Can methocarbamol and cyclobenzaprine be taken at the same time?

Combining Methocarbamol and Cyclobenzaprine

Do not combine methocarbamol and cyclobenzaprine routinely, as both are centrally-acting muscle relaxants that increase the risk of additive sedation, falls, and injury, particularly in older adults. 1

Why This Combination Should Be Avoided

Additive Central Nervous System Depression

• Both methocarbamol and cyclobenzaprine work through central mechanisms and cause sedation, drowsiness, and dizziness as their most common adverse effects 2, 3
• The American College of Emergency Physicians specifically recommends against co-prescribing multiple muscle relaxants/sedative-hypnotics due to increased toxicity when centrally acting drugs are combined 1
• This guidance explicitly lists both cyclobenzaprine and methocarbamol as agents that should not be routinely co-prescribed with other sedating medications 1

Increased Risk of Injury

• Methocarbamol use in older adults is associated with a 42% increased risk of injury requiring hospitalization or emergency care (OR 1.42,95% CI 1.16-1.75) 4
• Cyclobenzaprine use increases injury risk by 22% (OR 1.22,95% CI 1.02-1.45) 4
• Combining two agents from the same class would theoretically compound these risks through additive sedation 4

Lack of Evidence for Combination Therapy

• No clinical trials have evaluated the safety or efficacy of combining methocarbamol with cyclobenzaprine 5
• There is insufficient evidence to determine whether combining muscle relaxants provides any additional benefit over monotherapy 5
• All muscle relaxant trials were 2 weeks or less in duration, indicating these agents should only be used short-term regardless of whether they are combined 6

Clinical Pitfalls to Avoid

The Anticholinergic Burden

• Cyclobenzaprine is structurally related to tricyclic antidepressants and causes anticholinergic effects including dry mouth, sedation, and confusion 3
• The cumulative anticholinergic effect of multiple drugs may be associated with decline in cognition, functional status, and activities of daily living 7
• Adding methocarbamol to cyclobenzaprine increases the overall sedative burden even if methocarbamol lacks significant anticholinergic properties 3

Special Vulnerability in 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 7
• Older adults using skeletal muscle relaxants have a significantly increased risk of injury compared to non-users 4
• If a muscle relaxant is absolutely necessary in an older patient already on one agent, switching rather than adding is the safer approach 7

Alternative Approaches

If One Muscle Relaxant Is Ineffective

• Switch to tizanidine, which has the strongest evidence base as an alternative and works through a different mechanism (alpha-2 adrenergic agonism rather than central sedation) 6
• Consider that lack of response may indicate the need for a different therapeutic approach rather than adding another sedating agent 6
• Reassess the diagnosis, as muscle relaxants have limited evidence for chronic musculoskeletal pain 5

Safer Combination Strategies

• If additional pain control is needed, combine a single muscle relaxant with an NSAID or acetaminophen rather than adding a second muscle relaxant 8
• The efficacy of cyclobenzaprine has been shown to be independent of its sedative effects, suggesting that adding sedation through a second agent does not enhance benefit 2