By G. Peer. Pontifical University.
The number of dropouts due to adverse events was 17% lower with tenoxicam relative to piroxicam purchase 30mg remeron free shipping 2c19 medications, but similar to those for diclofenac or indomethacin generic remeron 30mg fast delivery medicine 230. This systematic review Nonsteroidal antiinflammatory drugs (NSAIDs) 30 of 72 Final Report Update 4 Drug Effectiveness Review Project did not provide any specific data on risks of serious cardiovascular or serious gastrointestinal effects. Several randomized controlled trials and a review of tiaprofenic acid studies reported no 62, 63, 151, 152 serious adverse events associated with its use. A statistically significant percentage of patients reported fewer nonserious gastrointestinal side effects with tiaprofenic acid when compared with indomethacin (nausea and vomiting, 3. Observational studies of tiaprofenic acid have found increased occurrence of potentially 153-155 serious cystitis in patients using tiaprofenic acid, particularly in patients >70 years old. Concomitant aspirin use appeared to reduce the risk of tiaprofenic acid-induced cystitis (odds 153 ratio, 0. Comparisons between topical drugs We found no head-to-head trials that directly compared harms between different topical drugs. Therefore, we considered indirect comparison of topical drugs based on 1 placebo-controlled 65 67, 68 trial of 1. In contrast, there was no significant difference between diclofenac 1% topical gel and placebo gel in incidence of withdrawal due to adverse events (pooled relative risk, 1. Application-site reaction reporting was heterogenous between the 2 sets of trials and did not permit qualitative indirect comparisons. Dry skin at the application site was the most frequent adverse event reported for diclofenac 1. In contrast, incidence of dry skin was not reported in trials of diclofenac 1% topical gel and rates of overall application site reactions were notably lower and not significantly different compared with placebo gel (pooled relative risk, 2. There was no significant difference between diclofenac 1% topical gel and placebo gel in risk of any gastrointestinal adverse event (pooled relative risk, 1. Incidence of any gastrointestinal adverse event was not reported in the trial of diclofenac 1. Comparisons between oral and topical drugs Patients treated with 1. Gastrointestinal adverse event rates were 35% and 48%, respectively, in the first trial that Nonsteroidal antiinflammatory drugs (NSAIDs) 31 of 72 Final Report Update 4 Drug Effectiveness Review Project compared 50 drops of 1. As both trials categorized all adverse events th according to the 4 edition of the US Food and Drug Administration Coding Symbols for Thesaurus of Adverse Reaction Terms (COSTART), the difference between trials in gastrointestinal adverse event rates could not be explained based on obvious differences in assessment methods. Also, although the dosages used in the first trial were slightly higher, this still likely wouldn’t account for such a large difference between the rates for the topical groups (35% compared with 6. Incidence of dry skin at the application site was significantly greater in the topical diclofenac groups than in the oral diclofenac groups (pooled relative risk, 12. However, withdrawals due to adverse events were similar in the topical and oral diclofenac treatment groups in both randomized controlled trials (pooled 74, 75 relative risk, 0. Cardiovascular events (undefined) were only reported in the most recent trial and rates were <2% in both the topical 74 and oral diclofenac groups. Are there subgroups of patients based on demographics, other medications (e. Summary of Evidence Comparisons between oral drugs • Evidence from randomized controlled trials of elderly populations consistently found no significant differences in efficacy outcomes between celecoxib and either naproxen or diclofenac • Results from a long-term randomized controlled trial and 4 retrospective cohort studies suggested that celecoxib may be associated with fewer selected serious adverse events than some nonselective NSAIDs when used in elderly populations; however, in elderly patients, there were significantly fewer gastrointestinal hospitalizations when a proton pump inhibitor was added to celecoxib compared with celecoxib alone when age was above 75 years, but not when age was 66 to 74 years • One randomized controlled trial found no significant differences between celecoxib and diclofenac on pain when used concomitantly with angiotensin-converting enzyme inhibitors in a small study of all black or Hispanic patients • A single, small crossover trial examining the effects of using NSAIDs in patients taking anticoagulants found no significant changes in the mean international normalized ratio values after 5 weeks of either celecoxib or codeine; comparative evidence of the safety of celecoxib relative to NSAIDs when used concomitantly with anticoagulants was limited to 2 small observational studies and was inconclusive due to flaws in design • For patients taking an NSAID and low-dose aspirin (325 mg or less), similar rates of endoscopically confirmed gastroduodenal ulcers were found with celecoxib alone Nonsteroidal antiinflammatory drugs (NSAIDs) 32 of 72 Final Report Update 4 Drug Effectiveness Review Project (20. Comparisons between topical drugs • No evidence was found regarding the comparative effectiveness and harms of topical diclofenac products in patient subgroups. Comparisons between oral and topical drugs • No evidence was found regarding the comparative effectiveness and harms between oral and topical NSAIDs in patient subgroups. Detailed Assessment Demographic subgroups Evidence from randomized controlled trials of elderly populations consistently found no 156 significant differences in efficacy outcomes between celecoxib and either naproxen or 157 diclofenac. Celecoxib and naproxen had similar effects on pain and quality of life in elderly 156 patients based on results from an original data meta-analysis of 3 randomized controlled trials. Celecoxib 200 mg and diclofenac 50 mg had similar effects on pain after 1 year in 925 elderly 157 patients with osteoarthritis of the knee and/or hip (mean age of 71 years). Only 1, fair-quality, population-based retrospective cohort study evaluated the gastroprotective effects of adding a proton pump inhibitor in elderly patients taking celecoxib 109 (age ≥ 65 years).
