efavirenz
Brand: Sustiva, Atripla (combination)
Prototype Drug
Drug Class: non-nucleoside reverse transcriptase inhibitor (NNRTI)
Drug Family: antiretroviral
Subclass: first-generation NNRTI
Organ Systems: infectious-disease
Mechanism of Action
Binds a hydrophobic pocket near the active site of HIV-1 reverse transcriptase, causing conformational change and blocking polymerization; resistance develops rapidly if used as monotherapy.
HIV reverse transcriptase (non-nucleoside binding site)
Indications
- HIV-1 infection (part of combination ART regimen)
Contraindications
- efavirenz hypersensitivity
- pregnancy (especially first trimester — neural tube defects)
- concurrent use with voriconazole (reduces voriconazole by >75%)
Adverse Effects
Common
- CNS/neuropsychiatric effects (dizziness, insomnia, vivid dreams, impaired concentration — often in first 2–4 weeks)
- rash
- elevated cholesterol
Serious
- severe CNS depression or psychiatric disturbances (psychosis, suicidal ideation)
- hepatotoxicity
- Stevens-Johnson syndrome (rare)
- neural tube defects (first trimester exposure)
Pharmacokinetics (ADME)
| Absorption | 50% oral bioavailability; high-fat meal increases Cmax by 50% — take on empty stomach to reduce CNS adverse effects |
| Distribution | large Vd; highly protein-bound; crosses placenta |
| Metabolism | CYP2B6 (primary), CYP3A4; both substrate and inducer of CYP3A4 |
| Excretion | fecal (16–61%) and renal (14–34%) |
| Half-life | 40–55 hours |
| Onset | 3–5 hours |
| Peak | 3–5 hours |
| Duration | 24 hours |
| Protein Binding | >99% |
| Vd | large |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| voriconazole | CYP3A4 induction reduces voriconazole by 77% and voriconazole increases efavirenz; contraindicated combination | major |
| methadone | CYP3A4 induction reduces methadone levels; opioid withdrawal | major |
| hormonal contraceptives | CYP3A4 induction reduces OCP levels; use alternative contraception | major |
Nursing Considerations
- Administer at bedtime on an empty stomach to minimize CNS adverse effects; drowsiness from the CNS effects may actually help patients sleep during the first few weeks.
- Counsel patients that neuropsychiatric symptoms (vivid dreams, dizziness, concentration difficulties) are common in the first 2–4 weeks but usually diminish; instruct to report suicidal thoughts immediately.
- Use with extreme caution in women who may become pregnant; requires reliable contraception.
- Monitor lipid panel; efavirenz raises total cholesterol and triglycerides.
Clinical Pearls
- Efavirenz was a cornerstone of HIV treatment for 20 years but has been largely supplanted by integrase strand transfer inhibitors (dolutegravir, bictegravir) which have fewer CNS side effects, better resistance barriers, and fewer drug interactions.
- The CNS adverse effects of efavirenz (vivid dreams, insomnia, dissociation) are related to CYP2B6 genotype — slow CYP2B6 metabolizers have higher drug exposure and more CNS toxicity.
Safety Profile
Pregnancy avoid
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Guideline Update pending
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.