Nedocromil sodium is a pyranoquinoline dicarboxylic acid derivative, formulated in a metered-dose inhaler. Because nedocromil sodium has in vitro and in vivo anti-inflammatory properties, it was evaluated in a group of steroid-dependent patients with asthma to observe how well it might be tolerated and for evidence of any beneficial effects. In a double-blind, group-comparative study, 127 patients received nedocromil sodium and 61 received placebo, administered as two puffs of 2 mg, four times per day, for 12 weeks. Ten patients developed adverse reactions, seven receiving active drug and three patients receiving placebo. Two patients of each group withdrew because of worsening asthma. Despite selecting patients whose asthma was stable, when they were receiving established therapeutic regimens that included steroids and bronchodilators, it was found that diary-card symptom scores, morning and evening peak expiratory flow rate values, and inhaled beta-agonist usage all demonstrated slight but significant benefit with addition of nedocromil sodium. It is concluded that the inhaled, anti-inflammatory agent, nedocromil sodium, may be added to asthma-treatment regimens with the reasonable expectation of further modest symptomatic benefit.
To assess the frequency of adverse drug reaction in patients with fibromyalgia in relation to medications prescribed for this condition. To evaluate the potential role of the P450IID6 phenotype in the pathogenesis of these adverse drug reactions.
Thirty-five patients with fibromyalgia were assessed using a structured questionnaire with demographic and clinical data and perceived adverse drug reactions. A sample of 60 patients with rheumatoid arthritis and 62 patients with localized back pain served as controls. The P450IID6 phenotype was determined for each of the fibromyalgia patients.
Overall, 141 patients had used NSAID and 79 (56%) of them reported adverse effects. Antidepressant drugs were used by 68 patients and 35 (51%) patients had adverse effects. Muscle relaxant drugs were used by 48 patients and 15 (31%) of them reported side effects. Analgesics were used by 122 patients and 22 (18%) had experienced adverse effects. Statistical differences in the frequency of adverse effects were found with antidepressant drugs in the fibromyalgia group, compared with rheumatoid arthritis (p=0.01) and back pain (p=0.02). Four of the 35 patients (11.4%) had a metabolic ratio (M.R.) greater than 0.30 (log M.R.= -0.52) indicative of the poor metabolizers (PM) phenotype. M.R. varied from 0.005 (log M.R. = -2.30) to 4.99 (log M.R. = 0.70).
The problem of adverse drug reactions in fibromyalgia patients does not appear to correlate with the PM phenotype of the P450IID6 oxidative enzyme. It also is unlikely that altered xenobiotic detoxification attributable to this PM phenotype would have a significant role in the development of fibromyalgia.
Agranulocytosis is a potentially lethal adverse drug reaction of dipyrone (metamizole). According to case-control studies, the frequency is low, approximately one per million users. The aim of the study was to describe the pattern of blood dyscrasias associated with dipyrone, identify possible risk factors and calculate the incidence of agranulocytosis associated with dipyrone.
All spontaneous reports of serious blood dyscrasias associated with dipyrone in Sweden were reviewed. The reports were scrutinised for additional information, including bone marrow findings. The reported incidence of agranulocytosis was estimated from total prescription sales of dipyrone.
