Twenty-six patients with gonarthrosis or coxarthrosis were entered in a double-blind study to compare tenoxicam 20 mg and piroxicam 20 mg. Both groups were statistically comparable prior to treatment regarding age, sex and clinical parameters. Both drugs were administered as a single daily 20 mg dose before breakfast for a period of six months. Clinical evaluations were performed monthly. The following parameters were considered: spontaneous pain, pain on movement, pain after a day of normal activity, tenderness, flexion in degrees, time to walk 10 metres, and functional status. Laboratory examinations were performed at baseline, in the third month, and at the end of therapy. Statistical analysis was based on the Student t-test and Chi-square test. Efficacy was considered excellent or good in seven patients treated with tenoxicam and in six with piroxicam, moderate in six tenoxicam and four piroxicam patients, and poor in three patients on piroxicam. No statistical differences were observed between the two groups for the final evaluation of efficacy. Side-effects appeared in three piroxicam patients: epigastric pain, dizziness and headache in one patient, epigastric pain in another case, and one patient with urticaria. Only one patient in the tenoxicam group experienced side-effects which presented as epigastric pain of mild intensity. No laboratory alterations were observed during and at the end of treatment.
Tenoxicam is a thienothiazine derivative with anti-inflammatory properties. Due to its long half-life (40-90 hours) the drug can be administered once daily. One-hundred patients with tendinitis or bursitis were allocated in a double-blind study comparing 20 mg of tenoxicam to 20 mg of piroxicam. Both drugs were administered once daily for a period of 15 days. Clinical evaluations were performed before, on the third and seventh days of therapy and after treatment. The parameters evaluated were: spontaneous pain, tenderness, pain on movement, swelling and functional limitation. Laboratory examinations were performed prior to and at the end of the therapy. Efficacy was considered excellent or good in 42 patients of each group, moderate in six treated with tenoxicam and in four with piroxicam and poor in two with tenoxicam and four with piroxicam. Statistical evaluation was based on the Wilcoxon and U-test. No significant differences were observed between the groups. Nausea of mild intensity occurred in four cases of the tenoxicam group and in one of the piroxicam group.
Thirty patients were allocated in a double-blind study comparing piroxicam 20 mg to tenoxicam 20 mg. Both drugs were administered once daily, before breakfast, for a period of 6 months. Clinical evaluations were performed weekly during the first 6 weeks and then monthly. The following parameters were evaluated: Ritchie articular index, pain on movement, pain at rest, grip strength, functional status, and morning stiffness. Laboratory examinations were performed before, on the 42nd day and on the 6th month of therapy. Efficacy was considered favourable in 10 cases treated with tenoxicam and in 12 with piroxicam and poor in five treated with the former and in three with piroxicam. Three patients of each group presented side effects of slight intensity. Considering the good results seen in the patients receiving tenoxicam, the treatment was maintained in nine cases for a further period of 6 months. Eleven other patients from the piroxicam group also received tenoxicam for a further period of 6 months. The efficacy was maintained in all 20 patients. Regarding adverse reactions, one patient complained of abdominal pain in the twelfth month of therapy and another patient had a brief episode of meteorism in the ninth month.
The aim of this study was to determine the efficacy and tolerance of tenoxicam (Ro 12-0068) versus piroxicam in patients with ankylosing spondylitis. The analgesic and anti-inflammatory activity of tenoxicam and piroxicam was measured for diurnal pain, nocturnal pain, pain on movement, maximum period of immobility tolerated when seated, morning stiffness, hand-floor distance and Schober index. In all except the last two parameters, improvement with tenoxicam was statistically significant, but there was no statistical difference between the two treatments. Slight side-effects were observed in one patient in the tenoxicam group and three in the piroxicam group.
Efficacy and toleration of piroxicam suppositories 20 mg, given once daily for 4 weeks were assessed in 96 patients suffering from degenerative joint disease and 20 patients suffering from rheumatoid arthritis. The mean scores of objective parameters measured (tenderness, swelling, limitation of movement) decreased significantly 2 and 4 weeks after initiation of therapy. Patients' self-evaluation of pain and stiffness also significantly improved during the trial. Overall evaluation of efficacy and toleration were excellent or good in more than 80% of patients. Local toleration was excellent in all but two patients.
