What topical cream is recommended for a patient with knee pain likely due to osteoarthritis (OA) or another form of arthritis?

Topical NSAIDs for Knee Pain

For knee pain due to osteoarthritis, use topical diclofenac as your first-line topical agent—it carries a strong recommendation and provides pain relief equivalent to oral NSAIDs with markedly fewer gastrointestinal adverse events. 1

Primary Recommendation: Topical Diclofenac

• Topical NSAIDs (specifically diclofenac) are strongly recommended for knee osteoarthritis pain by the 2020 VA/DoD guidelines 1
• Diclofenac is the only commercially manufactured topical NSAID currently available in the United States and comes in various formulations 1
• Topical diclofenac is superior to placebo and equivalent to oral diclofenac at reducing knee OA pain 1
• The recommended dose is 40 mg (2 pump actuations) applied to each painful knee twice daily 2

Application Instructions

• Apply to clean, dry skin by dispensing directly onto the knee or first into the hand, then spread evenly around front, back, and sides of the knee 2
• Wash hands completely after application 2
• Avoid showering/bathing for at least 30 minutes after application 2
• Wait until the area is completely dry before covering with clothing (typically wait before covering) 2
• Avoid skin-to-skin contact with others until the treated knee is completely dry 2

Safety Profile Advantage

• Topical NSAIDs have markedly fewer gastrointestinal adverse events compared to oral NSAIDs, though they have substantially more local adverse events (primarily mild skin reactions) 1
• Safety data at 1 year shows consistency with 12-week safety profiles 1
• Local skin irritation occurs in approximately 36% of patients but leads to discontinuation in only 6% 3

Alternative Option: Topical Capsaicin

• Topical capsaicin is conditionally recommended (weak recommendation) for knee OA as a second-line topical agent 1
• Capsaicin (0.025% to 0.075%) works by depleting substance P, reducing pain through a different mechanism than NSAIDs 1, 4

Important Capsaicin Considerations

• Requires continuous use for 2 to 4 weeks before experiencing therapeutic effects—this is a critical counseling point 1, 4
• Initially causes pain and burning sensation at the application site as it triggers substance P release before depletion occurs 1, 4
• Adverse events (burning or stinging) occur at the application site in a significant proportion of patients 1
• Evidence supports at least a moderate effect (standard mean difference 0.44) in reducing moderate knee pain 1
• In clinical trials, patients with both rheumatoid arthritis and osteoarthritis demonstrated mean pain reductions of 57% and 33% respectively after 4 weeks 5

Treatment Algorithm for Knee Pain

1. Start with topical diclofenac as first-line topical pharmacotherapy for knee OA 1
2. Consider topical capsaicin if patient cannot tolerate topical NSAIDs or as an adjunct therapy 1, 4
3. Integrate topical therapy with core non-pharmacological treatments including exercise, weight loss, and physical therapy—topical agents are adjuncts, not replacements 1, 4
4. If topical therapy provides inadequate relief, escalate to oral NSAIDs (which remain the mainstay of pharmacological management) 1

Common Pitfalls to Avoid

• Do not use topical NSAIDs for hip pain—the depth of the hip joint beneath the skin surface prevents adequate drug penetration, making topical agents ineffective 1, 6
• Do not discontinue capsaicin prematurely—patients must understand the 2-4 week delay before therapeutic benefit and the initial burning sensation 1, 4
• Do not combine topical and oral NSAIDs routinely unless the benefit outweighs the risk, and conduct periodic laboratory evaluations if combination therapy is used 2
• Do not apply topical NSAIDs to open wounds or allow contact with eyes and mucous membranes 2
• Do not apply external heat or occlusive dressings to treated knees 2
• Do not skip core treatments—topical agents should be part of a comprehensive management plan that includes exercise, weight management, and patient education, not monotherapy 1, 4

When Topical Therapy is Most Appropriate

• Topical NSAIDs should be considered prior to oral NSAIDs following the principle that medications with the least systemic exposure are preferable 1
• Particularly useful for patients aged ≥75 years or those with comorbidities at increased risk of cardiovascular, gastrointestinal, or renal side effects from oral NSAIDs 7
• Most appropriate when only a few joints are affected with mild to moderate pain 4