Tiaprofenic acid

Tiaprofenic acid is a Arylpropionic acid belonging to Non-Steroidal anti-inflammatory Drug

Tiaprofenic acid is used in the treatment of Osteoarthritis and rheumatoid arthritis.

Tiaprofenic acid is Rapidly absorbed from the gastrointestinal tract. Delayed absorption with food and Crosses the placenta and enters breast milk. Plasma protein binding: Approx 98%.

which get Metabolised into inactive metabolites (minimal) and get excreted Via urine (50% as unchanged drug, <10% as metabolites). Elimination half-life: Approx 2 hours.

The Tmax of Tiaprofenic acid was about 30-90 minutes.

Tiaprofenic acid shows common side effects like Bronchospasm, Na and water retention with oedema, severe cystitis or other urinary tract symptoms (e.g. bladder pain, dysuria, urinary frequency, haematuria), renal failure, arterial thrombotic events (e.g. MI, stroke), new-onset or worsening of hypertension, hyperkalaemia, blurred or diminished vision; renal papillary necrosis

Tiaprofenic acid is available in tablets

Tiaprofenic acid is available in India, Germany, Canada, France, USA.

Tiaprofenic acid binds to the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) isoenzymes, preventing the synthesis of prostaglandins and reducing the inflammatory response. Cyclooxygenase catalyses the formation of prostaglandins and thromboxane from arachidonic acid (itself derived from the cellular phospholipid bilayer by phospholipase A₂). Prostaglandins act (among other things) as messenger molecules in the process of inflammation. 

Tiaprofenic acid is available in the form of tablets.

Tiaprofenic acid is used in the treatment of Osteoarthritis and rheumatoid arthritis.

Tiaprofenic acid is used in the treatment of Osteoarthritis and rheumatoid arthritis.

Tiaprofenic acid is approved for use in the following clinical indications

Osteoarthritis: Relief of signs and symptoms of osteoarthritis (degenerative joint disease).

Rheumatoid arthritis: Relief of signs and symptoms of rheumatoid arthritis.

Osteoarthritis: Oral: Usual initial and maintenance dose: 600 mg/day in 2 to 3 divided doses; rarely, patients may be maintained on 300 mg/day in divided doses; maximum dose: 600 mg/day.

Rheumatoid arthritis: Oral: Usual initial and maintenance dose: 600 mg/day in 2 to 3 divided doses; maximum dose: 600 mg/day.

Tiaprofenic acid is available in the dosage strength of 200 mg and 300 mg.

Tiaprofenic acid is available in the form of tablets.

Dosage Adjustment in Kidney Patient:

• eGFR 30 to <60 mL/minute/1.73 m²: No dosage adjustment necessary; however, use the lowest effective dose for the shortest duration possible. Temporarily discontinue in patients with intercurrent disease that increases risk of acute kidney injury.
• eGFR <30 mL/minute/1.73 m²: Use is contraindicated.

Dosage Adjustment in Hepatic impairment Patient

• Hepatic impairment prior to treatment initiation:

Mild to moderate impairment: No dosage adjustment necessary; however, use the lowest effective dose for the shortest duration possible.

Severe impairment: Use is contraindicated.

• Hepatotoxicity during treatment:

Discontinue treatment if clinical signs and symptoms consistent with liver disease develop or if systemic manifestations occur.

Take after eating and with a full glass of water to decrease gastric upset.

Tiaprofenic acid is contraindicated in patients with:

Hypersensitivity to tiaprofenic acid or any component of the formulation; history of asthma, urticaria, or allergic-type reaction to aspirin or other nonsteroidal anti-inflammatory drugs; use in the setting of coronary artery bypass graft surgery; severe uncontrolled heart failure; active gastric/duodenal/peptic ulcer, active GI bleeding; inflammatory bowel disease; cerebrovascular bleeding or other bleeding disorders; severe hepatic impairment; active hepatic disease; severe renal impairment (CrCl <30 mL/minute); deteriorating renal disease; hyperkalemia; third trimester of pregnancy; breastfeeding; patients <18 years of age.

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.

• Cardiovascular events: Relative risk of serious adverse cardiovascular thrombotic events 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 angiotensin-converting-enzyme [ACE] inhibitors, thiazide diuretics, or loop diuretics); may contribute to cardiovascular events; monitor BP; use with caution in patients with hypertension. May cause sodium and fluid retention; use with caution in patients with edema. Avoid use in heart failure .Avoid use in patients with recent myocardial infarction unless benefits outweigh the risk of cardiovascular thrombotic events .Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce the 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).

