Treatment Prescription for Knee Osteoarthritis
Begin with a structured exercise program (land-based or aquatic cardiovascular/resistance training) combined with acetaminophen up to 4000 mg daily, and if the patient is overweight, initiate weight loss counseling. 1
Non-Pharmacological Foundation (Mandatory First-Line)
All patients with knee OA must receive:
- Cardiovascular and/or resistance land-based exercise or aquatic exercise programs—these are strongly recommended as they reduce pain and improve function 1
- Weight loss counseling if BMI ≥25 kg/m²—this is strongly recommended for all overweight patients 1
- Patient education and self-management programs—conditionally recommended to improve coping and outcomes 1
These interventions form the backbone of treatment and should never be omitted, regardless of pharmacological choices 1.
Pharmacological Management Algorithm
Step 1: Initial Oral Analgesic
Prescribe acetaminophen 1000 mg three to four times daily (maximum 4000 mg/day) as the first-line oral analgesic 1. This has a strong recommendation from the most recent AAOS 2022 guidelines for improving pain and function 1.
Important caveat: Counsel patients to avoid all other acetaminophen-containing products including OTC cold remedies and combination opioid products 1. Recent high-quality evidence suggests acetaminophen may be less effective than previously believed 2, 3, but guidelines still prioritize it due to superior safety profile 1.
Step 2: If Inadequate Response to Acetaminophen
Switch to oral NSAIDs or add topical NSAIDs 1:
- Oral NSAIDs (e.g., naproxen 500 mg twice daily, ibuprofen 600-800 mg three times daily): These provide superior pain relief compared to acetaminophen 1, 2, 3
- Topical NSAIDs: Effective for pain relief with lower systemic absorption and reduced GI risk 1
For patients with increased GI risk (age ≥60, history of peptic ulcer disease, GI bleeding, concurrent corticosteroids or anticoagulants):
- Use topical NSAIDs alone, OR
- Oral NSAIDs plus gastroprotective agent (PPI or misoprostol), OR
- COX-2 selective inhibitor 1
Avoid oral narcotics including tramadol—the 2022 AAOS guidelines strongly recommend against these due to notable increase in adverse events without effectiveness for pain or function 1.
Step 3: Intra-Articular Injections for Acute Flares
Intra-articular corticosteroid injections are recommended for short-term pain relief (1-3 weeks), especially when effusion is present 1, 4:
- Effective within 1 week with clinically important pain reduction 1
- Limited long-term benefit beyond 16-24 weeks 1
- Can be repeated for acute exacerbations 4
Do NOT routinely use hyaluronic acid injections—the 2022 AAOS guidelines (moderate strength) recommend against routine use, and the 2012 ACR conditionally recommends against them 1, 4. Evidence shows unclear clinical significance and potential publication bias 1, 4.
Step 4: What NOT to Prescribe
Strongly avoid or conditionally recommend against:
- Glucosamine and chondroitin sulfate: Conditionally recommended against by ACR 2012 1
- Topical capsaicin: Conditionally recommended against 1
- Opioid analgesics: Strong recommendation against due to adverse events without efficacy 1
Sample Prescription Format
Rx #1:
- Acetaminophen 1000 mg PO QID (not to exceed 4000 mg/24 hours)
- Dispense: #120 tablets
- Refills: 3
Rx #2 (if Step 1 fails after 2-4 weeks):
- Naproxen 500 mg PO BID with food
- Dispense: #60 tablets
- Refills: 3
- Add omeprazole 20 mg PO daily if age ≥60 or GI risk factors present 1
Rx #3 (alternative to oral NSAIDs):
- Diclofenac gel 1% topical, apply to affected knee(s) QID
- Dispense: 100 gm tube
- Refills: 3
Non-pharmacological orders:
- Physical therapy referral for supervised exercise program (land or aquatic-based) 1
- Nutritionist referral for weight management if BMI ≥25 1
Common Pitfalls to Avoid
- Do not combine acetaminophen with NSAIDs initially—start with acetaminophen alone, then switch if inadequate 1
- Do not prescribe tramadol or opioids—strong evidence of harm without benefit 1
- Do not use hyaluronic acid routinely—not supported by current evidence 1, 4
- Do not neglect exercise and weight loss—these are as important as medications 1
- Monitor for acetaminophen in combination products—patients often inadvertently exceed 4000 mg/day 1