Usage
- S-Etodolac is prescribed for the management of pain and inflammation associated with osteoarthritis and rheumatoid arthritis. It is also used for general pain relief in some cases.
- Pharmacological Classification: Non-Steroidal Anti-Inflammatory Drug (NSAID)
- Mechanism of Action: S-Etodolac inhibits cyclooxygenase (COX) enzymes, which are responsible for producing prostaglandins, chemical messengers that mediate pain and inflammation. By inhibiting COX enzymes, S-Etodolac reduces the production of prostaglandins, thereby alleviating pain and inflammation. It preferentially inhibits COX-2 over COX-1, theoretically reducing gastrointestinal side effects compared to non-selective NSAIDs.
Alternate Names
- Etodolac (racemic mixture)
- Brand Names: Lodine, Lodine XL, Setolac
How It Works
- Pharmacodynamics: S-Etodolac exerts its analgesic and anti-inflammatory effects through the inhibition of COX enzymes.
- Pharmacokinetics:
- Absorption: Well-absorbed orally. Bioavailability is nearly 100% for immediate-release formulations.
- Metabolism: Extensively metabolized in the liver, primarily by CYP3A4 and CYP2C9 enzymes to inactive metabolites.
- Elimination: Primarily eliminated through renal excretion, with a small amount excreted in the bile.
- Mode of Action: Binds to and inhibits COX enzymes, reducing prostaglandin synthesis. It preferentially inhibits COX-2.
- Receptor Binding/Enzyme Inhibition: Inhibits COX-1 and COX-2 enzymes.
- Elimination Pathways: Primarily renal excretion of metabolites.
Dosage
Standard Dosage
Adults:
- Osteoarthritis/Rheumatoid Arthritis:
- Immediate-release: 300 mg two to three times daily OR 400-500 mg twice daily.
- Extended-release: 400-1000 mg once daily.
- Pain: 200-400 mg every 6-8 hours, not exceeding 1000 mg/day.
- Maximum dose: 1000 mg/day for immediate-release; 1200 mg/day for extended-release (though doses above 1000 mg/day haven’t been rigorously studied).
Children:
- Juvenile Rheumatoid Arthritis (Extended-release only):
- 20-30 kg: 400 mg once daily
- 31-45 kg: 600 mg once daily
- 46-60 kg: 800 mg once daily
-
60 kg: 1000 mg once daily
- Immediate-release formulations are not recommended for children.
- Pediatric safety has not been thoroughly evaluated in children under 6.
Special Cases:
- Elderly Patients: Start with the lowest effective dose due to increased risk of side effects. Monitor renal function.
- Patients with Renal Impairment: Use with caution. Dosage adjustment may be necessary in moderate to severe impairment.
- Patients with Hepatic Dysfunction: Use with caution. Dosage adjustment may be necessary.
- Patients with Comorbid Conditions: Use cautiously in patients with cardiovascular disease, hypertension, asthma, peptic ulcer disease, and bleeding disorders.
Clinical Use Cases
- S-Etodolac’s clinical use is primarily focused on managing osteoarthritis, rheumatoid arthritis, and general pain. It’s not typically used in acute care settings like intubation, surgical procedures, mechanical ventilation, or ICU use. In emergency situations, other analgesics are usually preferred.
Dosage Adjustments
- Adjust dosages for renal/hepatic impairment based on the degree of dysfunction.
Side Effects
Common Side Effects:
- Nausea, diarrhea, heartburn, stomach pain, loss of appetite, dizziness, headache, rash, bloating, gas, ringing in the ears, blurred vision.
Rare but Serious Side Effects:
- Gastrointestinal bleeding, ulcers, perforation, myocardial infarction, stroke, kidney damage, severe allergic reactions (anaphylaxis), Stevens-Johnson Syndrome.
Long-Term Effects:
- Increased risk of cardiovascular events with prolonged use, particularly at high doses.
- Potential for renal and hepatic damage with chronic use.
Adverse Drug Reactions (ADR):
- Anaphylaxis, angioedema, gastrointestinal bleeding, acute renal failure, severe skin reactions.
Contraindications
- Hypersensitivity to etodolac.
- History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs.
