What are the recommended pharmacologic treatments for typical osteoarthritis in adults over 50, including first‑line and step‑up options?

Best Medications for Osteoarthritis

Start with acetaminophen (paracetamol) at regular scheduled doses up to 4000 mg daily as your first-line pharmacologic treatment for osteoarthritis pain—it provides the safest and most appropriate initial medication with the best safety profile compared to all other options. 1, 2

First-Line: Acetaminophen (Paracetamol)

• Use regular scheduled dosing rather than "as needed" for chronic osteoarthritis pain, which provides better sustained pain control. 1
• Maximum daily dose is 4000 mg, but strongly consider limiting to 3000 mg daily in patients over 50 years to reduce hepatotoxicity risk. 1, 2
• This recommendation comes from the American College of Physicians and represents the safest starting point before escalating to agents with higher adverse event profiles. 1, 2

Second-Line: Topical NSAIDs

If acetaminophen provides insufficient pain relief, apply topical NSAIDs (such as diclofenac gel or ketoprofen gel) before considering oral NSAIDs—they have minimal systemic absorption and substantially lower risk of gastrointestinal, renal, and cardiovascular complications. 3, 1, 2

• Topical diclofenac should be applied as 40 mg (2 pump actuations) on each painful knee twice daily to clean, dry skin. 4
• Ketoprofen gel achieves a 63% response rate versus 48% with placebo over 6–12 weeks. 2
• For knee and hand osteoarthritis specifically, topical NSAIDs are preferred over oral NSAIDs. 3
• Topical capsaicin is an alternative localized agent, though therapeutic benefit typically requires continuous application for 2–4 weeks. 2

Third-Line: Oral NSAIDs or COX-2 Inhibitors

Only prescribe oral NSAIDs or COX-2 inhibitors when acetaminophen and topical treatments have failed, and use at the lowest effective dose for the shortest possible duration. 3, 1, 2

Critical Safety Requirements:

• Always co-prescribe a proton pump inhibitor alongside any oral NSAID or COX-2 inhibitor for gastroprotection, choosing the one with lowest acquisition cost. 3, 1, 2
• Carefully assess cardiovascular, gastrointestinal, and renal risk factors before prescribing any oral NSAID, particularly in patients over 50 years. 1, 2
• Elderly patients face substantially higher risks of GI bleeding, renal insufficiency, platelet dysfunction, and cardiovascular complications with NSAIDs. 1, 2, 5
• All oral NSAIDs and COX-2 inhibitors have analgesic effects of a similar magnitude but vary in their potential gastrointestinal, liver, and cardiorenal toxicity. 3

When Oral NSAIDs Are Contraindicated:

• Avoid oral NSAIDs entirely in patients with gastrointestinal ulcer disease, chronic kidney disease, heart failure, or anticoagulation. 6
• In these patients, proceed directly to intra-articular corticosteroid injections or consider short-term weak opioids after exhausting other options. 6

Adjunct Option: Intra-Articular Corticosteroid Injections

Consider intra-articular corticosteroid injections for moderate to severe pain unresponsive to acetaminophen and topical agents, or when oral NSAIDs are contraindicated. 3, 2, 6

• These injections provide effective short-term pain relief lasting 1–3 weeks. 2
• Particularly appropriate for knee osteoarthritis with moderate-to-severe symptoms. 2

Fourth-Line: Opioids (Use With Extreme Caution)

A short course of a weak opioid (such as sustained-release tramadol) may be considered only after failure of acetaminophen, topical agents, and intra-articular corticosteroid injection in patients with severe, refractory symptoms. 2, 6

• Slow upward titration is recommended to improve tolerability. 2
• Opiates should generally be avoided in osteoarthritis management. 7

Essential Non-Pharmacologic Core Treatments (Must Accompany All Medications)

Every patient with osteoarthritis must receive these core treatments alongside any pharmacologic therapy—they are not optional adjuncts but essential components that improve morbidity, mortality, and quality of life:

• Activity and exercise programs focusing on local muscle strengthening and general aerobic fitness. 3, 1, 2
• Weight loss interventions if BMI ≥ 25 kg/m², as weight reduction lessens joint load and pain. 3, 1, 2
• Patient education to counter misconceptions that osteoarthritis is inevitably progressive and cannot be treated. 3, 1, 2

What NOT to Use

Do not use glucosamine or chondroitin products—current evidence does not support their efficacy for osteoarthritis. 3, 1, 2, 6

Do not recommend omega-3 fatty acid supplementation (EPA/DHA 2–3 g daily) as adjunct therapy for osteoarthritis pain—major clinical practice guidelines explicitly advise against this due to absence of robust efficacy data. 2

Electroacupuncture should not be used. 3, 6

Critical Pitfalls to Avoid

• Never exceed 4000 mg daily of acetaminophen, and strongly consider a lower ceiling of 3000 mg in elderly patients to prevent hepatotoxicity. 1, 2, 6
• Never prescribe oral NSAIDs without gastroprotection (proton pump inhibitor co-prescription). 3, 1, 2
• Avoid prolonged NSAID use at high doses, particularly in elderly patients who are at highest risk for serious adverse events including GI bleeding, renal failure, and cardiovascular complications. 1, 2, 5
• Do not allow any supplement to replace or delay proven core treatments such as exercise, weight management, and education. 2
• Avoid showering/bathing for at least 30 minutes after application of topical diclofenac to the treated knee. 4
• Wait until the treated area is dry before applying sunscreen, insect repellant, or other topical products over diclofenac. 4