Photosensitizing potential of certain nonsteroidal anti-inflammatory agents.

The nonsteroidal anti-inflammatory drugs (NSAIDs) have been repeatedly associated with photosensitivity reactions. The underlying mechanism however is not known, and the clinical features are not always consistent with either a phototoxic or a photoallergic mechanism. In this study, four NSAIDs were investigated for their phototoxicity potential in human volunteers using an oral dosing protocol. Phototoxicity, consisting of wheal-and-flare reactions following exposure to ultraviolet radiation, was demonstrated following the administration of naproxen and nabumetone, but was not seen in volunteers who received piroxicam, a drug reported to cause photosensitivity. Thus, although certain NSAIDs are potentially capable of producing phototoxicity reactions, others can presumably provoke clinical photosensitivity through other mechanisms.

Safety evaluation of nabumetone in United States clinical trials.

A total of 1,924 persons (rheumatoid arthritis, 835; osteoarthritis, 1,073; volunteers, 16) received nabumetone in United States clinical trials. Nine hundred eighty-eight patients have received nabumetone treatment for periods of more than one year, and 375 patients have received treatment for longer than two years. Four hundred eighty patients over 65 years of age have received treatment with nabumetone, and 224 of these elderly patients have received treatment for periods of more than one year. The nabumetone dose most commonly used in all double-blind trials was 1,000 mg at night. In long-term, open-label studies, which were usually extensions of the double-blind trials, patients could increase the dose to 2,000 mg per day. Nine hundred nineteen patients received doses of more than 1,000 mg per day. Adverse experience information was collected at each visit, including information for some patients receiving treatment for more than three years. Laboratory data were collected periodically throughout the trials, and the data were assessed for trends over time. The adverse experience pattern observed for nabumetone is similar to that described for clinical trial data for other nonsteroidal anti-inflammatory drugs. However, it is noteworthy that the pattern observed for nabumetone is from clinical trials with approximately 1,000 patients receiving treatment for periods of one year or more. This long-term patient exposure in clinical trials far exceeds long-term clinical trial data for other agents. The types and frequencies of adverse experiences reported by persons treated with nabumetone are relatively constant over the long time period covered by these trials. Also, the adverse experience patterns remained generally constant over time for various populations: all patients, patients 65 or older, female patients, male patients, and patients who received an increased dose of nabumetone. Although some statistically significant trends were detected for some laboratory parameters, there was little indication of significant clinical patterns. Although there were patients with individually important laboratory values, nabumetone was not associated with clinically important adverse laboratory patterns. Overall, the adverse experience data and laboratory data indicate that nabumetone is safe for the treatment of adult patients with rheumatoid arthritis or osteoarthritis.

Nabumetone: a single-center three-week comparison with placebo in the treatment of rheumatoid arthritis.

Forty-six patients with definite or classical rheumatoid arthritis were entered into a three-week, double-blind, randomized, parallel study of nabumetone, 1,000 mg at bedtime, compared with placebo. Fifteen nabumetone-treated and 12 placebo-treated patients were evaluated for efficacy variables including physician's opinion of rheumatoid arthritis activity, patient's opinion of rheumatoid arthritis activity, articular index, morning stiffness, 50-foot walking time, grip strength, and acetaminophen consumption. Between-group analysis of improvement over baseline was significantly (p less than 0.05) greater for nabumetone-treated patients for six of the seven variables. Nabumetone was significantly favored over placebo in three global evaluations and significantly more placebo-treated (75 percent) than nabumetone-treated (20 percent) patients withdrew from the study due to an unsatisfactory therapeutic response. Of the 38 patients receiving the study medication, 22 percent of nabumetone-treated and 5 percent of placebo-treated patients reported adverse experiences either related to treatment or for which the relationship to treatment was unknown. No patients were withdrawn from the study as a result of these experiences and no long-term sequelae or clinically significant laboratory abnormalities were reported.