Metaxalone (Skelaxin): A Centrally Acting Skeletal Muscle Relaxant
Metaxalone (Skelaxin) is an oral centrally acting skeletal muscle relaxant that does not act directly on skeletal muscle and is primarily used as an adjunct treatment for acute, painful musculoskeletal conditions. The precise mechanism of action of metaxalone is unclear, but it may be related to its sedative properties rather than direct muscle relaxation. 1, 2
Indications and Usage
- Metaxalone is indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomforts associated with acute, painful musculoskeletal conditions 1
- It is commonly used for skeletal pain, myalgias, and arthralgias 2
- Unlike some other muscle relaxants, metaxalone is not classified as a controlled substance 2
Pharmacology and Pharmacokinetics
- Chemical structure: 5-[(3,5-dimethylphenoxy)methyl]-2-oxazolidinone with a molecular weight of 221.25 1
- Absorption is significantly increased when taken with food (high-fat meal increases bioavailability by approximately 115-142%) 1
- Half-life ranges from 8-9 hours under fasted conditions 1
- Metabolized by the liver via multiple cytochrome P450 enzymes (CYP1A2, CYP2D6, CYP2E1, and CYP3A4) 1
- Bioavailability is higher in females compared to males and increases with age 1
Dosing
- Available as 800 mg tablets 1
- Standard dosing is typically 800 mg three to four times daily 1
- Should be used with caution in patients with significant hepatic or renal dysfunction 2, 1
Adverse Effects
- Central nervous system effects are most common: drowsiness, dizziness, and irritability 2
- Other reported adverse effects include headache, nausea, and gastrointestinal upset 3, 4
- At higher doses (>2400 mg), more serious adverse effects may occur, including tachycardia, agitation, slurred speech, and tremor 3
- Recent evidence suggests potential serotonergic effects at supratherapeutic concentrations, with risk of serotonin syndrome when combined with SSRIs 5
Precautions and Contraindications
- Contraindicated in patients with significant hepatic or renal dysfunction 2
- Has been associated with drug-induced, hemolytic, or other anemias 2
- Should be held on the day of surgical procedures 2
- Use with caution in elderly patients due to increased risk of central nervous system effects 2
- Should not be used for chronic pain management in older adults 2
Efficacy
- Evidence for efficacy in musculoskeletal conditions is limited compared to other muscle relaxants 6
- Cyclobenzaprine has been evaluated in more clinical trials and has more consistently been found effective for musculoskeletal pain 6
- There is insufficient evidence to determine the relative efficacy of metaxalone compared to other muscle relaxants 6
- Not recommended for chronic pain management in older adults due to limited evidence of efficacy and potential for adverse effects 2
- No evidence of efficacy for pain management in rheumatoid arthritis 7
Clinical Considerations
- When prescribing for acute musculoskeletal pain, consider metaxalone as part of a multimodal approach that includes physical therapy and other non-pharmacological interventions 1
- For perioperative management, metaxalone should be held on the day of surgery 2
- In patients with cardiovascular disease, metaxalone may be preferable to other muscle relaxants with more significant cardiovascular effects 2
- Avoid use for chronic pain conditions where evidence is lacking 2
- Monitor for signs of hepatic dysfunction during treatment 2
Safety Profile Compared to Other Muscle Relaxants
- Metaxalone has fewer reported side effects compared to carisoprodol (which has abuse potential) and cyclobenzaprine (which has significant anticholinergic effects) 4
- Unlike carisoprodol, metaxalone is not classified as a controlled substance and has less potential for dependence 2
- Unlike cyclobenzaprine, metaxalone does not have significant anticholinergic properties 2
- However, metaxalone is contraindicated in significant hepatic or renal dysfunction, which may limit its use in certain populations 2