Introduction
Voltaren (diclofenac) is a nonsteroidal anti-inflammatory drug (NSAID) widely used for its analgesic, anti-inflammatory, and antipyretic properties. First approved by the FDA in 1988, it remains one of the most prescribed NSAIDs globally for managing pain and inflammation associated with various musculoskeletal conditions.
Mechanism of Action
Diclofenac exerts its therapeutic effects through nonselective inhibition of cyclooxygenase (COX) enzymes, primarily COX-1 and COX-2. These enzymes catalyze the conversion of arachidonic acid to prostaglandins, thromboxanes, and prostacyclins. By inhibiting prostaglandin synthesis, particularly PGE₂, diclofenac reduces inflammation, pain, and fever. The drug also demonstrates preferential distribution to inflamed tissues and may have additional mechanisms involving arachidonic acid release and uptake.
Indications
FDA-approved indications:
- Osteoarthritis
- Rheumatoid arthritis
- Ankylosing spondylitis
- Acute pain (oral immediate-release formulations)
- Primary dysmenorrhea
- Migraine attacks (powder formulation)
Additional accepted uses:
- Acute gouty arthritis
- Postoperative pain management
- Soft tissue injuries (topical formulations)
Dosage and Administration
Oral formulations:- Tablets: 25-50 mg 2-3 times daily (max 150 mg/day)
- Delayed-release: 50 mg 2-3 times daily or 75 mg twice daily
- Extended-release: 100 mg once daily
- Gel: 4 g applied to affected area 4 times daily (max 32 g/day for lower extremities, 16 g/day for upper extremities)
- Solution: 40 drops applied to affected knee 4 times daily
- Renal impairment: Avoid in advanced renal disease (CrCl <30 mL/min)
- Hepatic impairment: Use lowest effective dose with close monitoring
- Elderly: Start with lowest effective dose due to increased NSAID sensitivity
- Pediatrics: Safety not established for children <18 years
Pharmacokinetics
Absorption: Rapid and complete oral absorption (fasting); food delays absorption but doesn't affect extent. Topical absorption approximately 6% of systemic dose. Distribution: Volume of distribution 1.3 L/kg; >99% protein bound; distributes well to synovial fluid Metabolism: Extensive first-pass metabolism via CYP2C9 and CYP3A4 to multiple metabolites including 4'-hydroxydiclofenac (active) Elimination: Terminal half-life 1-2 hours; urinary excretion (65%) and biliary excretion (35%); negligible unchanged drug in urineContraindications
- Hypersensitivity to diclofenac or other NSAIDs
- History of asthma, urticaria, or allergic reactions after taking NSAIDs
- Peri-operative pain in coronary artery bypass graft (CABG) surgery
- Third trimester of pregnancy
Warnings and Precautions
Boxed Warning:- Increased risk of serious cardiovascular thrombotic events, MI, and stroke
- Increased risk of serious GI adverse events including bleeding, ulceration, and perforation
- Hypertension exacerbation or new onset
- Heart failure and edema
- Renal toxicity, particularly in elderly or volume-depleted patients
- Hepatotoxicity (monitor LFTs at baseline and periodically)
- Anaphylactoid reactions
- Serious skin reactions (SJS, TEN)
- Hematologic effects (anemia, platelet inhibition)
Drug Interactions
Significant interactions:- Anticoagulants (warfarin): Increased bleeding risk
- Antiplatelets (aspirin, clopidogrel): Additive bleeding risk
- SSRIs/SNRIs: Increased GI bleeding risk
- ACE inhibitors/ARBs: Reduced antihypertensive effect, increased renal risk
- Diuretics: Reduced diuretic effectiveness, renal impairment risk
- Lithium: Increased lithium levels
- Methotrexate: Increased methotrexate toxicity
- Cyclosporine: Increased nephrotoxicity
- CYP2C9 inhibitors (fluconazole): May increase diclofenac levels
Adverse Effects
Common (>10%):- Gastrointestinal: Dyspepsia, nausea, abdominal pain, diarrhea
- Neurological: Headache, dizziness
- Dermatological: Rash, pruritus (topical: application site reactions)
- GI bleeding/perforation
- Cardiovascular events (MI, stroke)
- Hepatotoxicity (elevated LFTs, hepatitis)
- Renal impairment
- Severe skin reactions (SJS, TEN)
- Anaphylaxis
- Hematologic: Anemia, agranulocytosis
Monitoring Parameters
Baseline:- Complete blood count
- Renal function (BUN, creatinine)
- Liver function tests
- Blood pressure
- Cardiovascular risk assessment
- Blood pressure regularly
- Renal function periodically (3-6 months)
- LFTs periodically (3-6 months)
- CBC if clinical signs of anemia
- GI symptoms assessment
- Therapeutic efficacy and pain control
Patient Education
- Take with food or milk to minimize GI upset
- Report signs of GI bleeding (black stools, abdominal pain)
- Monitor for cardiovascular symptoms (chest pain, shortness of breath)
- Avoid alcohol during therapy
- Topical: Apply to clean, dry skin; avoid sun exposure to application sites
- Do not apply topical to open wounds or broken skin
- Report skin reactions or rash immediately
- Use lowest effective dose for shortest duration possible
- Avoid concomitant NSAIDs including aspirin
- Seek immediate care for signs of allergic reaction
References
1. FDA Prescribing Information: Voltaren (diclofenac sodium). 2022 2. Wongrakpanich S, et al. A Comprehensive Review of Non-Steroidal Anti-Inflammatory Drug Use in The Elderly. Aging Dis. 2018;9(1):143-150 3. Altman R, et al. Efficacy and safety of topical diclofenac solution in the treatment of knee osteoarthritis: a randomized controlled trial. BMC Musculoskelet Disord. 2020;21:435 4. McGettigan P, Henry D. Cardiovascular risk with non-steroidal anti-inflammatory drugs: systematic review of population-based controlled studies. PLoS Med. 2011;8(9):e1001098 5. Massó González EL, et al. Variability among nonsteroidal antiinflammatory drugs in risk of upper gastrointestinal bleeding. Arthritis Rheum. 2010;62(6):1592-1601 6. American College of Rheumatology. Guideline for the Management of Osteoarthritis. 2019 7. UpToDate: Diclofenac: Drug information. Accessed January 2024