This paper contains a detailed account of the results obtained in 1629 patients with osteoarthritis treated with indoprofen, a recently introduced non-steroidal anti-inflammatory drug. Several traditional objective variables were selected for evaluation of efficacy, and they were shown to be highly correlated. After four weeks' treatment with doses of indoprofen ranging in the great majority of cases from two to four 200 mg tablets daily, highly significant improvement of pain was observed along with amelioration of joint motion as measured with a new arthrogoniometer specially developed for the trial. On a 5 point semiquantitative scale, pain severity decreased on the average ofrom 2.31 (0.03 S.E.M.) to 0.66 (0.02); knee flexion increased on the average from 71.8 (2 . 00) degrees to 93.0 (1.74) (p less than 0.001). These results have confirmed on a much larger scale the conclusions of phase 2 studies. The multiclinic trial disclosed more adverse reactions than those found in phase 3 studies, thus confirming that phase 4 studies are more suitable for supplying information on the acceptance of drugs by practising physicians. The risk/benefit ratio turned out to be very favourable on account of the acceptable frequency of adverse reactions which were mainly confined to the gastrointestinal tract and forced withdrawal in only 6.0% of patients. Untoward clinical events were validated with a new algorithm: their relationship with the drug was in 51.5% probable and 35.6% definite. The results of this study have confirmed the usefulness of indoprofen in the treatment of osteoarthritis.
18,888 patients with chronic or extra-articular rheumatic diseases were treated for an average period of 36.1 or 26.9 days with the new non-steroidal anti-rheumatic agent piroxicam. In particular, piroxicam had a positive effect in terms of providing relief from pain. Side effects were relatively rare and seldom required discontinuation of treatment. In about 75% of the patients the maintenance dose was 20 mg piroxicam in a single daily dose. No influence on the laboratory values or accompanying diseases were observed.
The long-acting antiphlogistics tenoxicam (Ro 12-0068, Tilcotil) and piroxicam in single daily oral doses of 20 mg are compared in a double-blind, group-comparative, randomised trial planned to last for five years. Results of 12 months' treatment of 108 patients with osteoarthritis of the hip or knee have been reported. This interim analysis focuses mainly on the 12 to 24 month interval. The clinical improvements obtained within the first 12 months persisted during the second year in the 55 patients remaining on treatment. After 24 months, 53 patients had been withdrawn prematurely, three-quarters because of inefficacy or intolerance. Only six patients were withdrawn between 12 and 24 months, three for lack of efficacy, two for side-effects and one for reasons unrelated to therapy. There was no difference between the treatment groups with regard to incidence, time or reason for withdrawal, and only small, insignificant differences in efficacy and tolerability. This trial shows that long-term treatment of osteoarthritis with tenoxicam and with piroxicam is beneficial. Once efficacy and tolerability have been established, maintenance of therapy is feasible.
A multicenter study, involving 850 physicians (rheumatologists and orthopedists) and 3,309 patients with osteoarthritis was carried out to prepare an epidemiological survey of this disease, and to assess the efficacy of the new non-steroidal anti-inflammatory agent, piroxicam. This drug was administered to every patient in a single daily dose of 20 mg taken after dinner for 40 days. In our patient profile, the number of women was almost double the number of men. Most patients were between the ages of 50 to 59 years. The knee was the most frequently affected joint, primarily on the right side. Obesity did not seem to play an important role in provoking the arthritic disease in these patients (only 26.6% were obese). The majority had the disease from 25 to 60 months. Arterial hypertension was the most frequent concomitant disease. No association between this or other concomitant diseases could be linked to any specific joint involvement. The efficacy of the treatment was evaluated on the 20th and 40th days after treatment was begun. On admission, pain severity in 2,065 patients (62.4%) was classified as severe, and on the 20th day of evaluation this number fell to 105 patients (3.2%), showing a dramatic reduction in pain severity during the administration of the drug. The presence of a concomitant disease did not affect either the onset or level of therapeutic response. In the final evaluation, 1,441 patients (44.4%) were classified as excellent, and 1,341 (41.4%) as good, with a total of 85.8% of patients falling into one of these two categories. This is a highly satisfactory result in the evaluation of the efficacy of an anti-inflammatory agent. Most adverse reactions involved the gastrointestinal tract, followed by the central nervous system, cutaneous, and cardiovascular manifestations. Adverse reactions were present in 462 (13.96%) on the 20th day of evaluation, and in 110 (3.37%) on the 40th day of evaluation. Fifty-two patients needed to have their treatment discontinued because of severe reactions on the 20th day of evaluation and 13 on the 40th day of evaluation. This epidemiological study of 3,309 patients is the largest ever conducted in Brazil and in all of South America. It is also the only study in which the same anti-inflammatory drug was used in very patient in the same dosage.
