sulindac and Arthritis--Rheumatoid

Pain management is a high priority for patients with rheumatoid arthritis (RA). Muscle relaxants include drugs that reduce muscle spasm (for example benzodiazepines such as diazepam (Valium), alprazolam (Xanax), lorazepam (Ativan) and non-benzodiazepines such as metaxalone (Skelaxin) or a combination of paracetamol and orphenadrine (Muscol)) and drugs that prevent increased muscle tone (baclofen and dantrolene). Despite a paucity of evidence supporting their use, antispasmodic and antispasticity muscle relaxants have gained widespread clinical acceptance as adjuvants in the management of patients with chronic musculoskeletal pain.. The aim of this review was to determine the efficacy and safety of muscle relaxants in pain management in patients with RA. The muscle relaxants that were included in this review are the antispasmodic benzodiazepines (alprazolam, bromazepam, chlordiazepoxide,cinolazepam, clonazepam, cloxazolam, clorazepate, diazepam, estazolam, flunitrazepam, flurazepam, flutoprazepam, halazepam, ketazolam, loprazolam, lorazepam, lormetazepam, medazepam, midazolam, nimetazepam, nitrazepam, nordazepam, oxazepam, pinazepam, prazepam, quazepam, temazepam, tetrazepam, triazolam), antispasmodic non-benzodiazepines (cyclobenzaprine, carisoprodol, chlorzoxazone, meprobamate, methocarbamol, metaxalone, orphenadrine, tizanidine and zopiclone), and antispasticity drugs (baclofen and dantrolene sodium).. We performed a search of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 4th quarter 2010), MEDLINE (1950 to week 1 November 2010), EMBASE (Week 44 2010), and PsycINFO (1806 to week 2 November 2010). We also searched the 2008 to 2009 American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) abstracts and performed a handsearch of reference lists of relevant articles.. We included randomised controlled trials which compared a muscle relaxant to another therapy (active, including non-pharmacological therapies, or placebo) in adult patients with RA and that reported at least one clinically relevant outcome.. Two blinded review authors independently extracted data and assessed the risk of bias in the trials. Meta-analyses were used to examine the efficacy of muscle relaxants on pain, depression, sleep and function, as well as their safety.. Six trials (126 participants) were included in this review. All trials were rated at high risk of bias. Five cross-over trials evaluated a benzodiazepine, four assessed diazepam (n = 71) and one assessed triazolam (n = 15). The sixth trial assessed zopiclone (a non-benzodiazepine) (n = 40) and was a parallel group study. No trial duration was longer than two weeks while three single dose trials assessed outcomes at 24 hours only. Overall the included trials failed to find evidence of a beneficial effect of muscle relaxants over placebo, alone (at 24 hrs, 1 or 2 weeks) or in addition to non-steroidal anti-inflammatory drugs (NSAIDs) (at 24 hrs), on pain intensity, function, or quality of life. Data from two trials of longer than 24 hours duration (n = 74) (diazepam and zopiclone) found that participants who received a muscle relaxant had significantly more adverse events compared with those who received placebo (number needed to harm (NNTH) 3, 95% CI 2 to 7). These were predominantly central nervous system side effects, including dizziness and drowsiness (NNTH 3, 95% CI 2 to 11). . Based upon the currently available evidence in patients with RA, benzodiazepines (diazepam and triazolam) do not appear to be beneficial in improving pain over 24 hours or one week. The non-benzodiazepine agent zopiclone also did not significantly reduce pain over two weeks. However, even short term muscle relaxant use (24 hours to 2 weeks) is associated with significant adverse events, predominantly drowsiness and dizziness.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Arthralgia; Arthritis, Rheumatoid; Azabicyclo Compounds; Diazepam; Humans; Indomethacin; Muscle Relaxants, Central; Pain Management; Piperazines; Randomized Controlled Trials as Topic; Sulindac; Triazolam

A NEW CONCEPT: Chemoprevention of cancer consists in the administration of chemical agents to prevent or inhibit carcinogenesis. This strategy can be applied at any stage of carcinogenesis.. The development of such agents relies on classical bases: phases I, II and III. The approach consists in assessing the effect of the substance tested in patients with history of resected adenomas of the colon and at high risk of relapse and/or family risk of colon cancer.. Are aspirin, type 2 cyclo-oxygenase inhibitors, calcium, folic acid, certain vitamins, hormone replacement therapy for menopausal women and difluoromethylornithine (DFMO).