- Active peptic ulcer disease or gastrointestinal bleeding.
- Third trimester of pregnancy.
- Peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery.
Drug Interactions
- CYP450 Interactions: Primarily metabolized by CYP3A4 and CYP2C9. Inhibitors of these enzymes may increase etodolac levels.
- Other Drug Interactions:
- Antihypertensives (ACE inhibitors, ARBs, diuretics): May reduce antihypertensive effects.
- Anticoagulants (warfarin): Increased bleeding risk.
- Lithium: Increased lithium levels.
- Methotrexate: Increased methotrexate toxicity.
- Corticosteroids: Increased risk of gastrointestinal ulcers and bleeding.
- Aspirin: Increased risk of GI side effects
- Alcohol: Increased risk of GI bleeding.
- Smoking: Increased risk of GI bleeding.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (prior to 20 weeks); D (after 20 weeks). Avoid use after 20 weeks gestation due to risks of premature closure of ductus arteriosus and renal dysfunction in the fetus.
- Breastfeeding: Etodolac is excreted in breast milk. Use an alternate drug or avoid breastfeeding, especially when nursing a newborn or preterm infant.
Drug Profile Summary
- Mechanism of Action: COX inhibitor, preferentially inhibits COX-2.
- Side Effects: Nausea, diarrhea, GI upset, dizziness, headache; rarely, GI bleeding, MI, stroke, renal damage.
- Contraindications: Hypersensitivity, aspirin/NSAID allergy, active peptic ulcer, pregnancy (3rd trimester).
- Drug Interactions: Antihypertensives, anticoagulants, lithium, methotrexate, corticosteroids, aspirin, alcohol.
- Pregnancy & Breastfeeding: Avoid in the third trimester of pregnancy and use with caution when breastfeeding.
- Dosage: See detailed dosage guidelines above.
- Monitoring Parameters: Renal function, liver function, blood pressure, signs of GI bleeding.
Popular Combinations
- While sometimes used with gastroprotectants like proton pump inhibitors (PPIs) to reduce GI risks, there are not many other “popular” clinical combinations specific to etodolac.
Precautions
- Evaluate renal and hepatic function before initiating therapy.
- Monitor for GI bleeding.
- Assess cardiovascular risk.
- Caution in elderly patients.
- Avoid alcohol and smoking.
- Avoid during pregnancy (especially 3rd trimester) and use cautiously when breastfeeding.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for S-Etodolac?
A: See the detailed dosage section above for specific recommendations based on indication, age, and other factors.
Q2: What are the most common side effects?
A: The most common side effects include nausea, diarrhea, heartburn, stomach pain, dizziness, and headache.
Q3: Is S-Etodolac safe during pregnancy?
A: S-Etodolac should be avoided after 20 weeks of pregnancy. Consult the pregnancy and breastfeeding section for detailed information.
Q4: How does S-Etodolac differ from other NSAIDs?
A: S-Etodolac is the S-enantiomer of etodolac. While it exhibits some COX-2 selectivity, it is not as selective as some other COX-2 inhibitors.
Q5: Can I take S-Etodolac with other pain relievers?
A: Consult your doctor before combining S-Etodolac with other NSAIDs or pain relievers, as this can increase the risk of side effects. Avoid concomitant use of aspirin.
Q6: Are there any serious side effects I should be aware of?
A: Yes, serious side effects, while rare, can include gastrointestinal bleeding, ulcers, perforation, myocardial infarction, stroke, and kidney problems. Seek immediate medical attention if you experience any of these.
Q7: What should I do if I miss a dose?
A: Take the missed dose as soon as you remember, unless it’s almost time for your next dose. Do not double up on doses.
Q8: Can S-Etodolac interact with other medications I’m taking?
A: Yes, S-Etodolac can interact with several medications, including antihypertensives, anticoagulants, lithium, and methotrexate. It’s crucial to inform your physician about all medications you are currently taking.
Q9: What are the long-term effects of taking S-Etodolac?
A: Long-term use, especially at higher doses, can increase the risk of cardiovascular issues and kidney or liver damage. Regular monitoring is essential for patients on long-term S-Etodolac therapy.
