Piroxicam

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

Piroxicam is used in the treatment of arthritis as well as ankylosing spondylitis.

Piroxicam is Well absorbed from the gastrointestinal tract. Slightly delayed rate of absorption with food. Time to peak plasma concentration: 3-5 hours and Enters breast milk (small amounts) with Volume of distribution of 0.14 L/kg. Plasma protein binding: 99% and get Extensively metabolised in the liver mainly by CYP2C9 isoenzyme via hydroxylation and conjugation with glucuronic acid into inactive metabolites and get secreted Via urine and faeces (<5% as unchanged drug). Elimination half-life: Approx 50 hours.

The onset of action of Piroxicam was within 1 hour.

The Tmax of Piroxicam was within 3-5 hours.

Piroxicam shows common side effects like Nausea, vomiting, constipation, abdominal pain or discomfort, diarrhea, epigastric distress, indigestion, flatulence.

Piroxicam 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 precursors; has antipyretic, analgesic, and anti-inflammatory properties.

Piroxicam is available in the form of Capsules.

Piroxicam is used in the treatment of arthritis as well as ankylosing spondylitis.

Piroxicam is an oxicam derivative NSAID that reversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes, resulting in decreased formation of prostaglandin precursors. It has analgesic, anti-inflammatory, and antipyretic properties.

Piroxicam is approved for use in the following clinical indications

Arthritis: Relief of signs and symptoms of osteoarthritis and rheumatoid arthritis.

Although not approved there have been certain off label uses documented for Piroxicam which include:

Ankylosing spondylitis.

• Ankylosing spondylitis (off-label use): Oral: 10 to 20 mg/day in 1 to 2 divided doses .
• Osteoarthritis, rheumatoid arthritis: Oral: 20 mg once daily.

Piroxicam is available in the dosage strength of 10 mg and 20 mg.

Piroxicam is available in the form of Capsule.

Dosage Adjustment in Kidney Patient

• Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer’s labeling.
• Severe impairment: Use is not recommended (has not been studied); if therapy must be initiated, close monitoring is recommended.
• eGFR 30 to <60 mL/minute/1.73 m²: Temporarily discontinue in patients with intercurrent disease that increases risk of acute kidney injury.
• eGFR <30 mL/minute/1.73 m²: Avoid use.

Dosage Adjustment in Hepatic impairment Patient

• Hepatic impairment prior to treatment initiation:
• There are no specific dosage adjustments provided in the manufacturer’s labeling; however, a dosage reduction is recommended.
• Hepatotoxicity during treatment:
• Discontinue treatment if clinical signs and symptoms consistent with liver disease develop or if systemic manifestations occur.

Piroxicam is contraindicated in patients with:

Hypersensitivity to piroxicam or to any component of the formulation; patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs; in the setting of coronary artery bypass graft (CABG) surgery.

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 use in patients who experience bronchospasm, asthma, rhinitis, or urticaria with nonsteroidal anti-inflammatory drug (NSAID) or aspirin therapy.

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 patients with heart failure (FDA 2015). Avoid use in patients with recent myocardial infarction (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 that may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving). Discontinue use with blurred or diminished vision and perform ophthalmologic exam. Periodically evaluate vision in all patients receiving long term therapy.

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 due to increased risk of serious GI events. In patients with a history of acute lower GI bleeding, avoid use of nonaspirin 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), 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 (Bhatt 2008).

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 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. Patients with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics, and ACE inhibitors, angiotensin II receptor blockers, 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

Serum sickness: A serum sickness–like reaction can rarely occur; signs and symptoms include arthralgias, pruritus, fever, fatigue, and rash.

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

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

Piroxicam is present in breast milk.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are considered compatible for the treatment of rheumatic and musculoskeletal diseases in lactating patients; agents with a short half-life and established safety data in infants may be preferred .

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Maternal use of NSAIDs should be avoided if the breastfeeding infant has platelet dysfunction, thrombocytopenia, or a ductal-dependent cardiac lesion.

Pregnancy Category C prior to 30 weeks gestation; Category D starting at 30 weeks gestation.

Risk Summary

Use of NSAIDs, including Piroxicam, during the third trimester of pregnancy increases the risk of premature closure of the fetal ductus arteriosus. Avoid use of NSAIDs, including Piroxicam, in pregnant women starting at 30 weeks of gestation (third trimester). There are no adequate and well-controlled studies of Piroxicam in pregnant women. Data from observational studies regarding potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive. In the general U.S. population, all clinically recognized pregnancies, regardless of drug exposure, have a background rate of 2-4% for major malformations, and 15-20% for pregnancy loss. In animal reproduction studies in rats and rabbits, there was no evidence of teratogenicity at exposures up to 5 and 10 times the MRHD, respectively. In rat studies with piroxicam, fetotoxicity (postimplantation loss) was observed at exposures 2 times the MRHD, and delayed parturition and an increased incidence of stillbirth were noted at doses equivalent to the MRHD of piroxicam. Based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, administration of prostaglandin synthesis inhibitors such as piroxicam, resulted in increased pre- and post-implantation loss.

Increased risk of gastrointestinal bleeding with excessive alcohol ingestion. May slightly delay the rate, but not the extent of absorption with food.

• Common Adverse effects:

Anaphylactoid reactions, new-onset or exacerbation of hypertension; fixed drug eruption, Na and fluid retention, oedema, impaired female fertility, may decrease platelet adhesion and aggregation, anemia, elevated transaminase, hyperkaliemia.

• Less Common Adverse effects:

Mild to moderate local irritation, erythema, pruritus, and dermatitis at the application site, Headache, dizziness, somnolence.

• Rare Adverse effects

Interstitial nephritis, glomerulitis, papillary necrosis, nephrotic syndrome; serum sickness-like reaction.

Increased risk of gastrointestinal ulceration or bleeding with oral corticosteroids, SSRIs, or antiplatelet agents (e.g. low-dose aspirin). May enhance the nephrotoxic effect of ciclosporin and tacrolimus. May reduce the efficacy of diuretics and antihypertensive agents (e.g. ACE inhibitors, β-blockers, ARBs). May increase plasma levels of lithium, methotrexate, and digoxin. May increase the risk of convulsion with quinolones. May interfere with mifepristone-mediated termination of pregnancy.

Potentially Fatal: May enhance effects of anticoagulants (e.g. warfarin). Increased risk of serious gastrointestinal events with aspirin and other NSAIDs.

The common side effects of Piroxicam include the following :

Nausea, vomiting, constipation, abdominal pain or discomfort, diarrhea, epigastric distress, indigestion, flatulence.

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

Management: Symptomatic and supportive treatment. Consider inducing emesis and/or administering activated charcoal (60-100 g in adults and 1-2 g/kg in children) and/or osmotic cathartic in symptomatic patients within 4 hours of ingestion or during a large overdose (5-10 times the usual dosage). Gastric lavage may also be performed if appropriate.

• Pharmacodynamic

Piroxicam is in a class of drugs called nonsteroidal anti-inflammatory drugs (NSAIDs). Piroxicam works by reducing hormones that cause inflammation and pain in the body. Piroxicam is used to reduce the pain, inflammation, and stiffness caused by rheumatoid arthritis and osteoarthritis.

• Pharmacokinetics

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