Topics: Adenomatous Polyposis Coli; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Arthritis, Rheumatoid; Aspirin; Calcium, Dietary; Case-Control Studies; Cohort Studies; Colorectal Neoplasms; Controlled Clinical Trials as Topic; Cyclooxygenase Inhibitors; Dietary Supplements; Eflornithine; Enzyme Inhibitors; Female; Folic Acid; Hormone Replacement Therapy; Humans; Male; Mice; Mice, Knockout; Middle Aged; Risk Factors; Sulindac; Time Factors; Vitamins

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for rheumatic conditions. Their effects on the upper gastrointestinal tract are well recognised. Clinically important damage to the small intestines is less common and often unrecognised. We report a case of sulindac-induced jejunal perforation in a rheumatoid arthritis (RA) patient with previous gastrectomy for gastric carcinoma. The prevalence, diagnosis, pathogenesis and treatment options of NSAID-induced enteropathy will be discussed.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Disease-Free Survival; Enteritis; Humans; Intestinal Perforation; Jejunal Diseases; Male; Middle Aged; Sulindac; Tomography, X-Ray Computed

Topics: Acute Disease; Aged; Arthritis, Rheumatoid; Humans; Male; Pancreatitis; Sulindac

Rheumatoid Arthritis (RA) is a progressive disease of unknown aetiology which may be caused by faulty immune mechanisms. Early diagnosis and correct treatment can be extremely effective. Fast and lasting results can only be obtained by an appropriate combination of NSAID and DMARD drugs which both reduce subjective symptoms and halt the progression of the disease.

Topics: Adjuvants, Immunologic; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antimalarials; Arthritis, Rheumatoid; Azathioprine; Gold; Humans; Indomethacin; Levamisole; Penicillamine; Phenylbutazone; Propionates; Salicylates; Sulindac; Tolmetin

In doses of 1,200 mg/day or more, ibuprofen is as effective as aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of rheumatoid arthritis. The tolerability and safety of ibuprofen are superior to those of aspirin and compare favorably with those of other NSAIDs. Although additional controlled trials are indicated to determine optimal dose, ibuprofen's excellent therapeutic index establishes it as a useful drug in the treatment of rheumatoid arthritis.

Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Aspirin; Clinical Trials as Topic; Drug Tolerance; Fenoprofen; Humans; Ibuprofen; Indomethacin; Ketoprofen; Naproxen; Piroxicam; Sulindac; Thiazines; Tolmetin

Topics: Adult; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Aspirin; Clinical Trials as Topic; Diclofenac; Double-Blind Method; Drug Eruptions; Drug Interactions; Female; Gastrointestinal Diseases; Headache; Humans; Indomethacin; Male; Middle Aged; Osteoarthritis; Sulindac

Topics: Anti-Inflammatory Agents; Arthritis; Arthritis, Rheumatoid; Fenoprofen; Humans; Ibuprofen; Mefenamic Acid; Naproxen; Propionates; Sulindac; Tolmetin

The elderly (age > 65 years) are more vulnerable to side-effects induced by non-steroidal anti-inflammatory drugs (NSAIDs). We therefore performed a double-blind comparative study of ketoprofen SR and sulindac in patients with active rheumatoid arthritis, 65 years of age or older. Sulindac was chosen because of its possible renal sparing effects, and ketoprofen SR because of its short half life and sustained release delivery system. Eighty patients were entered. More patients withdrew from the study due to side-effects in the sulindac group; both treatment groups had a high incidence of side-effects during this study and during previous exposure to other NSAIDs, demonstrating that the elderly are susceptible to side-effects from NSAIDs.

Topics: Aged; Arthritis, Rheumatoid; Double-Blind Method; Female; Humans; Ketoprofen; Male; Sulindac; Treatment Outcome

Of the 160 patients (80 pirazolac/80 sulindac) who entered the study through 14 investigators, three-quarters completed a 12-weeks therapy and three-fifths completed the entire 24-weeks therapy. In the pirazolac group 15% of the patients and in the sulindac group 11% dropped out from the study due to adverse clinical experience. The drop-out rates due to unsatisfactory therapeutic response were respectively 15% and 16% in the pirazolac and the sulindac groups. Both treatment groups showed significant improvement from baseline for all parameters except for the erythrocyte sedimentation rate at weeks 4, 8, 12 and 16 for the sulindac group and weeks 4 and 8 for the pirazolac group. The two treatment groups were comparable as to effectiveness; however, the improvement rates in 36 out of 41 efficacy measurements based on the definition of clinically relevant changes in relation to baseline were estimated to be superior for the group under pirazolac therapy. The rate of improvement for the American Rheumatism Association functional class at the end of the study was 23% in the pirazolac group and 9% in the sulindac group (p less than 0.05). Of the patients in the pirazolac and sulindac groups, 45% and 44% respectively reported no adverse effects at all throughout the whole 24-weeks study. The rates of patients reporting at least one adverse reaction in a body system were not different between the two groups. An exception was the body as a whole where ten patients (12.5%) in the sulindac group and only two (2.5%) in the pirazolac group reported adverse reactions (p = 0.03). No differences occurred between the two treatment groups with regards to intensity, causality or the number of occurrences of adverse clinical experiences. One death in the sulindac treatment group was reported during the study. In both treatment groups, alterations in laboratory tests were minor or negligible or associated with abnormal pre-treatment values and, generally speaking, without any clinical relevance. There were some patients, who had increases from baseline in alkaline phosphate in both treatment groups. However, these were usually transient, occasionally complemented by a slight increase of serum glutamic oxaloacetic acid transaminase.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Double-Blind Method; Drug Administration Schedule; Drug Tolerance; Female; Humans; Male; Middle Aged; Multicenter Studies as Topic; Pyrazoles; Randomized Controlled Trials as Topic; Sulindac

