Piroxicam

Usage

Piroxicam is prescribed for the symptomatic relief of osteoarthritis, rheumatoid arthritis (including juvenile rheumatoid arthritis), and ankylosing spondylitis. It is also used to treat acute musculoskeletal disorders, acute gout, post-operative and post-traumatic pain, primary dysmenorrhea, and for the relief of fever and pain associated with acute upper respiratory tract inflammation. It’s classified pharmacologically as a nonsteroidal anti-inflammatory drug (NSAID). Piroxicam works by inhibiting cyclooxygenase (COX-1 and COX-2), enzymes responsible for prostaglandin synthesis. By reducing prostaglandins, piroxicam decreases inflammation and pain.

Alternate Names

Piroxicam is also known by various brand names such as Feldene, Feldene Flash among others. There aren’t widely used alternate generic names.

How It Works

Pharmacodynamics: Piroxicam exerts its anti-inflammatory, analgesic, and antipyretic effects primarily through the inhibition of COX-1 and COX-2 enzymes. This leads to a decrease in prostaglandin synthesis, which are mediators of inflammation, pain, and fever.

Pharmacokinetics:

• Absorption: Piroxicam is well-absorbed orally. Taking it with food may slightly delay absorption but does not affect the overall extent of absorption.
• Metabolism: Piroxicam is extensively metabolized in the liver, primarily by CYP2C9, to inactive metabolites. Genetic polymorphisms in CYP2C9 can affect piroxicam metabolism and clearance.
• Elimination: Piroxicam is primarily eliminated via renal excretion of its metabolites, with a small portion excreted in the feces. It has a long half-life of approximately 50 hours, allowing for once-daily dosing.

Mode of Action: Piroxicam binds to and inhibits COX-1 and COX-2 enzymes. This inhibition prevents the conversion of arachidonic acid to prostaglandin H2, a precursor to various prostaglandins involved in inflammation and pain.

Dosage

Standard Dosage

Adults:

The standard dosage for adults is 20 mg orally once daily or 10 mg twice daily. The maximum daily dose is generally 20mg, though in some cases, up to 30 mg may be used for short periods with careful monitoring for side effects. It should always be taken with food or a full glass of water to minimize gastrointestinal side effects.

Children:

Piroxicam use in children younger than 18 years is generally not recommended. For Juvenile rheumatoid arthritis: Dosage is determined by body weight:<15 kg: 5 mg/day; 16-25 kg: 10 mg/day; 26-45 kg: 15 mg/day; >45 kg: 20 mg/day.

Special Cases:

• Elderly Patients: Initiate therapy at the lower end of the dosing range (e.g., 10 mg daily) and monitor closely for adverse events. Due to age-related decreases in renal and hepatic function.
• Patients with Renal Impairment: A lower dose should be considered and patients should be carefully monitored.
• Patients with Hepatic Dysfunction: Close monitoring is recommended, and dosage adjustments may be necessary.
• Patients with Comorbid Conditions: Close monitoring is recommended, especially for patients with cardiovascular disease, hypertension, or a history of gastrointestinal bleeding.

Clinical Use Cases

Piroxicam is not typically used in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations requiring rapid onset of action.

Dosage Adjustments

Dosage adjustments may be necessary based on patient-specific factors such as renal or hepatic impairment, age, and concomitant medications.

Side Effects

Common Side Effects:

Diarrhea, dizziness, headache, heartburn, indigestion, nausea, abdominal pain, edema, anemia, constipation, vomiting, fever.

Rare but Serious Side Effects:

Gastrointestinal bleeding, ulceration, perforation, Stevens-Johnson syndrome, toxic epidermal necrolysis, severe allergic reactions (anaphylaxis), kidney failure, liver failure, heart failure, myocardial infarction, stroke.

Long-Term Effects:

Chronic kidney disease, gastrointestinal complications (e.g., ulcers, bleeding), cardiovascular events (e.g., heart attack, stroke).

Adverse Drug Reactions (ADR):

Any serious side effects mentioned above should be considered as potential ADRs requiring immediate medical intervention.

Contraindications

Absolute contraindications include: Hypersensitivity to piroxicam or any other NSAID, including aspirin; history of asthma, urticaria, or allergic-type reaction after taking aspirin or other NSAIDs, active peptic ulcer, recent gastrointestinal bleeding or perforation, severe heart failure, severe hepatic impairment, severe renal impairment, third trimester of pregnancy, perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.

Relative contraindications include: history of peptic ulcer disease, gastrointestinal bleeding, inflammatory bowel disease, bleeding disorders, asthma, cardiovascular disease, hypertension, renal impairment, hepatic impairment, elderly patients.

