What is the initial recommended medication for osteoarthritis (OA) of the knee?

Initial Medication Therapy for Osteoarthritis of the Knee

Acetaminophen is the recommended initial medication for osteoarthritis of the knee, with a full dosage of up to 4,000 mg/day as the preferred long-term oral analgesic. 1

First-Line Pharmacologic Treatment Options

• Acetaminophen should be tried first due to its favorable safety profile compared to NSAIDs, despite having somewhat lower efficacy 1, 2
• When initiating acetaminophen, counsel patients to avoid other products containing acetaminophen (including OTC cold remedies and combination products with opioid analgesics) to prevent exceeding the maximum daily dose 1
• Full dosage of acetaminophen (up to 4,000 mg/day) should be used before considering it ineffective 1

Alternative First-Line Options (if acetaminophen is contraindicated)

• Topical NSAIDs are conditionally recommended, especially for patients ≥75 years old 1, 3
• Oral NSAIDs at the lowest effective dose for the shortest duration 1, 4
• Tramadol is another conditionally recommended option 1
• Intraarticular corticosteroid injections may be considered, particularly for acute exacerbations with effusion 1

Second-Line Therapy (if acetaminophen is ineffective)

If a patient does not have a satisfactory clinical response to full-dose acetaminophen, consider:

• Oral or topical NSAIDs (strongly recommended as second-line therapy) 1
• For patients ≥75 years old, topical NSAIDs are strongly preferred over oral NSAIDs 1
• Intraarticular corticosteroid injections 1
• Tramadol or duloxetine may be conditionally considered 1

Efficacy Considerations

• While acetaminophen has been shown to be more effective than placebo, NSAIDs demonstrate greater efficacy for pain relief in OA knee (ES = 0.20,95% CI 0.10 to 0.30) 5
• Some studies have questioned acetaminophen's efficacy compared to placebo 6
• A recent network meta-analysis found topical NSAIDs superior to acetaminophen for function improvement (SMD = -0.29,95% CrI: -0.52 to -0.06) 3

Safety Considerations

• Acetaminophen has a better safety profile than oral NSAIDs, particularly regarding gastrointestinal adverse effects 5
• For patients with GI risk factors who require an oral NSAID, use either a COX-2 selective inhibitor or a nonselective NSAID with a proton-pump inhibitor 1
• Topical NSAIDs show lower risks of all-cause mortality (HR = 0.59), cardiovascular diseases (HR = 0.73), and gastrointestinal bleeding (HR = 0.53) compared to acetaminophen in real-world data 3
• Oral NSAIDs should be avoided in patients with contraindications to these agents 1

Treatments Not Recommended

• Nutritional supplements (chondroitin sulfate, glucosamine) are conditionally not recommended 1
• Topical capsaicin is conditionally not recommended 1

Integrated Approach

• Pharmacologic therapy should be combined with non-pharmacologic modalities for optimal management 1, 7
• Strongly recommended non-pharmacologic approaches include:
  • Cardiovascular/resistance land-based exercise 1
  • Aquatic exercise 1
  • Weight loss for overweight patients 1

Remember that medication therapy should be part of a comprehensive approach that includes appropriate non-pharmacologic interventions to maximize outcomes for patients with knee OA 1, 7.