What nonsteroidal (Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)) medication alternatives are available for a patient with arthritis?

Nonsteroidal Arthritis Alternative Medication

For patients with arthritis who cannot use NSAIDs, acetaminophen (up to 4 grams daily) should be the first-line pharmacologic option, followed by topical therapies (topical NSAIDs for knee OA or topical capsaicin), duloxetine for knee OA, and intra-articular corticosteroid injections for persistent pain. 1

First-Line Alternative: Acetaminophen

• Start with acetaminophen up to 4,000 mg daily in divided doses as the initial pharmacologic therapy for hip and knee osteoarthritis 1, 2
• Use fixed-interval dosing (every 6 hours) rather than as-needed administration for more consistent pain control 3
• Counsel patients to avoid all other acetaminophen-containing products, including over-the-counter cold remedies and combination opioid products 1
• Acetaminophen provides modest pain relief with a relative percent improvement of 5% and an absolute change of 4 points on a 0-100 scale compared to placebo 4

Important Caveat About Acetaminophen Efficacy

While guidelines recommend acetaminophen first due to safety, the evidence shows NSAIDs are superior to acetaminophen for pain reduction 4, 5. However, acetaminophen's favorable safety profile—particularly regarding gastrointestinal, cardiovascular, and renal risks—justifies its first-line position when NSAIDs are contraindicated 1, 6.

Second-Line Alternative: Topical Therapies

Topical NSAIDs (Preferred for Knee OA)

• Strongly recommend topical NSAIDs for knee osteoarthritis pain as they minimize systemic exposure while providing local anti-inflammatory effects 1, 3
• Apply topical diclofenac gel 3-4 times daily to affected joints 3
• For patients ≥75 years old, topical NSAIDs are strongly preferred over oral NSAIDs due to reduced systemic adverse effects 1
• Insufficient evidence exists for topical NSAIDs in hip osteoarthritis 1

Topical Capsaicin

• Consider topical capsaicin 0.025-0.075% applied 3-4 times daily for knee osteoarthritis 1, 3
• Warn patients about initial burning sensation that typically subsides with continued use 3
• Insufficient evidence for hip osteoarthritis 1

Third-Line Alternative: Duloxetine

• Offer duloxetine 30-60 mg daily as alternative or adjunctive therapy for knee osteoarthritis when acetaminophen provides inadequate relief or NSAIDs are contraindicated 1, 7
• Particularly effective for patients with moderate-to-severe OA pain 1
• No recommendation exists for hip osteoarthritis 1

Fourth-Line Alternative: Intra-Articular Corticosteroid Injections

• Offer intra-articular corticosteroid injections for persistent knee pain inadequately relieved by other interventions 1, 7
• Provides targeted relief without systemic medication exposure 3
• Triamcinolone hexacetonide is particularly beneficial for acute pain episodes with inflammation or effusion 3
• Use as bridge therapy while awaiting orthopedic consultation in refractory cases 7

Essential Non-Pharmacologic Components

All patients should receive comprehensive non-pharmacologic management regardless of medication choices:

• Self-management programs including exercise and weight loss for hip and knee OA 1
• Physical therapy as part of comprehensive management plan 1
• Strengthening exercises, aerobic fitness training, and local heat application 3
• Assistive devices and patient education for self-management 3
• Bracing for knee OA (must be combined with appropriate exercise to prevent atrophy) 1

Treatments to Avoid

• Do NOT initiate opioids (including tramadol) for hip and knee osteoarthritis pain due to limited efficacy and significant adverse effects 1, 7
• Do NOT use glucosamine or chondroitin sulfate as evidence does not support their efficacy 1, 3
• Insufficient evidence exists for complementary therapies including acupuncture, massage, tai chi, and yoga 1

Common Pitfalls to Avoid

• Do not combine multiple NSAIDs (including topical and oral formulations) as this increases adverse effects without additional benefit 8
• Do not use acetaminophen beyond 4,000 mg daily and ensure patients understand to check all medications for hidden acetaminophen content 1, 2
• Do not delay physical therapy and exercise programs while pursuing pharmacologic options, as non-pharmacologic interventions provide substantial pain relief without medication risks 1, 3
• Do not use modified-release NSAID preparations as they are more expensive without evidence of superior effectiveness 1

Algorithm for Medication Selection When NSAIDs Contraindicated

1. Start: Acetaminophen up to 4,000 mg daily (divided doses, fixed intervals) 1, 2
2. If inadequate relief: Add topical NSAID (for knee) or topical capsaicin 1, 3
3. If still inadequate: Add duloxetine 30-60 mg daily (for knee OA) 1, 7
4. If persistent pain: Intra-articular corticosteroid injection 1, 3
5. If refractory to all above: Consider orthopedic referral for surgical evaluation 7, 3