 September-October 2007; Issue 11
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; Paul W. Lofholm, PharmD, FACA; Seth I. Kaufman, MD; Steven Tucker, MD, FACP. Posting Date: October 23, 2007.
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 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.
Sleep Apnea Concerns With Methadone & Other Opioids
Investigators in Utah assessed the relationship between chronic pain medications and sleep apnea. In an observational study, 147 patients with chronic pain and on stable doses of 24-hour opioid therapy for a minimum of 6 months received overnight polysomnographic assessments. The apnea-hypopnea index (AHI) was the outcome measure to determine overall severity of sleep apnea (including sleep disruptions and decreases in oxygen saturation), and the central apnea index evaluated breathing pauses of >10 seconds.
In three-quarters (75%) of 140 patients with available data the AHI was abnormal (defined as >/= 5 sleep disruptions per hour) while 25% had no evidence of sleep apnea. Almost 40% of participants had obstructive sleep apnea (caused by a collapse of upper airways), 24% had central sleep apnea (caused by faulty brain control), 8% had both central and obstructive sleep apnea, and 4% had apnea of an indeterminate type.
One third of the patients were taking methadone (range 19 - 1500 mg/d). A significant relationship between the AHI and daily dosage of methadone was identified (p = 0.002). Additionally, a direct dose-response relationship was found between the central apnea index and methadone (p = 0.008) and also with benzodiazepines (p = 0.004).
Practice Perspective: In a related news story (Science Daily), the researchers reported that these results showed a higher than expected prevalence of sleep-disordered breathing in this population of chronic pain patients taking opioids. Furthermore, the dose-response relationship of methadone to sleep apnea demonstrated in this study, plus recent reports of fatal respiratory depression associated with methadone use, suggest the need for increased vigilance in patients prescribed this analgesic.
[Comment: A brief questionnaire for patients, to assess risk for obstructive sleep apnea, is available from the American Sleep Apnea Association at: http://www.sleepapnea.org/resources/pubs/snorescoreform.pdf. Accessed 10/22/07. -SBL]
Reference: Webster L, Choi Y, Desai H, et al. Sleep-disordered breathing and chronic opioid therapy. Pain Medicine. 2007. Early online publication prior to print — doi:10.1111/j.1526-4637.2007.00343.x.
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Long-Term Opioid Analgesics May Not Impair Driving
Despite warnings, long-term use of opioid pain medication may not impair a person's ability to drive safely, a US study found. Asokumar Buvanendran of Rush University Medical Center in Chicago compared two groups of patients: 51 chronically receiving oral morphine and 49 controls receiving no pain medication. Each study participant drove for approximately 12 minutes in a driving simulator that measured deviation from the center of the road, weaving, the number of accidents, and reaction time to surprise events.
The study found the amount of weaving was 3.83 feet for both sets of drivers, and the opioid group had 5.33 collisions compared with the non-opioid group having 5.04 — considered no statistical difference. Reaction time also was similar for both groups.
Practice Implication: The study suggests that patients needing long-term opioid analgesics may "become tolerant" to the medication side-effects that potentially impair function, according to Buvanendran.
[Comment: This study investigated only one type of opioid, and there could be variable effects of type of opioid, dose, timing of dose, and concurrent medications. Clinicians might be advised to consider each patient on a case-by-case basis when it comes to assessing their ability to drive or operate machinery while taking medications of any type that could affect cognitive or motor skills. -SBL]
Reference: Reported in Science Daily, October 15, 2007 (from United Press International). The findings were to be presented at the American Society of Anesthesiologists annual meeting in San Francisco, October 13-17, 2007.
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Why Opioids May Not Help Fibromyalgia Pain
The management of fibromyalgia pain and discomfort has been challenging for clinicians and patients alike. New research from the University of Michigan may begin to explain why patients with fibromyalgia do not appear to achieve pain relief with opioid analgesics. Positron emission tomography (PET) studies were done on an equal number of gender and age-matched individuals — 17 fibromyalgia patients and 17 healthy controls — to compare the availability of mu-opioid receptors (MORs - high-affinity binding sites for opioid chemicals).
