What is the typical dosage (sig) for Flexeril (cyclobenzaprine)?

Flexeril (Cyclobenzaprine) Dosing

The standard dosing for Flexeril is 5 mg three times daily, with the option to increase to 10 mg three times daily based on individual response, and treatment should not exceed 2-3 weeks. 1

Standard Dosing Regimen

• Starting dose: 5 mg orally three times daily 1
• Maximum dose: 10 mg orally three times daily if needed for adequate response 1
• Duration: Limited to 2-3 weeks maximum 1

The FDA-approved labeling explicitly states that most patients should begin with 5 mg three times daily, and this can be titrated up to 10 mg three times daily based on clinical response 1. Use beyond 2-3 weeks is not recommended 1.

Evidence Supporting Lower Dosing

Clinical trials demonstrate that 5 mg three times daily is as effective as 10 mg three times daily, with significantly less sedation. 2

• Two large randomized controlled trials (n=1,405) showed cyclobenzaprine 5 mg TID achieved comparable efficacy to 10 mg TID on all primary measures including patient-rated global impression of change, medication helpfulness, and relief from pain (P≤0.001 vs placebo) 2
• The 5 mg TID regimen produced lower rates of somnolence compared to 10 mg TID while maintaining therapeutic benefit 2
• Onset of relief was apparent within 3-4 doses of the 5 mg regimen 2
• The 2.5 mg TID dose was not significantly more effective than placebo and is not recommended 2

Special Population Considerations

Elderly and hepatically impaired patients require dose reduction and less frequent dosing. 1

• Consider lower doses or reduced frequency (e.g., 5 mg once or twice daily) in elderly patients 1
• Hepatic impairment necessitates dose reduction due to decreased metabolism 1
• Cyclobenzaprine appears on the American Geriatrics Society Beers Criteria as potentially inappropriate for older adults due to anticholinergic effects 3

Extended-Release Formulation Alternative

An extended-release formulation exists that allows once-daily dosing:

• CER 15 mg once daily was effective in treating muscle spasm after 4 days of treatment 4
• CER 30 mg once daily provides comparable systemic exposure to immediate-release 10 mg three times daily but with a single daily peak versus three peaks per day 5
• The extended-release formulation may produce less daytime drowsiness compared to immediate-release formulations 4

Critical Safety Warnings

Cyclobenzaprine has significant anticholinergic and sedative effects that limit its use. 3, 6

• Sedation occurs in >30% of patients, mediated by potent non-competitive antagonism of central histamine H1 receptors 6
• Cyclobenzaprine exhibits low nanomolar affinity for H1 receptors and readily crosses the blood-brain barrier 6
• Contraindicated with monoamine oxidase inhibitors due to risk of serotonin syndrome 3
• Long-term use can lead to dependence; taper over 2-3 weeks when discontinuing after extended use 3

Practical Prescribing Approach

Start with 5 mg three times daily for 7-14 days maximum, reserving 10 mg TID only for inadequate response. 1, 2

• Assess response after 3-4 days (approximately 9-12 doses) 2
• If inadequate relief with 5 mg TID, increase to 10 mg TID 1
• Discontinue after 2-3 weeks regardless of response 1
• For elderly or hepatically impaired patients, start with 5 mg once or twice daily 1