Introduction
Voltaren Arthritis Pain Gel (diclofenac sodium 1% gel) is a topical nonsteroidal anti-inflammatory drug (NSAID) approved for the relief of osteoarthritis pain in joints amenable to topical treatment, such as those of the hands and knees. As the first FDA-approved prescription topical NSAID for osteoarthritis pain, it provides targeted relief with lower systemic exposure compared to oral NSAIDs.
Mechanism of Action
Diclofenac exerts its therapeutic effects through inhibition of cyclooxygenase (COX) enzymes, primarily COX-1 and COX-2. This inhibition reduces the conversion of arachidonic acid to prostaglandin precursors, thereby decreasing the synthesis of prostaglandins, which are mediators of pain, inflammation, and fever. The topical formulation delivers diclofenac directly to affected tissues, achieving therapeutic concentrations at the site of application while minimizing systemic drug levels.
Indications
- Relief of the pain of osteoarthritis of joints amenable to topical treatment (e.g., knees, hands)
Dosage and Administration
For osteoarthritis of the knees:- Apply 4 grams of gel to the affected knee four times daily
- Maximum total body dose: 32 grams per day (for multiple affected joints)
- Apply 2 grams of gel to the affected hand four times daily
- Do not apply to more than both hands per day
- Apply gel to clean, dry, intact skin
- Gently massage into skin until absorbed
- Wash hands after application unless treating hands
- Do not apply to open wounds, infected skin, or exfoliative dermatitis
- Avoid contact with eyes and mucous membranes
- Renal impairment: Use with caution in advanced renal disease
- Hepatic impairment: Use with caution in severe hepatic impairment
- Elderly: No specific dosage adjustment required
- Pediatrics: Not studied in pediatric patients
Pharmacokinetics
Absorption: Systemic absorption is approximately 6% of the systemic exposure from oral diclofenac formulation. Peak plasma concentrations occur within 10-20 hours after topical application. Distribution: Diclofenac is highly protein-bound (>99%) and distributes poorly into synovial fluid after topical administration. Metabolism: Extensively metabolized in the liver via cytochrome P450 enzymes, primarily CYP2C9, with minor contributions from CYP3A4 and CYP2C8. Elimination: Metabolites are excreted mainly in the urine (65%) with the remainder in feces. Elimination half-life is approximately 1-3 hours.Contraindications
- Hypersensitivity to diclofenac sodium or any component of the formulation
- History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs
- Peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery
Warnings and Precautions
Cardiovascular risk: NSAIDs may increase the risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. Gastrointestinal risk: NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation. Hepatotoxicity: Severe hepatic reactions, including jaundice and fatal hepatitis, have been reported with NSAID use. Renal effects: Long-term NSAID administration may result in renal injury, including papillary necrosis and other renal injury. Serious skin reactions: Exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported. Use in pregnancy: Avoid use in late pregnancy due to risk of premature closure of ductus arteriosus.Drug Interactions
Anticoagulants: Increased risk of bleeding with warfarin, heparin, and other anticoagulants ACE inhibitors/ARBs: Reduced antihypertensive effect and potential renal impairment Diuretics: Reduced diuretic and antihypertensive effects Lithium: Increased lithium plasma levels Methotrexate: Increased methotrexate toxicity Cyclosporine: Increased nephrotoxicity risk Other NSAIDs: Avoid concomitant use with oral NSAIDs CYP2C9 inhibitors: May increase diclofenac exposureAdverse Effects
Common (≥1%):- Application site reactions (dryness, irritation, dermatitis)
- Pruritus
- Dyspepsia
- Nausea
- Cardiovascular thrombotic events
- GI bleeding, ulceration, and perforation
- Hepatotoxicity
- Renal impairment
- Severe skin reactions
- Anaphylactoid reactions
Monitoring Parameters
- Pain assessment and functional status
- Signs of gastrointestinal bleeding
- Renal function (BUN, creatinine) in at-risk patients
- Hepatic function (LFTs) with long-term use
- Blood pressure monitoring
- Signs of skin reactions at application site
- Signs of cardiovascular events in at-risk patients
Patient Education
- Use only as directed by healthcare provider
- Apply to clean, dry, intact skin only
- Wash hands after application unless treating hands
- Do not cover with occlusive dressings
- Do not apply to open wounds or broken skin
- Avoid sun exposure to treated areas (may increase photosensitivity)
- Report any signs of skin rash, itching, or irritation
- Seek immediate medical attention for signs of allergic reaction
- Inform all healthcare providers of Voltaren use
- Do not use with other topical products unless directed by physician
- Store at room temperature, away from heat and moisture
References
1. FDA Prescribing Information: Voltaren Arthritis Pain Gel (diclofenac sodium topical gel) 1% 2. Altman RD, Dreiser RL, Fisher CL, et al. Diclofenac sodium gel in patients with primary hand osteoarthritis: a randomized, double-blind, placebo-controlled trial. J Rheumatol. 2009;36(9):1991-1999. 3. Baraf HS, Gloth FM, Barthel HR, et al. Safety and efficacy of topical diclofenac sodium gel for knee osteoarthritis in elderly and younger patients: pooled data from three randomized, double-blind, parallel-group, placebo-controlled, multicentre trials. Drugs Aging. 2011;28(1):27-40. 4. Simon LS, Grierson LM, Naseer Z, et al. Efficacy and safety of topical diclofenac containing dimethyl sulfoxide (DMSO) compared with those of topical placebo, DMSO vehicle and oral diclofenac for knee osteoarthritis. Pain. 2009;143(3):238-245. 5. Tugwell PS, Wells GA, Shainhouse JZ. Equivalence study of a topical diclofenac solution (pennsaid) compared with oral diclofenac in symptomatic treatment of osteoarthritis of the knee: a randomized controlled trial. J Rheumatol. 2004;31(10):2002-2012. 6. American College of Rheumatology. Arthritis Care & Research. 2019;71(10):1285-1299.