Results showed that fibromyalgia patients had a significantly reduced binding potential of MORs overall (p < 0.01) and in 4 specific regions of the brain that are known to modulate pain (p < 0.05). Additionally, participants with fibromyalgia had a higher number of depressive symptoms (p < 0.05) along with reductions in MOR binding potential in the amygdala — thought to be the brain’s modulator of mood and emotional dimensions in pain.
Clinical Concept: In a related news story (Doctor’s Guide News), lead author Richard Harris, PhD, stated that “reduced availability of the receptor was associated with greater pain among people with fibromyalgia.” He added that these results showing a lower availability of MORs would explain why opioids, which reduce pain by chemically binding to opioid receptors in the brain, may not be able to bind as well or as thoroughly in patients with fibromyalgia.
Reference: Harris RE, Clauw DJ, Scott DJ, et al. Decreased central mu-opioid receptor availability in fibromyalgia. J Neurosci. 2007(Sep);27(37):10000-10006.
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Zolmitriptan Nasal Spray Effective for Headache Relief
Two recent studies evaluated the efficacy and tolerability of zolmitriptan nasal spray in the treatment of acute headache conditions.
A study published in the August issue of Neurology (Rapoport et al. 2007) compared 5 mg and 10 mg doses of zolmitriptan nasal spray (ZNS) with placebo for the treatment of cluster headache. This multicenter, double-blind, crossover study randomized 52 adult patients to 1 of 3 regimens for a total of 151 separate headache episodes. The primary outcome measure was pain reduction response at 30 minutes. Study results showed that both ZNS doses achieved significant relief (10 mg = 63%, 5 mg = 50%) at 30 minutes, with only 30% of the placebo group reporting relief. At 15 minutes, 22% of ZNS 10 mg patients were pain free compared with 6% of those on placebo. Side effects were mild and no serious adverse events occurred during the study.
A multicenter, double-blind, placebo-controlled trial reported in the journal Pediatrics, in August 2007, recruited adolescent patients with migraine aged 12 to 17 years. Patients with an established diagnosis of migraine were initially administered placebo treatment alone in single-blind fashion; if headache relief was achieved at 15 minutes, no additional therapy was provided. Teens with continued moderate to severe migraine intensity were treated with 5 mg ZNS or placebo (based on a randomized, crossover schedule). The primary outcome measure was headache response at 1 hour post-treatment and an important secondary endpoint included sustained headache response at 2 hours. Significant pain relief was demonstrated 15 minutes after treatment with ZNS, and at 1 hour ZNS was associated with a higher rate of response compared with placebo (58% vs 43%). ZNS offered additional significant improvements compared with placebo: pain intensity, pain-free rates, sustained resolution of headache, return to normal activities, and less frequent use of escape medication. The most frequently reported adverse effect was taste disturbance.
Practice Pointer: Because adult cluster headache and adolescent migraine can both be severe and debilitating, ZNS may offer a safe, fast-acting, effective treatment alternative. Note: zolmitriptan nasal spray has been FDA-approved for migraine therapy but not for use in cluster headaches.
References:
Rapoport AM, Mathew NT, Silberstein SD, et al. Zolmitriptan nasal spray in the acute treatment of cluster headache: a double-blind study. Neurology. 2007(Aug);69(9):821-826.
Lewis DW, Winner P, Hershey AD, et al. Efficacy of zolmitriptan nasal spray in adolescent migraine. Pediatrics. 2007(Aug);120(2):390-396.
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Verapamil for Cluster Headaches Can Hinder Heart Function
Cluster headache is uncommon, episodic, and affects men more than women, but the pain can be excruciating and develop rapidly. There are few medications that have been effective for the acute attack and, preventively, the drug verapamil (a calcium-channel antagonist used to treat arrhythmias and hypertension) has been shown to be an effective off-label therapy. To evaluate safety, a British study audited the incidence of heart rhythm abnormalities in patients with cluster headache who took high dose verapamil.
Patients taking the drug (n = 217) were on a treatment protocol that started at 240 mg daily and increased in 80 mg increments every 2 weeks until the headaches stopped, adverse effects intervened, or a maximum daily dose of 960 mg was reached. One patient reported taking 1,200 mg/day. While patients were instructed to have an electrocardiogram (ECG) test to monitor heart activity, the audit showed that only 59% had an ECG.
