Fenoprofen

3.1

3.45

Slight (calcium salt)

8.11e-02 g/L

Breast Feeding; Lactation; Milk, Human; Analgesic Agents; Anti-inflammatory Agents, Nonsteroidal

Pharmaceuticals

4.5

PKA= 7.3

WHEN FENOPROFEN WAS ADDED TO REGIMEN OF...PT WITH RHEUMATOID ARTHRITIS WHO WERE RECEIVING CORTICOSTEROID OR GOLD THERAPY, THERE WAS SOME EVIDENCE THAT DOSE OF STEROID COULD BE REDUCED & COMBINATION WITH GOLD WAS MORE EFFECTIVE.

FOOD DELAYS ABSORPTION...& REDUCES PEAK PLASMA CONCN (ABOUT 30%) & TOTAL ABSORPTION (ABOUT 20%), AS DOES COADMIN OF...ANTACIDS.

/PLASMA PROTEIN/ BINDING OF FENOPROFEN IS INHIBITED BY CONCOMITANT ADMIN OF INDOMETHACIN & PHENYLBUTAZONE... PLASMA T/2 OF FENOPROFEN IS DECR BY ASPIRIN...

FENPROFEN & PROPOXYPHENE ARE ADDITIVE WHEN GIVEN TOGETHER.

Prospective studies show that up to 15% of patients taking fenoprofen experience at least transient serum aminotransferase elevations. These elevations are generally transient, mild and asymptomatic, and may resolve even with drug continuation. Marked aminotransferase elevations (above 3 times the upper limit of normal (ULN) occur in less than 1% of patients.

MOST COMMON ADVERSE REACTIONS /ORAL ADMIN/...GI EFFECTS (EG, DYSPEPSIA, CONSTIPATION, NAUSEA, VOMITING)...FEW CASES OF ULCERATION... CNS REACTIONS INCL DROWSINESS, DIZZINESS, HEADACHE, NERVOUSNESS, & CONFUSION. PRURITUS, RASH, SWEATING, PALPITATIONS, TREMOR, TINNITUS, BLURRED VISION, & DECR HEARING...SENSITIVITY TO DRUG...

ELEVATIONS OF SERUM TRANSAMINASE, LACTIC DEHYDROGENASE, & ALKALINE PHOSPHATASE LEVELS...IN SOME PT. DECR IN HEMOGLOBIN & HEMATOCRIT...OCCASIONALLY. FENOPROFEN REDUCES PLATELET AGGREGATION & ADHESIVENESS & INCR BLEEDING TIME /ORAL ADMIN/.

.../FENOPROFEN, ORALLY/ EFFECTIVENESS IN RHEUMATOID ARTHRITIS APPEARS... COMPARABLE TO...ASPIRIN &...INCIDENCE OF GI REACTIONS & AMT OF GI BLEEDING IS LESS THAN WITH ASPIRIN.

...DRUGS /INCL FENOPROFEN/ HAVE BEEN ASSOC WITH FATAL GI HEMORRHAGE IN RARE CASES.

For more Human Toxicity Excerpts (Complete) data for FENOPROFEN (10 total), please visit the HSDB record page.

Benchmark Dataset for the Liver Toxicity Knowledge Base (LTKB)

fenoprofen

Nalfon®

NSAIDs

8

most-DILI-concern

M - Musculo-skeletal system

QM - Musculo-skeletal system

Fenoprofen is a propionic acid derivative with analgesic, antiinflammatory and antipyretic properties. Fenoprofen inhibits prostaglandin synthesis by decreasing the enzyme needed for biosynthesis. In patients with rheumatoid arthritis, the anti-inflammatory action of fenoprofen has been evidenced by relief of pain, increase in grip strength, and reductions in joint swelling, duration of morning stiffness, and disease activity (as assessed by both the investigator and the patient). In patients with osteoarthritis, the anti-inflammatory and analgesic effects of fenoprofen have been demonstrated by reduction in tenderness as a response to pressure and reductions in night pain, stiffness, swelling, and overall disease activity (as assessed by both the patient and the investigator). These effects have also been demonstrated by relief of pain with motion and at rest and increased range of motion in involved joints. In patients with rheumatoid arthritis and osteoarthritis, clinical studies have shown fenoprofen to be comparable to aspirin in controlling the aforementioned measures of disease activity, but mild gastrointestinal reactions (nausea, dyspepsia) and tinnitus occurred less frequently in patients treated with fenoprofen than in aspirin-treated patients. It is not known whether fenoprofen causes less peptic ulceration than does aspirin. In patients with pain, the analgesic action of fenoprofen has produced a reduction in pain intensity, an increase in pain relief, improvement in total analgesia scores, and a sustained analgesic effect.

