CYP2B6 and Efavirenz

Ultrarapid Metabolizer

Clinical Implication

  • Increased CYP2B6 enzyme activity.
  • Slightly lower dose-adjusted trough concentrations.

Therapeutic Recommendation

  • Initiate efavirenz with standard dosing (600 mg/day).

Rapid Metabolizer

Clinical Implication

  • Increased CYP2B6 enzyme activity.
  • Slightly lower dose-adjusted trough concentrations.

Therapeutic Recommendation

  • Initiate efavirenz with standard dosing (600 mg/day).

Normal Metabolizer

Clinical Implication

  • Normal CYP2B6 enzyme activity.
  • Normal response expected.

Therapeutic Recommendation

  • Initiate efavirenz with standard dosing (600 mg/day).

Intermediate Metabolizer

Clinical Implication

  • Decreased CYP2B6 enzyme activity.
  • Increased risk of CNS adverse effects (e.g., insomnia, impaired concentration, psychosis, suicidal ideation, depression).

Therapeutic Recommendation

  • Initiate efavirenz with decreased dose of 400 mg/day and consider utilizing therapeutic drug monitoring, if available.

Poor Metabolizer

Clinical Implication

  • Little to no CYP2B6 enzyme activity.
  • Significantly increased risk of CNS adverse effects (e.g., insomnia, impaired concentration, psychosis, suicidal ideation, depression).

Therapeutic Recommendation

  • Initiate efavirenz with decreased dose of 400 or 200 mg/day and consider utilizing therapeutic drug monitoring, if available.

Unable to Genotype or Assay Failure

  • The analysis failed to yield an informative result and thus no genotype is reported.

Reference

  • Desta Z et al. Clin Pharmacol Ther. 2019 Oct;106(4):726-733. PMID: 31006110.

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