Fenoprofen

Fenoprofen is Non- Steroidal Anti inflammatory Drugs belonging to Analgesic and Anti inflammatory agents.

Fenoprofen is used in the treatment of osteoarthritis, pain and rheumatoid arthritis.

Fenoprofen is Rapidly and almost completely absorbed from the gastrointestinal tract. Food and milk may reduce the rate and extent of absorption. Bioavailability: Approx 85%. Time to peak plasma concentration: 1-2 hours and Enters the breast milk with Plasma protein binding of 99%.

and get Extensively metabolised in the liver and get excreted Via urine (approx 90% as metabolite). With Elimination half-life of Approx 3 hours.

Fenoprofen shows common side effects like Anaphylactoid reactions, CNS effects (e.g. drowsiness, dizziness), visual disturbances (e.g. blurred vision), haematological effects (e.g. decreased platelet adhesion and aggregation, anaemia), increased transaminase, increased risk of hyperkalaemia; dysuria, cystitis, haematuria, interstitial nephritis, nephrotic syndrome.

Fenoprofen is available in Tablet and Capsule.

Fenoprofen is available in India, Germany, Canada, France, USA.

Reversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes, which results in decreased formation of prostaglandin precursor, has antipyretic, analgesic, and anti-inflammatory properties.

Fenoprofen is available in the form of tablets and Capsules.

Fenoprofen is used in the treatment of osteoarthritis, pain and rheumatoid arthritis.

Fenoprofen is a propionic acid derivative which reversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes resulting in decreased formation of prostaglandin precursors. It also has antipyretic, analgesic, and anti-inflammatory actions.

Fenoprofen is approved for use in the following clinical indications

• Osteoarthritis: Relief of the signs and symptoms of osteoarthritis.
• Pain: Relief of mild to moderate pain in adults.
• Rheumatoid arthritis (RA): Relief of the signs and symptoms of RA.

Osteoarthritis, rheumatoid arthritis: Oral: 400 to 600 mg 3 to 4 times daily; adjust dose based on patient response; maximum dose: 3,200 mg/day.

Pain (mild to moderate): Oral: 200 mg every 4 to 6 hours as needed.

Fenoprofen is available in the dosage strength of 200 mg, 400 mg, 600 mg.

Fenoprofen is available in the form of Tablets and Capsules.

Hypersensitivity to fenoprofen (eg, anaphylactic reactions, serious skin reactions) or any component of the formulation, history of asthma, urticaria, or allergic-type reaction to aspirin or other nonsteroidal anti-inflammatory drugs, in the setting of coronary artery bypass graft surgery, significantly impaired kidney function.

Concerns related to adverse effects:

• Anaphylactoid reactions: Even in patients without prior exposure anaphylactoid reactions may occur; patients with "aspirin triad" (bronchial asthma, aspirin intolerance, rhinitis) may be at increased risk. Contraindicated in patients who experience bronchospasm, asthma, rhinitis, or urticaria with nonsteroidal anti-inflammatory drug (NSAID) or aspirin therapy.

• Cardiovascular events: Relative risk appears to be similar in those with and without known cardiovascular disease or risk factors for cardiovascular disease; however, absolute incidence of cardiovascular events (which may occur early during treatment) was higher in patients with known cardiovascular disease or risk factors. New onset hypertension or exacerbation of hypertension may occur (NSAIDs may also impair response to ACE inhibitors, thiazide diuretics, or loop diuretics); may contribute to cardiovascular events; monitor blood pressure; use with caution in patients with hypertension. May cause sodium and fluid retention, use with caution in patients with edema. Avoid use in patients with heart failure. Avoid use in patients with recent MI unless benefits outweigh risk of cardiovascular thrombotic events. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of cardiovascular events; alternate therapies should be considered for patients at high risk.

• CNS effects: May cause drowsiness, dizziness, blurred vision, and other neurologic effects which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). If visual disturbances occur, preform ophthalmologic exam.

• Drug reaction with eosinophilia and systemic symptoms: Potentially serious, sometimes fatal, drug reaction with eosinophilia and systemic symptoms (DRESS), also known as multiorgan hypersensitivity reactions, has been reported with NSAIDs. Monitor for signs and symptoms (eg, fever, rash, lymphadenopathy, eosinophilia) in association with other organ system involvement (eg, hepatitis, nephritis, hematological abnormalities, myocarditis, myositis). Early symptoms of hypersensitivity reaction (eg, lymphadenopathy, fever) may occur without rash; discontinue therapy and further evaluate if DRESS is suspected.

• GI events: Avoid use in patients with active GI bleeding. In patients with a history of acute lower GI bleeding, avoid use of non-aspirin NSAIDs, especially if due to angioectasia or diverticulosis (Strate 2016). Use caution with a history of GI ulcers, concurrent therapy known to increase the risk of GI bleeding (eg, aspirin, anticoagulants and/or corticosteroids, selective serotonin reuptake inhibitors), advanced hepatic disease, coagulopathy, smoking, use of alcohol, or in elderly or debilitated patients. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of GI adverse events; alternate therapies should be considered for patients at high risk. When used concomitantly with aspirin, a substantial increase in the risk of GI complications (eg, ulcer) occurs; concomitant gastroprotective therapy (eg, proton pump inhibitors) is recommended.

• Hematologic effects: Platelet adhesion and aggregation may be decreased; may prolong bleeding time; patients with coagulation disorders or who are receiving anticoagulants should be monitored closely. Anemia may occur; patients on long-term NSAID therapy should be monitored for anemia. Rarely, NSAID use has been associated with potentially severe blood dyscrasias (eg, agranulocytosis, thrombocytopenia, aplastic anemia).

