What are the potential drug interactions of metaxolone, particularly with central nervous system (CNS) depressants?

Drug Interactions of Metaxalone

Metaxalone has significant potential for additive sedative effects when combined with CNS depressants, and at toxic concentrations can cause serotonin syndrome through MAO-A inhibition when used with serotonergic medications. Caution should be exercised with patients who take metaxalone simultaneously with other CNS depressants due to their additive sedative effects. 1

Key Drug Interactions

CNS Depressant Interactions

• Metaxalone has additive sedative effects when combined with other CNS depressants including alcohol, benzodiazepines, opioids, and tricyclic antidepressants 1
• The sedative effects may be particularly pronounced in elderly patients, who are especially susceptible to CNS depression 1
• Taking metaxalone with food may enhance general CNS depression, further increasing risk 1
• Due to these interactions, metaxalone should be held on the day of surgical procedures to avoid potentiating anesthetic agents 2

Serotonergic Drug Interactions

• At supratherapeutic or overdose concentrations, metaxalone demonstrates significant dose-related inhibition of monoamine oxidase A (MAO-A) 3
• This MAO-A inhibition can lead to serotonin syndrome when combined with serotonergic medications such as SSRIs 4, 3
• Case reports document severe serotonin toxicity in patients taking both metaxalone and SSRIs (escitalopram, paroxetine) 4
• Symptoms of serotonin syndrome include hyperthermia, rigidity, myoclonus, hyperreflexia, and altered mental status 4

Specific High-Risk Combinations

• Metaxalone + SSRIs: Risk of serotonin syndrome, particularly at high metaxalone concentrations 4, 3
• Metaxalone + alcohol: Enhanced CNS depression with increased risk of impaired psychomotor function 1, 5
• Metaxalone + opioids: Additive sedative effects with increased risk of respiratory depression 1
• Metaxalone + benzodiazepines: Potentiated sedation and impairment 1

Clinical Considerations and Precautions

Patient Monitoring

• Monitor for excessive sedation when metaxalone is combined with other CNS depressants 1
• Be vigilant for signs of serotonin syndrome (hyperthermia, rigidity, myoclonus) when metaxalone is used with serotonergic medications 4
• Patients with hepatic or renal impairment may have altered metaxalone metabolism, potentially increasing interaction risks 2

Special Populations

• Elderly patients are at increased risk for CNS effects and should be monitored closely 1
• Metaxalone is contraindicated in patients with significant hepatic or renal dysfunction 2
• Safety has not been established in children 12 years of age and below 1

Perioperative Considerations

• Metaxalone should be held on the day of surgical procedures 2
• The combination with anesthetic agents may increase risk of excessive sedation 2

Management of Drug Interactions

Preventive Strategies

• Consider alternative muscle relaxants when patients are on multiple CNS depressants 6
• Avoid combining metaxalone with MAOIs or multiple serotonergic medications 4, 3
• Counsel patients to avoid alcohol while taking metaxalone 1
• Advise patients about potential impairment of mental and physical abilities required for hazardous tasks 1

Management of Adverse Effects

• For serotonin syndrome: discontinue metaxalone and serotonergic agents, provide supportive care, consider benzodiazepines for muscle rigidity 4
• For excessive sedation: supportive care and close monitoring of respiratory status 1

Compared to other commonly prescribed skeletal muscle relaxants, metaxalone has fewer reported side effects than cyclobenzaprine or carisoprodol, but its potential for serious drug interactions, particularly at toxic concentrations, should not be underestimated 6.