The reported incidence of agranulocytosis with dipyrone in Sweden was estimated to be at least 1:1439 (95% confidence interval 1:850, 1:4684) prescriptions. Ninety-two percent of the cases of blood dyscrasias occurred during the first 2 months of treatment. Additional risk factors were identified in 36% of the patients. In a total of five cases of which four were fatal, all three haematopoieses were affected according to bone marrow sample findings. Among the fatal cases, a higher proportion had bi- or tricytopenia than among the non-fatal cases ( P
The present study aimed at determining the use of physician-prescribed medication in a large number of elite athletes compared with a representative control sample of the general population. Of all the athletes (N = 494) financially supported by the National Olympic Committee, 446 completed a structured questionnaire (response rate 90.3 %) in 2002. A control group (N = 1503, response rate 80.1 %) comprised an age-matched sample from the population-based study collected by the National Public Health Institute. Any prescribed medication was used by 34.5 % of the athletes and 24.9 % of the controls during the past seven days. The most frequently reported physician-prescribed medications among athletes during the previous seven days were anti-allergic medicines (12.6 % of the respondents), non-steroidal anti-inflammatory drugs (NSAIDs; 8.1 %), anti-asthmatic medicines (7.0 %), and oral antibiotics (2.7 %). The adjusted odds ratios (95 % CI) for the physician-prescribed medications used during the previous seven days was 2.42 (1.69 - 3.46), 3.63 (2.25 - 5.84), 3.42 (2.05 - 5.70), and 2.15 (1.03 - 4.45) for use of anti-allergic medication, NSAIDs, anti-asthmatic medication, and oral antibiotics, respectively, in the athletes compared with controls. Every fifth athlete reported some NSAID-related adverse effect. In conclusion, the athletes used NSAIDs, antibiotics, anti-asthmatic and anti-allergic medication significantly more often than a representative sample of age-matched controls. All these medicines have potential adverse effects that may have a deleterious impact on the maximum exercise performance of elite athletes. Adverse effects were commonly reported in connection with NSAID use.
The aim of the study was to evaluate the prevalence and character of non-steroid antiinflammatory drug (NSAID)-associated pathology in patients with rheumatic diseases (RD) in the Russian population. The study included questioning of 2537 RD patients (81% women and 19% men, mean age 55.8 +/- 14.2 years) who were taking NSAID, in 6 regions of Russia, between the October of 2003 and April of 2004. The results were analyzed using chi2 criterion, Fisher exact test, and Student t-criterion. 7.6% of the questioned and 14.7% of their relatives had ulcerous background [corrected] history (ulcers diagnosted prior to the beginning of treatment with NSAID). Most patients (70.1%) were taking non-selective NSAID (NSNSAID), chiefly diclophenac (50.9%). The most often used non-selective cyclooxygenasa-2 (COG-2) inhibitor was nimesulid, taken by 23.5% of the patients. 20.2% of patients were not aware of the influence of NSAID on the gastric and intestinal mucosa. 33.7% of the patients underwent esophagogastroduodenoscopy (EGDS) while taking NSAID. In 8.8% of the examined gastric or duodenal ulcers were found while they were taking NSAID; 1.5% of the examined developed gastro-duodenal hemorrhage or ulcer perforation. 53.1% of the questioned had gastroduodenal complaints; in most cases it was heartburn (37.3%), "heaviness" in the epigastral area (37.4%), and meteorism (37.4%). 51.3% of the patients associated gastroesopagial reflux and dyspepsia symptoms with intake of NSAID. 26.9% of the questioned associated stool disturbances and meteorism with NSAID intake. 32% of the patients took medications to eliminate gastrointestinal disorder symptoms. Patients taking selective COG-2 inhibitors had complaints less frequently than those who were taking NSNSAID (p = 0). Most frequently complaints were associated with intake of glucocorticoids (p = 0), low doses of aspirin (p = 0), smoking (p = 0), and elderly age (p = 0.007). Appearance of complaints was not associated with the dose of NSAID (diclophenac) (p = 0.257). 8.8% of the patients with ulcerous background were not aware of the effects of NSAID on the alimentory tract; 34.1% of the patients din not undergo EGDS withing the period of treatment with NSAID. Only 40.3% of patients were taking selective COG-2 inhibitors; 54.7% of patients were taking gastroprotective preparations. Alimentary tract pathology is a prevalent complication of therapy with NSAID in the Russian population. The most frequent gastrointestinal symptoms are subjective; they affect life quality substantially. Their risk factors are: elderly age, ulcer background, and glucocorticoid intake. Russian doctors do not take sufficient measures to prevent serious NSAID intake complications.
