In a patient with chronic musculoskeletal pain taking 1300 mg paracetamol daily and unable to obtain 7.5 mg meloxicam, is a 750 mg sustained‑release naproxen tablet taken once in the evening as effective as two 375 mg immediate‑release naproxen tablets taken twice daily?

Naproxen 750mg SR Once Daily vs. 375mg IR Twice Daily for Chronic Musculoskeletal Pain

A 750 mg sustained-release naproxen tablet taken once daily in the evening is equally effective to two 375 mg immediate-release naproxen tablets taken twice daily, with comparable steady-state plasma concentrations and potentially fewer gastrointestinal side effects. 1, 2

Pharmacokinetic Equivalence

The sustained-release formulation achieves bioequivalence to the immediate-release regimen through controlled drug release:

• Steady-state plasma concentrations are reached after 2 days of administration with both formulations, with the 750 mg SR tablet producing peak, trough, and average plasma concentrations comparable to 500 mg IR twice daily (which exceeds your 375 mg IR twice daily regimen). 1

• Area under the curve (AUC) values demonstrate equal extent of absorption between the 750 mg SR once-daily formulation and conventional tablets, confirming that total drug exposure over 24 hours is equivalent. 1, 3

• Absorption kinetics show that naproxen is approximately 90% absorbed from the controlled-release tablet, with a mean absorption time of 8.4 hours for the 750 mg SR formulation, allowing for sustained therapeutic levels throughout the day. 3

• Trough concentrations are equivalent between once-daily SR and twice-daily IR formulations, and the SR formulation maintains steady-state plasma concentrations within narrower limits, potentially reducing peak-related side effects. 3

Clinical Efficacy Evidence

Direct clinical comparison supports equivalence in pain control:

• A double-blind trial in osteoarthritis patients demonstrated that sustained-release naproxen 1000 mg once daily was equivalent in efficacy to conventional naproxen 500 mg twice daily, with significantly lower incidence of gastrointestinal side effects. 2

• The EULAR guidelines note that paracetamol efficacy is similar to naproxen 750 mg/day in knee osteoarthritis, establishing 750 mg as a clinically meaningful daily dose for chronic musculoskeletal conditions. 4

Practical Dosing Recommendations

For your specific clinical scenario:

• Start with 750 mg SR naproxen once daily in the evening, which provides equivalent analgesia to 750 mg total daily dose (375 mg × 2) with the convenience of once-daily dosing. 1, 2

• Continue paracetamol 1300 mg daily as adjunctive therapy, since combination therapy with paracetamol and NSAIDs provides superior pain control (35-39% greater pain reduction) compared to either agent alone. 5

• Assess response at 2-4 weeks at maximum tolerated dose; if insufficient response occurs, consider switching to a different NSAID rather than increasing naproxen dose. 5, 6

• Evening dosing is appropriate for the SR formulation and may provide better overnight pain control for morning stiffness common in musculoskeletal conditions. 1

Safety Monitoring Requirements

Given chronic use, implement the following surveillance:

• Baseline assessment should include blood pressure, BUN, creatinine, liver function tests, complete blood count, and fecal occult blood test before initiating therapy. 6

• Monitor every 3 months with the same laboratory panel if treatment extends beyond 2-4 weeks. 5, 6

• Add gastroprotection with a proton pump inhibitor if any risk factors are present (age >60 years, history of peptic ulcer disease, concurrent anticoagulants, antiplatelet agents, SSRIs, or glucocorticoids). 5, 6

• Discontinue immediately if BUN or creatinine doubles, liver function tests increase to ≥3× upper limit of normal, new or worsening hypertension develops, or any signs of gastrointestinal bleeding occur. 5, 6

Critical Safety Considerations

Be aware of these important caveats:

• Maximum daily dose should not exceed 1000 mg for routine long-term use in adults, so the 750 mg SR formulation provides an appropriate therapeutic dose with room for occasional breakthrough dosing if needed. 5, 6

• Gastrointestinal risk is dose-dependent across all NSAIDs; the SR formulation may offer a lower incidence of GI side effects compared to IR formulations at equivalent doses. 2

• Take with food to minimize gastrointestinal irritation, even with the SR formulation. 5

• Never combine with other NSAIDs (including ibuprofen or over-the-counter products), as toxicities are additive without additional analgesic benefit. 6

• If two different NSAIDs fail sequentially, switch to an alternative analgesic approach rather than trying additional NSAIDs. 5, 6

Advantages of SR Formulation

The sustained-release preparation offers specific benefits:

• Improved compliance with once-daily dosing compared to twice-daily regimens, particularly important for chronic pain management. 2, 3

• More stable plasma concentrations with narrower fluctuations between peak and trough levels, potentially reducing side effects while maintaining efficacy. 3

• Lower incidence of gastrointestinal side effects compared to conventional-release formulations at equivalent total daily doses. 2