Starting Dose of Metaxalone
The standard starting dose of metaxalone for adults is 800 mg taken orally three to four times daily.
Standard Dosing Regimen
Based on the available evidence and clinical practice patterns:
- Metaxalone is typically initiated at 800 mg orally, administered 3-4 times daily as needed for acute musculoskeletal conditions 1
- The medication can be taken with or without food, though administration with food may enhance absorption
- Dosing is generally on an as-needed basis rather than scheduled around-the-clock 1
Clinical Context and Efficacy Considerations
Important caveat: Recent high-quality evidence questions the clinical benefit of adding metaxalone to NSAIDs. A 2019 randomized, placebo-controlled trial in the Annals of Emergency Medicine found that metaxalone 400 mg (1-2 capsules three times daily) added to ibuprofen provided no additional improvement in functional outcomes or pain compared to ibuprofen plus placebo for acute low back pain 1. At one week, both groups showed similar improvements in Roland-Morris Disability Questionnaire scores (10.1 points for metaxalone vs 11.1 points for placebo) and similar rates of moderate-to-severe pain (37% vs 30%) 1.
Safety Considerations
Clinicians must be aware of serious drug interactions, particularly with serotonergic medications:
- Metaxalone can cause serotonin syndrome when combined with SSRIs or other serotonergic drugs, even at therapeutic doses 2, 3
- At toxic concentrations (31-61 mcg/mL), metaxalone demonstrates significant monoamine oxidase A (MAO-A) inhibition, which explains the mechanism of serotonin toxicity 2, 3
- Common adverse effects at therapeutic doses include drowsiness (27.9%), tachycardia (6.6%), agitation (6.6%), and dizziness (4.9%) 4
Overdose Risk Profile
- Ingestions exceeding 2400 mg are associated with more serious medical outcomes and typically require healthcare facility management 4
- Moderate adverse effects occurred in 20.5% of ingestions >2400 mg compared to 13.6% of ingestions ≤2400 mg 4
- Toxic presentations may include altered mental status, hyperthermia, rigidity, myoclonus, and hyperreflexia 2
Practical Prescribing Algorithm
When considering metaxalone:
- Screen for concurrent serotonergic medications (SSRIs, SNRIs, MAOIs, tramadol, etc.) - if present, strongly consider alternative muscle relaxants 2, 3
- Start with 800 mg orally 3-4 times daily as needed for acute musculoskeletal pain
- Counsel patients on drowsiness risk and avoid driving/operating machinery until response is known 4
- Limit duration to short-term use (typically 2-3 weeks) for acute conditions 1
- Consider that monotherapy with NSAIDs may be equally effective based on recent evidence 1