In an older adult with osteoarthritis and possible cardiovascular, renal, or gastrointestinal comorbidities, what are the safest oral analgesics to use when paracetamol (acetaminophen) is avoided?

Safest Oral Analgesics (Excluding Paracetamol) in Osteoarthritis

For older adults with osteoarthritis who cannot use paracetamol, topical NSAIDs (such as diclofenac gel) are the safest first-line option, followed by tramadol as a second-line agent, with oral NSAIDs reserved as a last resort only when other options have failed. 1, 2

First-Line: Topical NSAIDs

• Topical diclofenac or ketoprofen gel applied twice daily to the affected joint provides statistically significant pain relief with minimal systemic absorption, avoiding the gastrointestinal bleeding, renal impairment, and cardiovascular risks associated with oral NSAIDs. 1, 2

• Topical NSAIDs are particularly appropriate for knee and hand osteoarthritis, offering comparable local efficacy to oral agents while maintaining a superior safety profile in older adults. 1

• The minimal systemic absorption makes topical NSAIDs safe even in patients with cardiovascular disease, renal insufficiency, or gastrointestinal risk factors. 2

Second-Line: Tramadol (with Caution)

• Tramadol (with or without acetaminophen) is regarded as an alternative oral analgesic when topical agents fail, though it should be used at the lowest effective dose for the shortest duration. 3

• Moderate-quality evidence shows tramadol provides only modest benefit—approximately 5% more patients achieve a 20% pain reduction compared to placebo—with no clinically important improvement in mean pain scores. 4

• Tramadol carries substantial risks: it causes adverse events in 17% more patients than placebo (nausea, dizziness, fatigue) and leads to 12% more withdrawals due to side effects. 4

• Serious adverse events occur in 1% more tramadol users compared to placebo, and the drug poses risks of falls, cognitive impairment, constipation, and dependence in elderly patients. 4, 2

• Reserve tramadol only for patients in whom NSAIDs are contraindicated, ineffective, or poorly tolerated, and never as first-line therapy. 2

Third-Line: Oral NSAIDs (Last Resort Only)

• Oral NSAIDs should only be considered after topical NSAIDs and tramadol have failed, and must be prescribed at the lowest effective dose for the shortest possible duration with mandatory co-prescription of a proton-pump inhibitor. 3, 1, 2

• The choice between traditional NSAIDs and COX-2 inhibitors depends on individual risk factors:

  • For patients with gastrointestinal risk factors: prefer celecoxib (a COX-2 inhibitor) combined with a proton-pump inhibitor. 1, 2
  • For patients with cardiovascular risk factors: avoid COX-2 inhibitors entirely; if an NSAID is absolutely necessary, use a non-selective agent with extreme caution. 1, 2

• Elderly patients face substantially higher risks of gastrointestinal bleeding, renal insufficiency, platelet dysfunction, and cardiovascular complications with all oral NSAIDs. 2

• Assess renal function before prescribing any oral NSAID; these agents are contraindicated or require extreme caution in patients with renal impairment, heart failure, or uncontrolled hypertension. 2, 5

• Patients already taking low-dose aspirin should avoid oral NSAIDs if possible, as the combination markedly increases gastrointestinal bleeding risk. 1

Alternative: Chondroitin Sulfate

• Chondroitin sulfate may be used for pain relief and improved function in hand osteoarthritis based on one well-performed trial, though evidence in knee and hip osteoarthritis is less convincing. 3

• This recommendation is formulated more as a suggestion than a strong recommendation due to limited evidence. 3

Intra-Articular Corticosteroid Injections

• A single intra-articular corticosteroid injection provides short-term pain relief (1–3 weeks) for acute osteoarthritis flares, particularly when joint effusion is present, and is strongly recommended for elderly patients who cannot tolerate oral NSAIDs. 2

Critical Safety Considerations

• Never prescribe oral NSAIDs without gastroprotection (proton-pump inhibitor co-prescription is mandatory). 1, 2

• Monitor blood pressure, renal function, liver enzymes, and complete blood count every 3 months if oral NSAID use exceeds 2 weeks. 6

• In elderly patients on ACE inhibitors, ARBs, or diuretics, oral NSAIDs require particular caution due to increased risk of renal impairment and reduced diuretic efficacy. 5

• Avoid glucosamine supplements—current evidence does not support their use for osteoarthritis. 2

Essential Non-Pharmacologic Interventions

• Joint-specific strengthening exercises and general aerobic conditioning must accompany any pharmacologic therapy, producing pain-reduction effect sizes of 0.57–1.0. 2

• Weight loss in overweight or obese patients significantly reduces osteoarthritis symptoms and disease progression. 2

• Patient education, local heat or cold applications, assistive devices, and shock-absorbing footwear are essential core treatments. 2