Fenoprofen's exact mode of action is unknown, but it is thought that prostaglandin synthetase inhibition is involved. Fenoprofen has been shown to inhibit prostaglandin synthetase isolated from bovine seminal vesicles.

LIKE ASPIRIN, FENOPROFEN INHIBITS PROSTAGLANDIN SYNTHETASE, BUT SIGNIFICANCE OF THIS ACTION IN RELATION TO CLINICAL EFFECTS PRODUCED IS NOT KNOWN.

Plasma half-life is approximately 3 hours.

...RAPIDLY ABSORBED AFTER ORAL ADMIN; PEAK PLASMA LEVEL OCCURS WITHIN 90 MIN. IT HAS PLASMA T/2 OF ABOUT 160 MIN, WHICH DOES NOT APPEAR...DOSE DEPENDENT. ABSORPTION & AVAILABILITY ARE REDUCED WHEN...AGENT IS GIVEN WITH FOOD, BUT ARE NOT AFFECTED BY CONCOMITANT ADMIN OF AN ANTACID...

...T/2...2.5-3 HR...

About 90% of a single oral dose is eliminated within 24 hours as fenoprofen glucuronide and 4'-hydroxyfenoprofen glucuronide, the major urinary metabolites of fenoprofen.

...FENOPROFEN...FOUND TO YIELD 2 URINARY GLUCURONIDES IN MAN. ONE...ACCOUNTING FOR ALMOST 1/2 THE DOSE, IS THE ACYL GLUCURONIDE... THE SECOND...ACCOUNTING FOR THE OTHER 1/2 OF THE DOSE, IS A GLUCURONIDE OF THE PHENOLIC DERIVATIVE /OF FENOPROFEN/...AN ACYL GLUCURONIDE WITH A FREE PHENOLIC GROUP.

...FENOPROFEN...FOUND TO YIELD SMALL AMT OF ACID-LABILE CONJUGATE BEING NEITHER A GLYCINE NOR A GLUTAMINE CONJUGATE...

RA33EAC7KY

FENOPROFEN

Mechanisms of Action [MoA] - Cyclooxygenase Inhibitors

Chemical Structure [CS] - Anti-Inflammatory Agents, Non-Steroidal

Established Pharmacologic Class [EPC] - Nonsteroidal Anti-inflammatory Drug

Fenoprofen is a Nonsteroidal Anti-inflammatory Drug. The mechanism of action of fenoprofen is as a Cyclooxygenase Inhibitor.

Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions. They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects.

Compounds or agents that combine with cyclooxygenase (PROSTAGLANDIN-ENDOPEROXIDE SYNTHASES) and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of eicosanoids, prostaglandins, and thromboxanes.

Rapidly absorbed under fasting conditions, and peak plasma levels of 50 µg/mL are achieved within 2 hours after oral administration of 600 mg doses.

...RAPIDLY ABSORBED AFTER ORAL ADMIN; PEAK PLASMA LEVEL OCCURS WITHIN 90 MIN. ...ABSORPTION & AVAILABILITY ARE REDUCED WHEN...AGENT IS GIVEN WITH FOOD, BUT ARE NOT AFFECTED BY CONCOMITANT ADMIN OF AN ANTACID...

...FENOPROFEN...IS WELL ABSORBED FROM GI TRACT AS NA OR CA SALT, & IS RAPIDLY CLEARED BY KIDNEYS...

IN USUAL DOSES, FENOPROFEN...WELL ABSORBED (OVER 80%), RAPIDLY /ACHIEVES/... STEADY-STATE BLOOD LEVELS...HIGHLY PROTEIN BOUND (95-99%). ...BIOTRANSFORMED IN LIVER, & METABOLITES ARE EXCRETED IN URINE. ...T/2...2.5-3 HR...

FOLLOWING ABSORPTION, FENOPROFEN IS METAB & EXCRETED ALMOST EXCLUSIVELY IN URINE IN CONJUGATED FORM. ...IS HIGHLY BOUND TO PLASMA PROTEIN, & IT MAY DISPLACE OTHER PROTEIN-BOUND DRUGS FROM THEIR BINDING SITES, LEADING TO DRUG INTERACTIONS.

HUMAN PLASMA & URINE PHARMACOKINETICS AFTER ORAL & IV ADMIN OF FENOPROFEN.

LILLY 69323; FENOPRON; FEPRONA /CALCIUM SALT DIHYDRATE/

NALFON (DISTA). ORAL: CAPSULES 300 MG