What are the dosing guidelines, maximum duration, contraindications, and side effects of Flexeril (cyclobenzaprine) for acute musculoskeletal muscle spasm?

Flexeril (Cyclobenzaprine) Clinical Guide

Dosing Guidelines

Start with cyclobenzaprine 5 mg three times daily, which provides equivalent efficacy to 10 mg three times daily but with significantly lower sedation rates. 1

• The 5 mg dose three times daily was as effective as 10 mg three times daily in controlled trials, with onset of relief apparent within 3-4 doses 1
• A 2.5 mg three times daily dose was not significantly more effective than placebo and should be avoided 1
• Extended-release formulation (15-30 mg once daily) provides comparable systemic exposure with less somnolence (0.8-1.6%) compared to immediate-release 10 mg three times daily (7.3%) 2
• Median time to "a lot" or "complete" relief from local pain is 5-6 days with either formulation 2

Maximum Duration of Treatment

Never continue cyclobenzaprine beyond 2-3 weeks, even if symptoms persist. 3

• All clinical trials of skeletal muscle relaxants were 2 weeks or less in duration (with one exception of a single 3-week trial) 3
• Short-term pain relief (2-4 days) demonstrates early efficacy with relative risk of 0.80 compared to placebo 3
• Prolonged use increases central nervous system adverse events (RR 2.04 compared to placebo) without evidence of continued benefit 3
• There is insufficient evidence for chronic use of any muscle relaxant for musculoskeletal pain 3

Contraindications and Special Precautions

Cyclobenzaprine is contraindicated with monoamine oxidase inhibitors due to risk of serotonin syndrome. 3

• Structurally related to tricyclic antidepressants, acting as a centrally acting 5-HT₂ receptor antagonist 3
• Hold on the day of surgery to avoid intra-operative complications 3
• For patients on long-term therapy, taper gradually over 2-3 weeks before surgery to prevent withdrawal symptoms 3
• May interact with sedatives and anesthetic agents, requiring careful intra-operative monitoring 3

Side Effects and Adverse Events

Sedation and anticholinergic effects are the primary concerns, with somnolence being dose-related. 1, 3

Common Adverse Effects:

• Anticholinergic effects: hallucinations, confusion, drowsiness, constipation, urinary retention, and dry mouth 3
• Somnolence: 7.3% with immediate-release 10 mg three times daily versus 0.8-1.6% with extended-release formulations 2
• Dry mouth and dizziness: consistently reported across all formulations 1, 2
• Overall adverse event rate of 54-62% with cyclobenzaprine versus 35% with placebo 1

Withdrawal Symptoms:

• Malaise, nausea, and headache may occur for 2-4 days after discontinuation following long-term use 3
• Taper over 2-3 weeks when discontinuing after prolonged use to prevent withdrawal 3

Clinical Efficacy Context

Cyclobenzaprine has been the most heavily studied muscle relaxant and consistently demonstrates efficacy for acute musculoskeletal conditions. 4, 5

• Fair evidence supports effectiveness compared to placebo in patients with acute back or neck pain 5
• However, cyclobenzaprine has not been proven superior to acetaminophen or NSAIDs for low back pain 4
• The concept of "muscle relaxant" is a misnomer—these drugs work through sedative properties rather than direct muscle relaxation 6
• Efficacy is independent of sedation, as demonstrated in subanalysis of responders who did not report somnolence 1

Important Clinical Pitfalls

• Do not use for chronic pain: All evidence is limited to 2-week trials, and chronic use lacks supporting data 3, 4
• Adverse events are the primary reason for discontinuation in the 5 mg and 10 mg groups 1
• All skeletal muscle relaxants increase total adverse events by 50% and double CNS adverse events compared to placebo 7
• Sedation can be minimized by using the 5 mg dose or extended-release formulation, or by taking medication at night 1, 2