The purpose of the current investigation was to study the influence of sulindac and naproxen on renal function and urinary excretion of the stable hydration product of prostacyclin, 6-keto-PGF1 alpha, in patients with arthritis and impaired renal function.. In a placebo-controlled, double-blind, cross-over design, the effects of 7 days of oral sulindac 200 mg twice a day were compared with naproxen 500 mg in the morning and 250 mg in the evening in 10 patients with polyarthritis and stable impaired renal function. Inulin and para-amino-hippurate sodium were used to calculate glomerular filtration rate and renal plasma flow. The excretion rate of 6-keto-PGF1 alpha was measured in urine collected overnight. After patients ingested drugs in the morning, urine was collected in fractions by spontaneous voiding. Venous blood samples were drawn repeatedly for assay of electrolytes, creatinine, proteins, hormones, and drugs. Grip strength and Ritchie articular index were recorded as indicators of symptomatic antiarthritic effectiveness.. Naproxen decreased urine levels of 6-keto PGF1 alpha by 59% (p less than 0.01). Sulindac had no effect on renal prostaglandin excretion. Naproxen reduced the glomerular filtration rate and renal plasma flow by 18% (p less than 0.05) and 13% (p less than 0.05), respectively, while no significant change was observed during the sulindac treatment periods. Serum levels of creatinine and complement factor D were unaffected by either drug. Plasma renin activity decreased during naproxen and sulindac treatments by 38% (p less than 0.05) and 22% (p less than 0.05). No significant change in plasma aldosterone was observed during the two drug treatments, but urinary aldosterone declined significantly (p less than 0.05) by 34% with naproxen. Albuminuria decreased (p less than 0.05) during both naproxen (41%) and sulindac treatment (72%), while the albumin/creatinine clearance ratio decreased by 59% (p less than 0.05) only during treatment with sulindac. N-acetyl-beta-D-glucosaminidase in urine was not changed by either drug. Sulindac and naproxen had no discernible effects on base excess, excretion of water, sodium, or potassium, or on osmolal clearance. However, serum potassium increased slightly but significantly (p less than 0.01) during treatment with naproxen. Sulindac sulfide, the active metabolite of sulindac, could not be traced in the urine from any of the patients. Mean arterial blood pressure declined significantly (p less than 0.05) during sulindac treatment but did not change during treatment with naproxen. Both drugs produced equal clinical improvement as measured by grip strength and the Ritchie articular index.. The results suggest that when sulindac and naproxen are given in clinical equipotent doses to patients with impaired renal function, sulindac does not affect renal prostaglandin synthesis or renal function, whereas naproxen induces suppression of renal prostaglandin synthesis and a further decrease in renal function.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Arthritis, Rheumatoid; Chronic Disease; Clinical Trials as Topic; Double-Blind Method; Female; Glomerular Filtration Rate; Humans; Kidney Diseases; Male; Middle Aged; Naproxen; Placebos; Potassium; Renal Circulation; Renin; Sodium; Sulindac

Sulindac, an indene derivative of indomethacin, was compared at 2 dosages (400 mg and 600 mg daily) in patients with rheumatoid arthritis. One hundred sixty-two patients from 19 centers completed the study--85 in the low dose group and 77 in the high dose. No difference in efficacy was found between these 2 regimens. Overall adverse reactions were more frequent with the high dose group especially with respect to blood chemistry and gastrointestinal reactions.

Topics: Adolescent; Adult; Aged; Arthritis, Rheumatoid; Blood Chemical Analysis; Clinical Trials as Topic; Gastrointestinal Diseases; Humans; Indenes; Middle Aged; Sulindac

The effect of etodolac 50-600 mg/d on renal function was assessed in four- to 52-week trials in 1,382 patients with arthritides. No patient was withdrawn from treatment due to an abnormal renal function test related to etodolac administration. There were no significant differences in the incidence of definite renal function abnormalities between patients receiving etodolac and those receiving placebo. Both etodolac and placebo groups had a significantly lower incidence of deviant BUN results than either aspirin- or sulindac-treated patients. Fewer than 2% of patients receiving etodolac showed either a persistent or variably persistent pattern of deviant renal function tests. The results in these studies indicate that chronic etodolac therapy did not adversely affect renal function in patients with arthritis.

