What are the potential drug interactions between Cyclobenzaprine (Flexeril) and Methocarbamol (Robaxin)?

From the Guidelines

Cyclobenzaprine and methocarbamol should be used together with caution due to the potential for additive central nervous system (CNS) depression effects, as evidenced by the higher risk of adverse events associated with skeletal muscle relaxants compared to placebo 1. When considering the use of these muscle relaxants together, it is essential to weigh the benefits against the potential risks. The mechanism behind this interaction involves both medications affecting the CNS, with cyclobenzaprine acting centrally to reduce muscle tone and methocarbamol working through general CNS depression to provide muscle relaxation. Some key points to consider when using cyclobenzaprine and methocarbamol together include:

• The risk of CNS depression, which can manifest as enhanced drowsiness, dizziness, and impaired coordination 1
• The potential for increased adverse events, including central nervous system adverse events, compared to placebo 1
• The need for close monitoring of patients for excessive sedation or respiratory depression, particularly if other CNS depressants like opioids, benzodiazepines, or alcohol are used simultaneously
• The importance of informing patients about these potential interactions and advising them to report any concerning symptoms promptly
• The consideration of lower doses of each medication and careful monitoring of patients, especially elderly patients and those with liver or kidney impairment, who may be particularly susceptible to these additive effects 1

From the FDA Drug Label

Cyclobenzaprine may enhance the effects of alcohol, barbiturates, and other CNS depressants Patients should be cautioned about the risk of serotonin syndrome with the concomitant use of Cyclobenzaprine Hydrochloride and other drugs, such as selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), tramadol, bupropion, meperidine, verapamil, or monoamine oxidase (MAO) inhibitors Methocarbamol may possess a general CNS-depressant effect, patients should be cautioned about combined effects with alcohol and other CNS depressants Methocarbamol may inhibit the effect of pyridostigmine bromide

The combination of cyclobenzaprine and methocarbamol may increase the risk of CNS depression due to their individual CNS depressant effects. Additionally, there is a potential risk of serotonin syndrome with cyclobenzaprine when used with other serotonergic drugs, but methocarbamol is not typically considered a serotonergic agent.

• Key considerations:
  • CNS depression: increased risk of drowsiness, dizziness, and impaired mental and physical abilities
  • Serotonin syndrome: although methocarbamol is not typically associated with this risk, caution is still advised when combining cyclobenzaprine with other medications 2
  • Drug interactions: patients should be closely monitored for adverse effects when taking cyclobenzaprine and methocarbamol together 2 3

From the Research

Cyclobenzaprine and Methocarbamol Drug Interactions

• There is limited information available on the specific drug interactions between cyclobenzaprine and methocarbamol 4, 5.
• Both cyclobenzaprine and methocarbamol are skeletal muscle relaxants, and their combined use may increase the risk of adverse effects such as drowsiness, dizziness, and fatigue 6, 5.
• A study comparing the efficacy and safety of different skeletal muscle relaxants found that cyclobenzaprine and methocarbamol had similar adverse effect profiles, but the evidence was not sufficient to determine their relative efficacy or safety 5.
• Another study found that cyclobenzaprine was effective in treating muscle spasm associated with painful musculoskeletal conditions, but the study did not investigate interactions with methocarbamol 7.
• A recent analysis of data from randomized studies found that methocarbamol had a lower mean improvement in Roland-Morris Disability Questionnaire (RMDQ) scores compared to cyclobenzaprine, but the difference was not statistically significant 8.

Efficacy and Safety of Cyclobenzaprine and Methocarbamol

• Cyclobenzaprine has been shown to be effective in treating muscle spasm associated with acute, painful musculoskeletal conditions 6, 7.
• Methocarbamol has been found to be effective in treating musculoskeletal conditions, but the evidence is limited and inconsistent 5, 8.
• Both cyclobenzaprine and methocarbamol have been associated with adverse effects such as drowsiness, dizziness, and fatigue, and their combined use may increase the risk of these effects 6, 5.

Clinical Implications

• The use of cyclobenzaprine and methocarbamol together may require careful monitoring for adverse effects such as drowsiness, dizziness, and fatigue 6, 5.
• Patients should be advised to report any adverse effects or concerns to their healthcare provider 7, 8.
• Further studies are needed to determine the efficacy and safety of cyclobenzaprine and methocarbamol in combination, as well as their relative efficacy and safety compared to other skeletal muscle relaxants 4, 5.