Gary E. Ruoff

Tramadol/Acetaminophen combination tablets for the treatment of chronic lower back pain: A multicenter, randomized, double-blind, placebo-controlled outpatient study☆

BACKGROUND Tramadol and acetaminophen (APAP) have both shown efficacy in the treatment of lower back pain. The combination of these 2 agents has demonstrated synergistic analgesic action in animal models at specific ratios. OBJECTIVE This study assessed the long-term (3-month) efficacy and safety of tramadol 37.5 mg/APAP 325 mg combination tablets in the treatment of chronic lower back pain. METHODS Patients with at least moderate lower back pain (pain visual analog [PVA] score >/=40 mm on a 100-mm scale) were randomized to receive up to 8 tablets of tramadol/APAP per day or placebo for 91 days. Medication was titrated from 1 to 4 tablets/d by day 10. The primary efficacy measure was PVA score at the final visit. Secondary measures included scores on the Pain Relief Rating Scale (PRRS), Short-Form McGill Pain Questionnaire (SF-MPQ), Roland Disability Questionnaire (RDQ), and 36-Item Short-Form Health Survey (SF-36); the incidence of discontinuation due to insufficient pain relief (Kaplan-Meier analysis); and overall assessments of medication by the patients and investigators. RESULTS Three hundred eighteen patients (161 tramadol/APAP, 157 placebo) were included in the intent-to-treat population, defined as all patients who took >/=1 dose of study medication and had >/=1 postrandomization efficacy measurement. The mean age of the study population was 53.9 years, 63.2% were female, 90.3% were white, and the mean baseline PVA score was 70.0 mm. There were no significant differences between groups at baseline. Tramadol/APAP significantly improved final PVA scores (P = 0.015) and final PRRS scores (P < 0.001) compared with placebo. Tramadol/APAP also significantly improved RDQ scores (P </= 0.027) and scores on many subcategories of the SF-MPQ, including total score (P = 0.021). The tramadol/APAP group had significant improvements on the role-physical (P = 0.005), bodily pain (P = 0.046), role-emotional (P = 0.001), mental health (P = 0.026), reported health transition (P = 0.038), and mental component summary (P = 0.008) subscales of the SF-36. The cumulative incidence of discontinuation due to insufficient pain relief was 22.1% for tramadol/APAP and 41.0% for placebo (P < 0.001). Treatment-emergent adverse events in the tramadol/APAP group included nausea (13.0%), somnolence (12.4%), and constipation (11.2%). CONCLUSIONS In this study, tramadol 37.5 mg/APAP 325 mg combination tablets were effective and had a favorable safety profile in the treatment of chronic lower back pain.

The Impact of Nonsteroidal Anti-inflammatory Drugs on Hypertension: Alternative Analgesics for Patients at Risk

An estimated 25% of the overall population of the United States and 55% to 60% of the population aged 65 to 74 years are hypertensive. Many patients with hypertension, particularly elderly patients, also take nonsteroidal anti-inflammatory drugs (NSAIDs), the most commonly prescribed analgesic medications in the United States. It is estimated that as many as 20 million patients and 12% of the population aged > or = 60 years are taking concurrent NSAIDs and antihypertensive medication. This overlap is significant, because NSAIDs inhibit eicosanoid synthesis and can thus limit the effectiveness of antihypertensive drugs that exert all or part of their blood-pressure-lowering action through the stimulation of eicosanoid synthesis or release. Overviews of clinical trial data indicate that the blood pressure of patients with controlled hypertension can be raised by 3 to 6 mm Hg during concurrent treatment with NSAIDs, which can produce a significant increase in subsequent stroke, end-stage renal disease, or congestive heart failure. The incidence of these sequelae increases with age. Clinicians should have greater awareness of the potential impact of NSAIDs on blood pressure control, especially in high-risk patients such as the elderly and those with chronic pain or uncontrolled hypertension. Unless an NSAID is deemed absolutely necessary, the clinician should consider alternative analgesics that do not affect prostaglandin synthesis. These include acetaminophen, tramadol, and, in some cases, narcotic analgesics.