An open non-comparative study was conducted to assess the efficacy and tolerability of piroxicam in patients with acute musculoskeletal disease. A total of 3011 patients of both sexes, aged between 18 and 70, were treated with piroxicam: 4 capsules (40 mg) after dinner, on the first two days and two capsules (20 mg) on the following days. Patients were evaluated for a maximum period of 14 days. Assessment of efficacy was made including local pain and limitation of mobility. The patients' self-assessment of pain was also analyzed. A clear improvement in each of the parameters analyzed was found by the third day of treatment. The general self-assessment of efficacy by the patients presented excellent and good results in 97.5%; very similar to the final assessment of efficacy made by the doctors, 91.1%. Adverse reactions were found in 368 patients (12.22%).
Efficacy and safety of piroxicam 20 mg nocte and fenbufen 600 mg nocte were assessed in a placebo-controled cross-over comparison in thirty-nine osteoarthritic patients. When compared with placebo, piroxicam showed highly significant pain relief morning, afternoon and evening throughout the study. Fenbufen showed significant relief of morning pain only. There was a significantly and sustained relief of night pain with piroxicam compared with placebo, but no difference with fenbufen compared with placebo. This was confirmed by a statistical analysis directly comparing the results obtained for the two agents. Both piroxicam and fenbufen were well tolerated and produced markedly less side-effects than placebo.
A single oral dose of fenbufen 900 mg was administered to 12 elderly volunteers, average age 81 years. The plasma levels of fenbufen and its major metabolites were measured at intervals over 72 hours following dosing. Results were compared with previously obtained data from young healthy volunteers. No significant differences were seen, after corrections from body weight, between the two groups for fenbufen and 2 of its metabolites. The mean serum levels in the elderly of biphenylacetic acid were significantly higher at 36 hours and 48 hours than the means at these times in the young group. This was not thought to be clinically significant. The terminal half lives for fenbufen and its major metabolites were not significantly prolonged compared with young volunteers.
A young woman with systemic lupus erythematosus developed portal hypertension and pulmonary hypertension. This is the first report of such a case. We suggest that the presence of the lupus anticoagulant may have been related to the development of these two unusual features of her illness.
The absorption and disposition of ibuprofen was investigated in seven hemodialyzed uremic patients. Ibuprofen (400 mg) was orally administered to each patient 1 hr or 4 hr prior to hemodialysis. Uremic patients appeared to absorb ibuprofen at a slower rate as compared to normal subjects. The hemodialysis systems used in this study yielded a mean extraction efficiency of 16.7% for ibuprofen, with a mean dialysis plasma clearance of 22.7 ml/min. The drug recovery resulting from hemodialysis represented a small fraction of the ingested dose of ibuprofen (less than 4%). The half-life of ibuprofen (1.3-1.9 hr) was not significantly altered by hemodialysis. Observations of extraction efficiency, drug recovery and half-life during dialysis suggested nondialyzability of ibuprofen, probably due to its extensive protein binding (approximately 90%). Uremic patients may require a comparatively longer time to achieve the therapeutic concentration attained in normal volunteers. However, dosage adjustment is not required once a regimen is implemented in uremia.