Remission was considered grade 0 on any 212 esophagitis scale in most studies purchase remeron 30mg free shipping treatment 9mm kidney stones, although some allowed grade 1 as well purchase remeron 15mg fast delivery treatment 12mm kidney stone. All but 1 trial also reported recurrence rate of symptoms or the number of patients with mild or no symptoms at study end. Study characteristics are summarized in Table 12 and results are shown in Table 13. Time in remission The duration of remission was statistically significantly greater with higher compared with lower 212 doses of omeprazole at 6 months (P<0. Differences were not found between doses of lansoprazole in 3 studies. Endoscopically verified remission Examining Table 13, the higher doses resulted in greater numbers of patients being relapse-free at 6 or 12 months but differences between the higher and lower proton pump inhibitor dose strategies were examined statistically in only 5 studies. All 3 studies of lansoprazole found no 21, 207, 208 difference between the 15 mg daily and 30 mg daily doses at 12 months, and a single trial found no difference in relapse rates between the standard dose of omeprazole (20 mg) 211 compared with the lower dose (10 mg) at 12 months. However, 1 study of rabeprazole found that patients taking the standard dose (20 mg) had a higher remission rate than patients taking a 215 214 lower dose (10 mg) at 1 year and 5 years of follow-up. Proton pump inhibitors Page 53 of 121 Final Report Update 5 Drug Effectiveness Review Project Remission of symptoms Remission of symptoms was defined as no symptoms in most studies, although some allowed mild symptoms. Higher doses of a proton pump inhibitor compared to a lower dose of the same drug resulted in more patients being symptom-free at study end, but again statistical analyses 207, 208 were not undertaken to compare the doses in most studies. Two studies of lansoprazole and 211 1 of omeprazole found no difference between the lower and higher doses. With rabeprazole, the 1-year follow-up did not find a statistically significant difference between the doses, but the 5-year follow-up found the higher dose (30 mg daily) to be superior to the lower dose (15 mg daily). Withdrawals Differences in withdrawal (for any reason) rates were not apparent between the higher and lower doses in any of the studies. Proton pump inhibitors and treatment durations in longer-term studies of gastroesophageal reflux disease: Comparisons of standard doses with lower doses Initial short-term treatment (for Study N Duration healing) Strategy 1 Strategy 2 Strategy 3 Robinson 173 12 Lansoprazole Lansoprazole Lansoprazole 30 mg Placebo 1996 months 30 mg 15 mg Sontag 163 12 Lansoprazole Lansoprazole Lansoprazole 30 mg Placebo 1997 months 30 mg 15 mg Hatlebakk 103 12 Lansoprazole Lansoprazole Lansoprazole 30 mg 1997 months 30 mg 15 mg Bate 193 12 Omeprazole 20-40 Omeprazole Omeprazole Placebo 1995 months mg 20 mg 10 mg Laursen 168 Omeprazole 20-40 Omeprazole Omeprazole 6 months Placebo 1995 mg 20 mg 10 mg Caos 209 12 Rabeprazole 10 or 20 Rabeprazole Rabeprazole Placebo 2000 months mg 20 mg 10 mg Caos 497 Rabeprazole 10 or 20 Rabeprazole Rabeprazole a 5 years Placebo 2005 mg 20 mg 10 mg Johnson 318 Esomeprazole Esomeprazole Esomeprazole 6 months Not reported 2001 40 mg 20 mg 10 mg Omeprazole 20 mg or 375 Esomeprazole Esomeprazole Omeprazole Vakil 2001 6 months esomeprazole 20 or 40 mg 20 mg 20 mg 40 mg a Extension of Caos 2000 and Birbara 2000. Proton pump inhibitors Page 54 of 121 Final Report Update 5 Drug Effectiveness Review Project Table 13. Remission of gastroesophageal reflux disease erosions and symptoms in longer-term studies of proton pump inhibitors: Comparisons of standard doses with lower doses Percent of treatment group in