Is Aceclifenac and chlorzoxazone 250 mg twice daily for 5 days an appropriate regimen for an adult patient with musculoskeletal disorders or post-surgical pain?

Aceclofenac and Chlorzoxazone 250 mg BD for 5 Days: Clinical Recommendation

For acute musculoskeletal pain, aceclofenac 100 mg twice daily for 5 days is appropriate and effective, but chlorzoxazone 250 mg twice daily should NOT be added as it provides no proven analgesic benefit and the dose is subtherapeutic according to FDA labeling. 1, 2, 3

Rationale for Aceclofenac Use

Aceclofenac is an effective NSAID for acute musculoskeletal disorders with demonstrated pain reduction and functional improvement comparable to other NSAIDs. 4

• Aceclofenac shows significant pain reduction in acute musculoskeletal conditions including low back pain, with a favorable gastrointestinal safety profile compared to other NSAIDs. 4
• The American College of Physicians and American Academy of Family Physicians recommend oral NSAIDs as appropriate therapy for acute non-low back musculoskeletal injuries to reduce pain and improve physical function (moderate-certainty evidence). 1
• Clinical trials demonstrate aceclofenac reduces pain intensity significantly by day 3 and day 7 in acute musculoskeletal pain. 5

Critical Problem with Chlorzoxazone Dosing and Efficacy

The proposed chlorzoxazone dose of 250 mg twice daily is below FDA-approved dosing and lacks evidence of efficacy. 2, 3

• FDA labeling specifies chlorzoxazone dosing should be 500-750 mg three to four times daily for painful musculoskeletal conditions, not 250 mg twice daily. 2
• A 2020 randomized, double-blind, placebo-controlled trial of 393 patients undergoing total knee and hip replacement found chlorzoxazone 250 mg three times daily showed NO significant analgesic effects compared to placebo for acute postoperative pain (P>0.313). 3
• The American Geriatrics Society states that so-called "muscle relaxants" including chlorzoxazone do not directly relax skeletal muscle and have no evidence of efficacy in chronic pain. 1, 6

Evidence for Combination Therapy

Low-certainty evidence suggests acetaminophen plus chlorzoxazone may reduce pain at 1-7 days, but this does not support the proposed regimen. 1

• The American College of Physicians guideline found acetaminophen plus chlorzoxazone reduced pain (WMD -2.92 cm on 10-cm VAS) at 1-7 days compared to placebo, but this was low-certainty evidence and involved acetaminophen as the co-analgesic, not aceclofenac. 1
• No high-quality evidence supports combining aceclofenac with chlorzoxazone specifically. 1, 4

Recommended Alternative Approach

Prescribe aceclofenac 100 mg twice daily alone for 5-7 days as monotherapy. 4, 5

• If additional analgesia is needed, add acetaminophen 500-1000 mg three to four times daily rather than chlorzoxazone. 1
• The American College of Physicians recommends oral NSAIDs or acetaminophen as appropriate first-line pharmacologic options (moderate-certainty evidence). 1
• Topical NSAIDs with or without menthol gel are recommended as first-line therapy when applicable (strong recommendation, moderate-certainty evidence). 1

Important Safety Considerations

Monitor for NSAID-related gastrointestinal and cardiovascular adverse effects, particularly in patients with risk factors. 4

• Aceclofenac demonstrates a favorable GI tolerability profile compared to other NSAIDs, with adverse event rates of 0.86% in a large post-marketing study of 14,543 patients. 7
• Use the lowest effective dose for the shortest duration necessary. 4
• Avoid opioids for acute musculoskeletal injuries (conditional recommendation against use). 1

Clinical Pitfalls to Avoid

• Do not prescribe chlorzoxazone at subtherapeutic doses (250 mg BD is below FDA-recommended dosing). 2
• Do not assume muscle relaxants provide analgesic benefit without supporting evidence for the specific condition. 1, 6, 3
• Do not continue therapy beyond 7 days without reassessment, as most acute musculoskeletal pain improves substantially within the first week. 1, 5