Usage
Paracetamol + S-Etodolac is prescribed for mild to moderate pain relief and reduction of inflammation. It’s commonly used to treat osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, headaches, toothaches, menstrual cramps, back pain, and fever.
Pharmacological Classification:
- S-Etodolac: Non-steroidal anti-inflammatory drug (NSAID)
- Paracetamol: Analgesic and antipyretic
Mechanism of Action: S-Etodolac inhibits cyclooxygenase (COX) enzymes, reducing prostaglandin production, which are responsible for inflammation and pain. Paracetamol reduces pain and fever, likely by inhibiting prostaglandin synthesis in the central nervous system. The combination provides synergistic pain relief.
Alternate Names
- Setolac-P
- Etodolac + Paracetamol/Acetaminophen
- Etodolac Paracetamol Tablets
How It Works
Pharmacodynamics: S-Etodolac, as an NSAID, exerts its anti-inflammatory and analgesic effects primarily through the inhibition of COX enzymes. This leads to a decrease in prostaglandin synthesis, which are mediators of inflammation and pain. Paracetamol’s mechanism is not fully understood, but it is thought to inhibit prostaglandin synthesis in the central nervous system, contributing to its analgesic and antipyretic properties. The combination offers synergistic pain relief by targeting both peripheral and central pain pathways.
Pharmacokinetics: Both S-Etodolac and paracetamol are absorbed orally. S-Etodolac is extensively metabolized in the liver, while paracetamol is also metabolized in the liver, with both drugs and their metabolites primarily excreted renally. Specific CYP450 enzyme involvement in etodolac metabolism remains unclear.
Mode of Action/Receptor Binding/Enzyme Inhibition: S-Etodolac inhibits COX-1 and COX-2 enzymes. Paracetamol’s mechanism is less clear but may involve central COX inhibition and other pathways, including cannabinoid and serotonergic systems.
Elimination Pathways: Primarily renal excretion of metabolites for both drugs after hepatic metabolism.
Dosage
Standard Dosage
Adults:
- Typical starting dose: 400-600mg S-Etodolac and 325-500mg Paracetamol every 6-8 hours as needed.
- For rheumatoid arthritis or osteoarthritis: A single daily dose of S-Etodolac (400mg or 600mg) may be administered in the evening.
- Acute pain: 200-400mg S-Etodolac may be sufficient.
- Maximum daily dose of Paracetamol: Should not exceed 4g.
Children: Generally not recommended for children under 12 years of age.
Special Cases:
- Elderly Patients: Use with caution due to increased risk of side effects. Lower doses may be considered.
- Patients with Renal Impairment: Dose modification may be necessary based on creatinine clearance or eGFR. If creatinine clearance is less than 30 mL/minute, increase the dosing interval to at least 6 hours.
- Patients with Hepatic Dysfunction: Use with caution. Consider dose reduction due to hepatic metabolism of both drugs. Maximum daily dose of paracetamol may be reduced to 3g, especially in those with severe impairment (Child-Pugh C).
- Patients with Comorbid Conditions: Use cautiously in patients with hypertension, heart disease, history of stomach ulcers, or bleeding disorders.
Clinical Use Cases
The combination is not typically used in the specific clinical scenarios mentioned (intubation, surgical procedures, mechanical ventilation, ICU, emergencies). Paracetamol alone, particularly intravenous formulations, may be used in these settings. Dosing for intravenous paracetamol should be weight-based and adjusted for renal/hepatic impairment.
Dosage Adjustments
Dose adjustments are necessary based on patient-specific factors like renal/hepatic dysfunction, age, and other risk factors for hepatotoxicity (malnutrition, chronic alcohol use, etc.). Low body weight (<50 kg) may require lower doses of paracetamol, especially for intravenous administration.
Side Effects
Common Side Effects:
- Nausea
- Vomiting
- Dyspepsia
- Headache
- Dizziness
- Drowsiness
Rare but Serious Side Effects:
- Gastrointestinal bleeding or ulceration
- Hepatotoxicity (liver damage)
- Renal impairment
- Allergic reactions
- Stevens-Johnson syndrome
Long-Term Effects: With prolonged NSAID use, there’s a risk of cardiovascular events and renal damage.
