Flexeril (Cyclobenzaprine) Dosing
For most adults, cyclobenzaprine should be started at 5 mg three times daily, with the option to increase to 10 mg three times daily based on response; however, elderly patients (≥65 years) and those with hepatic impairment must start at 5 mg once daily with slow upward titration, and treatment duration should not exceed 2–3 weeks. 1
Standard Adult Dosing
- Initial dose: 5 mg orally three times daily is recommended for most patients 1
- Dose escalation: May increase to 10 mg three times daily if the 5 mg dose provides insufficient relief 1
- Duration: Use beyond 2–3 weeks is not recommended, as cyclobenzaprine is indicated only for acute musculoskeletal conditions 1
- Efficacy data: The 5 mg three-times-daily regimen is as effective as 10 mg three times daily for acute muscle spasm, with significantly lower rates of somnolence and dry mouth 2
Elderly Patients (≥65 Years)
Elderly patients require substantial dose reduction due to markedly elevated drug exposure and increased risk of anticholinergic adverse effects.
- Starting dose: 5 mg once daily (not three times daily) 1
- Titration: Increase slowly upward only if necessary, based on individual tolerance 1
- Pharmacokinetic rationale: Steady-state cyclobenzaprine AUC is approximately 1.7-fold higher in elderly patients compared to younger adults, with elderly males showing up to 2.4-fold higher exposure 1
- Safety concerns: The American Geriatrics Society 2019 Beers Criteria explicitly recommends avoiding cyclobenzaprine in older adults due to high risk of CNS adverse effects (sedation, falls) and anticholinergic toxicity (confusion, urinary retention, constipation) 3
- Clinical context: Cyclobenzaprine should not be used in elderly patients without compelling justification, as the risk-benefit ratio is poor in this population 3
Hepatic Impairment
Patients with liver dysfunction experience approximately double the drug exposure and require cautious dosing.
- Mild hepatic impairment: Start at 5 mg once daily and titrate slowly upward 1
- Moderate to severe hepatic impairment: Use is not recommended due to lack of safety data 1
- Pharmacokinetic basis: Both AUC and Cmax are approximately double in patients with hepatic impairment compared to healthy controls 1
Mechanism and Clinical Considerations
- Cyclobenzaprine acts primarily within the central nervous system at the brainstem level (not at the neuromuscular junction), reducing tonic somatic motor activity 1
- The drug is structurally related to tricyclic antidepressants and exhibits potent anticholinergic effects, which account for its side-effect profile 1
- Effective half-life: 18 hours (range 8–37 hours), with steady-state achieved after 3–4 days of three-times-daily dosing 1
- Drug accumulation: Plasma concentrations at steady state are approximately four-fold higher than after a single dose 1
Common Pitfalls to Avoid
- Do not prescribe 10 mg three times daily as the initial dose in elderly or hepatically impaired patients—this dramatically increases adverse effects without improving efficacy 1
- Do not continue cyclobenzaprine beyond 2–3 weeks—it is approved only for acute conditions and chronic use is not supported 1
- Avoid combining with other CNS depressants (benzodiazepines, opioids, alcohol) due to additive sedation risk 3
- Do not use in elderly patients with dementia—cyclobenzaprine is listed among anticholinergic medications that worsen confusion and agitation in this population 4
Alternative Formulation: Extended-Release
- Cyclobenzaprine extended-release (CER) 30 mg once daily provides systemic exposure comparable to immediate-release 10 mg three times daily, but with a single daily peak rather than three peaks 5, 6, 7
- In elderly patients (65–75 years), CER 30 mg once daily produces similar pharmacokinetic profiles to immediate-release formulations, though the same cautions regarding dose reduction apply 5
- CER exhibits a median time to peak concentration (tmax) of 6–8 hours, providing sustained plasma levels over 24 hours 6, 7