Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used as a core component of first-line antiretroviral therapy (ART) for HIV-1 infection. It is a once-daily medication, often combined with two nucleoside reverse transcriptase inhibitors (NRTIs). Its use is characterized by a high genetic barrier to resistance when used in combination therapy, but it is associated with central nervous system (CNS) side effects and potential teratogenicity.
Adult: 600 mg orally once daily, on an empty stomach, preferably at bedtime to improve tolerability of CNS side effects.
Note: Take on an empty stomach, preferably at bedtime. Swallow the tablet whole with water. Taking it with a high-fat meal increases absorption and may worsen side effects. For patients unable to swallow tablets, the tablet can be dispersed in a small amount of water (or infant formula/breast milk for pediatric patients). The resulting dispersion should be administered immediately, and the cup rinsed and the rinse also administered to ensure full dose.
Efavirenz is a non-competitive inhibitor of HIV-1 reverse transcriptase (RT). It binds to a hydrophobic pocket (allosteric site) on the p66 subunit of the RT enzyme, distinct from the active site used by nucleoside analogues. This binding induces a conformational change that disrupts the enzyme's catalytic activity, thereby blocking the conversion of viral RNA into DNA, a critical step in the HIV replication cycle.
Pregnancy: Pregnancy Category D. Use in the first trimester is associated with a risk of neural tube defects. Should not be used in women of childbearing potential unless they are using effective contraception and are not pregnant. For women already on a stable efavirenz regimen who become pregnant, continuation may be considered after the first trimester after detailed counseling, as the risk of neural tube defects is primarily in the first trimester. Alternative regimens (e.g., based on dolutegravir or ritonavir-boosted atazanavir) are preferred in pregnancy.
Driving: May cause dizziness, impaired concentration, and somnolence. Patients should be cautioned about driving or operating machinery, especially during the first 2-4 weeks of therapy or if dose is increased.
| Rifampicin | Decreases efavirenz plasma levels; may require efavirenz dose increase to 800 mg (under expert supervision). | Major |
| Voriconazole | Efavirenz decreases voriconazole levels; voriconazole increases efavirenz levels. Coadministration is contraindicated. | Contraindicated |
| Clarithromycin | Efavirenz decreases clarithromycin levels; azithromycin is preferred. | Major |
| Warfarin | Efavirenz may alter warfarin levels; requires close INR monitoring. | Moderate |
| Carbamazepine/Phenytoin/Phenobarbital | Decrease efavirenz plasma levels; alternative anticonvulsants (e.g., levetiracetam) are preferred. | Major |
| Atorvastatin/Simvastatin | Efavirenz decreases statin levels; may require dose adjustment of statin. Pravastatin or rosuvastatin are less affected. | Moderate |
| Ethinyl Estradiol (oral contraceptives) | Efavirenz may reduce contraceptive hormone levels; barrier methods or alternative/non-hormonal contraception is strongly advised. | Major |
| Artemether/Lumefantrine | Efavirenz may decrease lumefantrine levels, potentially reducing antimalarial efficacy. | Moderate |
| Methadone | Efavirenz induces methadone metabolism, leading to withdrawal symptoms; methadone dose may need significant increase. | Major |
| Ritonavir-boosted Protease Inhibitors (e.g., Lopinavir/r, Atazanavir/r) | Complex bidirectional interactions; efavirenz decreases levels of some PIs, and ritonavir may increase efavirenz levels. Specific dose adjustments required. | Major |