Usage
Aceclofenac + Paracetamol is prescribed for the relief of pain and inflammation in various conditions, including:
- Osteoarthritis
- Rheumatoid arthritis
- Ankylosing spondylitis
- Low back pain
- Dental pain
- Post-operative pain
- Other painful musculoskeletal conditions
Pharmacological Classification:
- Analgesic (pain reliever)
- Anti-inflammatory
- Antipyretic (fever reducer)
Mechanism of Action: Aceclofenac, a non-steroidal anti-inflammatory drug (NSAID), inhibits cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis, thereby decreasing inflammation and pain. Paracetamol has analgesic and antipyretic effects through central mechanisms, possibly involving inhibition of COX-3 in the brain and spinal cord.
Alternate Names
This combination is primarily known as Aceclofenac + Paracetamol. There may be regional variations in the name.
Brand Names: Numerous brand names exist worldwide; a few examples include Dolowin-Plus and Zsac-P. This list may not be exhaustive and can vary by region.
How It Works
Pharmacodynamics: Aceclofenac exerts its anti-inflammatory and analgesic effects by inhibiting COX-1 and COX-2 enzymes, which are responsible for the production of prostaglandins, mediators of pain and inflammation. Paracetamol’s mechanism is not fully understood but is thought to involve central COX inhibition and modulation of the endocannabinoid system.
Pharmacokinetics:
- Absorption: Both aceclofenac and paracetamol are readily absorbed from the gastrointestinal tract. Food may slightly delay the absorption of aceclofenac but not its overall extent.
- Metabolism: Aceclofenac is extensively metabolized in the liver, primarily by CYP2C9. Paracetamol is primarily metabolized by glucuronidation and sulfation in the liver. A small fraction is metabolized by CYP2E1 to a hepatotoxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI), which is usually detoxified by glutathione.
- Elimination: Aceclofenac metabolites are primarily excreted in urine, with a small amount in bile. Paracetamol metabolites are primarily excreted in urine.
Mode of Action (Cellular/Molecular): Aceclofenac, by inhibiting COX enzymes, reduces the production of prostaglandins, which are involved in inflammation, pain, and fever. Paracetamol’s central action likely involves inhibition of COX-3, a central nervous system-specific isoform of COX.
Receptor Binding, Enzyme Inhibition, Neurotransmitter Modulation: Aceclofenac primarily acts by inhibiting COX-1 and COX-2 enzymes. Paracetamol’s precise mechanism is less clear but may involve COX-3 inhibition, modulation of the endocannabinoid system, and serotonergic pathways.
Elimination Pathways: Aceclofenac is primarily eliminated via hepatic metabolism and renal excretion. Paracetamol is primarily eliminated by hepatic metabolism followed by renal excretion.
Dosage
Standard Dosage
Adults: One tablet (typically containing 100 mg aceclofenac and 500 mg paracetamol) twice daily, taken with or after food. The maximum recommended dose is two tablets per day. Maintain a gap of at least 4-6 hours between doses.
Special Cases:
- Elderly Patients: Start with the lowest effective dose and monitor closely for adverse effects. Dose adjustments may be necessary in patients with renal or hepatic impairment.
- Patients with Renal Impairment: Caution is advised in patients with mild to moderate renal impairment. Dose reduction might be necessary. Use with caution in severe renal impairment.
- Patients with Hepatic Dysfunction: Reduce the initial daily dose to 100mg of aceclofenac. Paracetamol should be used with caution in patients with hepatic impairment, and dose reduction may be necessary.
- Patients with Comorbid Conditions: Use with caution in patients with cardiovascular disease, hypertension, or a history of gastrointestinal bleeding.
Clinical Use Cases
Dosage adjustments in clinical use cases such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations should be determined on a case-by-case basis considering the patient’s specific condition and other medications. Consult specialist guidelines for these specific clinical situations.
Dosage Adjustments
Dosage adjustments should be made based on individual patient factors like renal or hepatic function, concomitant medications, and other medical conditions. Genetic polymorphisms affecting drug metabolism may also necessitate dose adjustments.
Side Effects
Common Side Effects
- Dyspepsia
- Nausea
- Abdominal pain
- Diarrhea
- Dizziness
- Headache
- Drowsiness
Rare but Serious Side Effects
- Gastrointestinal bleeding or ulceration
- Stevens-Johnson Syndrome
- Toxic Epidermal Necrolysis
- Hepatotoxicity (especially with high doses of paracetamol)
- Renal impairment
- Blood dyscrasias (e.g., thrombocytopenia, agranulocytosis)
Long-Term Effects
Chronic use of NSAIDs can increase the risk of gastrointestinal complications, renal dysfunction, and cardiovascular events. Long-term use of high doses of paracetamol can increase the risk of hepatotoxicity.
Adverse Drug Reactions (ADR)
Any severe or persistent side effects, signs of allergic reactions, or symptoms suggestive of gastrointestinal bleeding or hepatotoxicity require immediate medical attention.
