Diclofenac

Usage

Diclofenac is prescribed for the short-term treatment of pain and inflammation associated with various conditions, including:

• Osteoarthritis
• Rheumatoid arthritis
• Ankylosing spondylitis
• Acute gout
• Migraine attacks
• Post-traumatic and post-operative pain and swelling
• Primary dysmenorrhea (painful menstruation)
• Adnexitis (inflammation of the ovaries and fallopian tubes)
• Painful syndromes of the vertebral column
• Non-articular rheumatism

Pharmacological Classification: Non-steroidal anti-inflammatory drug (NSAID) and analgesic.

Mechanism of Action: Diclofenac inhibits cyclooxygenase (COX) enzymes, COX-1 and COX-2, which are responsible for the production of prostaglandins, substances that mediate pain and inflammation.

Alternate Names

Diclofenac is known by various names internationally. Brand names include Voltaren, Cataflam, Diclax, Voltfast, Zipsor, Zorvolex, Cambia, and others. It is also available as a sodium or potassium salt.

How It Works

Pharmacodynamics: Diclofenac reduces pain and inflammation by inhibiting prostaglandin synthesis through the blocking of COX-1 and COX-2 enzymes. It is a non-selective COX inhibitor.

Pharmacokinetics:

• Absorption: Diclofenac is well absorbed orally, reaching peak plasma concentrations in 1-2 hours for immediate release formulations and approximately 4 hours for delayed-release formulations. Absorption may be delayed if taken with food, especially with high-fat meals. Rectal absorption is slower and more variable. Intramuscular absorption is generally rapid and complete. Intravenous infusion provides 100% bioavailability.
• Metabolism: Extensively metabolized in the liver primarily by CYP2C9.
• Elimination: Primarily eliminated via renal excretion of metabolites. A smaller portion is eliminated in bile.

Mode of Action: Diclofenac competes with arachidonic acid for the active site on COX-1 and COX-2 enzymes. This inhibits the formation of prostaglandin G2 and H2, thereby reducing the production of downstream pro-inflammatory prostaglandins and thromboxanes.

Elimination Pathways: Primarily renal excretion (approximately 65%), with biliary/fecal excretion accounting for the remainder.

Dosage

Standard Dosage

Adults:

• Oral: 50 mg two or three times daily, or 75mg twice daily.
• Intravenous/Intramuscular: 75mg once or twice daily, max 150mg/day.
• Rectal: 50mg up to three times per day.

Children:

Use is generally not recommended for children under 14 years old. Dosages above this age must be determined by a doctor.

Special Cases:

• Elderly Patients: Start with the lowest effective dose. Careful monitoring is recommended.
• Patients with Renal Impairment: Use with caution; dosage adjustment may be needed in moderate to severe cases. Contraindicated in renal failure.
• Patients with Hepatic Dysfunction: Use with caution; dosage adjustment may be needed in moderate to severe cases. Contraindicated in liver failure.
• Patients with Comorbid Conditions: Use with caution in patients with cardiovascular disease, hypertension, or diabetes. Close monitoring is crucial.

Clinical Use Cases

Specific dosages for clinical use cases like intubation, surgical procedures, mechanical ventilation, and ICU use are not standardized and should be determined by a clinician based on the individual patient’s needs.

• Emergency Situations: Appropriate dosages must be determined by the treating physician based on the specific emergency situation. Diclofenac is indicated for mild to moderate acute pain, so other analgesics may be more appropriate.

Dosage Adjustments

Dosage adjustments are based on individual patient characteristics, comorbidities, and therapeutic response. Renal and hepatic impairment require careful consideration and possible dosage reductions.

Side Effects

Common Side Effects:

• Gastrointestinal upset (nausea, vomiting, diarrhea, constipation)
• Headache
• Dizziness
• Rash
• Fluid retention
• Elevated liver enzymes

Rare but Serious Side Effects:

• Gastrointestinal bleeding or ulceration
• Myocardial infarction
• Stroke
• Heart failure
• Severe allergic reactions (anaphylaxis)
• Renal dysfunction
• Stevens-Johnson Syndrome
• Toxic epidermal necrolysis
• Aplastic anemia

Long-Term Effects:

• Chronic kidney disease
• Cardiovascular complications
• Gastrointestinal issues (ulcers, bleeding)

Adverse Drug Reactions (ADR): As noted above, rare but serious side effects often require immediate intervention. Specifically, any signs of gastrointestinal bleeding, allergic reactions, cardiovascular events, or renal impairment should be treated immediately.

