Is sertraline (Zoloft) contraindicated with chlorzoxazone?

Sertraline and Chlorzoxazone: Potential Interaction Assessment

Sertraline is not contraindicated with chlorzoxazone, but caution should be exercised due to potential pharmacokinetic interactions.

Mechanism of Potential Interaction

• Sertraline is a selective serotonin reuptake inhibitor (SSRI) that has minimal inhibitory effects on major cytochrome P450 enzymes, though it may interact with drugs metabolized by CYP2D6 1, 2
• Chlorzoxazone is a centrally acting muscle relaxant that is metabolized primarily by CYP2E1 3
• The primary concern would be a pharmacokinetic interaction, as studies have shown that inhibition of CYP2E1 can increase chlorzoxazone levels 3

Safety Assessment

• Unlike monoamine oxidase inhibitors (MAOIs), which are absolutely contraindicated with sertraline due to risk of serotonin syndrome, chlorzoxazone does not have a documented contraindication with sertraline 1
• Sertraline has been shown to have fewer drug-drug interactions compared to other SSRIs such as fluvoxamine, which affects multiple CYP enzymes 1, 2
• The 2019 American Geriatrics Society Beers Criteria lists chlorzoxazone as a potentially inappropriate medication in older adults due to anticholinergic effects, but does not specifically contraindicate its use with sertraline 1

Monitoring Recommendations

• Monitor for potential signs of increased chlorzoxazone effects, which may include:

  • Enhanced sedation or drowsiness 1
  • Dizziness or impaired coordination 1
  • Potential for increased anticholinergic effects 1

• If both medications are necessary, consider:

  • Starting with lower doses of both medications 1
  • Monitoring more frequently during the initial period of co-administration, especially in the first 24-48 hours 1
  • Being particularly cautious in elderly patients or those with hepatic impairment 1

Important Distinctions

• This combination is distinctly different from the absolute contraindication of sertraline with MAOIs, which can cause potentially fatal serotonin syndrome 1, 4
• Chlorzoxazone is not known to have significant serotonergic properties that would increase risk of serotonin syndrome when combined with sertraline 5
• While sertraline may interact with drugs metabolized by CYP2D6, chlorzoxazone is primarily metabolized by CYP2E1, suggesting a lower risk of significant interaction 1, 3

Clinical Perspective

• Sertraline is generally well-tolerated in therapeutic dosages and relatively safe even in overdose situations compared to many other psychotropic medications 2, 6
• When prescribing muscle relaxants with sertraline, consider alternatives to chlorzoxazone if there are concerns about potential interactions 1
• The benefit-to-risk ratio should be evaluated, particularly in older adults where chlorzoxazone is generally considered potentially inappropriate regardless of co-medications 1