Usage
This combination medication is primarily prescribed for the management of pain and inflammation associated with osteoarthritis, particularly of the hip and knee. It may also be used for other musculoskeletal pain conditions, such as pain and inflammation associated with dental extractions and other surgical procedures.
Pharmacological Classification: Analgesic, Anti-inflammatory (NSAID - Non-Steroidal Anti-Inflammatory Drug), COX-2 Inhibitor (Polmacoxib), Antipyretic (Paracetamol).
Mechanism of Action: Polmacoxib selectively inhibits the cyclooxygenase-2 (COX-2) enzyme, which reduces the production of prostaglandins, key mediators of inflammation and pain. Paracetamol has a central analgesic and antipyretic effect, likely by activating descending serotonergic pathways and influencing the endocannabinoid system.
Alternate Names
Pumacoxib PCM; Justpolma P; Hisaka-P; Acelex (for Polmacoxib). Some regional variations may exist.
How It Works
Pharmacodynamics: Polmacoxib exerts its anti-inflammatory effect by selectively inhibiting COX-2, thus reducing prostaglandin synthesis. Paracetamol’s precise mechanism is not fully elucidated but involves central analgesic and antipyretic effects.
Pharmacokinetics: Polmacoxib is primarily metabolized by CYP3A4 in the liver. Paracetamol is metabolized in the liver primarily through glucuronidation and sulfation pathways, with a minor component undergoing CYP450-mediated metabolism to a reactive metabolite. Both are eliminated in the urine and feces. The pharmacokinetic parameters of the combined formulation are not precisely defined.
Mode of Action: Polmacoxib binds to the COX-2 enzyme’s active site, inhibiting its activity and reducing prostaglandin production. Paracetamol is thought to inhibit COX enzymes in the central nervous system, as well as activate descending serotonergic pathways, which modulate pain perception. It may also interact with the endocannabinoid system.
Dosage
Standard Dosage
Adults:
One tablet containing 2mg Polmacoxib and 325mg Paracetamol taken once or twice daily, preferably after meals. The maximum recommended daily dose of Polmacoxib is 2mg. Do not exceed the recommended dose of Paracetamol (4g/day) due to the risk of liver toxicity.
Children:
The safety and efficacy of this combination have not been established in children. Therefore, it is not recommended for pediatric use.
Special Cases:
- Elderly Patients: Dose adjustments may be necessary based on renal function and overall health status. Start with the lowest effective dose and monitor closely.
- Patients with Renal Impairment: For patients with creatinine clearance ≥ 30 ml/min, no dosage adjustment is necessary. Use is contraindicated in patients with creatinine clearance < 30 ml/min.
- Patients with Hepatic Dysfunction: Exercise caution, especially in patients with moderate hepatic impairment. Use is contraindicated in patients with severe hepatic dysfunction (Child-Pugh score ≥ 10).
- Patients with Comorbid Conditions: Patients with cardiovascular disease, hypertension, diabetes, bronchial asthma, a history of edema, peptic ulcer, or gastrointestinal bleeding should be monitored closely for adverse events. Those with uncontrolled hypertension should avoid this medication.
Clinical Use Cases
The primary clinical use case detailed in the sources is the management of osteoarthritis pain. Specific dosage recommendations for intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations are not available in the sources for this specific combination. Post-operative use for pain management after dental and other surgical procedures is noted.
Dosage Adjustments
Dose modifications should be made based on patient-specific factors such as renal or hepatic dysfunction, co-existing medical conditions, and concomitant medications. Closely monitor patients for adverse reactions and adjust the dose as needed.
Side Effects
Common Side Effects
Nausea, vomiting, heartburn, dizziness, stomach pain, gas, constipation, diarrhea, headache, indigestion.
Rare but Serious Side Effects
Allergic reactions (rash, swelling, difficulty breathing); liver toxicity (with excessive Paracetamol use); cardiovascular thrombotic events (myocardial infarction, stroke); bloody or black, tarry stools; bloody or cloudy urine; pinpoint red spots on the skin; sores, ulcers, or white spots in the mouth; unusual bleeding or bruising; jaundice.
