isoxicam and Arthritis--Rheumatoid

Topics: Adult; Aged; Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Arthritis, Rheumatoid; Clinical Trials as Topic; Collagen; Drug Interactions; Drug Tolerance; Edema; Half-Life; Humans; Kinetics; Muscular Diseases; Osteoarthritis; Oxygenases; Piroxicam; Rats; Thiazines

Nineteen patients, aged 60 years and over, with rheumatoid arthritis participated in a clinical trial to investigate the pharmacokinetics of isoxicam (a new non-steroidal anti-inflammatory drug) in this age group. The purpose of the study was to determine if the pharmacokinetics are different compared to a younger healthy population. The half-lives were independent of dosage, indicating linearity of pharmacokinetics. Furthermore, the half-lives after repeated dosing were not different from those found after single doses of 400 mg. This shows that there is neither undue accumulation of the drug nor induction of its own metabolism. These results are similar to the results obtained in other centres when isoxicam was administered to healthy subjects between 18 and 32 years.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Female; Half-Life; Humans; Male; Middle Aged; Piroxicam

1 Two multicentre, parallel group, randomised, double-blind, double-dummy comparison studies were conducted between isoxicam in the usual dose of 200 mg once daily and naproxen 500 mg twice daily. 2 The drugs were administered for 4 weeks to 230 patients suffering from osteoarthritis of the hip and/or knee in the first trial and to 249 patients suffering from rheumatoid arthritis in the second. 3 The studies compared treatments for both safety and overall effectiveness in the relief of pain. 4 In the osteoarthritis trial, overall pain was reduced by both drugs after 2 weeks of therapy but only isoxicam produced further improvement after 4 weeks. 5 Isoxicam produced reductions comparable to those produced by naproxen in pain on standing from the sitting position, pain on walking, and pain on movement of the affected joint, after 2 and 4 weeks. 6 After 4 weeks, isoxicam given once daily in the morning was significantly more effective than naproxen given in the morning and the evening in relieving not only total pain as assessed by a visual analogue scale but, as importantly, night pain. 7 Compared to naproxen therapy, isoxicam therapy was associated with significantly more patients whose disease state was improved at 2 weeks, as assessed by physicians. 8 In the rheumatoid arthritis trial, isoxicam was equally as effective as naproxen in reducing joint tenderness, joint swelling, and pain; at 4 weeks there was a trend in favour of isoxicam in reduction of joint swelling and pain. 9 Isoxicam reduced morning stiffness significantly more than naproxen after 4 weeks; this trend was apparent at 2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Double-Blind Method; Female; Humans; Male; Middle Aged; Naproxen; Osteoarthritis; Pain Measurement; Piroxicam; Random Allocation

A 4-week parallel-group, double-blind comparison of isoxicam 200 mg once daily and naproxen 250 mg 3 times daily was carried out on 30 patients with classic or definite rheumatoid arthritis. Fifteen patients were randomly assigned to each treatment group. The articular index, scoring on a pain scale and morning stiffness were significantly reduced after 2 and 4 weeks of treatment with both drugs. Grip strength was significantly increased after 4 weeks of naproxen treatment. The mean increase in grip strength was also comparable in isoxicam-treated patients, but did not reach statistical significance. Joint swelling and walking times showed improvement in both groups. One patient withdrew from isoxicam treatment with a pruritic rash considered to be drug-related and another stopped taking isoxicam because of dizziness, nausea and vomiting--also probably drug-related. Eight other patients, 4 treated with isoxicam and 4 with naproxen, reported adverse reactions associated with the digestive system. In this study isoxicam 200 mg taken once daily was similar in efficacy to and was associated with a similar incidence of adverse reactions as naproxen 250 mg taken 3 times daily. Both drugs were effective in the treatment of rheumatoid arthritis and were well tolerated.