remission a Study Proton pump (standard dose vs. Standard-dose proton pump inhibitor compared with intermittent or ‘on-demand’ proton pump inhibitor We identified 2 systematic reviews that compared intermittent or on-demand treatment to daily 218, 219 treatment for patients with gastroesophageal reflux disease. These reviews included studies of H2 receptor antagonists, studies comparing different doses of a proton pump inhibitor to one another, and different proton pump inhibitors with differing regimens (e. Additionally, quality assessments of included studies were not undertaken. Most of the studies included in these reviews did not make a comparison between continuous (daily) proton pump inhibitor therapy and intermittent (3 times a week) or on-demand (taken daily when symptoms occur, discontinue when symptoms resolve) and were not included here. We have used these reviews only to identify additional studies not found in our literature searches. Eight trials compared daily treatment with a proton pump inhibitor with intermittent or 208, 220-225, 226 on-demand treatment of the same proton pump inhibitor. One study followed 225 patients for 1 year, the rest followed patients for 6 months. Details of the study patients and Proton pump inhibitors Page 55 of 121 Final Report Update 5 Drug Effectiveness Review Project treatment strategies are presented in Table 14. In patients with healed endoscopically proven gastroesophageal reflux disease (Table 15), a regimen of daily proton pump inhibitor was superior to either 3 days a week or on-demand proton pump inhibitors of the same daily dose in 208, 221, 225 preventing recurrence of erosive esophagitis based on endoscopy. A 3-day-a-week regimen was also inferior to a daily regimen in preventing relapse of overall symptoms but no difference was found between daily treatment and on-demand treatment, although 1 study found 221 that severity of heartburn was lower with the daily regimen. Proton pump inhibitors and treatment durations in longer-term studies of gastroesophageal reflux disease: Comparisons of daily treatment with intermittent or on-demand treatment Study N Diagnosis Strategy 1 Strategy 2 Strategy 3 Healed Sontag Omeprazole 20 Omeprazole 20 mg 406 erosive Placebo 1997 mg daily 3 days a week esophagitis Healed Omeprazole 20 Omeprazole 20 mg Ranitidine 300 Dent 1994 204 erosive mg daily 3 days a week mg daily esophagitis Healed Sjostedt Esomeprazole 20 Esomeprazole 20 477 erosive 2005 mg daily mg on-demand esophagitis Lansoprazole Cibor a Lansoprazole 15 Lansoprazole 30 30 mg 65 NERD 2006 mg daily mg on-demand intermittent (4 weeks) a Rabeprazole 10 Rabeprazole 10 mg Bour 2005 181 NERD mg daily on-demand Janssen a Pantoprazole 20 Pantoprazole 20 432 NERD 2005 mg daily mg on-demand Symptoms of Morgan gastroesopha Rabeprazole 20 Rabeprazole 20 mg 268 2007 geal reflux mg daily on-demand disease Symptoms of Hansen 190 gastroesopha Esomeprazole 20 Esomeprazole 20 Ranitidine 300 2005, 2 geal reflux mg daily mg on-demand mg daily 2006 disease Abbreviations: NERD, non-erosive reflux disease. Proton pump inhibitors Page 56 of 121 Final Report Update 5 Drug Effectiveness Review Project Table 15. Remission of gastroesophageal reflux disease erosions and symptoms in longer-term studies of proton pump inhibitors: Comparisons of daily treatment with intermittent or on-demand treatment Percent of treatment group with result (daily vs. Assessment of overall satisfaction with treatment was not different between regimens in 1 222 study and final quality of life scores were also not different between groups in the other 224 study. However, the mean change in quality of life scores from baseline to 6 months was 224 significantly better in the daily treatment group compared to the on-demand group (P=0.