What is the recommended dosing for Flexeril (cyclobenzaprine)?

Flexeril (Cyclobenzaprine) Dosing

The FDA-approved dosing for cyclobenzaprine is 5 mg three times daily, which may be increased to 10 mg three times daily based on individual response, with treatment duration limited to 2-3 weeks. 1

Standard Dosing Regimen

• Start with 5 mg three times daily for most patients 1
• May increase to 10 mg three times daily if the 5 mg dose provides insufficient relief 1
• Duration should not exceed 2-3 weeks as efficacy beyond this period has not been established 1

Evidence Supporting Lower Dose Efficacy

The 5 mg three times daily regimen is supported by robust clinical trial data:

• Cyclobenzaprine 5 mg TID demonstrated equivalent efficacy to 10 mg TID in two large randomized controlled trials involving 1,405 patients with acute musculoskeletal spasm 2
• The 5 mg dose produced significantly less sedation compared to 10 mg while maintaining therapeutic benefit 2
• Onset of relief occurs within 3-4 doses of the 5 mg regimen 2
• The 2.5 mg TID dose was not significantly more effective than placebo and should not be used 2

Special Populations Requiring Dose Adjustment

Elderly patients and those with hepatic impairment require less frequent dosing 1:

• Consider starting with 5 mg once or twice daily rather than three times daily 1
• Monitor more carefully for adverse effects including sedation and anticholinergic symptoms 1

Extended-Release Formulation

An alternative formulation exists:

• Cyclobenzaprine extended-release 30 mg once daily provides comparable systemic exposure to immediate-release 10 mg three times daily 3
• This formulation provides sustained plasma concentrations without the fluctuating peaks and troughs seen with immediate-release dosing 3

Common Adverse Effects

Sedation and dry mouth are the most frequent side effects, occurring in a dose-dependent manner 2:

• Somnolence occurred in 54-62% of patients on 5-10 mg versus 35% on placebo 2
• These effects are mediated by potent non-competitive antagonism of central histamine H1 receptors 4
• Adverse effects are typically mild but may necessitate dose reduction or discontinuation 2

Safety Profile

Cyclobenzaprine has a favorable safety profile even in overdose 5:

• No deaths occurred in a 5-year review of 750 exposures 5
• Life-threatening cardiovascular or neurologic effects did not occur with doses under 1 gram 5
• Symptoms requiring treatment beyond gastrointestinal decontamination did not occur with ingestions less than 100 mg 5

Combination Therapy Considerations

Adding ibuprofen to cyclobenzaprine 5 mg TID provides no additional benefit over cyclobenzaprine monotherapy 6:

• A randomized trial of 867 patients showed no significant difference in patient global impression of change between cyclobenzaprine 5 mg alone versus combination with ibuprofen 400 mg or 800 mg TID 6
• All treatment groups showed 88% improvement at 3 days and 93% at 7 days 6

Key Clinical Pitfalls

• Do not prescribe for longer than 2-3 weeks as chronic use is not supported by evidence 1
• Do not start with 10 mg TID as 5 mg TID is equally effective with fewer side effects 2
• Avoid the 2.5 mg TID dose as it lacks efficacy over placebo 2
• Warn patients about sedation which occurs centrally via H1 receptor antagonism and may impair driving or operating machinery 4