Of the 108 patients who had ECGs, 19% had arrhythmias and 13% had first-degree heart block (on regimens of 240 to 960 mg verapamil per day). Nine additional patients had cardiac irregularities and 1 patient required a permanent pacemaker. A total of 36% had bradycardia, but only 4 patients experienced a severe enough rate reduction to require discontinuation of the drug.
Clinical Implications: In a related news story (Neuroscience News), Peter Goadsby, MD, one of the study’s authors, stated that it is important for physicians and patients to be aware of the need for regular ECGs when verapamil is prescribed. He recommends testing within 2 weeks of changing doses and every 6 months on maintenance dosing. Furthermore, he cautions that the benefit of verapamil’s ability to alleviate the pain of cluster headaches must be weighed against the risk of developing a heart rate abnormality.
Reference: Cohen AS, Matharu MS, Goadsby PJ. Electrocardiographic abnormalities in patients with cluster headache on verapamil therapy. Neurology. 2007;69(7):668-675.
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True or Sham Acupuncture Both Help Low Back Pain
Researchers in Germany recruited patients (n = 1162) with a history of chronic low back pain (mean = 8 years) from more than 300 patient practices to compare true (verum) acupuncture with sham acupuncture and conventional therapy. In a double-blind, controlled trial, patients were randomized to one of 3 groups: a) true acupuncture according to the principles of traditional Chinese medicine, b) sham acupuncture using superficial needling at nonacupuncture points, or c) conventional therapy. Both acupuncture groups had two 30-minute sessions per week and conventional treatment included a combination of drugs, physical therapy, and exercise. Up to 5 additional acupuncture sessions were offered to patients who had a partial response to treatment. Acupuncture groups were allowed to use nonsteroidal anti-inflammatory drugs for acute episodes of back pain on no more than 2 days per week during the treatment period.
Self-report questionnaires on pain and functional ability after 6 months were assessed and positive response was defined as a 33% improvement in pain or a 12% improvement in functional ability. In the true acupuncture group 47% reported a positive response rate, while 44% of participants in the sham acupuncture group reported improvement. Only 27% of the conventional therapy group met the response criteria. While the difference between the true vs. sham acupuncture was only about 3% (p = .39), the patients receiving sham and true acupuncture were nearly twice as likely to respond compared with those in the conventional group.
Practice Perspective: A related news story (Associated Press) noted that the study was not designed to identify how acupuncture works, but that findings are in line with the theory that pain messages to the brain can be blocked by competing stimuli. The study is reported to have influenced an expansion of acupuncture insurance coverage in Germany, but coverage for acupuncture therapy in the United States is somewhat inconsistent and may require pre-approval.
Reference: Haake M, Muller HH, Schade-Brittinger C, et al. German Acupuncture Trials (GERAC) for chronic low back pain: randomized, multicenter, blinded, parallel-group trial with 3 groups. Arch Intern Med. 2007(Sep 24);167(17):1892-1898.
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Magnets Ineffective for Pain Reduction
Surveys have indicated that static magnets (that is, permanent magnets with magnetic fields that do not change) have been marketed and used commonly among consumers to fight pain due to a variety of causes. Researchers in the United Kingdom performed a systematic review of the available literature and identified 9 placebo-controlled clinical trials for a meta-analysis. In each, the mean change in pain (measured on a 100 mm visual analog scale) was used to assess differences between the magnets and placebo. The analysis found no significant difference in pain reduction; the weighted mean difference was 2.1 mm (95% CI, -1.8 to 5.9 mm, p = 0.29).
Clinical Conclusion: The investigators concluded that there was no convincing evidence to support the use of static magnets for pain relief in the wide range of painful conditions studied. Although, the evidence did show some potential for pain relief in peripheral-joint osteoarthritis, and further investigation is recommended.
Reference: Pittler MH, Brown EM, Ernst E. Static magnets for reducing pain: systemic review and meta-analysis of randomized trials. Canadian Medical Association Journal. 2007(Sep);177(7):736-742.