Contraindications

• Hypersensitivity to diclofenac or other NSAIDs
• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs
• Active or recent peptic ulcer disease
• Gastrointestinal bleeding
• Severe renal impairment
• Severe hepatic impairment
• Coronary artery bypass graft (CABG) surgery perioperatively
• Pregnancy (third trimester)

Drug Interactions

• Anticoagulants: Increased risk of bleeding
• Lithium: Increased lithium levels
• Methotrexate: Increased methotrexate toxicity
• Diuretics: Reduced diuretic effect and increased risk of renal impairment
• Antihypertensives: Reduced antihypertensive efficacy
• Other NSAIDs or Salicylates: Increased risk of gastrointestinal side effects
• CYP2C9 Inhibitors and Inducers: Can alter diclofenac metabolism. Concomitant use of CYP2C9 inhibitors (e.g. voriconazole) may increase diclofenac plasma concentrations whereas CYP2C9 inducers (e.g. rifampicin) may reduce diclofenac levels.
• Alcohol: Increased risk of gastrointestinal bleeding

Pregnancy and Breastfeeding

• Pregnancy Safety Category: Avoid in the first and third trimesters. Limited data in the second trimester, use with caution if potential benefits outweigh risk.
• Fetal Risks: Premature closure of ductus arteriosus, prolonged labor, increased risk of bleeding.
• Breastfeeding: Present in small amounts in breast milk. Use with caution, monitor infant for any adverse effects.

Drug Profile Summary

• Mechanism of Action: Non-selective COX inhibitor, reducing prostaglandin synthesis.
• Side Effects: Gastrointestinal upset, headache, dizziness, rash. Serious: GI bleeding, myocardial infarction, stroke.
• Contraindications: Hypersensitivity, asthma/urticaria with aspirin, GI bleeding, severe renal/hepatic impairment.
• Drug Interactions: Anticoagulants, lithium, methotrexate, diuretics, antihypertensives, alcohol.
• Pregnancy & Breastfeeding: Avoid during the first and third trimesters. Caution during breastfeeding.
• Dosage: Adults: 50-75mg orally 2-3 times/day, or 75mg IM/IV once or twice daily. Max 150mg/day.
• Monitoring Parameters: Renal function, liver function, blood pressure, signs of gastrointestinal bleeding.

Popular Combinations

Diclofenac is sometimes used in combination with misoprostol (to reduce GI side effects) or other analgesics (for enhanced pain relief).

Precautions

• General Precautions: Assess for allergies, cardiovascular, renal, and hepatic function before initiating therapy.
• Specific Populations: As described above.
• Lifestyle Considerations: Avoid alcohol. Limit driving or operating machinery if dizziness or drowsiness occurs.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Diclofenac?

A: Adult oral dosage is typically 50 mg two or three times daily or 75mg twice daily. Intravenous/intramuscular dosing is 75mg once or twice daily, maximum 150mg/day. Rectal is 50mg up to three times per day. Dosage varies based on indication and patient factors. Pediatric dosing must be determined by a doctor.

Q2: What are the most common side effects of Diclofenac?

A: Common side effects include gastrointestinal issues like nausea, vomiting, diarrhea, and heartburn. Headache, dizziness, and rash can also occur.

Q3: What are the serious side effects of Diclofenac that warrant immediate attention?

A: Signs of gastrointestinal bleeding (e.g., black stools, bloody vomit), allergic reactions (e.g., difficulty breathing, hives, swelling), chest pain, signs of stroke, and significant changes in urine output should prompt immediate medical attention.

Q4: Can Diclofenac be used in patients with a history of peptic ulcers?

A: No, diclofenac is contraindicated in patients with active or recent peptic ulcer disease or a history of gastrointestinal bleeding.

Q5: How should Diclofenac be administered?

A: Oral formulations should be swallowed whole with water, preferably before or with meals (depending on the formulation). Intramuscular injections should be administered deep into the gluteal muscle. Intravenous administration requires dilution and should be infused over 30 minutes to 2 hours for post-operative pain.

Q6: Can Diclofenac be used during pregnancy?

A: Diclofenac should be avoided during the first and third trimesters of pregnancy. Limited data available for the second trimester; use only if benefit clearly outweighs the risk.

Q7: Is it safe to take Diclofenac with alcohol?

A: Alcohol should be avoided or limited while taking diclofenac, as it can increase the risk of gastrointestinal bleeding.

Q8: Can Diclofenac be used long-term?

A: Diclofenac is generally prescribed for short-term use due to potential long-term side effects. If long-term use is necessary, the lowest effective dose should be utilized, and patients should be closely monitored for adverse effects.

Q9: What are the key drug interactions with Diclofenac?

A: Diclofenac can interact with anticoagulants, lithium, methotrexate, diuretics, other NSAIDs and antihypertensive medications. Concomitant use with CYP2C9 inhibitors can increase diclofenac exposure.

Q10: How does renal or hepatic impairment affect Diclofenac dosage?

A: Caution should be exercised in patients with renal or hepatic impairment. Dose reduction may be needed. Diclofenac is contraindicated in severe hepatic or renal impairment.

Please note that this information is current as of February 16, 2025, and is intended for qualified Indian doctors. Always consult with the latest medical guidelines and tailor treatment to individual patients’ specific needs.