s-1743 and Pain

Selective cyclooxygenase-2 inhibitors (celecoxib) can minimize the gastrointestinal complications related to non-steroidal anti-inflammatory drug (NSAID) use. NAXOZOL is a new combination formulation designed to provide sequential delivery of a non-enteric-coated, immediate-release esomeprazole strontium tetrahydrate 20 mg mantle followed by an enteric-coated naproxen 500 mg core. However, there have been no studies comparing NAXOZOL to celecoxib with respect to gastrointestinal tract protection and pain relief in patients with osteoarthritis. This study was undertaken to compare the effects of NAXOZOL and celecoxib with respect to gastrointestinal tract protection and pain relief in patients with osteoarthritis.. The randomized enrolled patients were divided into two treatment groups: a NAXOZOL group and a celecoxib group. All participants received treatments (NAXOZOL, 500/20 mg (naproxen 500 mg, esomeprazole strontium tetrahydrate 20 mg) twice per day versus celecoxib, 200 mg daily) on a 1:1 allocation basis for 12 weeks. The primary outcome was the Leeds Dyspepsia Questionnaire (LDQ) score used for non-inferiority testing. Secondary outcome measures included the Gastrointestinal Symptom Rating Scale (GSRS) score, Visual Analogue Scale (VAS) score, European Quality of Life-5 dimensions (EQ-5D) scale and the EQ-5D Visual Analogue Scale (EQ VAS). Other outcome measures included the use of supplementary or rescue drugs, and the incidence of adverse events.. The baseline-adjusted LDQ scores immediately after 12 weeks of treatment in NAXOZOL group were not inferior to those in celecoxib group. The overall change in the baseline-adjusted GSRS score, VAS score, EQ-5D, and EQ VAS was not different between the two groups. The usage of supplementary drugs and the drug-related incidence of adverse events were not different. However, the days to use rescue drug were longer in celecoxib group than in NAXOZOL group.. NAXOZOL was not inferior to celecoxib in protecting the gastrointestinal tract and providing pain relief in patients with osteoarthritis.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Celecoxib; Double-Blind Method; Esomeprazole; Female; Gastrointestinal Diseases; Humans; Male; Naproxen; Osteoarthritis; Pain; Prospective Studies; Surveys and Questionnaires

This study investigated the safety and efficacy of fixed-dose combination tablets of naproxen/esomeprazole magnesium and nimesulide/pantoprazole to determine if both regimens are equally suited to relieve pain in patients with osteoarticular diseases and dyspeptic symptoms.. Patients were randomly assigned to receive either nimesulide/pantoprazole (100 mg/20 mg) twice daily or naproxen/esomeprazole magnesium (500 mg/20 mg) twice daily for 14 days. The primary endpoint was defined as the mean change in modified Western Ontario and McMaster Universities Osteoarthritis Index pain subscale. Secondary endpoints were mean visual analog scale score of dyspeptic symptoms (nausea, abdominal discomfort/pain, epigastric burning, postprandial fullness), mean visual analog scale score of individual dyspeptic symptoms, and individual score of dyspeptic symptoms according to patient diary. This study is registered at ClinicalTrials.gov: NCT01670552.. A total of 490 patients were enrolled and randomized, and 399 completed treatment (naproxen/esomeprazole, n=201; nimesulide/pantoprazole, n=198). The difference in mean change in the modified Western Ontario and McMaster Universities Osteoarthritis Index pain score after 7 days of treatment between the two treatment groups was 2.33 mm (95% CI, -1.22 to 5.89 mm). After 14 days of therapy, the difference was 0.45 mm (95% CI, -3.29 to 4.19 mm). The most common adverse events in the pooled group were abdominal discomfort, abdominal distention, dyspepsia, and nausea, but none of these was deemed to be clinically meaningful.. The present study demonstrated noninferiority of a 14-day regimen with a fixed-dose combination of nimesulide/pantoprazole compared to naproxen/esomeprazole for the treatment of osteoarticular pain.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Dose-Response Relationship, Drug; Double-Blind Method; Dyspepsia; Esomeprazole; Female; Humans; Male; Middle Aged; Naproxen; Osteoporosis; Pain; Pain Management; Pantoprazole; Sulfonamides; Tablets