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Spouse Affects Partner’s Response to Arthritis Pain
Patients with rheumatoid arthritis face many challenges in managing chronic pain, and previous studies have shown that one coping mechanism may involve catastrophizing — that is, pessimistically projecting an undesirable situation across many realms of life. A study from British Columbia examined factors that influence catastrophizing and its detrimental effects. Married individuals with rheumatoid arthritis (n = 69) were interviewed, then participated in twice-daily telephone interviews for a period of one week. The study examined the extent to which a supportive social environment plays a role in reduced catastrophizing and the degree that such support plays on the detrimental effects of catastrophizing on well-being. The telephone interviews solicited reports of pain intensity, negative affect, catastrophizing, and satisfaction with spousal responses.
Consistent with past research, episodes of catastrophizing were associated with increases in pain and negative affect. When participants reported satisfaction with spousal responses, however, they were not as likely to experience increases in negative affect due to catastrophizing. Furthermore, a satisfactory experience with a spouse reduced the likelihood of feeling overwhelmed and helpless in dealing with daily pain. Conversely, a decrease in satisfaction with spouse responses resulted in an increase in catastrophizing and negative affect.
Clinical Conclusion: Although the study was limited by a brief, one-week duration, these findings support an existing coping model showing that patient satisfaction with spousal responses serves as a coping resource. Since it is unlikely that patients will be aware of the results of this research, healthcare professionals must be alert for opportunities to convey the importance of good communication with spouses and caregivers. In some cases, it may be beneficial to recommend couples therapy to improve coping mechanisms for both patient and spouse or caregiver.
Reference: Holzman S, DeLongisa A. One day at a time: the impact of daily satisfaction with spouse responses on pain, negative affect and catastrophizing among individuals with rheumatoid arthritis. PAIN. 2007 (Sep);131(1-2):202-213.
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Numeric Pain-Rating Scale Can Be Misleading
The subjective experience of pain is challenging for healthcare providers to measure effectively. A prospective diagnostic accuracy study reported in the Journal of General Internal Medicine attempted to evaluate the accuracy of the numerical rating scale (NRS) as a screening tool for clinically important pain in primary-care patients. A total of 275 adult patients were asked to rate their pain on a 0 to 10 scale and to answer 2 questions designed to define “clinically important pain”: 1) the motivation for their physician visit, and 2) whether their pain interfered with daily functionality. Additionally, the Brief Pain Inventory (BPI) interference scale was used to measure functional impairment in 7 key areas: general activity, walking ability, sleep, ability to work, relations with others, enjoyment of life, and mood.
Results showed that even though a pain symptom was reported by 22% of patients as their main reason for the visit, 21% of these patients reported “no pain” on the NRS. Of participants who indicated that pain affected their everyday lives, 31% marked “0” on the numeric pain scale. The most common locations of pain in participants were lower extremities (21%) and back/neck areas (18%).
Practice Implications: The researchers found that the NRS was easy to administer, but stated that the tool demonstrated only modest accuracy in this population. Limitations of the study were potential patient-selection bias and the lack of a well-established definition and/or gold standard for clinically important pain. They also speculated that the effectiveness of the assessment tool may lie in the timing and the administration of the questions posed to patients during the assessment. Since chronic pain is complex and multidimensional, it may be necessary to structure questions that rate patients’ pain for a full day or week rather than just limiting the query to the current pain experience. It may also be helpful to use additional words — such as discomfort, ache, or tenderness — to assess the pain experience. The investigators stated that further research is needed to determine the usefulness of the NRS in improving patient outcomes in primary-care pain management.
[Comment: The literature generally recommends that when using the NRS it should be in conjunction with assessments of pain impact on quality of life. For a variety of pain scales and checklists to clinically assess pain dimensions and monitor treatment effectiveness at different points in time, see: http://pain-topics.org/clinical_concepts/index.php#Assessment. Accessed 10/22/07. -SBL]
Reference: Krebs EE, Carey TS, Weinberger M. Accuracy of the pain numeric rating scale as a screening test in primary care. J Gen Intern Med. 2007(Oct);22(10):1453-1458.
