What alternative medications can be given to a patient with arthritis who cannot take Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?

Alternative Medications for Arthritis When NSAIDs Are Contraindicated

For patients with arthritis who cannot take NSAIDs, acetaminophen up to 3 grams daily should be tried first, followed by duloxetine as the preferred next-line agent if acetaminophen fails, with intra-articular corticosteroid injections reserved for acute exacerbations. 1, 2

First-Line Pharmacological Alternative

Acetaminophen (Paracetamol)

• Start with acetaminophen at doses up to 3,000 mg per day in divided doses for knee, hip, and hand osteoarthritis 1
• While effect sizes are very small and meta-analyses suggest acetaminophen may be ineffective as monotherapy for most individuals, it remains appropriate for short-term and episodic use when NSAIDs are contraindicated 1
• Critical caveat: Regular monitoring for hepatotoxicity is required for patients receiving acetaminophen regularly, particularly at the recommended maximum dosage 1
• Despite guideline recommendations, recent high-quality evidence shows acetaminophen may not be significantly better than placebo in patients with symptomatic knee osteoarthritis 3

Second-Line Pharmacological Alternative

Duloxetine (Preferred Centrally-Acting Agent)

• Duloxetine is conditionally recommended as the next-line treatment for knee, hip, and hand osteoarthritis when patients have contraindications to NSAIDs or find acetaminophen ineffective 1, 2
• Duloxetine has adequate evidence demonstrating efficacy in osteoarthritis when used alone or in combination with NSAIDs, though tolerability and side effects must be considered 1
• Start at a low dose and taper gradually when discontinuing 2
• While studied primarily in knee osteoarthritis, effects may plausibly extend to hip or hand osteoarthritis 1

Tramadol (Use With Caution)

• Tramadol is conditionally recommended for patients with knee, hip, and hand osteoarthritis, but should not be used long-term 1, 2
• Recent evidence highlights only very modest beneficial effects in long-term (3 months to 1 year) management of non-cancer pain with opioids 1
• Tramadol may be appropriate when patients have contraindications to NSAIDs, find other therapies ineffective, or have no available surgical options 1
• The 2021 VA/DoD guidelines suggest against initiating opioids (including tramadol) for osteoarthritis pain, representing a shift toward more conservative opioid use 1

Intra-Articular Corticosteroid Injections

For Acute Exacerbations

• Intra-articular glucocorticoid injections are conditionally recommended for patients with knee, hip, and/or hand osteoarthritis 1
• Strongly recommended for patients with persistent pain inadequately relieved by other interventions, particularly those with joint effusion 2
• Ultrasound guidance is strongly recommended for hip joint injections; it may help ensure accurate drug delivery for knee and hand joints but is not required 1
• Intra-articular glucocorticoid injection is conditionally recommended over other forms of intra-articular injection, including hyaluronic acid preparations, as the evidence for efficacy of glucocorticoid injections is of considerably higher quality 1

Topical Alternatives

Topical NSAIDs (If Systemic NSAIDs Contraindicated)

• Topical NSAIDs are strongly recommended for knee osteoarthritis pain, especially for patients ≥75 years old 1, 2
• Topical NSAIDs are strongly preferred over oral NSAIDs in elderly patients due to reduced systemic absorption and lower risk of adverse effects 2
• Insufficient evidence exists for topical NSAIDs in hip osteoarthritis 1

Topical Capsaicin

• Topical capsaicin is conditionally recommended for knee osteoarthritis 1
• The American College of Rheumatology conditionally recommends against topical capsaicin, though other guidelines suggest it as an option 2
• Insufficient evidence exists for hip osteoarthritis 1

Essential Non-Pharmacological Interventions

These must be optimized alongside pharmacological therapy:

• Exercise therapy (land-based or aquatic) is strongly recommended as core treatment 2
• Weight loss is strongly recommended for overweight/obese patients; even modest weight reduction significantly improves symptoms 2
• Physical therapy should be offered as part of comprehensive management 1
• Assistive devices such as walking aids, braces, or joint supports are useful 2

Treatments NOT Recommended

• Non-tramadol opioids are conditionally recommended against due to limited benefit and high risk of adverse effects 2
• Glucosamine and chondroitin are not recommended due to lack of proven efficacy 1, 2
• Colchicine, fish oil, vitamin D, and bisphosphonates are conditionally recommended against 2

Treatment Algorithm for NSAID-Intolerant Patients

1. Confirm NSAID contraindication is absolute (not just intolerance to one specific NSAID) 2

2. Initiate acetaminophen at full dose (up to 3,000 mg/day in divided doses) for 2-4 weeks 1, 2

3. If inadequate response to acetaminophen:

   • Add duloxetine as preferred next agent 1, 2
   • Consider topical NSAIDs for knee osteoarthritis, especially in elderly patients 1, 2

4. For acute pain exacerbations:

   • Offer intra-articular corticosteroid injection 1, 2

5. If duloxetine ineffective or not tolerated:

   • Consider tramadol for short-term use only (avoid long-term) 1, 2
   • Consider topical capsaicin for localized knee pain 1

6. Throughout treatment:

   • Optimize exercise therapy and weight loss 2
   • Ensure physical therapy involvement 1
   • Provide assistive devices as needed 2

7. If all pharmacological options fail and pain remains severe:

   • Refer for surgical consultation 2

Critical Pitfalls to Avoid

• Do not exceed 3,000 mg/day of acetaminophen to prevent hepatotoxicity 1
• Do not use tramadol or other opioids long-term due to modest benefits and addiction potential 1
• Do not prescribe glucosamine or chondroitin as they lack proven efficacy despite widespread use 1, 2
• Do not rely solely on pharmacological therapy; non-pharmacological interventions are essential and strongly recommended 2
• Monitor liver function regularly in patients on chronic acetaminophen therapy 1