Etodolac: Targeted Pain Relief with Joint-Sparing Precision
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Synonyms | |||
Etodolac is a nonsteroidal anti-inflammatory drug (NSAID) from the pyranocarboxylic acid class, specifically formulated to provide potent analgesia and anti-inflammatory action. It is distinguished by its preferential inhibition of cyclooxygenase-2 (COX-2), which allows for effective management of pain and inflammation with a potentially improved gastrointestinal tolerability profile compared to non-selective NSAIDs. Clinically, it is indicated for the acute and chronic management of osteoarthritis and rheumatoid arthritis, offering patients sustained symptomatic relief and improved functional mobility. Its pharmacokinetic profile, including high oral bioavailability and extensive protein binding, supports consistent therapeutic levels with standard dosing regimens.
Features
- Active Ingredient: Etodolac
- Drug Class: Nonsteroidal Anti-inflammatory Drug (NSAID), Pyranocarboxylic acid derivative
- Available Formulations: Immediate-release tablets (400 mg, 500 mg), Extended-release tablets (400 mg, 500 mg, 600 mg)
- Mechanism of Action: Preferential inhibition of cyclooxygenase-2 (COX-2) enzyme, reducing prostaglandin synthesis
- Bioavailability: >80% following oral administration
- Protein Binding: >99%, primarily to albumin
- Half-life: Approximately 7 hours for immediate-release; 8-12 hours for extended-release formulations
- Metabolism: Hepatic, primarily via CYP2C9 and CYP3A4 isoenzymes
- Excretion: Primarily renal (72%) as metabolites, with fecal elimination accounting for approximately 16%
Benefits
- Provides effective relief from inflammatory pain associated with arthritic conditions
- Reduces joint swelling and morning stiffness, improving range of motion and physical function
- Offers convenient once-daily dosing with extended-release formulations for consistent therapeutic coverage
- Demonstrates a favorable gastrointestinal tolerability profile relative to non-selective NSAIDs due to COX-2 preference
- Supports long-term management of chronic inflammatory conditions with maintained efficacy
- Improves quality of life measures through reduction in pain interference with daily activities
Common use
Etodolac is primarily prescribed for the management of signs and symptoms of osteoarthritis and rheumatoid arthritis in adults. It is clinically employed to reduce pain, tenderness, swelling, and stiffness in affected joints, thereby improving physical function and mobility. The medication may also be used off-label for other painful inflammatory conditions, though such use requires careful clinical evaluation. Treatment is typically initiated at the lowest effective dose for the shortest duration consistent with individual patient treatment goals, with regular assessment of therapeutic response and tolerability.
Dosage and direction
For osteoarthritis and rheumatoid arthritis management in adults, the recommended initial dosage for immediate-release etodolac tablets is 300 mg twice daily or 400 mg twice daily. Alternatively, 500 mg twice daily may be prescribed for patients requiring higher anti-inflammatory activity. For maintenance therapy, the total daily dose may be adjusted within the range of 600-1200 mg divided into two or three doses. Extended-release tablets are typically administered once daily at doses of 400 mg, 500 mg, or 600 mg based on individual patient needs. Tablets should be swallowed whole with a full glass of water, preferably with food or milk to minimize gastrointestinal discomfort. Dosage adjustments are necessary for elderly patients, those with renal impairment, or those taking concomitant medications that may interact with etodolac.
Precautions
Patients should be advised to use the lowest effective dose for the shortest duration possible. Cardiovascular risk assessment is recommended before initiating long-term therapy, as NSAIDs may increase the risk of serious cardiovascular thrombotic events. Gastrointestinal monitoring is essential, as etodolac can cause ulceration, bleeding, and perforation of the stomach or intestines, which may occur without warning symptoms. Renal function should be monitored periodically, particularly in elderly patients, those with volume depletion, heart failure, hepatic dysfunction, or taking diuretics or ACE inhibitors. Hepatic enzyme monitoring is recommended within the first few months of therapy initiation. Patients with pre-existing asthma should be monitored closely for exacerbations, as NSAIDs may cause severe bronchospasm.
Contraindications
Etodolac is contraindicated in patients with known hypersensitivity to etodolac or any components of the formulation. It should not be used in patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Contraindications include peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery. The medication is contraindicated in patients with active gastrointestinal bleeding or peptic ulcer disease. Severe hepatic impairment or active liver disease represents another contraindication. Etodolac should not be administered during the third trimester of pregnancy due to risk of premature closure of the ductus arteriosus.