Comparison of tramadol and acetaminophen with codeine for long-term pain management in elderly patients

Abstract A 4-week, double-blind study was conducted to compare tramadol hydrochloride, a new centrally acting binary analgesic, with acetaminophen/codeine for the management of chronic pain in patients older than 65 years of age. A total of 390 patients with chronic pain due to a variety of conditions, 84% to 88% of whom reported moderate or severe baseline pain intensity, ingested capsules containing 50-mg tramadol (n = 234) or 300-mg acetaminophen plus 30-mg codeine (n = 156). After the initial dose, patients were allowed to titrate the dose according to pain severity to a maximum of eight capsules per day. Efficacy was evaluated on the objective measures of pain relief (visual analog pain scale), medication acceptability, and overall therapeutic response; safety assessment was based on number and degree of adverse experiences, vital sign measurements, clinical laboratory evaluations, and electrocardiographic findings. Mean pretreatment pain intensities were moderate for both treatment groups. The mean total pain relief score (scale: 0=no relief; 16=complete relief) for each group on day 1 of week 1 was 6.1. On day 1 of week 3, mean total pain relief score was 7.4 for the tramadol group and 6.7 for the acetaminophen/codeine group. Both treatments were rated as good, very good, or excellent by 55% of patients in each group. Response to medication was rated moderate or marked by investigators for 53% of patients taking tramadol and 58% of patients taking acetaminophen/codeine. Patients in both groups took an average of four to five capsules daily (mean tramadol dose, 244 mg; mean acetaminophen/codeine dose, 1407/140.7 mg). Nausea, constipation, dizziness, and somnolence were the most common adverse effects in both groups. Adverse events considered by investigators as probably related to treatment occurred in 40 (17.1%) patients in the tramadol group and 19 (12.2%) patients in the acetaminophen/codeine group (difference not significant). Adverse experiences led to discontinuation in 18.8% of patients taking tramadol and in 9.6% of patients taking acetaminophen/codeine ( P

Strategies in Pain Management: New and Potential Indications for COX-2 Specific Inhibitors

The role of the coxibs in the management of osteoarthritis and rheumatoid arthritis has been widely discussed, but there are other potential applications for the coxibs that have received less attention. Here we consider the use of the coxibs in acute pain syndromes such as primary dysmenorrhea and the pain associated with dental extraction, as well as considering their application in chronic low back pain and cancer pain. Another area where the coxibs may prove particularly beneficial is in the management of post-surgical pain. Traditional post-surgical analgesia has involved the use of non-selective NSAIDs and opioids, but these agents can be associated with side effects such as post-operative bleeding, gastrointestinal problems, nausea, and constipation. Because the coxibs do not inhibit COX-1 dependent platelet aggregation like traditional NSAIDs, the risk of post-surgical bleeding is reduced. The careful application of coxibs as part of a multi-modal approach to pain management in the perioperative period can reduce the requirement for opioid medications and thus reduce the risk of post-operative complications such as ileus. In the future, coxibs are likely to play an important role in multi-modal perioperative analgesic regimens with the aim of reducing post-operative periods of convalescence.

Efficacy and tolerability of 5-day, once-daily telithromycin compared with 10-day, twice-daily clarithromycin for the treatment of group A beta-hemolytic streptococcal tonsillitis/pharyngitis: A multicenter, randomized, double-blind, parallel-group study