Topics: Acetates; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Aspirin; Blood Urea Nitrogen; Clinical Trials as Topic; Creatinine; Double-Blind Method; Etodolac; Humans; Ibuprofen; Kidney Function Tests; Middle Aged; Osteoarthritis; Sulindac

The efficacy and safety of the nonsteroidal anti-inflammatory drugs imidazole.2-hydroxybenzoate and sulindac were compared in 30 patients with classical or definite rheumatoid arthritis. The trial was designed as a randomized parallel-group study comprising 15 patients given imidazole.2-hydroxybenzoate and 15 given sulindac orally for 28 days. Patients in both groups improved significantly in almost all of the variables evaluated. Imidazole.2-hydroxybenzoate was more effective than sulindac on Ritchie's articular index, left hand proximal interphalangeal joint circumference, erythrocyte sedimentation rate, and C-reactive protein. The incidence of side effects was significantly higher in patients treated with sulindac.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Blood Sedimentation; C-Reactive Protein; Clinical Trials as Topic; Female; Humans; Imidazoles; Indenes; Male; Middle Aged; Pain; Random Allocation; Salicylates; Sulindac

Topics: Adult; Aged; Arthritis, Rheumatoid; Benzothiadiazines; Diuretics; Female; Humans; Indenes; Male; Middle Aged; Naproxen; Prostaglandins; Renin; Rheumatic Heart Disease; Sodium Chloride Symporter Inhibitors; Sulindac

The efficacy of piroxicam 20 mg/qd was compared with that of sulindac 200 mg twice a day in 49 patients with rheumatoid arthritis. Both nonsteroidal anti-inflammatory agents showed statistically significant improvement in efficacy variables including duration of morning stiffness, disease activity as judged by the examiner and by the patient, patient assessment of feeling, total joint pain, total joint swelling, and performance of daily activities. The overall frequency of adverse reactions was similar with both treatment regimens, and required discontinuance in three patients in each treatment group. However, the number of moderate/severe adverse reactions in the sulindac-treated patients was greater than that in the piroxicam-treated patients, and there was a trend toward the differences between the two groups being statistically significant (P = .06). Both drugs were effective in the treatment of rheumatoid arthritis and resulted in comparable improvement in efficacy variables.

Topics: Arthritis, Rheumatoid; Clinical Trials as Topic; Female; Humans; Indenes; Male; Piroxicam; Random Allocation; Sulindac; Thiazines; Time Factors

In doses of 1,200 mg/day or more, ibuprofen is as effective as aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of rheumatoid arthritis. The tolerability and safety of ibuprofen are superior to those of aspirin and compare favorably with those of other NSAIDs. Although additional controlled trials are indicated to determine optimal dose, ibuprofen's excellent therapeutic index establishes it as a useful drug in the treatment of rheumatoid arthritis.

Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Aspirin; Clinical Trials as Topic; Drug Tolerance; Fenoprofen; Humans; Ibuprofen; Indomethacin; Ketoprofen; Naproxen; Piroxicam; Sulindac; Thiazines; Tolmetin

Ten patients with rheumatoid arthritis (RA) and concomitant heart failure were treated with either naproxen or sulindac in an open randomized study to study the drugs' effects on the urinary excretion of prostaglandins on the plasma renin level and on the renal function of the group. Both drugs were given for 14 days and caused a similar and marked decrease in renal excretion of the prostaglandins PGE2 and PGF2 alpha and in plasma renin in all patients. There was no significant effect on the diastolic blood pressure, the body weight or the 24-h creatinine clearance and the clinical effect on the joint symptoms was identical. We conclude that both sulindac and naproxen inhibit the renal prostaglandin synthesis in patients with RA.

Topics: Adult; Aged; Arthritis, Rheumatoid; Benzothiadiazines; Diuretics; Female; Heart Failure; Humans; Indenes; Kidney; Male; Middle Aged; Naproxen; Prostaglandins; Renin; Sodium Chloride Symporter Inhibitors; Sulindac

Oxaprozin, an anti-inflammatory agent with a half-life of 50 hours, was compared in regard to efficacy and tolerance with sulindac in a 12-week double-blind parallel treatment trial of rheumatoid arthritis. Oxaprozin was given as a single morning daily dose of 1200 mg, sulindac was given as 200 mg twice daily. Analysis of the results from the 20 patients (10 in each group) who completed the trial indicated that both drugs produced statistically significant improvement in morning stiffness, walking speed and the Ritchie index, but only sulindac produced significant improvement in hand function. Neither drug was associated with significant side-effects.

Topics: Adult; Aged; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Indenes; Male; Middle Aged; Oxaprozin; Propionates; Sulindac

Forty patients with definite or classical rheumatoid arthritis were entered for 3 months in a double-blind trial, 20 patients on 400 mg fentiazac or 200 mg sulindac daily. Statistically significant improvements on fentiazac were reported during the course of the study for 3 of 7 parameters: pain score, total joint score and number of swollen joints, while for sulindac a significant improvement was reported for 6 parameters: pain score, grip strength, joint size, total joint score, number of swollen joints and erythrocyte sedimentation rate. Side-effects were reported during the 3-month comparative period for 3 patients receiving fentiazac, consisting of rash, headache, epigastric pain, and for 1 patient receiving sulindac who suffered from gastro-intestinal intolerance. Because of ineffectiveness and/or side-effects, the treatment had to be discontinued for 5 patients in the fentiazac group and for 3 in the sulindac treatment group. The results support earlier evidence that fentiazac and sulindac have analgesic and anti-inflammatory properties controlling disease activity in rheumatoid arthritis, sulindac being the more effective. During a long-term tolerance study, 3 of 33 patients continued on fentiazac developed a reversible hepatotoxicity possibly due to the drug.