Drug Interactions

Piroxicam can interact with numerous medications, including:

• NSAIDs, aspirin: Increased risk of gastrointestinal side effects.
• Anticoagulants (e.g., warfarin): Increased risk of bleeding.
• Antihypertensives (e.g., ACE inhibitors, beta-blockers, diuretics): Decreased antihypertensive effect.
• Methotrexate: Increased methotrexate toxicity.
• Lithium: Increased lithium levels.
• Corticosteroids: Increased risk of gastrointestinal ulcers and bleeding.
• CYP2C9 inhibitors (e.g., fluconazole): Increased piroxicam levels.
• Alcohol: Increased risk of gastrointestinal bleeding.

Pregnancy and Breastfeeding

Piroxicam is contraindicated during the third trimester of pregnancy due to the risk of premature closure of the ductus arteriosus and other potential fetal complications. It should be avoided during the first and second trimesters unless the potential benefits outweigh the risks. Piroxicam is excreted in breast milk and may cause adverse effects in nursing infants. Breastfeeding is generally not recommended while taking piroxicam.

Drug Profile Summary

• Mechanism of Action: Inhibits COX-1 and COX-2, reducing prostaglandin synthesis.
• Side Effects: Diarrhea, dizziness, headache, heartburn, GI bleeding, ulceration.
• Contraindications: Hypersensitivity to NSAIDs, third-trimester pregnancy.
• Drug Interactions: Anticoagulants, antihypertensives, methotrexate.
• Pregnancy & Breastfeeding: Contraindicated in third trimester; avoid breastfeeding.
• Dosage: 20 mg once daily or 10 mg twice daily (max 20-30 mg/day).
• Monitoring Parameters: Renal function, liver function, blood pressure, signs of GI bleeding.

Popular Combinations

Piroxicam is not typically used in combination with other NSAIDs. Gastroprotective agents (e.g., proton pump inhibitors, misoprostol) may be co-prescribed to reduce the risk of GI side effects.

Precautions

• General Precautions: Assess for allergies, renal/hepatic function, cardiovascular risks.
• Specific Populations: As detailed above.
• Lifestyle Considerations: Limit alcohol, avoid driving if dizziness occurs.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Piroxicam?

A: The recommended adult dose is 20 mg once daily or 10 mg twice daily, not to exceed 20 mg/day generally, though some patients may take up to 30mg/day for short periods. Lower doses are recommended for elderly patients and those with renal or hepatic impairment. Pediatric dosing is weight-based and not generally recommended.

Q2: What are the common side effects of Piroxicam?

A: Common side effects include gastrointestinal issues such as diarrhea, heartburn, indigestion, nausea, and abdominal pain. Headache and dizziness are also frequently reported.

Q3: What are the serious side effects of Piroxicam?

A: Serious side effects include gastrointestinal bleeding, ulceration, and perforation, cardiovascular events (heart attack, stroke), and severe skin reactions (Stevens-Johnson syndrome). Renal and hepatic impairment are also possible.

Q4: Can Piroxicam be used during pregnancy?

A: Piroxicam is contraindicated during the third trimester and should generally be avoided during the first and second trimesters.

Q5: Can Piroxicam be used during breastfeeding?

A: Piroxicam is excreted in breast milk and can potentially harm the nursing infant. Breastfeeding while taking Piroxicam is not generally recommended.

Q6: What medications interact with Piroxicam?

A: Piroxicam can interact with anticoagulants, antihypertensives, methotrexate, lithium, corticosteroids, and other NSAIDs.

Q7: What are the contraindications for Piroxicam use?

A: Contraindications include hypersensitivity to Piroxicam or other NSAIDs, history of NSAID-induced asthma or allergic reactions, active peptic ulcer, severe heart, liver, or kidney disease, and the third trimester of pregnancy.

Q8: How does Piroxicam work?

A: Piroxicam inhibits COX-1 and COX-2 enzymes, reducing the production of prostaglandins, which are responsible for inflammation, pain, and fever.

Q9: What should patients be monitored for while taking Piroxicam?

A: Patients should be monitored for signs of gastrointestinal bleeding (e.g., black stools, abdominal pain), changes in renal and liver function, blood pressure fluctuations, and allergic reactions.

Q10: Can Piroxicam be used for acute pain management?

A: While piroxicam possesses analgesic properties, due to its long half-life and safety profile, it is not a first-line treatment for acute conditions like post-operative or acute musculoskeletal pain. Other NSAIDs with shorter half-lives might be more suitable depending on the specific case.