BACKGROUND Telithromycin, a ketolide antibacterial, has been developed for the treatment of community-acquired respiratory infections. OBJECTIVE This study compared the efficacy and tolerability of 5-day, once-daily telithromycin with 10-day, twice-daily clarithromycin in adolescents and adults with acute tonsillitis/pharyngitis caused by group A beta-hemolytic streptococci ([GABHS] Streptococcus pyogenes). METHODS In this multicenter, randomized, double-blind, parallel-group study, adolescent (aged > or = 13 years) and adult patients with a diagnosis of GABHS tonsillitis/pharyngitis received once-daily telithromycin 800 mg for 5 days (followed by placebo for 5 days) or twice-daily clarithromycin 250 mg for 10 days. Bacteriologic and clinical outcomes were assessed at a test-of-cure visit (days 16 to 23) and a late posttherapy visit (days 31 to 45). RESULTS A total of 526 patients were enrolled in the study, of which 463 (288 females, 175 males) were randomized to receive treatment (telithromycin, n = 232; clarithromycin, n = 231). The mean age of the telithromycin group was 30.9 years; in the clarithromycin group, it was 30.0 years. Bacterial eradication was achieved in 91.3% of telithromycin-treated patients and 88.1% of clarithromycin recipients (difference, 3.2%; 95% CI, -4.5 to 11.0). Clinical cure was achieved in 92.7% of telithromycin recipients and 91.1% of clarithromycin-treated patients (difference, 1.6%; 95% CI, -5.5 to 8.6). Bacteriologic and clinical cures for the 2 treatment groups also were similar at the late posttherapy visit. Treatment-related adverse events occurred more frequently in the telithromycin group than the clarithromycin group (67.2% vs 57.5%, respectively); diarrhea, nausea, and vomiting were significantly more common with telithromycin than with clarithromycin (P = 0.004, 0.010, and 0.001, respectively). Adverse events were generally mild. CONCLUSION This study demonstrates that telithromycin 800 mg once daily for 5 days was an effective and generally well-tolerated treatment for tonsillitis/pharyngitis caused by GABHS, providing similar bacteriologic and clinical efficacy to clarithromycin 250 mg twice daily for 10 days in the per-protocol population.

Prevalence of COPD among symptomatic patients in a primary care setting

Abstract Objective: Spirometry is recognized as the gold standard assessment for the diagnosis of COPD. However, spirometry continues to be underused, perpetuating the underdiagnosis of COPD. The aim of this study was to evaluate the prevalence of COPD in a primary care setting in patients with a smoking history and self-reported chronic bronchitis symptoms. Research design and methods: This was a multi-center, cross-sectional study. The primary assessment was the percentage of patients with airway obstruction (post-bronchodilator FEV1/FVC ratio ≤ 0.70) compared to those without obstruction (post-bronchodilator FEV1/FVC ratio > 0.70). Results: Airflow obstruction consistent with COPD was confirmed in 26% of patients (mean age 52.9 years, FEV1 81.4% predicted and smoking history 39.8 pack-years) that reported chronic bronchitis symptoms. Airflow obstruction increased with age and smoking history. Slight or moderate dyspnea was reported by 68% of patients and the majority had not talked to their doctor about cough and continued to smoke. Limitations: Patients were evaluated at a single visit. The definition of airway obstruction used may have lead to overdiagnosis in patients aged 70 and older. Conclusion: This study confirms that many patients with COPD remain undiagnosed in the primary care setting. Evaluation of spirometry in patients with a smoking history and chronic bronchitis symptoms can aid in the diagnosis of COPD, allowing earlier treatment thereby reducing the burden of this debilitating disease. Clinical trial registration: Study code ADC109043; clinicaltrials.gov #NCT00442468.

Twelve-month tolerability and safety of sumatriptan-naproxen sodium for the treatment of acute migraine

OBJECTIVES To evaluate the long-term safety and tolerability of sumatriptan-naproxen sodium for the treatment of moderate to severe acute migraines and to assess the safety of administration of an optional second dose. PATIENTS AND METHODS A 12-month, multicenter, open-label safety study was conducted in adults treated for migraine attacks of moderate to severe intensity from April 14, 2004, to August 18, 2005. Safety evaluations included adverse events and laboratory tests. RESULTS Of 600 patients enrolled, 565 (94%) were treated for at least 1 migraine. Of treated patients, 414 (73%) and 362 (64%) completed 6 and 12 months of treatment, respectively. Of the 24,485 attacks treated, 17,144 (70%) were treated with only 1 dose. On average, patients treated 5 migraine attacks per month, with a median of 6 days between attacks. The most common treatment-related adverse events were nausea, muscle tightness, and dizziness. Fourteen patients reported 1 or more serious adverse event with only 1 judged probably related to treatment. No deaths occurred. Eight percent of patients discontinued participation in the study because of adverse events or pregnancy. The rates of adverse events reported were no higher after treatment with 2 tablets (at least 2 hours apart) compared with 1 tablet. CONCLUSIONS In this 12-month data set of more than 24,000 migraine attacks in 565 patients, sumatriptan-naproxen sodium formulated in a single tablet was well tolerated when used episodically for the treatment of acute migraine. The adverse events did not differ from those expected for the individual components alone, and no new or unexpected findings occurred.