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Spinal Cord Stimulation Relieves “Failed Back” Pain
Failed back surgery syndrome (FBSS, sometimes called “failed back syndrome”) is characterized by persistent neuropathic pain and varying degrees of functional disability after spinal surgery. Spinal cord stimulation (SCS) involves a small implantable device that uses low level electrical energy to interfere with pain impulses. A multicenter study, to be published in the November 2007 edition of the journal Pain, evaluated the effectiveness of SCS to reduce pain and disability in an FBSS population. Patients with FBSS and predominant leg pain of neuropathic radicular origin (n = 100) were randomized to a 6 month course of spinal cord stimulation plus conventional medical management (SCS group) or to conventional medical management alone (CMM group).
The primary outcome measure was the achievement of 50% or greater pain relief in the legs. Additional outcome measures included improvements in back and leg pain, functional capacity, health-related quality of life, use of drug and nondrug pain therapy, level of patient satisfaction, incidence of complications, and adverse effects. All patients were followed up to 1 year; crossover after 6 months was allowed.
Results at 6 months showed that 48% of the SCS group versus only 9% of patients in the CMM group (p < 0.001) achieved the primary outcome. Compared with the CMM group, patients using the SCS protocol reported improved leg/back pain relief, quality of life, and functional capacity, plus greater treatment satisfaction (p </= 0.05 for all comparisons). During the second 6-month period, 5 SCS patients crossed to CMM, while 32 patients in the CMM group crossed to SCS. At 1 year, 32% had experienced some device-related complications.
Clinical Perspective: While a 50% reduction in pain is important for patients who suffer the pain of FBSS, the procedure requires multidisciplinary care and careful patient selection. The researchers stated that SCS along with CMM for suitable candidates can provide improved pain relief and quality of life compared with CMM alone.
Reference: Kumar K, Taylor RS, Jacques L, et al. Spinal cord stimulation versus conventional medical management for neuropathic pain: a multicenter randomised controlled trial in patients with failed back surgery syndrome. Pain. 2007(Nov);132(1-2):179-188. Also see the editorial on SCS in the same issue of Pain (Turner JA, Deyo RA, Loeser JD. pp 10-11).
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Topical Anesthetics Underused for Childhood Injections
Because the pain of childhood immunizations can leave a negative imprint on a child for years or a lifetime, researchers in Canada evaluated current analgesic practices through a cluster-sampling survey of pediatricians and mothers. Pediatricians (n = 140) reported data on analgesic use in their practices for injection (needle puncture and administration) and postinjection periods (hours to days following immunization). Mothers (n = 200) were asked to report on their analgesic use in their child following the immunization.
Survey results showed that 58% of pediatricians rarely/never used analgesics during the injection phase, while local anesthetics were used in 14% of practices at least a quarter of the time. About one third of doctors used oral analgesics for the pain of administration, while the majority of doctors used postinjection oral analgesics at least 25% of the time to prevent pain or fever. Mothers used analgesics in their children during the injection phase in 25% of immunizations and 33% of the time for postinjection pain or fever. Nondrug strategies (distraction, holding child) were used by 97% of pediatricians and 92% of mothers.
Practice Pointers: Overall, only a minority pediatricians and mothers used topical local anesthetics during the injection phase. Some physicians reported that the added cost and the time (30 - 60 minutes from application to effectiveness) needed for topical anesthetics is a barrier to their use. Many parents reported being unfamiliar with the use of topical local anesthetics and stated that the option was not presented. Scientific evidence does not support the effectiveness of oral analgesics for procedural pain. Previous studies have shown that topical local anesthetics reduce pain by almost half and, with careful instruction, parents have demonstrated successful administration. Parental education on the use of topical local anesthetics may help to reduce acute patient distress as well as the impact of a negative experience by the child that may affect a parental decision to seek medical care in the future. The researchers recommend that pain management instructions, including topical local analgesia, be included with information on immunization schedules.
Reference: Taddio A, Manley J, Potash L, et al. Routine immunization practices: use of topical anesthetics and oral analgesics. Pediatrics. 2007(Sep);120(3):e637-e643.