• Cystitis: Severe cases of cystitis (bladder pain, dysuria, urinary frequency, hematuria) have been reported. Avoid use in patients with prior history of urinary symptoms and discontinue at first sign of genitourinary problems.

• 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 nonaspirin NSAIDs, especially if due to angioectasia or diverticulosis. 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 ethanol, 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. In patients with a history of GI ulcer bleeding requiring NSAID therapy, a COX-2 inhibitor in combination with a proton pump inhibitor (PPI) is recommended to reduce the risk of recurrent bleeding . When used concomitantly with aspirin, a substantial increase in the risk of GI complications (eg, ulcer) occurs; concomitant gastroprotective therapy (eg, PPIs) 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. Rare (sometimes fatal), severe hepatic reactions (eg, fulminant hepatitis, hepatic necrosis, hepatic failure) have occurred with NSAID use; discontinue if signs or symptoms of liver disease develop, if systemic manifestations occur, or with persistent or worsening abnormal hepatic function tests.

• Hyperkalemia: NSAID use may increase the risk of hyperkalemia, particularly in patients ≥65 years of age, 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. Patients with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics, and ACE inhibitors, angiotensin II receptor blockers, and patients ≥65 years of age 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.

• Skin reactions: NSAIDs may cause potentially fatal serious skin adverse events including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN); discontinue use at first sign of skin rash or hypersensitivity.

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

Delayed absorption with food.

• Common Adverse effects: Bronchospasm, Na and water retention with oedema, severe cystitis or other urinary tract symptoms (e.g. bladder pain, dysuria, urinary frequency, hematuria), renal failure, arterial thrombotic events (e.g. MI, stroke), new-onset or worsening of hypertension, hyperkaliemia, blurred or diminished vision; renal papillary necrosis.

• Less Common Adverse effects: Upper abdominal pain, nausea, vomiting, dyspepsia, diarrhea, constipation, pancreatitis.

• Rare Adverse Effects: Exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, hepatitis.

Increased risk of ulceration or bleeding with oral corticosteroids, anticoagulants (e.g. heparin, warfarin, ticlopidine, clopidogrel, dabigatran, apixaban, rivaroxaban, edoxaban), SSRIs, anti-platelet agents (e.g. aspirin), thrombolytics, nicorandil, pentoxifylline. May increase the plasma concentration of cardiac glycosides, lithium, methotrexate. Increased risk of nephrotoxicity with tacrolimus, ciclosporin, tenofovir disoproxil fumarate. Increased risk of haematological toxicity with zidovudine. May increase the risk of developing convulsion with quinolone antibiotics. May reduce the effects of antihypertensive agents (e.g. ACE inhibitors, angiotensin II receptor antagonists, β-blockers), diuretics, and mifepristone (avoid tiaprofenic acid for at least 8-12 days after mifepristone use). Decreased metabolism and elimination with probenecid. May inhibit the metabolism of sulfonylurea drugs. May decrease the elimination of aminoglycosides.

Potentially Fatal: Increased risk of adverse effect (particularly upper gastrointestinal disorders) with other NSAIDs and high-dose salicylates.

The common side effects of Tiaprofenic acid include the following :

Bronchospasm, Na and water retention with oedema, severe cystitis or other urinary tract symptoms (e.g. bladder pain, dysuria, urinary frequency, haematuria), renal failure, arterial thrombotic events (e.g. MI, stroke), new-onset or worsening of hypertension, hyperkalaemia, blurred or diminished vision; renal papillary necrosis.

• Symptoms: Headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, diarrhea (rare), disorientation, excitation, drowsiness, dizziness, tinnitus, fainting, convulsion (occasional), coma; in cases of significant poisoning, acute renal failure and liver damage may occur.

• Management: Symptomatic and supportive treatment. Administer activated charcoal within 1 hour of ingesting a potentially toxic amount. Alternatively, gastric lavage may be performed in adults within 1 hour of ingestion. Ensure good urine output. Administer IV diazepam for frequent or prolonged convulsions. Closely monitor hepatic and renal function. Observe patient for at least 4 hours following ingestion of potentially toxic amount.

• Pharmacodynamics

Tiaprofenic acid belongs to a group of medicines called non-steroidal anti-inflammatory drugs (NSAIDs). It works by blocking the production of a chemical (prostaglandin) which the body produces in response to injury or certain diseases. This prostaglandin would otherwise go on to cause swelling, pain and inflammation.

• Pharmacokinetics

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