• Hepatic effects: Transaminase elevations have been reported with use; closely monitor patients with any abnormal LFT. Rare (sometimes fatal) severe hepatic reactions (eg, fulminant hepatitis, hepatic necrosis, hepatic failure) have occurred with NSAID use; discontinue immediately if signs or symptoms of hepatic disease develop or if systemic manifestations occur.

• Hyperkalemia: NSAID use may increase the risk of hyperkalemia, particularly in the elderly, diabetics, renal disease, and with concomitant use of other agents capable of inducing hyperkalemia (eg, ACE-inhibitors). Monitor potassium closely.

• Renal effects: NSAID use may compromise existing renal function; dose-dependent decreases in prostaglandin synthesis may result from NSAID use, reducing renal blood flow which may cause renal decompensation (usually reversible). Patients with impaired renal function, dehydration, hypovolemia, heart failure, hepatic impairment, those taking diuretics, and ACE inhibitors, and the elderly are at greater risk of renal toxicity. Rehydrate patient before starting therapy; monitor renal function closely. Long-term NSAID use may result in renal papillary necrosis and other renal injury.

• Skin reactions: NSAIDs may cause serious skin adverse events including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN); may occur without warning; discontinue use at first sign of skin rash (or any other hypersensitivity).

Disease-related concerns:

• Asthma: Contraindicated in patients with aspirin-sensitive asthma; severe bronchospasm may occur. Use caution in patients with other forms of asthma.

• Bariatric surgery: Gastric ulceration: Avoid chronic use of oral nonselective NSAIDs after bariatric surgery; development of anastomotic ulcerations, perforations, and leaks may occur Short-term use of celecoxib or IV ketorolac are recommended as part of a multimodal pain management strategy for postoperative pain.

• Coronary artery bypass graft surgery: Risk of MI and stroke may be increased with use following CABG surgery.

• Hearing impairment: Periodically monitor auditory function in patients with hearing impairment during prolonged therapy.

• Hepatic impairment: Use with caution in patients with hepatic impairment; patients with advanced hepatic disease are at an increased risk of GI bleeding with NSAIDs.

• Renal impairment: Discontinue use with persistent or worsening abnormal renal function tests. Use is contraindicated in patients with significantly impaired kidney function.

Fenoprofen may cause liver problems, and using it with substantial quantities of ethanol may increase that risk.

Pregnancy Category C & D

Fenoprofen falls into category C at weeks 0 to 29 of pregnancy and category D starting at week 30 of pregnancy. There are no adequate and well-controlled studies in pregnant women.

• At weeks 0 to 29, fenoprofen should be used during pregnancy only if the possible benefit outweighs the possible risk to the unborn baby.
• Starting at 30-weeks of pregnancy, fenoprofen and other NSAIDs should be avoided by pregnant women as they can cause harm to the unborn baby when given to a pregnant woman starting at 30-weeks gestation.

Rate and extent of absorption may be reduced when taken with food or milk. Increased risk of gastrointestinal bleeding with alcohol.

• Common Adverse effects:

Anaphylactoid reactions, CNS effects (e.g. drowsiness, dizziness), visual disturbances (e.g. blurred vision), hematological effects (e.g. decreased platelet adhesion and aggregation, anemia), increased transaminase, increased risk of hyperkaliemia; dysuria, cystitis, hematuria, interstitial nephritis, nephrotic syndrome.

• Less Common Adverse effects:

Dyspepsia, nausea, abdominal pain, diarrhea, vomiting, constipation.

• Rare Adverse effects

Severe hepatic reactions (e.g. fulminant hepatitis, hepatic necrosis, hepatic failure), serious skin reactions (e.g. exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis).

Increased risk of adverse effects (e.g. gastrointestinal toxicity, bleeding) with other NSAIDs, anticoagulants (e.g. warfarin), antiplatelets (e.g. aspirin), SSRIs, and corticosteroids. May reduce antihypertensive effects of ACE inhibitors, angiotensin II receptor antagonists, and β blockers (e.g. propranolol). May reduce the natriuretic effects of loop and thiazide diuretics. May increase plasma concentration and toxicity of digoxin. May increase toxicity of lithium and methotrexate. May increase nephrotoxic effect of ciclosporin. May increase the risk of pemetrexed-associated myelosuppression, renal and gastrointestinal toxicity. Decreased plasma half-life with phenobarbital. May increase the risk of convulsions with quinolone antibiotics. Increased risk of hematological toxicity with zidovudine.

The common side effects of Fenoprofen include the following :

Anaphylactoid reactions, CNS effects (e.g. drowsiness, dizziness), visual disturbances (e.g. blurred vision), hematological effects (e.g. decreased platelet adhesion and aggregation, anemia), increased transaminase, increased risk of hyperkaliemia; dysuria, cystitis, hematuria, interstitial nephritis, nephrotic syndrome.

Symptoms: Lethargy, drowsiness, nausea, vomiting, epigastric pain, gastrointestinal bleeding. Rarely, hypertension, acute renal failure, respiratory depression, coma.

Management: Supportive and symptomatic treatment. Consider emesis, activated charcoal, and/or osmotic catharsis within 4 hours of ingestion or in case of large overdosage.

• Pharmacodynamic

Fenoprofen is a propionic acid derivative which reversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes resulting in decreased formation of prostaglandin precursors. It also has antipyretic, analgesic, and anti-inflammatory actions.

• Pharmacokinetics

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1364710/
2. https://reference.medscape.com/drug/colestid-Fenoprofen -342452
3. https://go.drugbank.com/drugs/DB00375
4. https://www.sciencedirect.com/topics/medicine-and-dentistry/Fenoprofen
5. https://europepmc.org/article/med/6988203