Usage
Dexketoprofen + Paracetamol is prescribed for the short-term symptomatic treatment of moderate to severe acute pain, such as postoperative pain, musculoskeletal pain (including osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis), dysmenorrhea (painful periods), dental pain, and other conditions requiring potent analgesic effects. It is also effective in reducing fever.
It is classified pharmacologically as an analgesic and antipyretic combination.
The mechanism of action involves two components: Dexketoprofen, a nonsteroidal anti-inflammatory drug (NSAID), inhibits cyclooxygenase (COX-1 and COX-2) enzymes, reducing prostaglandin synthesis, which are mediators of pain and inflammation. Paracetamol (acetaminophen) acts centrally, likely inhibiting prostaglandin synthesis in the central nervous system and modulating the hypothalamic heat-regulating center.
Alternate Names
There is no single official alternate name for this specific combination drug. However, the individual components are known by various names:
- Dexketoprofen: Dexketoprofen trometamol
- Paracetamol: Acetaminophen (primarily used in the United States and Canada)
Brand names vary depending on the region and manufacturer. Some popular brand names include Aseket and Infuen-P. Ketesse is a brand name for Dexketoprofen.
How It Works
Pharmacodynamics: Dexketoprofen exerts its analgesic and anti-inflammatory effects peripherally by inhibiting COX enzymes and reducing prostaglandin synthesis. Paracetamol’s central action contributes to pain relief by elevating the pain threshold and reduces fever through its action on the hypothalamic heat-regulating center.
Pharmacokinetics: Both drugs are well-absorbed orally. Food may delay the absorption of Dexketoprofen but does not significantly affect its bioavailability. Both drugs are extensively metabolized in the liver. Dexketoprofen is mainly conjugated with glucuronic acid and excreted in the urine. Paracetamol is metabolized via glucuronidation, sulfation, and a minor pathway involving CYP2E1, with metabolites excreted in the urine.
Mode of Action: Dexketoprofen inhibits COX-1 and COX-2 enzymes, preventing the conversion of arachidonic acid to prostaglandins. Paracetamol’s precise mechanism is not fully elucidated but involves central inhibition of prostaglandin synthesis and possible modulation of endocannabinoid and serotonergic pathways.
Elimination: Dexketoprofen is primarily eliminated renally. Paracetamol is predominantly eliminated renally after hepatic metabolism.
Dosage
Standard Dosage
Adults: The recommended oral dose is generally 12.5 mg of Dexketoprofen + 325 to 500 mg Paracetamol every 4-6 hours, or 25 mg of Dexketoprofen + 500 mg Paracetamol every 8 hours. The total daily dose of Dexketoprofen should not exceed 75 mg, and the total daily dose of Paracetamol should not exceed 4000 mg (4g) per day.
Children: This combination is not recommended for children and adolescents under 18 years of age as safety and efficacy have not been established.
Special Cases:
- Elderly Patients: Start with a lower dose (50 mg total daily dose of Dexketoprofen) and increase only if well-tolerated.
- Patients with Renal Impairment: Reduce the dose based on creatinine clearance. For mild impairment (CrCl 60-89 ml/min), start with 50 mg total daily dose of Dexketoprofen. Contraindicated in moderate to severe renal impairment (CrCl < 60 ml/min).
- Patients with Hepatic Dysfunction: Reduce the initial dose to 50 mg daily dose of Dexketoprofen for mild to moderate impairment. Contraindicated in severe hepatic dysfunction.
- Patients with Comorbid Conditions: Exercise caution in patients with a history of gastrointestinal ulcers, bleeding, inflammatory bowel disease, severe heart failure, asthma triggered by NSAIDs, or other relevant comorbidities.
Clinical Use Cases
Dosage recommendations for specific clinical use cases (intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations) generally follow the standard adult dosing adjusted for renal or hepatic impairment as necessary. For IV administration, the usual dose is 50 mg of Dexketoprofen every 8-12 hours, administered slowly over at least 15 seconds. The maximum IV dose is 150 mg daily. Dexketoprofen + paracetamol can be combined with opioids if pain is not controlled by the combination alone.
Dosage Adjustments:
Dose adjustments are necessary for patients with renal or hepatic dysfunction, as specified above. Consider also adjusting the dose for patients with other conditions affecting drug metabolism or clearance.