To further characterize time-to-first pain relief, effect size, correlations between various outcome measures and durability of relief for single-tablet naproxen 500 mg/esomeprazole 20 mg (NAP/ESO) given twice daily and celecoxib (CEL) (200 mg) given once daily versus placebo in knee osteoarthritis (OA).. Unpublished data from two double-blind, double-dummy, placebo-controlled trials in which patients aged ≥ 50 years with knee OA were randomized to NAP/ESO (n = 487), CEL (n = 486) or placebo (n = 246) were pooled (NCT00664560 and NCT00665431). Acute response endpoints: 1) Time to first significant pain response, 2) Western Ontario and McMaster Osteoarthritis Index (WOMAC) pain subscale and 3) American Pain Society Patient Outcome Questionnaire (APS-POQ) scores. Sustainability endpoints: 1) Routine Assessment of Patient Index Data (RAPID3) and 2) WOMAC Stiffness, Pain and Total scores; and Patient Global Assessment (PGA) at 6 and 12 weeks. Effect sizes for all measures were calculated. Rescue pain medication use also was analyzed, as was the correlation of WOMAC to RAPID3.. NAP/ESO produced statistically significant decreases in WOMAC Pain on Days 2-7 and at Weeks 6 and 12 (all p < 0.05); most APS-POQ pain assessments with NAP/ESO were significantly improved on Days 2-7 compared with placebo (all p < 0.05). A good or excellent response occurred in a median of 6 days. RAPID3 and WOMAC total/stiffness/function/PGA scores decreased significantly at Weeks 6 and 12 (all p < 0.05). Placebo-adjusted WOMAC pain effect sizes were 0.44, 0.34 and 0.25 at Day 7, week 6 and week 12, respectively. RAPID3 to WOMAC total and WOMAC pain to RAPID3: Pain scores were highly correlated at 6 and 12 weeks (correlation coefficients >0.80). No significant differences in overall responses were found between CEL and NAP/ESO.. Naproxen/esomeprazole produced a significant absolute moderate early pain response, which was maintained for 12 weeks. RAPID3 was found to be highly correlated with the typical OA measure (WOMAC) and might be a useful clinical tool for measuring NSAID response. NCT00664560: https://clinicaltrials.gov/ct2/show/NCT00664560, NCT00665431: https://www.clinicaltrials.gov/ct2/show/NCT00665431.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Celecoxib; Cyclooxygenase 2 Inhibitors; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Esomeprazole; Female; Humans; Male; Middle Aged; Naproxen; Osteoarthritis, Knee; Pain; Pain Measurement; Proton Pump Inhibitors

Upper gastrointestinal (GI) symptoms are common in patients using non-steroidal antiinflammatory drugs (NSAIDs) including selective cyclooxygenase (COX)-2 inhibitors and may be acid related. We therefore assessed esomeprazole treatment for upper GI symptoms in these patients.. A total of 794 and 848 continuous NSAID users, free of gastroduodenal ulcers, erosive esophagitis, and Helicobacter pylori, were enrolled into two identical, multinational, multicenter double-blind studies (NASA1, SPACE1). Moreover, 608 and 556 patients were randomized to receive 4 wk esomeprazole 20 mg, or 40 mg, or placebo once daily. The primary variable was the patient-reported change in the upper GI symptom (pain, discomfort, or burning in the upper abdomen) score on a 7-graded severity scale (0-6) from the 7 days prior to treatment to the last 7 days in the study.. Esomeprazole was associated with highly significant symptom improvement compared to placebo. Symptom improvements were 2.30 mean [SD 1.63] on esomeprazole 20 mg and 2.03 [1.56] on esomeprazole 40 mg versus 1.64 [1.57] on placebo in NASA1 and 2.17 [1.34] and 2.12 [1.48]versus 1.56 [1.26], respectively, in SPACE1 (all placebo comparisons at least p < 0.001). Esomeprazole-improved symptoms in patients taking selective COX-2 inhibitors, with changes of 2.21 [1.46] and 1.92 [1.38]versus 1.64 [1.46] in NASA1 and 2.20 [1.26] and 2.24 [1.62]versus 1.58 [1.37] in SPACE1 (all placebo comparisons at least p < 0.05), as well as those on non-selective NSAIDs. Esomeprazole was well tolerated and associated with significant improvements in HRQL.. Esomeprazole 20 mg and 40 mg improve upper GI symptoms associated with continuous, daily NSAID therapy, including selective COX-2 inhibitors.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Double-Blind Method; Esomeprazole; Female; Follow-Up Studies; Gastroesophageal Reflux; Heartburn; Humans; Isoenzymes; Male; Membrane Proteins; Middle Aged; Nausea; Pain; Peroxidases; Placebos; Prostaglandin-Endoperoxide Synthases; Quality of Life; Treatment Outcome; Upper Gastrointestinal Tract

Carisoprodol is a skeletal muscle relaxant prescribed to treat pain. Carisoprodol is metabolized to meprobamate, an active metabolite with anxiolytic effects, by the genetically polymorphic CYP2C19 enzyme. Concomitant use of CYP2C19 substrates or inhibitors may alter carisoprodol metabolism, with therapeutic and/or toxic implications for effectively treating patients with pain. This was a retrospective analysis of urinary excretion data collected from patients with pain from March 2008 to May 2011. Carisoprodol and meprobamate urine concentrations were measured by liquid chromatography-tandem mass spectrometry, and the metabolic ratio (MR) of meprobamate to carisoprodol concentrations was determined in 14,965 subjects. The MR geometric mean and 95% confidence interval (95% CI) of the young group (105, 95% CI = 99.1-113) were ∼47.4% higher than the middle-aged group (71.9, 95% CI = 70-73.8) and nearly two times higher than the elderly group (54.4, 95% CI = 51.3-57.6). Females had a 20.7% higher MR compared with males. No significant change in the MR was observed with overall CYP2C19 inhibitor or substrate use. However, evaluation of individual inhibitors showed co-administration with esomeprazole or fluoxetine was associated with a 31.8 and 24.6% reduction in MR, respectively, compared with controls (P < 0.05). Omeprazole did not significantly affect the MR. Patient-specific factors such as age, sex and co-medications may be important considerations for effective carisoprodol therapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aryl Hydrocarbon Hydroxylases; Carisoprodol; Chromatography, Liquid; Cytochrome P-450 CYP2C19; Dose-Response Relationship, Drug; Drug Interactions; Esomeprazole; Female; Fluoxetine; Humans; Male; Meprobamate; Middle Aged; Muscle Relaxants, Central; Pain; Retrospective Studies; Specimen Handling; Tandem Mass Spectrometry; Young Adult