(±)-2-Fluor-α-methyl[1,1'-biphenyl]-4-essigsure

Pharmaceuticals -> Musculo-skeletal system -> Anti-inflammatory and antirheumatic products

Pharmaceuticals

Pharmaceuticals -> Analgesics and anti-inflammatories

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

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Pharmaceuticals

110-111 °C

110 - 111 °C

4.03

4.22

4.3

Danger

H301 (98.2%): Toxic if swallowed [Danger Acute toxicity, oral]

P203, P261, P264, P264+P265, P270, P271, P280, P301+P316, P302+P352, P304+P340, P305+P351+P338, P318, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 114 reports by companies from 15 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Patients should be managed by symptomatic and supportive care following overdose with a nonsteroidal anti-inflammatory drug. There are no specific antidotes. Emesis and/or activated charcoal (60 to 100 g in adults, 1 to 2 g/kg in children) and/or osmotic cathartic may be indicated in patients seen within 4 hours of ingestion with symptoms, or following a large overdose (5 to 10 times the usual dose). Forced diuresis, alkalization of urine, hemodialysis, or hemoperfusion may not be useful due to high protein binding. (L1712)

Prospective studies show that mild elevations in serum aminotransferase levels can occur in up to 15% of patients taking NSAIDs such as flurbiprofen, but the abnormalities are generally transient, mild and asymptomatic, often resolving even with drug continuation. Marked aminotransferase elevations above 3 times the upper limit of normal (ULN) occur in less than 1% of patients. Clinically apparent liver injury with jaundice from flurbiprofen is rare and only individual case descriptions have been published. The latency to onset is within 1 to 4 weeks of starting. The pattern of enzyme elevations is typically cholestatic, but hepatocellular cases have been described. Immunoallergic features are present in some cases (low grade fever, rash), but are generally not prominent, and autoantibody formation is rare. Most cases resolve promptly on stopping therapy. Flurbiprofen is not mentioned in large case series on drug induced liver injury or acute liver failure from the United States, but was listed as the second most common agent implicated in drug-induced liver injury in a case series from Turkey, one of which was fatal.

Similar to other NSAIAs, the anti-inflammatory effect of flurbiprofen occurs via reversible inhibition of cyclooxygenase (COX), the enzyme responsible for the conversion of arachidonic acid to prostaglandin G2 (PGG2) and PGG2 to prostaglandin H2 (PGH2) in the prostaglandin synthesis pathway. This effectively decreases the concentration of prostaglandins involved in inflammation, pain, swelling and fever. Flurbiprofen is a non-selective COX inhibitor and inhibits the activity of both COX-1 and -2. It is also one of the most potent NSAIAs in terms of prostaglandin inhibitory activity.

Benchmark Dataset for the Liver Toxicity Knowledge Base (LTKB)

flurbiprofen

Ocufen®

NSAIDs

3

less-DILI-concern drugs

R02AX01

S - Sensory organs

M - Musculo-skeletal system

M - Musculo-skeletal system

R - Respiratory system

QM - Musculo-skeletal system

Flurbiprofen, a nonsteroidal anti-inflammatory agent (NSAIA) of the propionic acid class, is structually and pharmacologically related to fenoprofen, ibuprofen, and ketoprofen, and has similar pharmacological actions to other prototypica NSAIAs. Flurbiprofen exhibits antiinflammatory, analgesic, and antipyretic activities. The commercially available flurbiprofen is a racemic mixture of (+)S- and (-) R-enantiomers. The S-enantiomer appears to possess most of the anti-inflammatory, while both enantiomers may possess analgesic activity.

Similar to other NSAIAs, the anti-inflammatory effect of flurbiprofen occurs via reversible inhibition of cyclooxygenase (COX), the enzyme responsible for the conversion of arachidonic acid to prostaglandin G2 (PGG2) and PGG2 to prostaglandin H2 (PGH2) in the prostaglandin synthesis pathway. This effectively decreases the concentration of prostaglandins involved in inflammation, pain, swelling and fever. Flurbiprofen is a non-selective COX inhibitor and inhibits the activity of both COX-1 and -2. It is also one of the most potent NSAIAs in terms of prostaglandin inhibitory activity.

Hepatic. Cytochrome P450 2C9 plays an important role in the metabolism of flurbiprofen to its major metabolite, 4’-hydroxy-flurbiprofen. The 4’-hydroxy-flurbiprofen metabolite showed little anti-inflammatory activity in animal models of inflammation.

Hepatic. Cytochrome P450 2C9 plays an important role in the metabolism of flurbiprofen to its major metabolite, 4’-hydroxy-flurbiprofen. The 4’-hydroxy-flurbiprofen metabolite showed little anti-inflammatory activity in animal models of inflammation. Route of Elimination: Flurbiprofen is poorly excreted into human milk. Following dosing with flurbiprofen, less than 3% of flurbiprofen is excreted unchanged in the urine, with about 70% of the dose eliminated in the urine as parent drug and metabolites. Renal elimination is a significant pathway of elimination of flurbiprofen metabolites. Half Life: R-flurbiprofen, 4.7 hours; S-flurbiprofen, 5.7 hours

5GRO578KLP

FLURBIPROFEN

Mechanisms of Action [MoA] - Cyclooxygenase Inhibitors

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

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

Flurbiprofen is a Nonsteroidal Anti-inflammatory Drug. The mechanism of action of flurbiprofen is as a Cyclooxygenase Inhibitor.

Compounds capable of relieving pain without the loss of CONSCIOUSNESS.

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.

Fluribiprofen is rapidly and almost completely absorbed following oral administration. Peak plasma concentrations are reached 0.5 - 4 hours after oral administration.

Flurbiprofen is poorly excreted into human milk. Following dosing with flurbiprofen, less than 3% of flurbiprofen is excreted unchanged in the urine, with about 70% of the dose eliminated in the urine as parent drug and metabolites. Renal elimination is a significant pathway of elimination of flurbiprofen metabolites.

14 L [Normal Healthy Adults]

Use (kg; approx.) in Germany (2009): >250

Flurbiprofen tablets are indicated for the acute or long-term symptomatic treatment of rheumatoid arthritis, osteorarthritis and anklosing spondylitis. It may also be used to treat pain associated with dysmenorrhea and mild to moderate pain accompanied by inflammation (e.g. bursitis, tendonitis, soft tissue trauma). Topical ophthalmic formulations may be used pre-operatively to prevent intraoperative miosis.