Fenoprofen

Publisher Website
Google Scholar
Abstract
Synopsis: Fenoprofen1 (dl-2-[3-phenoxyphenyl]propionic acid) is a new non-steroidal anti-inflammatory, antipyretic, analgesic agent advocated for use in rheumatoid arthritis, degenerative joint disease, ankylosing spondylitis and gout. Published data suggest that in rheumatoid arthritis, fenoprofen 2.4g daily is comparable in effectiveness with moderate doses of aspirin (3.6 to 4g daily), but generally causes fewer and milder side-effects at the dosages used. In published comparisons with other non-steroidal anti-inflammatory agents of the same chemical group, it is closely comparable with naproxen in effectiveness but tends to cause more minor side-effects than naproxen. However, as no one of the non-steroidal anti-inflammatory agents is the most suitable drug for all patients requiring such therapy, fenoprofen should be considered along with the other drugs of its type in the initial treatment of the arthritic patient. Fenoprofen has compared favourably with phenylbutazone in osteoarthrosis of the hips and with aspirin in osteoarthrosis of the shoulders, hips, knees and spine. Its exact place in the management of gout and ankylosing spondylitis remains to be determined. Animal pharmacology: The anti-inflammatory activity of fenoprofen has been demonstrated in its ability to inhibit the ultraviolet-induced erythema in guinea-pigs, the development of carrageenin-induced paw oedema, of swelling and bone damage in rats with adjuvant-induced arthritis and of experimental uveitis in rabbits. An analgesic effect was demonstrated in mice and rats where the effects of fenoprofen were additive to those of dextropropoxyphene. A significant antipyretic effect was exerted in febrile rats. Like aspirin and phenylbutazone, fenoprofen inhibited collagen-induced platelet aggregation but had little, if any, effect on adenosine phosphate-induced platelet aggregation. Also, like many other non-steroidal anti-inflammatory agents fenoprofen inhibits the synthesis and release of prostaglandin F and E in vitro and possibly in vivo as evidenced by the reduction in uterine activity in pregnant monkeys. Single doses of 25, 100 and 200mg/kg of fenoprofen caused ulceration of the gastric mucosa and submucosa in a high proportion of fasted rats. In dogs with Heidenhain pouches, aspirin and indomethacin caused more total back diffusion of acid and had a longer duration of effect on sodium ion efflux than an equal weight and equimolar concentrations of fenoprofen. Human pharmacology: In man, fenoprofen in a single dose of 400mg has been shown to exert an antipyretic effect, whilst at doses of 300 to 600mg it delays or decreases ultraviolet-induced erythema. Usual therapeutic doses of fenoprofen appear to cause less gastro-intestinal bleeding than aspirin when both drugs are given in capsules at doses similar to those used to treat arthritic conditions. In a study on human platelets, fenoprofen inhibited collagen-induced platelet aggregation at lower concentrations than either aspirin or phenylbutazone. Fenoprofen exhibited marked inhibition of the activity of myometrial strips excised from uteri of pregnant and non-pregnant patients, an effect which may be associated with its inhibition of prostaglandin release and synthesis. Studies in healthy volunteers indicate that fenoprofen is readily absorbed after oral administration. Plasma levels attained with the sodium salt tend to be higher than those attained with the calcium salt. Plasma levels of fenoprofen are reduced when taken with food and by the concomitant ingestion of aspirin. However, the clinical significance of this reaction is not certain. Fenoprofen has a serum half-life of about 150 to 180 minutes and is at least 99% bound to plasma proteins. It is extensively metabolised after oral administration, the main metabolites being fenoprofen glucuronide and 4-hydroxy-fenoprofen glucuronide. Only about 2 to 5% of a single-dose is excreted unchanged. Fenoprofen and its metabolites are rapidly excreted in the urine with about 96% of a 250mg dose being recovered in 24 hours. Clinical studies ranging in duration from single-dose studies to 1 week have shown fenoprofen to produce analgesia in patients with pain associated with osteoarthrosis, rheumatoid arthritis and other causes. These findings have been confirmed in therapeutic trials. Relatively short-term and longer-term therapeutic trials published to date have shown the efficacy of fenoprofen to be greater than that of placebo and generally indistinguishable from that of aspirin in patients with active rheumatoid arthritis. Most studies to date have compared fenoprofen 2.4g daily with high doses of aspirin (3.9 to 6g daily) and have usually not been able to find any statistically significant difference between the two drugs with regard to their effects on objective and subjective criteria of effectiveness. Almost invariably, side-effects have been more frequent with aspirin than with fenoprofen at the dosages used. In two studies which have compared fenoprofen with other propionic acid derivatives naproxen has been the drug of choice followed by fenoprofen. There was little to choose between these two drugs with regard to effectiveness, but side-effects tended to be less of a problem with naproxen. However, no one of these drugs was the best for all patients and a short trial of each may be advisable to ensure the best possible response in a particular patient, as it is not possible to predict which will be most suitable. Long-term studies in which the efficacy of fenoprofen 2 to 2.4g and aspirin 3.6 to 4g daily have been compared for periods of at least 24 weeks, have reported a tendency for fenoprofen to be preferable to aspirin at the dosages used. In patients with osteoarthrosis, fenoprofen has been compared with phenylbutazone, ibuprofen, paracetamol alone or combined with dextropropoxyphene and with aspirin. Fenoprofen 2g daily was indistinguishable from phenylbutazone 300mg daily. Similarly no significant difference could be detected between fenoprofen 2.4g daily and ibuprofen 1.6g daily, but fenoprofen 2g daily was more effective than the simple analgesics. Aspirin 2.275 to 3.1g daily was indistinguishable from fenoprofen 1.4 to 1.8g daily. Although 2.4g fenoprofen daily was rated better than 3.6g aspirin in patients with ankylosing spondylitis the exact place of fenoprofen relative to other non-steroidal anti-inflammatory agents in the management of this disease has yet to be determined. Initial results with fenoprofen in acute gout have been favourable, but further studies are needed to determine the best dosage regimen and its efficacy relative to that of drugs commonly used in acute gout. At the dosages used in the treatment of rheumatoid arthritis and osteoarthrosis fenoprofen has generally been well tolerated and it has seldom been necessary to discontinue treatment because of side-effects. Abdominal discomfort, dyspepsia, nausea and skin rash have been the most frequently reported side-effects associated with fenoprofen therapy. Fenoprofen should be given only under close supervision to patients with a history of upper gastrointestinal disease and should be avoided in patients with active peptic ulcer. Since the drug is eliminated principally via the kidneys it should be given with caution in the presence of impaired renal function. Fenoprofen decreases platelet aggregation and prolongs bleeding time in animals. Patients whose health may be adversely affected by prolongation of the bleeding time should be carefully observed during fenoprofen therapy. The usual initial adult dose of fenoprofen in rheumatoid arthritis is 600mg 4 times a day. If necessary, the dosage may be increased, but a total above 3g daily is not recommended.