Can a patient take Robaxin (methocarbamol) 750 mg three times a day (TID) and cyclobenzaprine 5 mg at bedtime?

Combining Methocarbamol and Cyclobenzaprine: Not Recommended

You should not routinely combine Robaxin (methocarbamol) 750 mg TID with cyclobenzaprine 5 mg at bedtime, as the American College of Emergency Physicians explicitly recommends against co-prescribing multiple muscle relaxants or sedative-hypnotics due to increased toxicity from additive central nervous system depression. 1

Why This Combination Is Problematic

Guideline-Based Contraindication

• The American College of Emergency Physicians specifically lists both cyclobenzaprine and methocarbamol as agents that should not be routinely co-prescribed with other sedating medications 1
• This recommendation is based on increased risk of additive sedation, falls, and injury—particularly concerning in older adults 1
• Both agents work centrally to produce muscle relaxation, creating overlapping mechanisms of CNS depression 1, 2

Additive Sedation Risk

• Cyclobenzaprine exhibits high-affinity antagonism at histamine H1 receptors, which explains why >30% of patients experience drowsiness and sedative-hypnotic effects 3
• Methocarbamol also produces central nervous system depression, though it is considered less sedating than cyclobenzaprine 2
• The combination significantly amplifies the risk of excessive daytime sedation, impaired cognition, and motor vehicle accidents 1

Lack of Evidence for Combination Therapy

• All muscle relaxant trials were 2 weeks or less in duration, and no studies have evaluated the safety or efficacy of combining two muscle relaxants 1, 4
• There is insufficient evidence that combining muscle relaxants provides additional benefit over monotherapy 5

What You Should Do Instead

If Current Therapy Is Inadequate

• Switch rather than add: If methocarbamol 750 mg TID is ineffective, discontinue it and switch to cyclobenzaprine 5 mg TID (not just at bedtime) 1, 6
• Consider tizanidine as an alternative, which has the strongest evidence base and works through a different mechanism (alpha-2 adrenergic agonism) 4
• Reassess whether lack of response indicates the need for a different therapeutic approach entirely rather than adding another sedating agent 1

Appropriate Cyclobenzaprine Dosing

• The FDA-approved dosing for cyclobenzaprine is 5 mg three times daily, with potential increase to 10 mg TID based on response 6
• Using cyclobenzaprine only at bedtime is suboptimal, as its duration of action is 4-6 hours, creating untreated intervals during the day 7
• If sedation is the primary concern, cyclobenzaprine 5 mg TID provides equivalent efficacy to 10 mg TID with lower sedation rates 7

Duration of Treatment

• Neither agent should be continued beyond 2-3 weeks, as all clinical trials were limited to this duration and there is insufficient evidence for chronic use 1, 4, 6
• If symptoms persist beyond 2-3 weeks, reevaluate the diagnosis and consider alternative non-pharmacologic approaches 4

Special Populations at Higher Risk

Older Adults

• The American Geriatrics Society identifies muscle relaxants, including cyclobenzaprine, as potentially inappropriate medications for older adults due to increased risk of anticholinergic effects, sedation, and falls 1
• If a muscle relaxant is absolutely necessary in an older patient already on one agent, switching rather than adding is the safer approach 1
• Elderly patients should start with cyclobenzaprine 5 mg and titrate slowly, with less frequent dosing considered 6

Hepatic Impairment

• Cyclobenzaprine AUC and Cmax are approximately double in patients with hepatic impairment 6
• Use cyclobenzaprine with caution in mild hepatic impairment starting with 5 mg and titrating slowly; it is not recommended in moderate to severe impairment 6
• Methocarbamol has significantly impaired elimination in liver disease 4

Clinical Pitfalls to Avoid

• Don't assume bedtime-only dosing is adequate: Cyclobenzaprine's 4-6 hour duration requires TID dosing for continuous coverage 7
• Don't continue beyond 2-3 weeks: Prolonged use increases CNS adverse events (RR 2.04 vs placebo) without proven benefit 4
• Don't combine with other CNS depressants: The FDA has issued a black box warning about combining sedating medications, particularly opioids and benzodiazepines, due to risk of respiratory depression and death 8
• Don't abruptly discontinue after prolonged use: Taper cyclobenzaprine over 2-3 weeks to prevent withdrawal symptoms (malaise, nausea, headache) 9