EFAVIRENZ
Clinical safety rating: avoid
Contraindicated (not allowed)
Non-nucleoside reverse transcriptase inhibitor (NNRTI) that binds to and inhibits HIV-1 reverse transcriptase, blocking RNA-dependent and DNA-dependent DNA polymerase activities.
| Metabolism | Primarily metabolized by CYP2B6 and to a lesser extent by CYP3A4 and CYP2A6; forms inactive metabolites. |
| Excretion | Efavirenz is primarily metabolized by the liver via CYP2B6 and CYP3A4/5. Renal excretion of unchanged drug is minimal (<1%). Approximately 14-34% of a dose is recovered in urine as metabolites, and 16-61% in feces as unchanged drug or metabolites. |
| Half-life | Terminal elimination half-life is approximately 52-76 hours after single doses and 40-55 hours after multiple doses. The long half-life supports once-daily dosing and allows for steady-state concentrations within 6-10 days. |
| Protein binding | Efavirenz is approximately 99.5-99.75% bound to plasma proteins, mainly albumin. |
| Volume of Distribution | Apparent volume of distribution (Vd/F) is approximately 2.4 L/kg, indicating extensive tissue distribution and penetration into tissues including the CNS (cerebrospinal fluid concentrations are about 0.5-1% of plasma concentrations). |
| Bioavailability | Oral bioavailability is approximately 40-45% under fasted conditions. Administration with food, especially high-fat meals, increases absorption (AUC increased by about 50%) and may reduce peak concentrations due to delayed absorption. |
| Onset of Action | Oral: Antiviral effect begins within 1-2 weeks; maximal virologic suppression typically by 12-24 weeks when used in combination therapy. |
| Duration of Action | Duration of antiviral effect persists for the dosing interval (24 hours) due to sustained plasma concentrations above the protein-adjusted IC95 (0.6-1.2 mg/L). The long half-life provides drug concentrations for days after discontinuation, which may select for resistance if not replaced. |
| Molecular Weight | 315.68 |
600 mg orally once daily, taken on an empty stomach, preferably at bedtime.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for any degree of renal impairment including hemodialysis. |
| Liver impairment | Child-Pugh Class A: 600 mg once daily; Child-Pugh Class B: 400 mg once daily; Child-Pugh Class C: not recommended (contraindicated). |
| Pediatric use | For patients weighing ≥40 kg: 600 mg once daily; 32.5 to <40 kg: 400 mg once daily; 25 to <32.5 kg: 350 mg once daily; 17.5 to <25 kg: 300 mg once daily; 15 to <17.5 kg: 250 mg once daily; 10 to <15 kg: 200 mg once daily; 5 to <10 kg: 150 mg once daily. Administer as oral solution or capsules; for children ≥3 months and weighing 3.5 to <5 kg: 100 mg once daily. |
| Geriatric use | No specific dose adjustment is recommended; however, caution is advised due to age-related decreases in hepatic function and increased sensitivity to central nervous system effects. Monitor for neuropsychiatric adverse effects and consider bedtime dosing. |
| 1st trimester | Teratogenic in animal studies; human data show neural tube defects and other malformations. Avoid in first trimester unless benefit outweighs risk. |
| 2nd trimester | Use only if clearly needed; limited human data, but risk of teratogenicity persists throughout pregnancy. |
| 3rd trimester | Avoid use unless no alternative; may cause neonatal toxicity including CNS depression, hyperbilirubinemia. |
Clinical note
Induces CYP3A4 and inhibits CYP2C9/CYP2C19 affecting many drugs Can cause severe psychiatric symptoms and rash.
| Placental transfer | Crosses placenta extensively; fetal concentrations approximate maternal levels. |
| Breastfeeding | Efavirenz is excreted in human milk at low levels. Potential for adverse effects in nursing infant including CNS effects, hepatotoxicity. No data on long-term effects. Avoid breastfeeding while on efavirenz. |
■ FDA Black Box Warning
May cause severe, life-threatening hepatotoxicity; monitor hepatic function closely. Contraindicated in patients with moderate to severe hepatic impairment.
| Common Effects | Rash |
| Serious Effects |
Hypersensitivity to efavirenz or any componentConcomitant use with elbasvir/grazoprevir due to risk of ALT elevations
| Precautions | Hepatotoxicity: monitor LFTs; discontinue if severe, Psychiatric symptoms: may cause depression, suicidal ideation, psychosis, Skin rash: usually mild to moderate; monitor for severe reactions, CNS effects: dizziness, insomnia, impaired concentration; avoid driving, Fetal risk: avoid pregnancy; use effective contraception |
| Food/Dietary | Efavirenz should be taken on an empty stomach, at least 1 hour before or 2 hours after a meal, as high-fat meals increase absorption and may worsen CNS side effects. Avoid grapefruit juice as it may increase drug levels. |
Loading safety data…
| Lactation Rating | L4 (Hazardous) |
| Teratogenic Risk | First trimester: Significant risk of neural tube defects (1.4-2.9% incidence) based on animal and human data. Avoid in first trimester unless no alternative. Second/third trimester: No association with major malformations but monitor for infant toxicity. Efavirenz is considered contraindicated in pregnancy. |
| Fetal Monitoring | Monitor liver function tests due to hepatotoxicity risk; monitor for rash (Stevens-Johnson syndrome); assess neuropsychiatric effects (dizziness, insomnia). In pregnancy, fetal ultrasound for neural tube defects; consider therapeutic drug monitoring. |
| Fertility Effects | No significant adverse effects on fertility reported in human studies. In animal studies, no impairment of fertility observed at clinically relevant doses. |
| Clinical Pearls | Efavirenz is a potent non-nucleoside reverse transcriptase inhibitor (NNRTI) used in combination antiretroviral therapy (ART). It is associated with central nervous system (CNS) side effects such as dizziness, insomnia, and vivid dreams, which often improve within 2-4 weeks. Administer on an empty stomach, preferably at bedtime, to reduce CNS toxicity. Avoid in pregnancy (first trimester) due to teratogenicity; consider alternative if patient is trying to conceive. Efavirenz induces CYP3A4 and CYP2B6, leading to multiple drug interactions; check co-medications for dose adjustments. Monitor for rash (common, usually mild), hepatotoxicity, and lipid abnormalities. Genetic variants in CYP2B6 affect metabolism; slow metabolizers may have higher drug levels and increased CNS effects. |
| Patient Advice | Take efavirenz exactly as prescribed, usually once daily on an empty stomach at bedtime to reduce dizziness and sleep disturbances. · Do not miss doses; if you miss a dose, take it as soon as you remember unless it is almost time for the next dose. Do not double up. · Common side effects include dizziness, trouble sleeping, vivid dreams, and rash. These often improve after 2-4 weeks. Contact your doctor if side effects are severe or persist. · Avoid alcoholic beverages as they may worsen side effects. · Efavirenz can interact with many other drugs, including herbal supplements (e.g., St. John's wort) and birth control pills. Use a non-hormonal method of contraception to prevent pregnancy. · Report any signs of liver problems (yellowing of skin or eyes, dark urine, abdominal pain) or severe skin rash with blistering immediately. · Do not breastfeed while taking this medication as it passes into breast milk and may harm the baby. · Take with a full glass of water; Do not crush or chew the tablets. |