Topics: Adult; Aged; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Middle Aged; Naproxen; Piroxicam; Thiazines

Topics: Adult; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Aspirin; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Indomethacin; Osteoarthritis; Piroxicam; Spondylitis, Ankylosing; Thiazines

Topics: Adolescent; Adult; Aged; Animals; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Clinical Trials as Topic; Drug Interactions; Humans; Kinetics; Middle Aged; Osteoarthritis; Piroxicam; Spondylitis, Ankylosing; Thiazines

A 4-week parallel-group, double-blind study comparing isoxicam with naproxen was carried out in patients with rheumatoid arthritis. Both isoxicam and naproxen were found to be effective. In patients on isoxicam significant improvements in the articular index, grip strength, joint swelling, morning stiffness and the patients' overall clinical condition were observed: the results for naproxen were similar, but joint swelling did not improve. At the 2-week assessment naproxen produced significantly better results than isoxicam in terms of the articular index and the physician's assessment of the patients' condition, but this difference was not maintained at the 4-week assessment. This apparently more rapid onset of activity of naproxen is probably related to its shorter elimination half-life. No adverse experiences were reported during isoxicam treatment and this drug was better tolerated than naproxen.

Topics: Adult; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Middle Aged; Naproxen; Piroxicam; Thiazines

Three multicenter studies evaluating the long-term efficacy of isoxicam (Maxicam) were conducted in 745 patients with active classic or definite rheumatoid arthritis. Initially, all patients in the one-year open-label phase received isoxicam, 200 to 400 mg per day. Dosage was then reduced to 200 mg a day for all patients. Objective and subjective parameters for efficacy included the number of tender joints, number of swollen joints, grip strength, duration of morning stiffness, time to walk 50 feet, overall assessment of the patient's condition, and global assessment of change in the patient's condition since the beginning of isoxicam therapy. All parameters of efficacy showed improvement. Patients who had received aspirin or placebo in the double-blind phase experienced marked and progressive improvement while receiving open-label isoxicam. Those who had received isoxicam continued to improve. The mean erythrocyte sedimentation rates showed significant decreases (p less than 0.0005) after one year of isoxicam therapy in all three studies. The results of these studies confirm that isoxicam is clinically effective in the long-term treatment of patients with rheumatoid arthritis.

Topics: Administration, Oral; Adult; Aged; Arthritis, Rheumatoid; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Female; Humans; Male; Middle Aged; Piroxicam; Thiazines

Data collected from more than 1,800 patients with rheumatoid arthritis or degenerative joint disease in Phase 3 clinical studies of isoxicam (Maxicam) indicated that the drug is well tolerated on both a short-term and a long-term basis. The most common type of adverse reaction to all medications (isoxicam, aspirin, and indomethacin) was gastrointestinal: 22.6 percent with isoxicam, at a dosage greater than 200 mg per day; 14.2 percent with isoxicam at 200 mg per day; 31.6 percent with buffered aspirin at 3,600 to 4,800 mg per day; 24.6 percent with indomethacin at 150 mg per day; and 7.2 percent with placebo. The incidence of tinnitus and deafness was significantly greater with buffered aspirin than with isoxicam, and the number of patients who had at least one episode of dizziness, vertigo, or headache was significantly greater with indomethacin than with isoxicam. In open-label, long-term studies, in which approximately 70 percent of the patients participated, the types and frequencies of adverse effects were similar to those observed with isoxicam during the controlled studies. The overall frequency of withdrawal for adverse reactions during the long-term studies was 11.5 percent, similar to that during the controlled studies. At the recommended dosage for isoxicam of 200 mg per day, the incidence of gastrointestinal ulcers was 0.81 percent, well within the range expected among arthritic patients receiving nonsteroidal anti-inflammatory drugs. From the data collected in Phase 3 clinical studies, it may be concluded that isoxicam is better tolerated than either aspirin or indomethacin and should not create unusual problems in the short-term or long-term treatment of rheumatoid arthritis or degenerative joint disease.

Topics: Aged; Arthritis, Rheumatoid; Aspirin; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Gastrointestinal Diseases; Hip Joint; Humans; Indomethacin; Joint Diseases; Knee Joint; Middle Aged; Piroxicam; Safety; Thiazines

The frequencies of adverse reactions in patients younger than 65 years and 65 and older were compared for dosages of isoxicam ranging from 200 to 600 mg per day. Data were collected from the records of 2,184 patients younger than 65 years and 1,059 patients 65 years or older from controlled and open studies of patients with osteoarthritis, rheumatoid arthritis, or musculoskeletal disorders. For both age groups, the most common adverse reactions were gastrointestinal. For other adverse reactions, the frequencies were notably lower than for gastrointestinal reactions. For virtually all adverse reactions, the frequencies were similar for the two age groups. Among patients who received only the recommended dosage of 200 mg per day, the frequencies of all reactions were lower than among the entire population and were similar between the two age groups. On the basis of this study, it appears that isoxicam is equally well tolerated in patients who are younger than 65 and those 65 and older.

