Etodolac
Etodolac
Generic Name
Etodolac
Mechanism
- Selective COX‑2 inhibition: Etodolac competitively blocks the binding of arachidonic acid to COX‑2 enzymes in inflamed tissues, reducing the synthesis of prostaglandin E₂ (PGE₂) and other prostaglandins that mediate pain, swelling, and fever.
- Reduced COX‑1 activity: Minimal inhibition of COX‑1 preserves gastric prostaglandin production, thereby decreasing the risk of GI mucosal injury.
- Modulation of leukotriene pathways: By shifting arachidonic acid metabolism away from COX, it can indirectly favor leukotriene formation in some settings, but clinically this effect is modest.
Pharmacokinetics
| Parameter | Typical Value | Notes |
| Absorption | Rapid; peak plasma concentration (Tmax) ≈ 1–2 h post‑oral dosing | Oral tablet, well tolerated |
| Bioavailability | ~70 % | Food increases Cmax slightly but not clinically relevant |
| Distribution | ~2 L/kg; 96–98 % plasma protein bound (mainly albumin and α1‑acid glycoprotein) | Extensive tissue distribution |
| Metabolism | Hepatic via CYP2C9 and CYP2C19 → mainly glucuronide conjugates | Slow in patients with hepatic impairment |
| Elimination half‑life | 5–6 h | Enables once‑daily dosing in many regimens |
| Excretion | Primarily renal (≈70 % as metabolites); remainder biliary | Dose adjustment required for CrCl <30 mL/min |
*Key pharmacology terms:* COX‑2 inhibition, β‑glucuronidation, half‑life, renal excretion.
Indications
- Osteoarthritis (OA) of the knee, hip, or hand
- Rheumatoid arthritis (RA) (maintenance and flare control)
- Ankylosing spondylitis and other spondyloarthropathies
- Bursitis and tendinitis (acute pain management)
- Post‑surgical pain (when COX‑2 selectivity desired)
Contraindications
- Absolute contraindications:
- Hypersensitivity to etodolac or other NSAIDs
- Active peptic ulcer disease or GI bleeding
- History of severe asthmatic reaction to aspirin or NSAIDs
- Known severe hepatic impairment (Child‑Pugh C)
- Relative cautions:
- Cardiovascular disease: increased risk of thromboembolic events; avoid in patients with uncontrolled hypertension, congestive heart failure, or recent MI.
- Renal impairment: reduce dose or avoid in CrCl <30 mL/min.
- Pregnancy & lactation: Category D; use only if benefit outweighs risk (e.g., second‑trimester therapeutic needs).
- Elderly & liver‑disease patients: monitor for hepatic/renal complications.
Dosing
| Condition | Typical Adult Dose | Administration |
| OA/RA | 200 mg PO BID | Once or twice daily; adjust for renal function |
| Ankylosing spondylitis | 200 mg PO twice daily | Same as OA/RA |
| Acute pain | 200‑400 mg PO BID as needed | Not to exceed 800 mg/day |
| Renal impairment (CrCl 30‑59 mL/min) | 200 mg PO BID | Consider dose reduction if CrCl <30 mL/min |
| Hepatic impairment (Child‑Pugh B) | 200 mg PO BID | Reduce dose or discontinue if Child‑Pugh C |
• Titration: Start at the lowest effective dose and titrate upward if needed, monitoring for adverse effects.
• Food: No specific requirement, but taking with food may reduce GI upset.
Adverse Effects
Common (≥10 %)
•
• GI upset (nausea, dyspepsia)
•
• Dyspepsia, heartburn
•
• Headache, dizziness
Serious (≤1 %)
•
• GI ulceration/bleeding, perforation
•
• Renal dysfunction (acute interstitial nephritis, papillary necrosis)
•
• Hepatotoxicity (transient enzyme elevation, rare acute hepatic failure)
•
• Cardiovascular events (thrombotic, heart failure)
•
• Hypersensitivity reactions (hives, angioedema, anaphylaxis)
Monitoring for serious effects should be implemented early in therapy, especially in high‑risk patients.
Monitoring
- Baseline: CBC, CMP (LFTs), creatinine & eGFR, BP.
- During therapy:
- *Every 4–6 weeks* first 6 months, then every 6–12 months:
- Renal function: CrCl or eGFR
- Liver enzymes: AST, ALT, bilirubin
- Urinalysis if signs of nephrotoxicity
- *If cardiovascular risk factors*: monitor BP, weight, and signs of heart failure
- Adherence & compliance: assess at each visit, particularly in patients on long‑term NSAIDs.
Clinical Pearls
- COX‑2 Selectivity vs. GI Safety: Etodolac’s selective COX‑2 inhibition offers a moderate GI safety profile but does not eliminate GI risk; co‑prescribe proton‑pump inhibitors (PPIs) when GI risk remains high.
- Renal Dose Adjustment: In patients with CrCl 30–59 mL/min, the standard dose (200 mg BID) is acceptable; for CrCl Key Takeaway:** Etodolac is a valuable oral NSAID offering analgesia with a relatively improved GI safety profile. Optimal efficacy is achieved by starting at the lowest effective dose, adjusting for renal/hepatic function, and monitoring for GI, renal, hepatic, and cardiovascular toxicity.