Topics: Acetates; Adult; Aged; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Clinical Trials as Topic; Drug Tolerance; Female; Follow-Up Studies; Humans; Indenes; Male; Middle Aged; Sulindac; Thiazoles

Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Clinical Trials as Topic; Double-Blind Method; Gastrointestinal Diseases; Humans; Indomethacin; Phenylbutazone; Phenylbutyrates; Propionates; Sulindac

The efficacy and safety of benoxaprofen and sulindac were compared in patients with rheumatoid arthritis and osteoarthritis. A double-blind, crossover protocol was used with three placebo periods. Fixed doses--600 mg of benoxaprofen once a day and 200 mg of sulindac twice a day--were used. Rheumatoid arthritis patients showed significant improvement in most measurements with both drugs, but overall results favored benoxaprofen, particularly in erythrocyte sedimentation rate and physician's global assessment. Results were fairly equal in osteoarthritis patients. Propoxyphene consumption was less during the benoxaprofen therapy period for both groups of patients. Adverse reactions in combined rheumatoid arthritis and osteoarthritis patients generally were mild to moderate. Gastrointestinal complaints were more common with sulindac, while skin reactions were more common with benoxaprofen. No serious abnormalities in laboratory values were noted.

Topics: Adult; Aged; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Indenes; Male; Middle Aged; Osteoarthritis; Propionates; Sulindac; Time Factors

Topics: Adult; Aged; Arthritis, Rheumatoid; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Indenes; Indomethacin; Male; Middle Aged; Sulindac

Topics: Adult; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Aspirin; Clinical Trials as Topic; Diclofenac; Double-Blind Method; Drug Eruptions; Drug Interactions; Female; Gastrointestinal Diseases; Headache; Humans; Indomethacin; Male; Middle Aged; Osteoarthritis; Sulindac

The effects of indomethacin and sulindac in relieving troublesome morning stiffness and nighttime pain were tested in a double-blind cross-over trial. Thirteen of the 17 patients who completed the trial preferred indomethacin which was found to be superior to sulindac in all the parameters tested. Sulindac did, however, have some beneficial effect and can be used as an alternative to indomethacin when this drug cannot be used as the agent of first choice.

Topics: Adult; Aged; Arthritis, Rheumatoid; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Indenes; Indomethacin; Male; Middle Aged; Sulindac

Unlike other nonsteroidal antiinflammatory agents, benoxaprofen has only minor antiprostaglandin synthetase activity. This property may explain the lack of gastric irritation seen in animal studies. To evaluate gastric irritation in man, benoxaprofen was compared with aspirin, naproxen, ibuprofen, sulindac, and indomethacin by measuring fecal blood loss with chromium-51 tagged red blood cells in randomized double-blind crossover and parallel studies. Benoxaprofen produced significantly less blood loss than aspirin, naproxen, or indomethacin, and less blood loss than ibuprofen or sulindac. Benoxaprofen also caused the fewest gastrointestinal complaints.

Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Aspirin; Benzoxazoles; Clinical Trials as Topic; Double-Blind Method; Gastrointestinal Hemorrhage; Humans; Indomethacin; Melena; Naproxen; Propionates; Prostaglandins; Sulindac; Time Factors

Topics: Arthritis, Rheumatoid; Aspirin; Clinical Trials as Topic; Humans; Indenes; Osteoarthritis; Placebos; Sulindac

Forty-two patients with definite or classical rheumatoid arthritis were included in a 6-week double-blind study to compare sulindac with indomethacin. Patients were randomly assigned to therapy, either sulindac 100 mg b.i.d. (plus indomethacin placebo) or indomethacin 25 mg t.i.d. (plus sulindac placebo). As required dosage was increased to either sulindac 200 mg b.i.d. or indomethacin 50 mg t.i.d. Efficacy of the two drugs was found to be equal but sulindac was better tolerated than indomethacin.