Topics: Aged; Aging; Arthritis, Rheumatoid; Clinical Trials as Topic; Edema; Female; Gastrointestinal Diseases; Humans; Male; Middle Aged; Osteoarthritis; Piroxicam; Thiazines

The results of a six-month, double-blind comparison of isoxicam (Maxicam), 200 mg once a day, with buffered aspirin, 3,600 mg per day (900 mg four times a day), showed that isoxicam was statistically significantly better than aspirin in eight of 12 measures of efficacy. The study was carried out in 15 centers around the United States in 191 patients with classic or definite rheumatoid arthritis. The measures for which improvement with isoxicam was significantly better than aspirin were number of tender joints, sum of tenderness scores, number of swollen joints, sum of swelling scores, number of joints involved, grip strength, and overall assessment of the patient's condition by physician and patient. The measures for which the difference favoring isoxicam was not statistically significant were duration of morning stiffness, time to walk 50 feet, and global assessment of change in the patient's condition by physician and patient. The results indicate that 200 mg of isoxicam once daily is effective for treating rheumatoid arthritis. Compared with 3,600 mg of buffered aspirin daily, isoxicam is better in relief of symptoms and at least as effective regarding improvement in function.

Topics: Administration, Oral; Adult; Aged; Arthritis, Rheumatoid; Aspirin; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Female; Humans; Male; Middle Aged; Piroxicam; Thiazines

Topics: Aged; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Double-Blind Method; Female; Half-Life; Humans; Male; Osteoarthritis; Piroxicam; Thiazines

Topics: Adult; Aged; Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Arthritis, Rheumatoid; Clinical Trials as Topic; Collagen; Drug Interactions; Drug Tolerance; Edema; Half-Life; Humans; Kinetics; Muscular Diseases; Osteoarthritis; Oxygenases; Piroxicam; Rats; Thiazines

1 Isoxicam was found to inhibit monocyte and neutrophil cell chemotaxis at therapeutic concentrations. 2 The effect was observed after in vitro incubation of normal cells and in vivo in patients with rheumatoid arthritis. 3 Compared to other NSAIDs studied in our laboratory, isoxicam was shown to have a broader spectrum of inhibitory action on the cells involved in the chronic inflammation associated with rheumatoid arthritis.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Chemotaxis, Leukocyte; Female; Humans; In Vitro Techniques; Male; Monocytes; Neutrophils; Piroxicam

Topics: Aminosalicylic Acids; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Auranofin; Aurothioglucose; Gold; Humans; Mesalamine; Metalloproteins; Penicillamine; Phenylacetates; Piroxicam; Propionates; Thiazines

Several studies are under way to determine the pharmacokinetics of isoxicam in the elderly; this report presents preliminary results of these studies. Data have been collected from: eight healthy subjects older than 65 years old receiving single oral doses of 200 mg; eight patients with rheumatoid arthritis, 61 to 69 years old, receiving oral doses of 400 mg per day; and the same eight patients with arthritis receiving 100 mg per day (four patients), 200 mg per day (one patient), or 300 mg per day (three patients). The plasma levels of isoxicam were determined in the subjects for 96 hours following administration. The results indicate that the mean half-life of isoxicam is approximately 24 hours and is independent of dosage. The results were compared with those in 30 healthy subjects aged 18 to 32 years. The comparison showed that the half-life of isoxicam appears to be independent of dosage, duration of treatment, and age of subject. On the basis of these preliminary results, it appears that elderly patients are not at risk of excessive accumulation of isoxicam during treatment with therapeutic dosages.

Topics: Absorption; Administration, Oral; Adult; Aged; Aging; Arthritis, Rheumatoid; Female; Half-Life; Humans; Kinetics; Male; Middle Aged; Piroxicam; Random Allocation; Thiazines

Topics: Adult; Aged; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Drug Tolerance; Female; Humans; Male; Middle Aged; Osteoarthritis; Piroxicam; Thiazines

Topics: Arthritis, Rheumatoid; Humans; Legislation, Medical; Piroxicam; Quinazolines; Thiazines; United States; United States Food and Drug Administration