The effectiveness, safety and acceptability of indoprofen (IP) and acetylsalicylic acid (ASA) were assessed in patients with osteoarthritis, in a double-blind comparative trial. Each patient received IP 600 mg/day or ASA 2100 mg/day for a four-week period; after a one-week wash-out period, the same drug was given at a higher dosage (IP 800 or ASA 2800 mg/day) for another four weeks. Seventeen patients on indoprofen and 14 on SAS completed the trial. A significant improvement was obtained with indoprofen in the different parameters measuring pain, from the first treatment period; results were similar at the end of the second period. Results with ASA, at both dosages, appeared less impressive. Two patients on indoprofen and five on ASA complained of side effects.
This randomised, double-blind, placebo-controlled, parallel-group trial was carried out to assess the efficacy and tolerability of a new, locally acting, transcutaneous flurbiprofen preparation (flurbiprofen LATTM, Boots Company PLC) in the treatment of scapulohumeral periarthritis. The new preparation consists of a nonwoven polyester patch supporting a mentholated formulation containing flurbiprofen 40 mg. Eighty patients suffering from the acute, painful phase of scapulohumeral periarthritis entered the trial, three of which failed to provide follow-up data. Each patient applied one patch every 12 hours for the 14 day trial period. Efficacy was assessed in terms of reduction of pain, improvement in shoulder movement and overall clinical assessment of the severity of the condition after treatment. Statistically significant improvements from baseline were observed in both treatment groups, with a constant overall trend in favour of flurbiprofen. The differences between the two treatment groups, however, did not reach statistical significance.
Thirty out-patients with rheumatoid arthritis aged from 3 yrs. (+/- 0.5 SEM) were included in a between-patient controlled trial comparing effectiveness and safety of flurbiprofen 300 mg daily and indomethacin 150 mg daily. The duration of the treatment was nine weeks. Both drugs allowed to reduce the initial dose of corticosteroids administered (-21% on flurbiprofen and -12% on indomethacin) and were effective in improving clinical signs of the disease such as number of swollen joints, grip strength, articular index and morning stiffness. Flurbiprofen was better tolerated (p less than 0.01).
The mechanism of action of various types of drugs for treating inflammation and arthritis is reviewed. Three classes of agents, the steroidal, the acidic non-steroidal and the basic therapy drugs, are discussed. The first two types of drugs act rapidly on the symptoms of inflammation, interfering at various points in the inflammatory response. The non-steroidal agents are especially linked to a mechanism involving, at least in part, the prostaglandins. Piroxicam, a potent, structurally unique member of the non-steroidal class, is discussed in some detail. The basic therapy drugs act slowly, generally exhibit more severe side effects and probably affect some immunological aspects of rheumatoid arthritis. The precise mechanisms of action of this latter class of structurally diverse drugs is generally poorly understood at this time.
One hundred and thirty-one male and female outpatients, aged 18-70 yr, with acute pain in the ankle joint caused by a post-traumatic sprain, entered a multicentre, randomised, double-blind, parallel-group, study. The patients were assigned to a 40 mg flurbiprofen patch (n = 65) or a non-medicated (but otherwise identical) control (n = 66), 12-hourly over 7 days, and were assessed at entry and after 3 and 7 days treatment. On day 7, spontaneous pain (the prime efficacy parameter), as evaluated by the patient on a visual analogue scale in the physician's office, showed significant improvement in the 40 mg flurbiprofen patch group compared to control (change from baseline) (p = 0.039), a result corroborated by the evaluation of the periarticular oedema: a reduction of 77.4% was observed in the 40 mg flurbiprofen patch group, compared with 63.8% in the control group (p = 0.025). The other selected efficacy criteria showed changes with a trend in favour of the 40 mg flurbiprofen patch but without statistical significance. Two mild and local adverse events were reported by two flurbiprofen patch patients, but neither patients discontinued the treatment prematurely. Physicians and patients found the flurbiprofen patch to be efficacious and well tolerated. Compliance was excellent in both groups. The efficacy and tolerability of the 40 mg flurbiprofen patch are therefore confirmed in the treatment of acute ankle sprains.