Dexketoprofen

Usage

• Dexketoprofen is prescribed for the symptomatic treatment of mild to moderate pain, including musculoskeletal pain (such as sprains and strains), dental pain, dysmenorrhea (painful menstrual periods), and postoperative pain. It is also used in the treatment of acute and chronic pain associated with osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis.
• Pharmacological Classification: Non-Steroidal Anti-Inflammatory Drug (NSAID). Specifically it belongs to the propionic acid class of NSAIDs.
• Mechanism of Action: Dexketoprofen is the S(+)-enantiomer of ketoprofen. It works by inhibiting the cyclooxygenase (COX) enzymes, COX-1 and COX-2 which are responsible for producing prostaglandins. Prostaglandins are mediators of pain, inflammation, and fever. By inhibiting COX enzymes, dexketoprofen decreases prostaglandin synthesis, thereby reducing pain and inflammation.

Alternate Names

• The active ingredient is often listed as dexketoprofen trometamol.
• Brand Names: Keral®, Skudexa® (in combination with tramadol), Ketesse®.

How It Works

• Pharmacodynamics: Dexketoprofen exerts its analgesic and anti-inflammatory effects primarily through the inhibition of COX enzymes and subsequent reduction of prostaglandin synthesis. It preferentially inhibits COX-2 over COX-1, although this selectivity is not absolute. This inhibition reduces peripheral and central sensitization, thereby alleviating pain.
• Pharmacokinetics:
  • Absorption: Dexketoprofen is rapidly and completely absorbed after oral administration, reaching peak plasma concentrations within approximately 30 minutes on an empty stomach. Food can delay the absorption rate. Following intramuscular or intravenous administration, absorption is rapid and complete.
  • Metabolism: Primarily metabolized in the liver through glucuronidation.
  • Elimination: Excreted mainly by the kidneys, predominantly as the glucuronide conjugate.
• Mode of Action: Dexketoprofen binds to and inhibits COX-1 and COX-2 enzymes. This inhibition prevents the conversion of arachidonic acid to prostaglandins, reducing pain and inflammation.
• Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Dexketoprofen’s primary mechanism is COX-1 and COX-2 enzyme inhibition.
• Elimination Pathways: Renal excretion, primarily as dexketoprofen glucuronide.

Dosage

Standard Dosage

Adults:

• Oral: 12.5 mg every 4-6 hours or 25 mg every 8 hours. Maximum daily dose: 75 mg. For faster pain relief in acute pain, administer on an empty stomach at least 30 minutes before meals.
• Intravenous/Intramuscular: 50 mg every 8-12 hours (can be given every 6 hours if needed). Maximum daily dose: 150 mg for a maximum of 2 days. Switch to oral administration as soon as possible.

Children:

• Not recommended for use in children below 18 years of age as safety and efficacy haven’t been established.

Special Cases:

• Elderly Patients: Initiate therapy at the lower end of the dosage range (50 mg total daily dose for oral; and 50 mg total daily dose for intravenous/intramuscular). Increase dose cautiously if tolerated.
• Patients with Renal Impairment:
  • Mild impairment (CrCl 60-89 ml/min): Reduce initial dose to 50 mg total daily dose.
  • Moderate to severe impairment (CrCl ≤59 mL/min): Contraindicated.
• Patients with Hepatic Dysfunction:
  • Mild to moderate impairment (Child-Pugh score 5-9): Reduce initial dose to 50 mg total daily dose and monitor closely.
  • Severe impairment (Child-Pugh score 10-15): Contraindicated.
• Patients with Comorbid Conditions: Careful consideration and dose adjustment might be necessary in patients with cardiovascular disease, hypertension, diabetes mellitus, or a history of gastrointestinal disease.

Clinical Use Cases

• Intubation/Surgical Procedures/Mechanical Ventilation/ICU Use/Emergency Situations: Intravenous/intramuscular administration of 50 mg every 8-12 hours (or every 6 hours if necessary) for a maximum of 2 days is recommended for managing moderate to severe acute pain in these settings.

Dosage Adjustments:

• Adjust dosage based on renal/hepatic function, patient response, and concomitant medications. Close monitoring is essential in patients with renal or hepatic impairment.

Side Effects

Common Side Effects:

• Nausea, vomiting, abdominal pain, diarrhea, dyspepsia, dizziness, headache, drowsiness, insomnia.

Rare but Serious Side Effects:

• Gastrointestinal bleeding, ulceration, or perforation; Stevens-Johnson syndrome, toxic epidermal necrolysis, acute renal failure, exfoliative dermatitis, angioedema, bronchospasm.