Possible side effect
Common adverse reactions (>1%) include dyspepsia (10-15%), abdominal pain (5-10%), nausea (5-10%), diarrhea (5-10%), flatulence (5-10%), and headache (5-10%). Less frequent side effects include dizziness, peripheral edema, rash, pruritus, tinnitus, and elevated liver enzymes. Serious adverse reactions occurring in <1% of patients include gastrointestinal ulceration with bleeding and perforation, cardiovascular thrombotic events, hypertension, heart failure, renal papillary necrosis, interstitial nephritis, hepatotoxicity, anaphylactoid reactions, and severe skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis. Hematologic effects may include anemia, leukopenia, and thrombocytopenia.
Drug interaction
Etodolac may increase the anticoagulant effect of warfarin through protein binding displacement, requiring close monitoring of INR. Concomitant use with aspirin or other NSAIDs may increase the risk of gastrointestinal adverse effects without therapeutic benefit. ACE inhibitors and angiotensin II receptor blockers may have their antihypertensive effects diminished by etodolac. Diuretics may have reduced efficacy when co-administered with etodolac. Lithium levels may increase due to reduced renal clearance, necessitating monitoring. Methotrexate toxicity may be enhanced due to decreased renal clearance. Cyclosporine and tacrolimus nephrotoxicity may be increased. Etodolac may reduce the antihypertensive effect of beta-blockers. Concomitant use with corticosteroids increases the risk of gastrointestinal ulceration.
Missed dose
If a dose is missed, it should be taken as soon as remembered unless it is almost time for the next scheduled dose. In that case, the missed dose should be skipped and the regular dosing schedule resumed. Patients should not double the dose to make up for a missed one. For extended-release formulations taken once daily, if remembered within 12 hours of the missed dose, it may be taken; if more than 12 hours have passed, the dose should be skipped. Maintenance of consistent dosing intervals is important for optimal therapeutic effect, particularly in chronic inflammatory conditions.
Overdose
Symptoms of acute overdose may include lethargy, drowsiness, nausea, vomiting, epigastric pain, gastrointestinal bleeding, hypertension, acute renal failure, respiratory depression, and coma. Management is supportive and symptomatic. There is no specific antidote. Gastric lavage may be considered if performed within 4 hours of ingestion. Activated charcoal may be effective in reducing absorption. Hemodialysis is not effective due to high protein binding. Forced diuresis, alkalinization of urine, or hemoperfusion are not expected to be beneficial. Supportive care should include monitoring of vital signs, renal function, electrolyte balance, and hematologic parameters. Symptomatic treatment of gastrointestinal effects may include proton pump inhibitors or H2 antagonists.
Storage
Store at controlled room temperature between 20°C to 25°C (68°F to 77°F), with excursions permitted between 15°C to 30°C (59°F to 86°F). Keep in the original container tightly closed to protect from moisture and light. Keep out of reach of children and pets. Do not store in bathroom cabinets where humidity and temperature fluctuations may occur. Do not use beyond the expiration date printed on the packaging. Properly discard any unused medication that is no longer needed or has expired through medication take-back programs or according to FDA-recommended disposal methods.
Disclaimer
This information is provided for educational purposes only and does not constitute medical advice. Etodolac is a prescription medication that should be used only under the supervision of a qualified healthcare professional. Individual response to therapy may vary, and the prescribing physician should determine the appropriate dosage and treatment duration based on the patient’s specific medical condition, response to treatment, and risk factors. Patients should not discontinue or modify their dosage without consulting their healthcare provider. The complete prescribing information should be reviewed before initiating therapy.
Reviews
Clinical studies demonstrate etodolac’s efficacy in managing arthritic symptoms, with significant improvements in pain scores and functional indices compared to placebo. In comparative trials, etodolac has shown similar efficacy to naproxen and diclofenac with potentially improved gastrointestinal tolerability. Long-term extension studies indicate maintained effectiveness over 12-24 months of continuous therapy. Patient-reported outcomes consistently show improvements in quality of life measures, particularly in physical function and pain-related interference with daily activities. Real-world evidence supports the favorable benefit-risk profile of etodolac in appropriately selected patients, with particular value noted in elderly populations requiring long-term anti-inflammatory therapy.