Diclofenac + Eperisone

Usage

• Medical Conditions: Diclofenac + Eperisone is prescribed for the relief of pain and muscle stiffness associated with musculoskeletal conditions, particularly acute lower back pain accompanied by muscle spasms. It is also used in conditions like cervical spondylosis and other myotonic conditions.

• Pharmacological Classification: Analgesic (Diclofenac), Muscle Relaxant (Eperisone), Nonsteroidal Anti-inflammatory Drug (NSAID) (Diclofenac), Antispasmodic (Eperisone).

• Mechanism of Action: This combination medication works through two distinct mechanisms:

  • Diclofenac: Inhibits cyclooxygenase (COX) enzymes, reducing the production of prostaglandins, which are key mediators of pain and inflammation.
  • Eperisone: Acts centrally on the spinal cord, suppressing pain reflexes and reducing muscle stiffness and spasms. The precise mechanism of Eperisone is not fully elucidated, but is thought to involve modulation of alpha-2 adrenergic receptors and decreased excitability of motor neurons.

Alternate Names

• No widely recognized alternate names exist for the combination itself. The individual components are sometimes referred to as Diclofenac Sodium and Eperisone Hydrochloride.

• Brand Names: Numerous brand names exist, varying by region and manufacturer. Examples include Epridol-D, Myoset-D, Eperifen, Eprisan-D.

How It Works

• Pharmacodynamics: Diclofenac reduces pain, inflammation, and fever. Eperisone alleviates muscle stiffness and spasms by decreasing muscle tone and improving blood circulation to the affected muscles.

• Pharmacokinetics:

  • Absorption: Both Diclofenac and Eperisone are well-absorbed orally. Taking the medication with food can help reduce gastrointestinal side effects associated with Diclofenac.
  • Metabolism: Primarily hepatic metabolism for both drugs. Diclofenac undergoes extensive metabolism via CYP2C9 (major pathway), CYP2C8, and CYP3A4 isoenzymes. Eperisone metabolism is less well-characterized but involves hepatic pathways.
  • Elimination: Primarily renal excretion for both drugs, although some biliary excretion occurs.

• Mode of Action:

  • Diclofenac: Inhibits COX-1 and COX-2 enzymes, resulting in decreased prostaglandin synthesis. This leads to reduced pain and inflammation.
  • Eperisone: While not fully understood, Eperisone’s action is believed to be central, influencing the spinal cord to decrease reflex muscle contractions. It potentially modulates alpha-2 adrenergic receptors and reduces motor neuron excitability.

• Receptor Binding/Enzyme Inhibition:

  • Diclofenac: COX-1 and COX-2 enzyme inhibition.
  • Eperisone: Potential interaction with alpha-2 adrenergic receptors.

• Elimination Pathways: Both are predominantly excreted via the kidneys, following hepatic metabolism. Some biliary excretion also occurs.

Dosage

Standard Dosage

Adults: The typical dose is 50 mg of Eperisone and 50-100 mg of Diclofenac, taken three times a day, or a sustained-release formulation once daily as 150mg of Eperisone + 100mg of Diclofenac. The maximum recommended daily dose of Diclofenac is generally 150 mg.

Children: Not recommended for children under 12 years of age.

Special Cases:

• Elderly Patients: Start with the lowest effective dose and monitor closely for adverse effects. Dose adjustments may be necessary due to age-related decline in renal and hepatic function.
• Patients with Renal Impairment: Use with caution and consider dosage reduction based on the degree of impairment.
• Patients with Hepatic Dysfunction: Use with caution and consider dosage reduction. Close monitoring of liver function is recommended.
• Patients with Comorbid Conditions: Exercise caution in patients with cardiovascular disease, hypertension, diabetes, asthma, or history of gastrointestinal bleeding. Dosage adjustments or alternative therapies may be considered.

Clinical Use Cases

Diclofenac + Eperisone is not typically used in the clinical settings of intubation, surgical procedures, mechanical ventilation, ICU, or emergency situations. Its primary indication is the management of musculoskeletal pain and spasms in an outpatient setting.

Dosage Adjustments

Dosage adjustments are required based on patient-specific factors such as renal or hepatic dysfunction and other comorbid conditions, as mentioned above.

Side Effects

Common Side Effects:

Nausea, vomiting, heartburn, stomach pain, diarrhea, loss of appetite, dizziness, weakness, drowsiness, headache, skin rash.