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Vitamin C May Help Prevent CRPS
Complex regional pain syndrome (CRPS) type 1 (formerly called ‘reflex sympathetic dystrophy’) is typically treated symptomatically, but a double-blind, prospective study in the Netherlands focused on vitamin C for the prevention of complex regional pain syndrome after trauma to the wrist. Patients (n = 416) with a total of 427 wrist fractures were randomly assigned to treatment with placebo or 200 mg, 500 mg, or 1500 mg of vitamin C (ascorbic acid) daily for 50 days. The relationships of gender, age, fracture type, and cast-related complaints to the occurrence of complex regional pain syndrome were analyzed.
The primary endpoint was evidence of CRPS any time within 1 year following the fracture. Overall, the prevalence of complex regional pain syndrome was limited to elderly women and affected about 2% of the vitamin C group and 10% of the placebo group (p = 0.002). Dosing variations resulted in a CRPS prevalence of about 4% in the 200 mg group (p = ns), and under 2% in both the 500 mg group (p = .007) and the 1500 mg group (p = .005). Early complaints related to the plaster cast were strongly predictive of the development of CRPS (Relative Risk 5.35; 95% CI, 2.13 to 13.42).
Clinical Perspective: Based on the results of the study, the authors recommend administration of 500 mg of vitamin C (ascorbic acid) daily for 50 days following a wrist fracture as a preventive measure against complex regional pain syndrome. This is an inexpensive, low-risk therapy that is hypothesized to reduce the incidence of CRPS by reducing the toxic oxygen radicals that are produced following the fracture. Additionally, since this study only evaluated patients following wrist fracture, the authors also suggested that further studies on the protective effect of vitamin C in complex regional pain syndrome be initiated.
Reference: Zollinger PE, Tuinebreijer WE, Breederveld RS, et al. Can vitamin C prevent complex regional pain syndrome in patients with wrist fractures? A randomized, controlled, multicenter dose-response study. J Bone Joint Surg Am. 2007;89(7):1424-1431.
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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 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.
Codeine — FDA Warning to Nursing Mothers
A September 2007 public health advisory from the FDA alerted healthcare providers and the public to a rare, but potentially serious, side effect in nursing infants for a small population of mothers taking codeine. Some people are “ultra-rapid metabolizers” of codeine and would not know that their bodies convert codeine to morphine very quickly. This condition can result in a higher than normal level of blood morphine and, consequently, a high level of morphine in breast milk that can lead to life-threatening respiratory depression or fatal toxic effects in a nursing baby. Because codeine is an ingredient in many prescription pain relievers and cough syrups, the FDA has asked healthcare professionals who must prescribe codeine to nursing mothers to recommend the lowest dose of codeine for the shortest period of time. In addition, it is important to alert a nursing mother to potential signs of high morphine levels and to provide an explanation of cautionary practices to reduce infant risk.
For more information, see the FDA public health advisory at: http://www.fda.gov/Cder/drug/advisory/codeine.htm (access checked 10/02/07).
 A journal article (Madadi P, et al. Canadian Family Physician. 2007[Jan];53:33-35) describing the pathophysiology of codeine metabolism in breastfeeding mothers plus recommendations to reduce the risk can be downloaded at: http://www.cfp.ca/cgi/reprint/53/1/33 (access checked 10/02/07).
Fentora™ (fentanyl buccal) — Improper Use Causes Deaths
An FDA press release in September 2007 warned healthcare professionals and consumers that Fentora™ (fentanyl buccal tablet) is approved only for the treatment of breakthrough pain in opioid-tolerant cancer patients. Reports of deaths and severe adverse effects have occurred through improper patient selection, dosing, or product substitutions. Cephalon, the manufacturer, has issued formal letters to remind healthcare practitioners to prescribe the product carefully according to package insert information and, additionally, to educate patients regarding the dangers of improper use.
For more information, see the FDA press release at: http://www.fda.gov/bbs/topics/NEWS/2007/NEW01711.html (access checked 10/01/07).
Fentanyl Transdermal System — Generic Patch Approved by the FDA
In August, the FDA approved the manufacture and marketing of the generic version of the fentanyl transdermal patch. Watson Pharmaceuticals and the Actavis Group were both given approvals. These products have been approved as the generic equivalent of Duragesic® for continuous management of moderate to severe chronic pain that cannot be managed by other pain relievers. The generic patch will be available in 25, 50, 75, and 100 mcg/hour strengths.
