Side Effects of Flexeril (Cyclobenzaprine) and Robaxin (Methocarbamol)
Flexeril (cyclobenzaprine) causes significantly more drowsiness, dry mouth, and dizziness compared to Robaxin (methocarbamol), making methocarbamol a better choice for patients who need to remain alert during daily activities.
Common Side Effects of Cyclobenzaprine (Flexeril)
According to FDA drug labeling, the most frequent adverse reactions with cyclobenzaprine include:
- Drowsiness/Sedation (29-38%) - significantly higher than placebo (10%) 1
- Dry mouth (21-32%) - compared to 7% with placebo 1
- Dizziness (3-11%) 1
- Fatigue (6%) 1
- Headache (5%) 1
Less common side effects (1-3%) include:
- Constipation
- Nausea
- Confusion
- Blurred vision
- Mental acuity decrease
- Nervousness 1
Common Side Effects of Methocarbamol (Robaxin)
According to FDA drug labeling, methocarbamol has a more favorable side effect profile with less frequent adverse reactions:
- Dizziness/lightheadedness
- Drowsiness
- Nausea
- Headache
- Blurred vision 2
Comparative Safety Profile
Central Nervous System Effects
Cyclobenzaprine: Has more pronounced CNS effects due to its tricyclic structure. The American Geriatrics Society Beers Criteria® identifies cyclobenzaprine as potentially inappropriate in older adults due to its strong anticholinergic effects and sedation 3.
Methocarbamol: Generally causes less sedation and has fewer anticholinergic effects, making it better tolerated in many patients, particularly older adults 2, 4.
Risk of Serious Adverse Events
Cyclobenzaprine:
Methocarbamol:
Special Population Considerations
Elderly Patients
Cyclobenzaprine: Plasma concentrations are approximately 1.7-fold higher in elderly individuals (≥65 years), with elderly males showing the highest increase (2.4-fold). The American Geriatrics Society recommends avoiding cyclobenzaprine in older adults due to anticholinergic effects 3, 1.
Methocarbamol: Generally better tolerated in elderly patients due to fewer anticholinergic effects and less sedation 2.
Patients with Hepatic Impairment
Cyclobenzaprine: Both AUC and Cmax are approximately double in patients with hepatic impairment. Should be used with caution starting with 5 mg and titrating slowly. Not recommended in moderate to severe hepatic impairment 1.
Methocarbamol: May cause jaundice (including cholestatic jaundice) but has less hepatotoxicity risk compared to other muscle relaxants 2, 4.
Drug Interactions
Cyclobenzaprine:
Methocarbamol:
- Fewer significant drug interactions
- Still has additive CNS depression with alcohol and other CNS depressants 2
Risk with Concomitant Opioid Use
Recent research shows that when combined with opioids, cyclobenzaprine has a lower risk of opioid overdose compared to baclofen. Methocarbamol showed similar risk to cyclobenzaprine in this context 6.
Practical Considerations
- If sedation must be avoided (e.g., for patients who need to drive or operate machinery), methocarbamol is generally preferable to cyclobenzaprine.
- For elderly patients or those with hepatic impairment, methocarbamol is typically better tolerated.
- If a patient requires a stronger muscle relaxant effect and can tolerate sedation, cyclobenzaprine may be more effective, particularly at the 10 mg dose 7.