Contraindications
- Hypersensitivity to paracetamol or S-Etodolac.
- Severe hepatic impairment or active liver disease.
- History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs.
- Severe heart failure.
Drug Interactions
- Other NSAIDs: Increased risk of gastrointestinal adverse effects.
- Anticoagulants (warfarin): Increased risk of bleeding.
- Lithium: S-Etodolac can increase lithium levels.
- Methotrexate: S-Etodolac can increase methotrexate toxicity.
- Alcohol: Increased risk of liver damage with paracetamol.
- Liver enzyme-inducing drugs (e.g., rifampicin, phenytoin): May increase the risk of paracetamol hepatotoxicity.
Pregnancy and Breastfeeding
- Pregnancy: S-Etodolac should be avoided, especially during the third trimester, due to the risk of premature closure of the ductus arteriosus. Paracetamol is generally considered safe during pregnancy at recommended doses.
- Breastfeeding: Both S-Etodolac and paracetamol are excreted in breast milk. While paracetamol is generally considered compatible with breastfeeding, caution is advised with S-Etodolac.
Drug Profile Summary
- Mechanism of Action: S-Etodolac: COX inhibitor; Paracetamol: Central analgesic and antipyretic.
- Side Effects: Nausea, vomiting, dyspepsia, GI bleeding (rare), hepatotoxicity (rare).
- Contraindications: Hypersensitivity, severe liver disease, late pregnancy.
- Drug Interactions: NSAIDs, anticoagulants, alcohol.
- Pregnancy & Breastfeeding: Avoid S-Etodolac in pregnancy, especially third trimester. Paracetamol is generally considered safe.
- Dosage: Adults: S-Etodolac 400-600mg, paracetamol 325-500mg every 6-8 hours. Adjust for renal/hepatic impairment.
- Monitoring Parameters: Liver function tests, renal function, signs of GI bleeding.
Popular Combinations
This combination itself is a popular one. Sometimes, it’s further combined with opioid analgesics for managing severe pain, though this should be done cautiously due to increased risk of side effects.
Precautions
- Assess for allergies, liver and kidney function, history of GI bleeds, and alcohol use.
- Caution in the elderly.
- Adjust dose in renal/hepatic impairment.
- Avoid in late pregnancy.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Paracetamol + S-Etodolac?
A: Adults: S-Etodolac 400-600mg + Paracetamol 325-500mg every 6-8 hours as needed, not exceeding 4g of paracetamol daily. Adjust for renal/hepatic impairment and other risk factors. Not generally recommended for children under 12.
Q2: What are the common side effects?
A: Nausea, vomiting, dyspepsia, headache, dizziness.
Q3: Are there any serious side effects?
A: Yes, though rare. GI bleeding, liver damage, and allergic reactions are possible.
Q4: Can this combination be used in pregnancy?
A: S-Etodolac should be avoided, particularly in the third trimester. Paracetamol is generally considered safe at recommended doses.
Q5: What are the drug interactions I should be aware of?
A: Other NSAIDs, anticoagulants (e.g., warfarin), alcohol, and liver enzyme-inducing drugs.
Q6: What precautions are necessary for elderly patients?
A: Use with caution due to increased risk of side effects. Lower doses may be considered. Monitor renal and hepatic function.
Q7: How should the dose be adjusted in renal impairment?
A: If creatinine clearance is less than 30 mL/minute, increase the minimum dosing interval to 6 hours or longer.
Q8: Can this drug be used for long-term pain management?
A: Long-term use, especially of the S-Etodolac component, should be carefully considered due to the potential for cardiovascular and renal complications. Regular monitoring is essential.
Q9: How does this combination work differently from paracetamol or S-Etodolac alone?
A: It targets both peripheral and central pain pathways, offering synergistic pain relief.
Q10: What should I do in case of a suspected overdose?
A: Immediately seek medical attention. Paracetamol overdose can cause severe liver damage.