Contraindications
- Hypersensitivity to aceclofenac or paracetamol
- Active or history of recurrent peptic ulcer/hemorrhage
- Severe heart failure
- Severe hepatic impairment
- Severe renal impairment
- Third trimester of pregnancy
- History of hypersensitivity reactions (asthma, rhinitis, angioedema, urticaria) to NSAIDs or aspirin
Drug Interactions
- Anticoagulants (e.g., warfarin): Increased risk of bleeding
- Lithium, Digoxin, Methotrexate: Increased plasma levels of these drugs
- Diuretics: Reduced diuretic effect; increased risk of nephrotoxicity with potassium-sparing diuretics
- Other NSAIDs and Corticosteroids: Increased risk of gastrointestinal side effects
- Cholestyramine: Reduced absorption of paracetamol
- Metoclopramide, Domperidone: Altered absorption of aceclofenac and paracetamol
- Alcohol: Increased risk of hepatotoxicity with paracetamol
- CYP450 Interactions: Aceclofenac is primarily metabolized by CYP2C9. Drugs that inhibit or induce CYP2C9 may alter aceclofenac’s metabolism.
Pregnancy and Breastfeeding
Aceclofenac + Paracetamol is generally not recommended during pregnancy, especially during the third trimester. Aceclofenac is contraindicated in the third trimester. Paracetamol is generally considered safe during pregnancy at recommended doses but should be used with caution.
This combination should be used with caution during breastfeeding. Paracetamol passes into breast milk in small amounts. While generally considered safe for use during breastfeeding at recommended doses, potential effects on the nursing infant should be considered. Aceclofenac’s presence in breast milk is minimal, but the drug should only be used if the benefits outweigh the risks.
Drug Profile Summary
- Mechanism of Action: Aceclofenac: COX inhibitor; Paracetamol: Central analgesic and antipyretic.
- Side Effects: Dyspepsia, nausea, abdominal pain, dizziness, headache, GI bleeding (rare), hepatotoxicity (rare).
- Contraindications: Hypersensitivity, peptic ulcers, severe heart/liver/kidney disease, third-trimester pregnancy.
- Drug Interactions: Anticoagulants, lithium, digoxin, methotrexate, diuretics, other NSAIDs, alcohol.
- Pregnancy & Breastfeeding: Use with caution; contraindicated in the third trimester.
- Dosage: Adults: 1 tablet twice daily; dosage adjustments may be necessary for elderly patients or those with hepatic/renal impairment.
- Monitoring Parameters: Liver function tests, renal function tests, blood counts (with long-term use).
Popular Combinations
While Aceclofenac + Paracetamol is itself a combination product, it is sometimes used in combination with serratiopeptidase (an enzyme with anti-inflammatory properties) in some regions.
Precautions
- General Precautions: Assess for allergies, history of gastrointestinal bleeding, renal/hepatic dysfunction, cardiovascular disease.
- Specific Populations: Use with caution in pregnant/breastfeeding women, elderly patients, and those with pre-existing medical conditions (asthma, hypertension, heart failure).
- Lifestyle Considerations: Avoid alcohol during treatment with this combination. Caution while driving or operating machinery due to potential dizziness and drowsiness.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Aceclofenac + Paracetamol?
A: The standard adult dosage is one tablet (usually 100 mg aceclofenac and 500 mg paracetamol) twice daily, taken with or after food.
Q2: Can Aceclofenac + Paracetamol be used in children?
A: The safety and efficacy haven’t been fully established. Consult pediatric dosing guidelines and consider a syrup formulation.
Q3: What are the common side effects?
A: Common side effects include dyspepsia, nausea, abdominal pain, dizziness, and headache.
Q4: What are the serious side effects?
A: Rare but serious side effects include GI bleeding, Stevens-Johnson syndrome, hepatotoxicity, and blood dyscrasias.
Q5: What are the contraindications?
A: Contraindications include hypersensitivity, peptic ulcers, severe heart/liver/kidney disease, third-trimester pregnancy, and hypersensitivity to NSAIDs or aspirin.
Q6: What drug interactions should be considered?
A: Important drug interactions exist with anticoagulants, lithium, digoxin, methotrexate, diuretics, and alcohol.
Q7: Can it be taken during pregnancy or breastfeeding?
A: Use cautiously; contraindicated in the third trimester of pregnancy. Paracetamol is generally considered safe during breastfeeding at recommended doses, but aceclofenac should only be used if the benefits outweigh the risks.
Q8: What precautions should be taken in elderly patients?
A: Start with the lowest effective dose and monitor closely for adverse reactions, especially in those with renal or hepatic impairment.
Q9: How does food affect the absorption of this medicine?
A: Food may slightly delay but doesn’t significantly affect the overall absorption of aceclofenac. It’s recommended to take the medication with or after meals to reduce gastrointestinal irritation.
A: Seek immediate medical attention for any severe or persistent side effects, signs of allergic reactions, or symptoms suggestive of gastrointestinal bleeding or hepatotoxicity.
