Introduction
Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) that has been widely used clinically since the 1970s. It belongs to the phenylacetic acid derivative class and is one of the most commonly prescribed NSAIDs worldwide. Diclofenac provides analgesic, anti-inflammatory, and antipyretic effects through inhibition of prostaglandin synthesis.
Mechanism of Action
Diclofenac exerts its therapeutic effects primarily through nonselective inhibition of cyclooxygenase (COX) enzymes, both COX-1 and COX-2 isoforms. By inhibiting these enzymes, diclofenac blocks the conversion of arachidonic acid to prostaglandin precursors, particularly prostaglandins E2 and I2, which are mediators of pain, inflammation, and fever. The drug also inhibits prostaglandin synthesis in the central nervous system, contributing to its antipyretic effects.
Indications
- Osteoarthritis
- Rheumatoid arthritis
- Ankylosing spondylitis
- Acute pain management (including postoperative pain)
- Primary dysmenorrhea
- Acute migraine attacks (oral formulations)
- Topical formulations for actinic keratosis (3% gel)
Dosage and Administration
Oral formulations:- Tablets: 25-50 mg 2-3 times daily (maximum 150 mg/day)
- Extended-release tablets: 100 mg once daily
- Enteric-coated tablets: 50 mg 2-3 times daily
- Gel: 4 g applied to affected area 4 times daily (maximum 32 g/day)
- Solution: 40 drops applied to affected knee 4 times daily
- Renal impairment: Use with caution; avoid in advanced renal disease
- Hepatic impairment: Use lowest effective dose; monitor closely
- Elderly: Start with lowest effective dose
- Pediatrics: Safety not established for children <18 years
Pharmacokinetics
Absorption: Rapid and complete oral absorption; food delays absorption but doesn't affect extent Distribution: Volume of distribution ~0.12-0.17 L/kg; 99.7% protein-bound Metabolism: Extensive hepatic metabolism via CYP2C9 and CYP3A4; significant first-pass metabolism Elimination: Half-life 1-2 hours; excreted primarily in urine (65%) and feces (35%) Bioavailability: ~50% due to first-pass metabolismContraindications
- Hypersensitivity to diclofenac, aspirin, or other NSAIDs
- History of asthma, urticaria, or allergic reactions after taking NSAIDs
- Perioperative pain in coronary artery bypass graft (CABG) surgery
- Third trimester of pregnancy
- Active peptic ulcer disease or GI bleeding
- Severe heart failure
- Severe renal impairment (CrCl <30 mL/min)
Warnings and Precautions
Cardiovascular risk: Increased risk of serious cardiovascular thrombotic events, including MI and stroke GI risk: Significant risk of GI bleeding, ulceration, and perforation Hepatotoxicity: Severe hepatic reactions, including liver failure, have been reported Hypertension: May worsen existing hypertension or contribute to new-onset hypertension Renal toxicity: Risk of renal papillary necrosis and other renal injury Skin reactions: Serious skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis Hematologic effects: May cause anemia, thrombocytopenia, or neutropeniaDrug Interactions
Anticoagulants: Increased risk of bleeding with warfarin Antiplatelets: Additive effects with aspirin, clopidogrel ACE inhibitors/ARBs: Reduced antihypertensive effects; increased renal risk Diuretics: Reduced diuretic efficacy; increased nephrotoxicity risk Lithium: Increased lithium levels and toxicity risk Methotrexate: Increased methotrexate toxicity Cyclosporine: Increased nephrotoxicity SSRIs/SNRIs: Increased bleeding risk Other NSAIDs: Avoid concomitant useAdverse Effects
Common (>10%): Dyspepsia, nausea, abdominal pain, diarrhea, headache, dizziness Less common (1-10%): Constipation, flatulence, peptic ulcer, elevated liver enzymes, edema, hypertension Rare but serious (<1%):- GI bleeding/perforation
- Hepatotoxicity
- Acute renal failure
- Stevens-Johnson syndrome
- Anaphylaxis
- Myocardial infarction
- Stroke
Monitoring Parameters
- Baseline and periodic CBC, renal function, and LFTs
- Blood pressure monitoring
- Signs/symptoms of GI bleeding
- Signs of cardiovascular events
- Skin reactions
- Fluid retention/edema
- Pain assessment and functional status
- Therapeutic response evaluation
Patient Education
- Take with food or milk to minimize GI upset
- Report any signs of bleeding (unusual bruising, black stools)
- Report symptoms of hepatotoxicity (nausea, fatigue, jaundice, dark urine)
- Monitor for signs of cardiovascular events (chest pain, shortness of breath)
- Avoid alcohol consumption during therapy
- Use lowest effective dose for shortest duration
- Do not crush or chew enteric-coated tablets
- For topical forms: Apply to intact skin only; wash hands after application
- Inform all healthcare providers about diclofenac use before procedures
- Avoid concurrent use of other NSAIDs or aspirin
References
1. American Geriatrics Society. (2019). American Geriatrics Society 2019 Updated AGS Beers Criteria® for Potentially Inappropriate Medication Use in Older Adults. Journal of the American Geriatrics Society, 67(4), 674-694. 2. FDA. (2020). Diclofenac Sodium Prescribing Information. 3. McGettigan, P., & Henry, D. (2013). Use of non-steroidal anti-inflammatory drugs that elevate cardiovascular risk: an examination of sales and essential medicines lists in low-, middle-, and high-income countries. PLoS Medicine, 10(2), e1001388. 4. Varga, Z., et al. (2017). Cardiovascular risk of nonsteroidal anti-inflammatory drugs: an under-recognized public health issue. Cureus, 9(4), e1144. 5. Wongrakpanich, S., et al. (2018). A comprehensive review of non-steroidal anti-inflammatory drug use in the elderly. Aging and Disease, 9(1), 143-150. 6. European League Against Rheumatism. (2018). EULAR recommendations for the management of osteoarthritis. 7. American College of Rheumatology. (2019). Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee.