Initial Medication Therapy for Osteoarthritis of the Knee

First-Line Pharmacologic Treatment Options

The American College of Rheumatology recommends acetaminophen as the initial medication for osteoarthritis of the knee, with a full dosage of up to 4,000 mg/day, due to its favorable safety profile compared to NSAIDs, despite having somewhat lower efficacy 1, 2, 3, 4
When initiating acetaminophen, patients should be counseled to avoid other products containing acetaminophen to prevent exceeding the maximum daily dose 1, 5
A full dosage of acetaminophen (up to 4,000 mg/day) should be used before considering it ineffective 1, 5

Topical NSAIDs are conditionally recommended, especially for patients ≥75 years old, as an alternative to acetaminophen 1, 5
Tramadol is another conditionally recommended option for patients who cannot use acetaminophen or topical NSAIDs 1, 5
Intraarticular corticosteroid injections may be considered, particularly for acute exacerbations with effusion, as an alternative to oral medications 1, 6

Oral or topical NSAIDs are strongly recommended as second-line therapy for patients who do not respond to acetaminophen 1, 5
For patients ≥75 years old, topical NSAIDs are strongly preferred over oral NSAIDs due to their better safety profile 1, 5
Intraarticular corticosteroid injections may be considered as second-line therapy for patients who do not respond to oral medications 1, 5

For patients with GI risk factors who require an oral NSAID, a COX-2 selective inhibitor or a nonselective NSAID with a proton-pump inhibitor should be used to minimize gastrointestinal adverse effects 1, 7
Oral NSAIDs should be avoided in patients with contraindications to these agents, such as those with a history of gastrointestinal bleeding or cardiovascular disease 1, 5

Nutritional supplements, such as chondroitin sulfate and glucosamine, are conditionally not recommended due to lack of evidence for their efficacy 1, 5
Topical capsaicin is conditionally not recommended due to limited evidence for its efficacy and potential side effects 1, 5

The American College of Rheumatology recommends combining pharmacologic therapy with non-pharmacologic modalities, such as cardiovascular/resistance land-based exercise, aquatic exercise, and weight loss for overweight patients, for optimal management of osteoarthritis of the knee 1, 5, 6