Etodolac

Approved Indications:

• Osteoarthritis (OA): For relief of signs and symptoms of osteoarthritis in adults.
• Rheumatoid Arthritis (RA): Management of moderate to severe rheumatoid arthritis symptoms.
• Juvenile Rheumatoid Arthritis (JRA): Treatment of active arthritis in children aged 6 years and older.
• Acute Pain: Relief of mild to moderate acute pain in adults.
• Ankylosing Spondylitis: Management of symptoms associated with ankylosing spondylitis.

Off-label / Clinically Accepted Uses:

• Management of musculoskeletal pain such as strains, sprains, and soft tissue injuries.
• Treatment of dysmenorrhea (menstrual pain).
• Use in certain chronic inflammatory conditions requiring NSAID therapy.

Route of Administration: Oral

Adults:

• Osteoarthritis & Rheumatoid Arthritis:
• Initial: 200 mg twice daily or 300 mg once daily.
• Maintenance: Adjust dose based on response, typically 300–500 mg twice daily.
• Maximum dose: Up to 1,000 mg per day in divided doses.
• Acute Pain:
• 400 mg initially, then 200 mg every 6 to 8 hours as needed.
• Do not exceed 1,200 mg per day.

Pediatrics (Juvenile Rheumatoid Arthritis):

• 5–10 mg/kg/day divided into two doses.
• Maximum: 300 mg twice daily.
• Use only in children aged 6 years and older.

Elderly:

• Start at the lower end of dosing range; monitor for adverse effects.
• Dose adjustments may be necessary based on renal function.

Renal/Hepatic Impairment:

• Use with caution.
• Avoid use in severe hepatic impairment.
• Dose adjustments recommended in moderate to severe renal impairment; avoid if severe.

Etodolac is a nonsteroidal anti-inflammatory drug (NSAID) that exerts its effect primarily by inhibiting cyclooxygenase (COX) enzymes, particularly COX-2, which reduces the synthesis of prostaglandins involved in inflammation, pain, and fever. By decreasing prostaglandin production, etodolac alleviates inflammation and pain associated with arthritis and other conditions. Its relative selectivity for COX-2 over COX-1 may result in a somewhat reduced risk of gastrointestinal side effects compared to nonselective NSAIDs.

• Absorption: Well absorbed orally with peak plasma concentrations in 1–2 hours.
• Bioavailability: Approximately 100%.
• Distribution: Widely distributed; protein binding ~99%.
• Metabolism: Extensively metabolized in the liver via CYP enzymes (primarily CYP2C9).
• Active Metabolites: None of clinical significance.
• Elimination Half-life: Approximately 7 hours.
• Excretion: Mainly renal (~75%) with some biliary excretion.

• Pregnancy:
  Classified as FDA Category C during the first two trimesters; avoid in the third trimester due to risk of premature closure of the fetal ductus arteriosus and other adverse effects.
• Lactation:
  Etodolac is excreted in breast milk in small amounts. Use with caution; benefits must be weighed against potential risks to the infant.

• Primary Class: Nonsteroidal Anti-inflammatory Drug (NSAID)
• Subclass: Preferential COX-2 inhibitor (partially selective)

• Known hypersensitivity to etodolac, other NSAIDs, or aspirin.
• History of asthma, urticaria, or allergic-type reactions after NSAID use.
• Active or history of recurrent gastrointestinal bleeding or ulceration.
• Severe heart failure, severe hepatic or renal impairment.
• Third trimester of pregnancy.
• Concurrent use with ketorolac or pentoxifylline.

• Cardiovascular Risk: Increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke. Use lowest effective dose for shortest duration.
• Gastrointestinal Risk: Risk of serious GI bleeding, ulceration, and perforation; especially in elderly or history of ulcers.
• Renal Effects: Risk of renal impairment or failure, especially in volume-depleted patients.
• Hepatic Effects: Monitor liver function periodically; risk of severe liver injury.
• Hypersensitivity Reactions: May cause anaphylaxis or severe skin reactions (e.g., Stevens-Johnson syndrome).
• Monitoring: Regular assessment for GI bleeding, renal and hepatic function recommended during prolonged therapy.

Common Adverse Effects:

• Gastrointestinal: Dyspepsia, nausea, abdominal pain, diarrhea.
• Central Nervous System: Headache, dizziness, somnolence.
• Dermatologic: Rash, pruritus.

Serious/Rare Side Effects:

• GI bleeding, ulceration, perforation.
• Hepatotoxicity.
• Renal impairment or failure.
• Severe allergic reactions including anaphylaxis.
• Cardiovascular thrombotic events.
• Hematologic abnormalities (anemia, leukopenia).

• Anticoagulants (e.g., warfarin): Increased risk of bleeding.
• ACE Inhibitors / ARBs: May reduce antihypertensive effect; increased risk of renal toxicity.
• Diuretics: Reduced efficacy; increased risk of renal impairment.
• Other NSAIDs or corticosteroids: Increased GI risk.
• Lithium: Increased lithium toxicity.
• Methotrexate: Increased toxicity.
• CYP2C9 inhibitors/inducers: May affect etodolac metabolism and plasma levels.

• Recent guidelines emphasize caution in prescribing NSAIDs, including etodolac, to patients with cardiovascular risk factors.
• FDA and EMA updated labeling to strengthen warnings on cardiovascular and GI risks.
• No new approved indications; continued use in arthritis and acute pain per established protocols.
• Recommendations for routine monitoring of renal and hepatic function in long-term therapy reiterated.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep container tightly closed.
• Keep out of reach of children.
• No refrigeration required.