Topics: Adult; Aged; Arthritis, Rheumatoid; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Indenes; Indomethacin; Male; Middle Aged; Random Allocation; Sulindac

Forty-six patients (seventeen male, twenty-nine female) with musculo-skeletal disease were put on a controlled clinical study comparing sulindac with ibuprofen and soluble aspirin. Twenty patients were treated with sulindac 200 mg twice daily, twelve received sulindac 100 mg twice daily, eight had ibuprofen 400 mg thrice daily and six treated with soluble aspirin 600 mg thrice daily. All patients did well on these drugs, but the ones on sulindac 200 mg twice daily showed better response than sulindac 100 mg twice daily. It proved to have the same efficiency as ibuprofen and soluble aspirin; but had less side-effects and also patients required to take the drug only twice daily to get relief because of its prolonged duration of action.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Arthritis, Rheumatoid; Aspirin; Back Pain; Clinical Trials as Topic; Female; Humans; Ibuprofen; Indenes; Lumbosacral Region; Male; Middle Aged; Osteoarthritis; Random Allocation; Sulindac; Tenosynovitis

Newer nonsteroidal antiinflammatory agents (NSAI's) such as ibuprofen, neproxen, fenoprofen, and tolmetin have broadened the therapeutic choice and increased the chances of providing optimum arthritis control, but require careful assessment of the possibilities for unwanted drug effects when long-term therapy is required. A review of the literature on the gastrointestinal effects of the promising newer NSAIs, as compared with the older agents, aspirin, indomethacin, and phenylbutazone, is presented, highlighting animal toxicology and human adverse reaction surveillance data and the evidence for various suggested pathophysiological mechanisms.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Aspirin; Clinical Trials as Topic; Diclofenac; Double-Blind Method; Drug Evaluation; Fenoprofen; Gastric Mucosa; Gastritis; Gastrointestinal Hemorrhage; Gastroscopy; Humans; Ibuprofen; Ketoprofen; Naproxen; Phenylbutazone; Registries; Sulindac; Tolmetin

A double-blind crossover trial was carried out in 24 patients to compare the effects of mefenamic acid, flurbiprofen, sulindac and placebo. Each drug was given for 2 weeks, the treatment sequence being randomized. Daily doses were 1500 mg mefenamic acid, 150 mg flurbiprofen or 150 mg sulindac. All of the active drugs were significantly superior to placebo in terms of pain score, patients' assessment, articular index of joint tenderness, and duration and severity of morning stiffness. There was improvement in grip strength compared with placebo, but the differences were not statistically significant with sulindac. There was slight reduction in joint circumference but this was only statistically significant in the right hand with flurbiprofen and sulindac. No significant differences were found in technetium uptake in knee joints. The three drugs appeared to be equally effective and tolerated, and no significant differences were noted.

Topics: Adult; Aged; Arthritis, Rheumatoid; Clinical Trials as Topic; Double-Blind Method; Female; Flurbiprofen; Humans; Indenes; Male; Mefenamic Acid; Middle Aged; Propionates; Sulindac

Topics: Adult; Aged; Arthritis, Rheumatoid; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Female; Humans; Indenes; Male; Middle Aged; Sulindac

Sulindac 200mg b.i.d. was compared with ibuprofen 400mg t.d.s. in a double-blind controlled trial in patients with rheumatoid arthritis. Both drugs produced a measurable and significant improvement from baseline levels, in both objective and subjective parameters. All parameters favoured sulindac but the differences were not statistically significant. Side effects were infrequent with both drugs and in all but three cases did not necessitate withdrawal from the trials. Sulindac appears to be an effective anti-inflammatory analgesic drug for the management of rheumatoid arthritis with a low incidence of side effects.

Topics: Adult; Aged; Arthritis, Rheumatoid; Clinical Trials as Topic; Double-Blind Method; Humans; Ibuprofen; Indenes; Middle Aged; Sulindac

Topics: Arthritis, Rheumatoid; Clinical Trials as Topic; Female; Humans; Indenes; Male; Middle Aged; Sulindac

Herein we report the design as well as the synthesis of a new series of dual hybrid compounds consisting of the therapeutically used nonsteroidal-anti-inflammatory drugs (NSAIDs; i.e., indometacin, sulindac, ketoprofen, ibuprofen, diclofenac, ketorolac, etc., cyclooxygenase inhibitors) and the carbonic anhydrase inhibitor (CAIs) fragments of the sulfonamide type. Such compounds are proposed as new tools for the management of ache symptoms associated with rheumatoid arthritis (RA) and related inflammation diseases. The majority of the hybrids reported were effective in inhibiting the ubiquitous human (h) CA I and II as well as the RA overexpressed hCAs IX and XII isoforms, with K

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Carbonic Anhydrase Inhibitors; Humans; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship; Sulfonamides

A case of drug-associated cholelithiasis (sulindac chlecystohepatolithiasis) in a 63-yr-old woman is reported. The patient was admitted to our hospital to undergo treatment for rheumatoid arthritis of 20 yr duration. She was treated with nonsteroidal anti-inflammatory drugs (NSAID: sulindac). Two months later, she presented with right upper quadrant pain. Diagnostic studies including ultrasonography (US), computed tomography (CT) and endoscopic retrograde cholangiography (ERC), led to the diagnosis of cholecystohepatolithiasis. She underwent cholecystectomy and choledochotomy with an extraction of intrahepatic stones. The intrahepatic stones were light yellow in color with a claylike appearance. Unexpectedly, an infrared spectroscopic analysis of the stone showed it to consist of sulindac metabolites. In addition, the dilated segment of the intrahepatic bile duct naturally returned to its normal size after the discontinuation of the drug administration. This is the first reported case of sulindac stone formation in the bile duct. No similar problems with other NSAIDs have been reported previously.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Cholelithiasis; Female; Humans; Middle Aged; Spectrophotometry, Infrared; Sulindac