Side Effects
Common Side Effects:
Nausea, vomiting, dyspepsia, abdominal pain, diarrhea, dizziness, headache, drowsiness.
Rare but Serious Side Effects:
Gastrointestinal bleeding or perforation, myocardial infarction, stroke, severe allergic reactions (anaphylaxis), hepatotoxicity, acute renal failure.
Long-Term Effects:
Chronic use of NSAIDs can increase the risk of cardiovascular and renal complications. Long term use of Paracetamol at high doses can lead to hepatotoxicity.
Adverse Drug Reactions (ADR):
Any severe or unexpected reaction should be considered a potential ADR and reported appropriately.
Contraindications
- Hypersensitivity to dexketoprofen, paracetamol, or any NSAIDs.
- History of asthma, bronchospasm, or allergic-type reactions after taking NSAIDs.
- Active peptic ulcer or gastrointestinal bleeding.
- Severe heart failure.
- Severe renal or hepatic impairment.
- Third trimester of pregnancy.
Drug Interactions
- Other NSAIDs (increased risk of gastrointestinal side effects)
- Anticoagulants (increased risk of bleeding)
- Diuretics and ACE inhibitors (reduced antihypertensive effect)
- Lithium (increased lithium levels)
- Methotrexate (increased methotrexate toxicity)
- CYP2E1 inducers (e.g., rifampicin) (increased risk of paracetamol hepatotoxicity).
Pregnancy and Breastfeeding
Dexketoprofen + Paracetamol is contraindicated during the third trimester of pregnancy. Its use is not recommended during the first and second trimesters unless clearly necessary. Consult with a healthcare professional if use during pregnancy or breastfeeding is being considered. Excretion in breast milk is minimal and considered low risk.
Drug Profile Summary
- Mechanism of Action: Dexketoprofen: COX-1 and COX-2 inhibitor; Paracetamol: Central analgesic and antipyretic.
- Side Effects: Nausea, vomiting, dyspepsia, dizziness, headache, GI bleeding (rare), cardiovascular events (rare).
- Contraindications: Hypersensitivity, GI bleeding, severe hepatic/renal impairment, third trimester of pregnancy.
- Drug Interactions: Other NSAIDs, anticoagulants, diuretics.
- Pregnancy & Breastfeeding: Use with caution; contraindicated in the third trimester. Low risk during breastfeeding.
- Dosage: Adults: 12.5/325-500mg every 4-6 hours or 25/500mg every 8 hours. Max: 75 mg dexketoprofen, 4000 mg paracetamol daily. Elderly/Hepatic/Renal impairment: Lower initial doses. Not for children <18.
- Monitoring Parameters: Liver and kidney function, signs of gastrointestinal bleeding, blood pressure.
Popular Combinations
This combination itself is a popular choice.
Precautions
Standard precautions apply to pre-existing conditions and specific populations.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Dexketoprofen + Paracetamol?
A: Adults: 12.5mg/325-500mg every 4-6 hours or 25mg/500mg every 8 hours, max 75 mg dexketoprofen and 4000mg paracetamol daily. Dosage should be adjusted in elderly, renally impaired, and hepatically impaired patients.
Q2: Can this combination be used in children?
A: No, it is not recommended for children under 18 years old.
Q3: What are the major contraindications?
A: Hypersensitivity, active peptic ulcer/GI bleeding, severe heart, liver, or kidney disease, third trimester of pregnancy.
Q4: How does this combination interact with other NSAIDs?
A: Concomitant use with other NSAIDs increases the risk of gastrointestinal side effects and is generally not recommended.
Q5: What are the common side effects?
A: Nausea, vomiting, dyspepsia, abdominal pain, diarrhea, dizziness, headache.
Q6: What precautions should be taken for elderly patients?
A: Start with a lower dose (50 mg total daily dose of dexketoprofen) and monitor for adverse effects.
Q7: What is the maximum daily dose?
A: 75 mg of dexketoprofen and 4000 mg (4 g) of paracetamol.
Q8: Can this be used during pregnancy?
A: It is contraindicated in the third trimester and not recommended during the first and second trimesters unless clearly necessary.
Q9: How is this drug administered?
A: Orally, typically as tablets. Can also be administered intravenously.
Q10: What to do in case of an overdose?
A: Seek immediate medical attention. Supportive care may be required, and specific antidotes are available for paracetamol overdose.