While aspirin and other non-steroid anti-inflammatory drugs (NSAIDs) are associated with gastric mucosal damage, they might reduce the risk for gastric cancer. In a population-based case-control study in 5 Swedish counties, we interviewed 567 incident cases of gastric cancer and 1165 controls about their use of pain relievers. The cases were uniformly classified to subsite (cardia/non-cardia) and histological type and information collected on other known risk factors for gastric cancer. Helicobacter pylori serology was tested in a subset of 542 individuals. Users of aspirin had a moderately reduced risk of gastric cancer compared to never users; odds ratio (OR) adjusted for age, gender and socioeconomic status was 0.7 (95% CI = 0.6-1.0). Gastric cancer risk fell with increasing frequency of aspirin use (P for trend = 0.02). The risk reduction was apparent for both cardia and non-cardia tumours but was uncertain for the diffuse histologic type. No clear association was observed between gastric cancer risk and non-aspirin NSAIDs or other studied pain relievers. Our finding lends support to the hypothesis that use of aspirin reduces the risk for gastric cancer.
To evaluate the association between rofecoxib, celecoxib, diclofenac, and ibuprofen and the risk of hospitalization for acute myocardial infarction (AMI) in an elderly population.
We conducted a retrospective cohort study, using data from the government of Quebec health insurance agency databases, among patients 65-80 years of age who filled a prescription for any of the study drugs during 1999-2002. Cox regression models with time-dependent exposure were used to compare the incidence rates of hospitalization for AMI adjusting for patients' baseline characteristics. Analyses stratified by dose and number of supplied days were also conducted.
At the index date, a total of 91 062 patients were taking rofecoxib, 127 928 celecoxib, 49 193 diclofenac, and 15 601 ibuprofen. The adjusted hazard ratio (HR) (95%CI) of hospitalization for AMI were: celecoxib versus rofecoxib: 0.90 (0.79, 1.01); ibuprofen versus rofecoxib: 0.95 (0.65, 1.37); diclofenac versus rofecoxib: 1.01 (0.84, 1.22). In secondary analyses based on intended duration of use, neither COX-2 selective inhibitor was associated with a higher risk than ibuprofen or diclofenac. The unadjusted risk of AMI for all NSAIDs increased with dose. In the direct two way adjusted comparison of each NSAID stratified by dose, the only statistically significant difference was with rofecoxib >25 mg/day versus celecoxib >200 mg/day.
In this study there was no difference between AMI occurrence in elderly patients taking rofecoxib or celecoxib at recommended doses for chronic indications versus those taking ibuprofen/diclofenac. However, the risk of AMI was higher among patients using higher doses of rofecoxib (>25 mg/day) compared to patients using higher doses of celecoxib (>200 mg/day).
A clinical trial of arthrotek (Searle) in 60 RA patients aged 16-77 years demonstrated its high anti-inflammatory activity in 47 of them. These patients have received a complete treatment course, 10 patients were not included in the overall estimations because of side affects (gastric pains and nausea) causing them to withdraw early in the treatment course, 3 patients were nonresponders. The responders experienced attenuation of joint pain, morning stiffness. Inflammation in some joints declined, the articular index decreased.
In a 2-year, randomized, double-blind Nordic multicentre trial, auranofin was compared with placebo in early (disease duration less than or equal to 2 years), active rheumatoid arthritis (RA). Efficacy and safety were analysed in 67 patients receiving auranofin and 65 receiving placebo. Life table analysis demonstrated a significantly higher withdrawal rate due to insufficient therapeutic effect in the placebo group, whereas more patients dropped out due to side effects in the auranofin group. More auranofin than placebo patients (35 vs. 24) completed the 2 years. Clinical and inflammatory activity improved in both groups, but consistently more so in the auranofin group, in spite of the greater consumption of local steroids and NSAIDs in the placebo group. The most frequent side effects leading to withdrawal in the auranofin group were cutaneous and gastrointestinal reactions. The study demonstrated that most patients exhibit improvement in clinical signs and symptoms and about half of all patients with early RA continue to take auranofin for at least 2 years.