Piroxicam

1. Drug Name

• Generic Name: Piroxicam

• Brand Names: Feldene, Rexicam, Brexidol, Dolonex

2. Drug Classification

• Class: Nonsteroidal Anti-Inflammatory Drug (NSAID)

• Subclass: Oxicam derivative

3. Mechanism of Action

• Piroxicam works by inhibiting cyclooxygenase (COX) enzymes, particularly COX-1 and COX-2, which reduces the synthesis of prostaglandins responsible for pain, inflammation, and fever.

• COX-1 inhibition is associated with gastrointestinal side effects, while COX-2 inhibition provides anti-inflammatory and analgesic benefits.

• Additionally, piroxicam reduces leukocyte migration to inflamed areas and stabilizes lysosomal membranes, enhancing its anti-inflammatory effects.

4. Pharmacokinetics

• Absorption: Well absorbed orally, with bioavailability reaching approximately 100%; peak plasma concentrations occur within 3-5 hours.

• Distribution: Volume of distribution (Vd) is about 0.14-0.2 L/kg, with 99% bound to plasma proteins.

• Metabolism: Primarily metabolized in the liver via CYP2C9 into inactive metabolites.

• Excretion: Half-life (t½) is approximately 50 hours, allowing for once-daily dosing; excreted mainly via urine and feces.

• Special Considerations: Elderly patients may experience slower clearance, requiring careful monitoring or dosage adjustments.

5. Indications

• Primary Indications:

  • Management of pain and inflammation in conditions such as osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis.

• Off-Label Uses:

  • Short-term treatment of acute musculoskeletal pain.

• Specific Populations: Primarily indicated for adult use; use in pediatrics is limited and should be undertaken with caution.

6. Dosage and Administration

• Adults:

  • Osteoarthritis/Rheumatoid Arthritis: 20 mg once daily or 10 mg twice daily.

  • Acute Pain: Initial dose of 40 mg daily for a limited period (usually up to 14 days).

• Pediatric: Not typically recommended due to safety concerns, especially in long-term use.

• Route: Oral or rectal.

• Dosing Adjustments:

  • Use with caution in patients with renal or hepatic impairment; dose reduction may be necessary.

• Maximum Safe Dose: 40 mg per day, generally limited to short-term use.

7. Contraindications

• Absolute Contraindications:

  • Known hypersensitivity to piroxicam or other NSAIDs.

  • Active peptic ulcer disease or recent history of gastrointestinal bleeding.

  • Severe hepatic or renal impairment.

• Relative Contraindications:

  • Cardiovascular disease or high risk of thrombotic events.

  • Asthma or nasal polyps (may precipitate an allergic reaction).

8. Warnings and Precautions

• Black Box Warnings:

  • Increased risk of serious cardiovascular events such as myocardial infarction and stroke, particularly with prolonged use.

  • Increased risk of gastrointestinal bleeding, ulceration, and perforation, which can be fatal.

• Special Warnings:

  • Use with caution in elderly patients due to an elevated risk of GI and renal complications.

  • Not recommended in pregnancy, especially in the third trimester.

• Monitoring Parameters:

  • Routine monitoring of renal and liver function tests, CBC, and signs of GI bleeding during long-term therapy.

9. Adverse Effects

• Common Adverse Effects (≥10%): GI discomfort, nausea, dizziness, headache.

• Less Common but Clinically Significant: Edema, GI ulceration, elevated liver enzymes.

• Rare/Serious Adverse Reactions:

  • Severe GI bleeding and ulceration.

  • Hepatotoxicity and nephrotoxicity.

  • Stevens-Johnson syndrome and toxic epidermal necrolysis (rare but life-threatening).

10. Drug Interactions

• Major Drug Interactions:

  • Anticoagulants (e.g., warfarin): Increased risk of bleeding.

  • ACE inhibitors/ARBs: May reduce the antihypertensive effect and increase the risk of renal impairment.

  • Methotrexate: Risk of increased methotrexate toxicity due to reduced clearance.

• Food-Drug Interactions: Food can delay the absorption of piroxicam but does not impact the extent of absorption.

• Interactions with Lab Tests: May cause elevated liver enzyme levels and prolong bleeding time.

11. Clinical Pharmacology

• Piroxicam’s pharmacodynamics include COX enzyme inhibition and anti-inflammatory properties via leukocyte migration inhibition and lysosomal membrane stabilization.

• Its long half-life (about 50 hours) allows for once-daily dosing, though caution is needed due to its potential for serious side effects with prolonged use.

12. Special Populations

• Pregnancy: Contraindicated, particularly in the third trimester due to risks of fetal ductus arteriosus closure.

• Lactation: Excretion in breast milk is minimal, but use with caution as long-term safety in lactating mothers is not well established.

• Geriatrics: Increased risk of gastrointestinal and renal side effects; dose cautiously and monitor closely.

• Renal/Hepatic Dysfunction: Use with caution and consider dose adjustment; avoid in severe impairment.

13. Therapeutic Uses

• First-Line Therapy: Effective for inflammatory conditions like osteoarthritis and rheumatoid arthritis.

• Second-Line or Adjunctive Therapy: Sometimes used with other analgesics in pain management, particularly for short-term inflammatory pain.

14. Monitoring and Follow-Up

• Recommended Lab Tests: Periodic CBC, liver and renal function tests, especially with chronic use.

• Patient-Reported Symptom Checklists: Monitor for signs of GI bleeding (e.g., melena) and symptoms of liver dysfunction.

• Monitoring of Therapeutic and Toxic Levels: Clinical monitoring of signs of toxicity is essential given its narrow therapeutic margin in long-term use.

15. Overdose Management

• Symptoms of Overdose: Nausea, vomiting, abdominal pain, dizziness, respiratory depression; severe cases can cause acute renal failure, seizures, or coma.

• Treatment Protocols:

  • Activated charcoal if overdose occurred within 1-2 hours.

  • Supportive care with IV fluids and symptomatic treatment.

  • Hemodialysis may help in severe toxicity due to piroxicam's moderate dialyzability.

16. Patient Counseling Information

• Instruct patients to take piroxicam with food or milk to reduce GI irritation.

• Inform patients about the risk of serious GI side effects and advise them to report symptoms like black stools or severe abdominal pain.

• Advise patients to avoid other NSAIDs or aspirin unless instructed by a healthcare provider due to increased risk of adverse effects.