Rare but Serious Side Effects:

Gastrointestinal bleeding or ulceration, myocardial infarction, stroke, severe allergic reactions (anaphylaxis, angioedema), hepatotoxicity, nephrotoxicity, Stevens-Johnson syndrome.

Long-Term Effects:

Long-term use of Diclofenac can increase the risk of cardiovascular events and gastrointestinal complications. Chronic use of Eperisone may lead to tolerance or dependence.

Adverse Drug Reactions (ADR):

Severe skin reactions, gastrointestinal bleeding, cardiovascular events, anaphylaxis.

Contraindications

• Hypersensitivity to Diclofenac, Eperisone, or any component of the formulation.
• Active peptic ulcer or gastrointestinal bleeding.
• Severe hepatic or renal impairment.
• Aspirin triad (asthma, nasal polyps, aspirin sensitivity).
• Pregnancy (especially the third trimester).
• Breastfeeding.
• Myasthenia gravis (Eperisone).

Drug Interactions

• Other NSAIDs: Increased risk of gastrointestinal adverse effects.
• Anticoagulants (e.g., warfarin): Increased bleeding risk.
• Lithium: Increased lithium levels.
• Methotrexate: Increased methotrexate toxicity.
• Diuretics: Decreased diuretic effect.
• Antihypertensives: Reduced antihypertensive effect.
• Alcohol: Increased risk of gastrointestinal bleeding and drowsiness.
• CYP450 interactions: Diclofenac is primarily metabolized by CYP2C9. Drugs that inhibit or induce CYP2C9 can alter Diclofenac levels.

Pregnancy and Breastfeeding

• Pregnancy: Avoid, especially in the third trimester, due to the risk of premature closure of the ductus arteriosus in the fetus and other potential complications.
• Breastfeeding: Not recommended as both drugs can be excreted in breast milk.

Drug Profile Summary

• Mechanism of Action: Diclofenac: COX inhibitor, analgesic, anti-inflammatory. Eperisone: Centrally acting muscle relaxant.
• Side Effects: Nausea, vomiting, gastrointestinal upset, drowsiness, dizziness, rash. Serious: Gastrointestinal bleeding, cardiovascular events, renal/hepatic dysfunction.
• Contraindications: Hypersensitivity, active peptic ulcer, severe liver/kidney disease, pregnancy (third trimester), breastfeeding.
• Drug Interactions: Other NSAIDs, anticoagulants, lithium, methotrexate, diuretics, antihypertensives, alcohol.
• Pregnancy & Breastfeeding: Avoid.
• Dosage: Adults: Eperisone 50mg + Diclofenac 50/100mg TID or sustained-release formulation once daily.
• Monitoring Parameters: Renal function, liver function, blood pressure, signs of gastrointestinal bleeding.

Popular Combinations

Diclofenac + Eperisone is commonly used as a standalone combination. There are no widely established alternative combinations used clinically.

Precautions

• Pre-existing cardiac, renal, or hepatic disease requires careful monitoring.
• History of peptic ulcer disease or gastrointestinal bleeding.
• Asthma or allergic rhinitis.
• Elderly patients.
• Avoid alcohol and limit or cease smoking.
• Photosensitivity: Protect skin from sun exposure.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Diclofenac + Eperisone?

A: Adults: Eperisone 50 mg + Diclofenac 50-100 mg three times daily or a sustained-release formulation of Eperisone 150 mg + Diclofenac 100 mg once daily. Not recommended for children under 12.

Q2: What are the common side effects?

A: Nausea, vomiting, heartburn, diarrhea, dizziness, drowsiness, and headache.

Q3: Is it safe to take during pregnancy?

A: No, it should be avoided, especially during the third trimester.

Q4: Can I drink alcohol while taking this medication?

A: No, alcohol can increase the risk of gastrointestinal side effects.

Q5: What if I miss a dose?

A: Take the missed dose as soon as you remember, unless it is almost time for your next dose. Do not double the dose to catch up.

Q6: How long does it take to work?

A: Pain relief is typically experienced within a few hours. Maximum benefit may take several weeks.

Q7: Are there any serious drug interactions I should be aware of?

A: Yes, it can interact with other NSAIDs, anticoagulants like warfarin, lithium, methotrexate, and some antihypertensives.

Q8: What should I do if I experience severe side effects?

A: Discontinue use immediately and seek medical attention.

Q9: Can it be used long-term?

A: Long-term use should be carefully considered and monitored due to potential cardiovascular and gastrointestinal risks associated with Diclofenac.