The pharmacokinetics of low dose methotrexate (MTX) were evaluated in 12 rheumatoid arthritis patients in the presence and absence of steady-state levels of salicylic acid (ASA) and sulindac (SU). Using a Latin square design, patients were given MTX plus ASA (mean 3.4 g/day), MTX plus SU (mean 400 mg/day), or MTX alone. On a background of at least one year of regular MTX therapy, patients received 10 mg/m2 MTX iv (mean 17.8 mg) given after at least 2 weeks of treatment with each of the above regimens. Plasma concentrations of MTX and 7-hydroxymethotrexate (7-OH-MTX) were measured using HPLC. No differences in MTX clearance (Cl) were found comparing MTX alone, MTX + ASA, and MTX + SU. However, if one particular subject that had a very low clearance when receiving MTX alone was excluded, there was a statistically significant decrease in MTX clearance when either ASA or SUL were present. It is also noteworthy that ASA significantly increased the exposure of the subject to 7-OH-MTX and, to a lesser extent, so did sulindac. Since 7-OH-MTX has been shown to be an active metabolite when given for cytotoxic effects at higher doses and because it has been show to be nephrotoxic at doses a thousand-fold greater than used in rheumatoid arthritis, nonsteroidal anti-inflammatory drugs should be used cautiously with MTX until further large scale safety studies are conducted. The data indicate that if a clinically significant interaction were to occur, ASA is more likely than SU to interact with MTX.

Topics: Arthritis, Rheumatoid; Aspirin; Drug Interactions; Female; Humans; Male; Methotrexate; Sulindac

A patient with severe rheumatoid arthritis (RA) receiving chronic anticoagulation therapy developed acute life threatening airway obstruction. The source of obstruction was a retropharyngeal hematoma compressing the upper airway rather than acute laryngeal dysfunction from the patient's RA. Our case illustrates a new cause of acute stridor and airway obstruction in RA. Publications on upper airway obstruction in RA and airway obstruction secondary to retropharyngeal hematoma are discussed.

Topics: Airway Obstruction; Arthritis, Rheumatoid; Drug Interactions; Female; Hematoma; Humans; Middle Aged; Pharynx; Pressure; Sulindac; Warfarin

Toxic epidermal necrolysis with epidermal shedding over almost the entire body occurred in a patient with classical rheumatoid arthritis treated with sulindac, penicillamine and a combination analgesic containing paracetamol and chlormezanone. Erosions in the lower respiratory tract and the intestine contributed to a lethal outcome of the disease and showed a microscopical picture similar to that of the skin involved. The histopathological picture of these extracutaneous lesions have been only briefly reported previously.

Topics: Acetaminophen; Arthritis, Rheumatoid; Biopsy; Chlormezanone; Drug Combinations; Female; Humans; Intestine, Large; Middle Aged; Penicillamine; Respiratory System; Skin; Stevens-Johnson Syndrome; Sulindac

The disposition and effect on hemostasis of a single 150 mg dose of sulindac was studied in young healthy subjects and in older patients with arthritis. Older patients were restudied after 2 weeks of sulindac, 150 mg b.i.d. The only difference in disposition of the first dose was a reduced plasma sulfone metabolite concentration in the elderly patients with arthritis. Chronic sulindac dosing resulted in accumulation of the drug and its sulfone and sulfide metabolites in plasma to a greater extent than previously reported for young subjects. No differences in renal clearance of sulindac and its sulfone metabolite related to age or chronic drug dosing were observed. No renal excretion of the active sulfide metabolite was detected. Bleeding time in the elderly patients was shorter than in the young healthy subjects before sulindac dosing, but was prolonged in the elderly patients after 2 weeks of dosing to values similar to control data from the young healthy subjects. This change correlated weakly with plasma sulfide metabolite concentrations. Differences in bleeding time were not reflected in changes in platelet aggregation induced by adenosine diphosphate either with respect to age or chronic drug dosing. Our data provide no justification for lowering the recommended dose of sulindac for patients older than 65 years of age.

Topics: Adult; Aged; Aging; Arthritis, Rheumatoid; Blood Coagulation; Female; Humans; Indenes; Kinetics; Male; Osteoarthritis; Platelet Aggregation; Sulindac

Topics: Arthritis, Rheumatoid; Aspirin; Diclofenac; Double-Blind Method; Humans; Indomethacin; Naproxen; Osteoarthritis; Sulindac; Tolmetin

The pharmacokinetics of ibuprofen (Motrin) are best described by a two-compartment open model. Ibuprofen pharmacokinetics are only minimally influenced by advanced age, the presence of alcoholic liver disease, or rheumatoid arthritis. Levels of ibuprofen in breast milk are negligible. In addition, ibuprofen can be combined with acetaminophen without altering the pharmacokinetic profile. However, although not yet clinically proved, the concomitant use of ibuprofen and aspirin appears to reduce ibuprofen plasma levels to less than half those observed with ibuprofen alone.

