized double-blind clinical trials were selected for quantitative evaluation of renal and proarrhythmic events (Zhang et al, 2006). Six drugs were reviewed for adverse effects individually and by drug class, to identify evidence of a class effect. Collectively, data from more 116,000 participants demonstrated a total of 6394 renal events and 286 arrhythmia events.
  
  When compared with controls, rofecoxib demonstrated a significantly increased relative risk for arrhythmia (RR 2.90, 95% CI, 1.07-7.88), while other Cox-2 inhibitors were not associated with a significant increase in risk. Rofecoxib was positively associated with an increase in relative risk for renal events; namely, renal dysfunction (RR 2.31, 95% CI, 1.05-5.07), hypertension (RR 1.55, 95% CI, 1.29-1.85), and peripheral edema (RR 1.43, 95% CI, 1.23-1.66). These risks were escalated by increase in dose and duration of treatment. In this analysis, none of the other Cox-2 inhibitors were associated with renal effects or arrhythmias, and celecoxib showed a decrease in risk for renal dysfunction and hypertension when compared with controls. Thus, there was no evidence for a class Cox-2 inhibitor effect.
  
  
• Another systematic review included 13 investigations of Cox-2 inhibitors, 23 studies of patients on NSAIDs, and 13 trials reporting on both groups of drugs (McGettigan et al, 2006). The analysis showed a dose-related increase in cardiovascular risk for rofecoxib, including use during the first 30 days of treatment. At 25 mg/day or less of rofecoxib, the RR summary value was 1.33 (95% CI, 1.00-1.79), while at total doses greater than 25 mg/day the RR increased to 2.19 (95% CI, 1.64-2.91).
  
  This analysis did not demonstrate an increased risk for celecoxib at doses of approximately 200 mg/day, although the results were not conclusive at higher doses. Diclofenac had a summary RR of 1.40 (95% CI, 1.16-1.70), but other drugs did not show a significant increase in risk.

Sources:

McGettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase. A systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase 2. JAMA. 2006(Oct);296(13):1633-1644.

Zhang J, Ding EL, Song Y. Adverse effects of cyclooxygenase 2 inhibitors on renal and arrhythmia events. A meta-analysis of randomized trials. JAMA. 2006(Oct);296(13):1619-1632.

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Recent Drug Approvals and Announcements

Following are briefs on new pain-management drug approvals as well as items related to safety concerns for existing products. If the FDA news website 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.

Fentora™: New Fentanyl Buccal Tablet for Cancer Breakthrough Pain
This new formulation of the opioid fentanyl was approved by the FDA in September and will be available in 5 tablet strengths (100, 200, 400, 600, and 800 mcg). The tablet uses Cephalon’s proprietary OraVescent® drug-delivery system which monitors and reacts to salivary pH changes to optimize the delivery of the drug. Fentora is intended to treat cancer breakthrough pain in opioid-tolerant patients who are already receiving opioid therapy.

Ibuprofen Can Reduce Cardioprotection of Low-dose Aspirin
For patients on low-dose aspirin (81 mg per day), the concomitant use of ibuprofen can potentially reduce the anti-platelet cardioprotective effect of aspirin. Current data suggests that the interactive effect occurs with the concurrent administration of 400 mg of ibuprofen and 81 mg of aspirin; therefore, the FDA recommends taking the ibuprofen 8 hours before or 30 minutes after an immediate-release formulation aspirin tablet. The FDA also states that it does not have information regarding the effects of interaction for ibuprofen dosing above or below the 400mg dosage.

Once-Daily Tramadol for Moderate to Severe Chronic Pain
In September 2006, the FDA approved an extended-release formulation of tramadol HCl (brand name undisclosed, made by Biovail Technologies, Inc.) for use in adults with chronic moderate to moderately severe pain requiring around-the-clock therapy for an extended time. According to a company news release, market launch of the once-daily product is expected in early 2006 and will include 100-, 200-, and 300-mg dose strengths.

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