Sumatriptan-Naproxen and Butalbital: A Double-Blind, Placebo-Controlled Crossover Study

Objectives.— The primary objective was to compare the efficacy of a sumatriptan and naproxen combination medication (SumaRT/Nap—85 mg sumatriptan and 500 mg naproxen sodium), a butalbital‐containing combination medication (BCM—50 mg butalbital, 325 mg acetaminophen, 40 mg caffeine), and placebo when used to treat moderate to severe migraine headache pain in subjects who used BCMs in the past.

Cyclobenzaprine ER for muscle spasm associated with low back and neck pain: two randomized, double-blind, placebo-controlled studies of identical design

ABSTRACT Objective: To evaluate efficacy and tolerability of once-daily cyclobenzaprine extended release (CER) 15- and 30-mg capsules in patients with muscle spasm associated with acute, painful musculoskeletal conditions. Methods: Two identically designed, randomized, double-blind, placebo- and active-controlled, parallel-group studies in patients aged 18–75 years with muscle spasm associated with neck or back pain. Patients received CER 15 or 30 mg once daily, cyclobenzaprine immediate release (CIR) 10 mg three times daily, or placebo for 14 days. Primary efficacy measures were patients rating of medication helpfulness and physicians clinical global assessment of response to therapy at day 4. Secondary measures were patients rating of medication helpfulness and physicians clinical global assessment of response (days 8 and 14), relief from local pain, global impression of change, restriction in activities of daily living, restriction of movement, daytime drowsiness, quality of nighttime sleep (days 4, 8, and 14), and quality of life (days 8 and 14). Results: A total of 156/254 randomized patients in study 1 and 174/250 in study 2 completed 14 days of treatment. Significant improvements in patients rating of medication helpfulness were reported with CER versus placebo (CER 30 mg, study 1, p = 0.007; CER 15 mg, study 2, p = 0.018) at day 4. Significant improvements with CER 30 mg versus placebo were also seen at day 4 in study 1 for patient-rated global impression of change (p = 0.008), relief of local pain (p = 0.004), and restriction of movement (p = 0.002). Neither study reported differences between study groups on the physicians clinical global assessment. Improvements with CER were comparable to that of CIR. In both studies, daytime drowsiness was reported more frequently in active treatment groups than in the placebo group; however, reports of drowsiness decreased over time in all groups. In general, daytime drowsiness was reported more frequently in CIR groups than in CER groups. More adverse events were reported in the active treatment groups versus placebo and were similar in the CER and CIR groups, except somnolence, which occurred more frequently with CIR. Conclusions: Once-daily CER 15 mg (study 2) and CER 30 mg (study 1) were effective in treating muscle spasm associated with painful musculoskeletal conditions after 4 days of treatment. Differences between CER and placebo groups did not reach statistical significance on all efficacy measures, and the protocols were not powered to detect differences between active treatment arms. CER was generally safe and well tolerated, with low rates of somnolence.

A Double-Blind, Randomized Trial of the Efficacy and Safety of Short-Course, Once-Daily Levofloxacin Versus Ofloxacin Twice Daily in Uncomplicated Urinary Tract Infections

&NA; Uncomplicated UTIs are a frequently occurring infection, especially in young women. In this comparative study, patients were assigned randomly to 3 days of levofloxacin 250 mg once daily or ofloxacin 200 mg twice daily. Microbiologic and clinical outcomes were assessed after therapy (5‐9 days) and after the study (4‐6 weeks). At the posttherapy (test‐of‐cure) visit, 96.3% of pathogens were eradicated in the levofloxacin group, compared with 93.6% for ofloxacin. Symptoms were resolved or improved to the point where no further antibiotics were required in 98.1% of patients receiving levofloxacin and 97% of those receiving ofloxacin. The authors conclude that the short course regimens of levofloxacin and ofloxacin were equally effective and well‐tolerated for the treatment of uncomplicated urinary tract infections in women.