Topics: Acetaminophen; Adult; Age Factors; Aged; Arthritis, Rheumatoid; Aspirin; Biological Availability; Chromatography, Gas; Chromatography, High Pressure Liquid; Drug Interactions; Female; Humans; Ibuprofen; Intestinal Absorption; Kinetics; Liver Diseases, Alcoholic; Male; Milk, Human; Models, Chemical; Sulindac; Time Factors

This article reviews the efficacy of NSAIDs and their pharmacokinetic and pharmacodynamic properties. The assumption that classic pharmacokinetic dose/plasma concentration response relationships can be applied to NSAIDs has tenuous support in the biomedical literature. Comparative efficacy studies, using ASA and indomethacin as the standards for comparison, ignore the fact that the major outcome variables are subjective responses among patients, not among drugs. Comparing inhibition of platelet malonyldialdehyde, synovial drug concentrations, urinary prostaglandin metabolites, and plasma free and total concentration with the clinical outcome provides no guidelines to serve as predictors of response. The individual agents, indomethacin, salicylates, sulindac, piroxicam, and naproxen, illustrate the complexities of NSAID pharmacotherapy. Recent proliferation of newer NSAIDs will not add significantly to the efficacy of these agents in the treatment of pain and inflammatory disease states. However, knowledge of pharmacokinetic population parameters for the individual NSAIDs will increase the likelihood of therapeutic success and diminish the possibilities for adverse reactions.

Topics: Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Dose-Response Relationship, Drug; Humans; Indomethacin; Kinetics; Naproxen; Piroxicam; Prostaglandin Antagonists; Salicylates; Sulindac; Thiazines

A 31-year-old man with rheumatoid arthritis, who had previously been treated with sulindac, fenoprofen calcium, high dose salicylates and gold salts, developed renal papillary necrosis (RPN) 4 months after institution of naproxen therapy. No other factor predisposing to RPN could be discovered. Sulindac was substituted for naproxen and no further adverse renal effects occurred over the next 12 months. We review previous reports linking RPN to antiinflammatory drug use and discuss possible advantages of sulindac in patients who have experienced renal toxicity from other antiinflammatory agents.

Topics: Adult; Arthritis, Rheumatoid; Humans; Kidney Papillary Necrosis; Male; Naproxen; Sulindac

We report 2 patients who had serious adverse effects after taking sulindac. One of these patients developed toxic hepatitis and Stevens-Johnson/toxic epidermal necrolysis syndrome which resulted in death. Such fatal reaction to sulindac therapy has not been reported previously. There was temporal relation of ingestion of sulindac to 2 episodes of acute pancreatitis in the 2nd patient, strongly suggesting drug induction. Recent reports of similar side effects with other nonsteroidal antiinflammatory drugs suggest that these drugs may have potentially more serious toxicity than has been recognized.

Topics: Acute Disease; Arthritis, Rheumatoid; Back Pain; Chemical and Drug Induced Liver Injury; Female; Humans; Indenes; Middle Aged; Pancreatitis; Stevens-Johnson Syndrome; Sulindac

Topics: Arthritis, Rheumatoid; Gynecomastia; Humans; Indenes; Male; Middle Aged; Sulindac

Topics: Arthritis, Rheumatoid; Female; Humans; Indenes; Kidney; Middle Aged; Nephritis, Interstitial; Sulindac

Topics: Agranulocytosis; Arthritis, Rheumatoid; Blood Cell Count; Female; Humans; Indenes; Middle Aged; Sulindac

New pharmacodynamic chemical agents have been released for the treatment of rheumatoid arthritis and other arthritides. These agents, the aryl-alkanoic acid derivatives, which are classified as nonsteroidal anti-inflammatory agents, exert an anti-inflammatory effect on locally affected tissues. A suggested mechanism of action may be to inhibit the synthesis of prostaglandins, which are involved in the basic inflammatory tissue response. These agents have been found to be not significantly more effective than aspirin, but they may be useful in patients who cannot tolerate aspirin.

Topics: Anti-Inflammatory Agents; Arthritis; Arthritis, Rheumatoid; Drug Administration Schedule; Fenoprofen; Humans; Ibuprofen; Naproxen; Prostaglandins; Sulindac; Tolmetin

Topics: Adolescent; Arthritis, Rheumatoid; Drug Hypersensitivity; Humans; Indenes; Leukopenia; Liver; Male; Pain; Pharyngitis; Pneumonia; Pruritus; Sulindac

Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Humans; Indomethacin; Phenylbutazone; Sulindac

Topics: Arthritis, Rheumatoid; Dose-Response Relationship, Drug; Ibuprofen; Indenes; Joint Diseases; Sulindac