Long-Term Effects:

• Chronic use can lead to gastrointestinal complications, renal impairment, and cardiovascular issues.

Adverse Drug Reactions (ADR):

• Anaphylaxis, severe skin reactions (SJS/TEN), gastrointestinal bleeding, hepatotoxicity, renal failure.

Contraindications

• Hypersensitivity to dexketoprofen or other NSAIDs.
• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs.
• Active or history of recurrent peptic ulcer/hemorrhage.
• Severe heart failure, severe renal or hepatic impairment.
• Third trimester of pregnancy and lactation.

Drug Interactions

• Other NSAIDs (including aspirin): Increased risk of gastrointestinal bleeding and ulceration.
• Anticoagulants (e.g., warfarin, heparin): Enhanced anticoagulant effect.
• Corticosteroids: Increased risk of gastrointestinal ulceration or bleeding.
• Lithium: Increased lithium levels.
• Methotrexate: Increased methotrexate toxicity.
• Antihypertensives: Reduced antihypertensive effect.
• SSRIs: Increased risk of gastrointestinal bleeding.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: Contraindicated in the third trimester. Use with caution during the first and second trimesters only if clearly needed. Dexketoprofen can cause premature closure of the ductus arteriosus in the fetus.
• Breastfeeding: Not recommended as it is excreted in breast milk.

Drug Profile Summary

• Mechanism of Action: COX-1 and COX-2 inhibitor, reducing prostaglandin synthesis.
• Side Effects: Nausea, vomiting, abdominal pain, dizziness, headache, GI bleeding (rare).
• Contraindications: Hypersensitivity, peptic ulcer disease, severe heart/renal/hepatic impairment, third trimester of pregnancy.
• Drug Interactions: Other NSAIDs, anticoagulants, corticosteroids, lithium, methotrexate.
• Pregnancy & Breastfeeding: Contraindicated in third trimester, use with caution in other trimesters; not recommended during breastfeeding.
• Dosage: Adults: 12.5-25 mg PO every 4-8 hours, max 75 mg/day; 50 mg IV/IM every 8-12 hours, max 150 mg/day for up to 2 days. Elderly/renal/hepatic impairment: lower doses.
• Monitoring Parameters: Renal function, liver function, signs of gastrointestinal bleeding.

Popular Combinations

• Dexketoprofen + Tramadol (Skudexa®): Provides synergistic analgesic effects for moderate to severe pain.

Precautions

• Pre-existing gastrointestinal disorders, cardiovascular disease, renal or hepatic impairment, pregnancy, breastfeeding. Monitor for signs of gastrointestinal bleeding, fluid retention, and renal function.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Dexketoprofen?

A: Adults: 12.5 mg every 4-6 hours or 25 mg every 8 hours, max 75 mg/day orally; 50 mg IV/IM every 8-12 hours, max 150 mg/day for up to 2 days. Elderly/renal/hepatic impairment: lower doses. Not recommended for children under 18.

Q2: How should Dexketoprofen be administered?

A: Available as oral tablets, granules for oral solution, and solution for intravenous or intramuscular injection. Oral forms should be taken with food to minimize gastrointestinal side effects, but may be taken on an empty stomach for faster pain relief in acute pain. Injectable forms should only be administered by healthcare professionals.

Q3: What are the common side effects of Dexketoprofen?

A: Nausea, vomiting, abdominal pain, diarrhea, dyspepsia, dizziness, headache, and drowsiness.

Q4: Is Dexketoprofen safe during pregnancy?

A: Contraindicated in the third trimester. Use with caution during the first and second trimesters only if the potential benefit outweighs the risk.

Q5: Can Dexketoprofen be used in patients with renal impairment?

A: Dose reduction is needed in mild renal impairment. Contraindicated in moderate to severe renal impairment.

Q6: What are the serious side effects of Dexketoprofen?

A: Gastrointestinal bleeding, ulceration, perforation, Stevens-Johnson syndrome, toxic epidermal necrolysis, acute renal failure.

Q7: What are the drug interactions of Dexketoprofen?

A: Interacts with other NSAIDs, anticoagulants, corticosteroids, lithium, methotrexate, and some antihypertensives.

Q8: Can patients with a history of peptic ulcers take Dexketoprofen?

A: No, it is contraindicated in patients with active or a history of recurrent peptic ulcer/hemorrhage.

Q9: How long can Dexketoprofen be used for?

A: Generally prescribed for short-term use. Long-term use should be avoided unless the benefits outweigh the risks and under close medical supervision.

Q10: Can Dexketoprofen be used with alcohol?

A: Alcohol should be avoided or limited while taking Dexketoprofen, as it can increase the risk of gastrointestinal side effects and drowsiness.