Long-Term Effects
Chronic complications from prolonged use can include liver damage (Paracetamol) and cardiovascular issues (Polmacoxib).
Adverse Drug Reactions (ADR)
Clinically significant ADRs include severe allergic reactions, hepatotoxicity, and cardiovascular events. These necessitate immediate intervention.
Contraindications
Hypersensitivity to Polmacoxib, Paracetamol, sulphonamides, aspirin, or other NSAIDs. Active peptic ulcer or gastrointestinal bleeding. History of bronchospasm, acute rhinitis, nasal polyps, angioedema, urticaria, or allergic-type reactions after taking aspirin or NSAIDs, including COX-2 inhibitors. Severe hepatic dysfunction. Renal impairment (creatinine clearance < 30 ml/min). Pregnancy and lactation. Coronary artery bypass surgery (CABG). Hyperkalemia or coagulation disorders. Patients receiving anticoagulants. Uncontrolled hypertension.
Drug Interactions
Anticoagulants (increased risk of bleeding), other NSAIDs (additive adverse effects), CYP3A4 inhibitors (ketoconazole, erythromycin - increased Polmacoxib levels), alcohol (increased risk of liver damage and GI bleeding). Other interactions can occur with antihypertensives, certain antibiotics, and other medications.
Pregnancy and Breastfeeding
Contraindicated in both pregnancy and breastfeeding due to potential harm to the fetus or infant.
Drug Profile Summary
- Mechanism of Action: Polmacoxib: Selective COX-2 inhibition. Paracetamol: Central analgesic and antipyretic.
- Side Effects: Nausea, vomiting, GI upset, dizziness, headache, liver toxicity (Paracetamol), cardiovascular events (Polmacoxib).
- Contraindications: Hypersensitivity, active peptic ulcer, GI bleeding, severe hepatic/renal dysfunction, pregnancy, breastfeeding.
- Drug Interactions: Anticoagulants, NSAIDs, CYP3A4 inhibitors, alcohol.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Adults: One tablet (2mg Polmacoxib/325mg Paracetamol) once or twice daily.
- Monitoring Parameters: Liver function tests (especially with prolonged Paracetamol use), renal function, blood pressure, signs of GI bleeding.
Popular Combinations
The combination of Polmacoxib and Paracetamol itself is designed for synergistic effects, offering combined anti-inflammatory and analgesic action.
Precautions
- General Precautions: Pre-screening for allergies, metabolic disorders, organ dysfunction, and concomitant medications.
- Specific Populations: Use with caution in the elderly and patients with hepatic or renal impairment. Contraindicated in pregnancy and breastfeeding.
- Lifestyle Considerations: Limit alcohol intake to reduce the risk of liver damage and GI bleeding.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Paracetamol + Polmacoxib?
A: The typical adult dosage is one tablet (2mg Polmacoxib and 325mg Paracetamol) once or twice daily.
Q2: Can this combination be used in children?
A: No, the safety and efficacy in children have not been established.
Q3: What are the most serious side effects?
A: Liver damage (Paracetamol), cardiovascular events (Polmacoxib), and allergic reactions.
Q4: What are the contraindications?
A: Hypersensitivity, active peptic ulcer, severe liver or kidney disease, pregnancy, and breastfeeding.
Q5: Can I take this medication if I have high blood pressure?
A: Caution is advised. Patients with uncontrolled hypertension should avoid this medication.
Q6: What should I do if I experience side effects?
A: Contact your doctor immediately, especially if the side effects are severe.
Q7: How does this combination work for osteoarthritis?
A: Polmacoxib reduces inflammation, while Paracetamol relieves pain.
Q8: Can this drug be used after surgery?
A: Yes, it can be used for pain management after certain surgical procedures, such as dental extractions, but consult your doctor for appropriate usage and dosage.
Q9: Are there any drug interactions I should be aware of?
A: Yes, significant interactions can occur with anticoagulants, other NSAIDs, and CYP3A4 inhibitors. Alcohol should also be avoided. Always inform your doctor of all other medications you are taking.
Q10: What is the maximum daily dose of Paracetamol I can take with this combination?
A: Do not exceed 4000mg (4g) of Paracetamol per day, including any other Paracetamol-containing products.