 Warning: The FDA has issued warnings concerning the dangers of using patches inappropriately. The fentanyl transdermal system should ONLY be used in patients who are already receiving opioid therapy, who have demonstrated opioid tolerance, and who require a total daily dose at least equivalent to 25 mcg/hour. See a summary of warning information from the Institute for Safe Medication Practices at: http://www.ismp.org/Newsletters/acutecare/articles/20070628.asp (accessed 10/16/07).
Zingo™ (lidocaine hydrochloride monohydrate) — Novel Topical Anesthetic Approved
A powder intradermal injection system for rapid, topical local analgesia to reduce the pain of venipuncture was approved by the FDA in August 2007. In 3 clinical trials of 1100 children, Zingo™ demonstrated statistically significant effectiveness in reducing the pain associated with venous access procedures in children aged 3 to 18 years. The needle-free, disposable system is helium-powered and contains 0.5 mg of sterile lidocaine powder. It is easy to administer and works within 1 to 3 minutes of application. Overall, Zingo was well-tolerated in trials; adverse reactions included redness, petechiae, and swelling at the administration site. The manufacturer, Anesiva, Inc., has announced plans to proceed with additional clinical trials to gather data for an FDA filing that could expand the label indication to include use in adults.
To download the FDA ‘Highlights of Prescribing Information’, see: http://www.fda.gov/cder/foi/label/2007/022114lbl.pdf (access checked 10/11/07).
Hydrocodone — Manufacturers Must End Production/Sales of Unapproved Products
The FDA has announced a campaign to take action against companies that market and sell pain relievers and cough suppressants containing unapproved versions of the potent, often-abused painkiller hydrocodone. An overdose of hydrocodone can result in breathing problems, cardiac arrest, or the impairment of motor skills and judgment.
The ingredient, which is legal in approved drugs like Vicodin®, is now widely used and abused in unapproved prescription products to curb coughing. Since the 1940s, when hydrocodone became available, regulations regarding product clearance have changed many times. Due to reports of overdoses and deaths related to misuse of the drug, attention to hydrocodone is one part of the FDA’s strategy to crack-down on drugs that have slipped through the approval process.
Roughly 200 available products contain an unapproved version of hydrocodone, and particular attention will be paid to products that are marketed for children because the drug has not been proved safe in that group. Companies selling unapproved cough suppressants for children under the age of 6 were to stop manufacturing and distribution before October 31st of this year. Manufacturers of other unapproved hydrocodone drug products must stop on or before December 31, 2007 and distribution must end by March 31, 2008.
For more information, see the FDA press release at: http://www.fda.gov/bbs/topics/NEWS/2007/NEW01713.html (access checked 10/01/07).
For FDA answers to more questions, including a list of 7 approved hydrocodone-containing cough suppressant products, see: http://www.fda.gov/cder/drug/unapproved_drugs/hydrocodone_qa.htm (access checked 10/01/07).
Soma® (Carisoprodol) — Approved in an Effective Lower Strength
In September, the FDA approved a new 250 mg strength of Soma® for the relief of acute musculoskeletal pain and discomfort. The results of 2 randomized, double-blind, placebo-controlled studies in more than 1300 patients with acute low back muscle spasm demonstrated that the 250 mg dosage offers comparable efficacy to the 350 mg strength. In addition, fewer adverse events were reported in patients taking 250 mg, including a reduction in drowsiness when compared with the 350 mg strength (13% versus 17%, respectively). The maker, MedPointe Pharmaceuticals, plans to make the new tablet available immediately.
Hydrocodone Bitartrate and Acetaminophen — Generic Offers New Dosing Strengths
The FDA approved the manufacture and marketing of additional strengths of the generic combination of hydrocodone bitartrate and acetaminophen. Ranbaxy Pharmaceuticals, Inc. stated that the new strengths will be available in November 2007 and will allow more convenient management of moderate to moderately severe pain. Available dosages of the combination product will be 5 mg/500 mg, 7.5 mg/750 mg, 10 mg/325 mg, and 10 mg/500 mg. The FDA has determined that the Ranbaxy generic is bioequivalent to Vicodin® at equal dosages
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