Cyclobenzaprine (Flexeril®) versus Methocarbamol (Robaxin®)

Based on "Essential Pain Pharmacology"
written by Howard S. Smith, MD; Marco Pappagallo, MD

In comparison trials, no single skeletal muscle relaxant has been proven to be superior to another muscle relaxant. The most widely studied agent is cyclobenzaprine, with demonstrated efficacy for various musculoskeletal conditions, but with significant sedation.

Cyclobenzaprine advantages over Methocarbamol

  • Cyclobenzaprine is the most heavily studied antispasmodic drug.
  • Available in once-daily formulation under the trade name Amrix®.
  • The sedative properties of cyclobenzaprine may benefit patients with insomnia.
  • FDA pregnancy category B.

Methocarbamol advantages over Cyclobenzaprine

  • Methocarbamol is available in parenteral form for intravenous or intramuscular use.
  • Few drug interactions.
  • Useful in the treatment of tetanus.
  • Methocarbamol costs less than cyclobenzaprine.


Cyclobenzaprine Methocarbamol
Brand names
• Flexeril ®
• Amrix ®
• Robaxin®
Drug class
Skeletal muscle relaxant,
centrally acting
• Structurally related to the tricyclic antidepressants
• Carbamate derivative of guaifenesin
• Methocarbamol is pharmacologically but not structurally related to the tricyclic antidepressants
Dose formulations
• Tablets
• Capsules, extended-release
• Tablets
• Injection
FDA-approved indications
• Acute painful musculoskeletal conditions
  • Tetanus
"Off-label" uses
• Fibromyalgia
• Sleep aid
• Acute low back pain
Mechanism of action
• Treatment goals for musculoskeletal conditions include relief of muscle pain and improvement in functional ability, allowing return to work and daily activities.
Both medications relieve acute musculoskeletal pain and increase mobility.
• Both medications have no direct action on skeletal muscles.
• Cyclobenzaprine works mainly at the brainstem level to decrease tonic muscle activity. It influences both the alpha and gamma motor neurons. Also, cyclobenzaprine has activity at spinal cord level at some extent. • Methocarbamol works at the spinal cord level by inhibiting polysynaptic reflex activity.
Onset of action
• within 1 hour • within 30 minutes
Duration of action
• 12 to 24 hours • 4 to 6 hours
•~18 hours (range from 8 hours to 3 days) • 1-2 hours
Metabolism, Elimination
• Cyclobenzaprine is extensively metabolized by the liver via glucoronide conjugation and N-demethylation.
• It is primarily eliminated by the kidneys.
• Excreted in urine, feces.
• Methocarbamol is metabolized by liver via dealkylation and hydroxylation.
• Methocarbamol is eliminated mainly in the urine.
• Hypersensitivity to cyclobenzaprine
• Hyperthyroidism
• Cardiac arrhythmias
• Conduction disturbances
• Congestive heart failure
• Acute recovery phase of myocardial infarction
• Concomitant use with MAO inhibitors - risk of life-threatening interactions with MAO inhibitors
• Hypersensitivity to methocarbamol
• Latex hypersensitivity (for injection)
Side effects
• Drowsiness
• Dry mouth
• Dizziness
• Headache
• Nausea
• Constipation
• Drowsiness
• Loss of physical coordination
• Dizziness
• Black, brown, or green urine
Pregnancy category

Cyclobenzaprine vs Methocarbamol for back pain

Both methocarbamol and cyclobenzaprine effectively relieve symptoms of acute low back pain, including pain intensity, pain-related disability and quality of life1, 2. These muscle relaxants produce sedation, fatigue, and dizziness.


And as a class, the skeletal muscle relaxants (SMRs) include a number of diverse drugs that do not share many similarities other than their intended purpose. This makes it difficult to identify any single drug as the "best muscle relaxant".

The head-to-head trial 3 of cyclobenzaprine versus methocarbamol in patients with localized muscle spasm found that there were no significant differences in the reducing muscle spasm, limitation of motion, and limitation of daily activities.

A slightly greater proportion of patients on cyclobenzaprine reported mild or absent local pain compared to methocarbamol (40% vs. 48%), but only when patients with mild baseline scores were excluded from analysis.

Cyclobenzaprine was associated with more somnolence (58% vs. 31%), but the rate of withdrawals due to side effects was equivalent (7% vs. 6%).

Cyclobenzaprine vs Methocarbamol for Fibromyalgia

Muscle relaxers may be used for fibromyalgia in patients with significant stiffness. Cyclobenzaprine can improve mood and pain symptoms in addition to its improvement of stiffness.

Methocarbamol is less sedating and can be used in persons who do not tolerate cyclobenzaprine. However, evidence for its effectiveness in managing fibromyalgia symptoms is limited.

Further reading


  • 1. Emrich OM, Milachowski KA, Strohmeier M. Methocarbamol in acute low back pain. A randomized double-blind controlled study. MMW Fortschr Med. 2015 Jul;157 Suppl 5:9-16.
  • 2. Überall MA, Emrich OMD, Müller-Schwefe GHH. Real-life efficacy and tolerability of methocarbamol in patients suffering from refractory muscle-related low/back pain. MMW Fortschr Med. 2017 Dec;159(Suppl 7):6-17
  • 3. Preston EJ, Miller CB, Herbertson RK. A double-blind, multicenter trial of methocarbamol (Robaxin) and cyclobenzaprine (Flexeril) in acute musculoskeletal conditions. Todays Ther Trends. 1984;1(4):1–11.

Published: March 31, 2008
Last reviewed: January 26, 2018


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