EFAVIRENZ 200MG SCORED TABLETS
Clinical safety rating: avoid
Induces CYP3A4 and inhibits CYP2C9/CYP2C19 affecting many drugs Can cause severe psychiatric symptoms and rash.
Non-nucleoside reverse transcriptase inhibitor (NNRTI); binds to reverse transcriptase, causing conformational change and inhibiting RNA-dependent and DNA-dependent DNA polymerase activity.
| Metabolism | Primarily metabolized by CYP2B6 and to a lesser extent CYP3A4, CYP2A6, and CYP1A2. |
| Excretion | Primarily hepatic metabolism via CYP2B6 and CYP3A4/5; <1% excreted unchanged in urine; ~14-34% of dose recovered in feces as metabolites; <1% in bile. |
| Half-life | Terminal half-life: 40-55 hours after single dose; 52-76 hours after multiple doses due to autoinduction; clinical context: allows once-daily dosing, but steady-state reached in 2-3 weeks; extended half-life in CYP2B6 poor metabolizers. |
| Protein binding | 99.5-99.75% bound, primarily to albumin (98-99%) and also to alpha-1-acid glycoprotein. |
| Volume of Distribution | 252-420 L (3.6-6.0 L/kg), indicating extensive tissue distribution; crosses blood-brain barrier with CSF concentrations 0.26-1.19% of plasma; high Vd contributes to long half-life. |
| Bioavailability | Oral bioavailability: 40-48% under fed conditions (high-fat meal increases absorption); take on empty stomach to reduce side effects; absolute bioavailability not determined due to lack of IV formulation. |
| Onset of Action | Oral: Plasma concentrations above therapeutic threshold (1 mg/L) achieved within 2-4 hours; antiviral effect begins within 24-48 hours of first dose. |
| Duration of Action | Approximately 24 hours with once-daily dosing; due to long half-life, missed doses up to 1-2 days may not significantly reduce efficacy, but consistent adherence is critical. |
| Molecular Weight | 315.68 |
600 mg orally once daily, on an empty stomach, preferably at bedtime.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for renal impairment, including hemodialysis. |
| Liver impairment | Child-Pugh Class A: 600 mg daily. Child-Pugh Class B: 400 mg daily. Child-Pugh Class C: contraindicated. |
| Pediatric use | Body weight 10-<15 kg: 200 mg once daily; 15-<20 kg: 250 mg; 20-<25 kg: 300 mg; 25-<32.5 kg: 350 mg; 32.5-<40 kg: 400 mg; ≥40 kg: 600 mg. |
| Geriatric use | No specific dose adjustment, but monitor for CNS effects and hepatic function due to increased sensitivity. |
| 1st trimester | Avoid: associated with neural tube defects in first trimester; use only if benefit outweighs risk. Effective contraception required. |
| 2nd trimester | Caution: limited data; use if alternatives unsuitable. Monitor for adverse effects. |
| 3rd trimester | Caution: risk of neonatal CNS depression, hyperbilirubinemia, and hepatic toxicity; monitor neonate. |
Clinical note
Induces CYP3A4 and inhibits CYP2C9/CYP2C19 affecting many drugs Can cause severe psychiatric symptoms and rash.
| FDA category | Contraindicated |
| Placental transfer | Crosses placenta readily; fetal concentrations reach maternal levels. |
| Breastfeeding |
■ FDA Black Box Warning
Not recommended for use in patients with moderate to severe hepatic impairment (Child-Pugh class B or C).
| Common Effects | Rash |
| Serious Effects |
Concomitant use with certain drugs (e.g., astemizole, terfenadine, ergot derivatives, midazolam, triazolam, cisapride, pimozide, St. John's wort)Severe hepatic impairment (Child-Pugh class C)
| Precautions | Hepatotoxicity, Psychiatric symptoms (severe depression, suicidal ideation), Nervous system symptoms (dizziness, insomnia, somnolence), Seizures, Rash (including Stevens-Johnson syndrome), Lipid elevation, Redistribution/accumulation of body fat, Embryo-fetal toxicity, Contraindicated with CYP3A4 inducers/inhibitors that may reduce efavirenz exposure |
| Food/Dietary | Avoid high-fat meals (e.g., fatty foods, fried items) as they increase drug absorption and risk of side effects. Take on an empty stomach, at least 1 hour before or 2 hours after a meal. |
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| Excreted into breast milk in concentrations similar to maternal plasma; potential for infant CNS effects. Consider risk/benefit; alternative agents may be preferred. |
| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | FDA Pregnancy Category D. First trimester exposure associated with neural tube defects (e.g., myelomeningocele, anencephaly) at an incidence of 0.5-1.0%. Second and third trimester risks include decreased fetal growth and preterm delivery. Contraindicated in pregnancy unless no alternative. |
| Fetal Monitoring | Monitor maternal liver function tests, HIV RNA, CD4 count, and adverse effects. Perform fetal ultrasound for neural tube defects if exposure occurs in first trimester. Monitor for maternal hepatotoxicity and rash. |
| Fertility Effects | No known adverse effects on fertility in animal studies. Human data limited; consider hormonal contraceptive interactions (reduces ethinyl estradiol levels). |
| Clinical Pearls | Take on an empty stomach to reduce side effects; avoid high-fat meals as they increase absorption and toxicity. Monitor for CNS symptoms (dizziness, insomnia) which often improve after 2-4 weeks. Contraindicated in pregnancy (category D); test for pregnancy before initiation. Use with caution in patients with hepatic impairment. May cause false positive urine cannabinoid tests. |
| Patient Advice | Take this medication on an empty stomach, preferably at bedtime, to reduce dizziness and sleep problems. · Do not take with high-fat meals as they can increase the risk of side effects. · Common side effects include dizziness, trouble sleeping, drowsiness, trouble concentrating, and vivid dreams. These usually improve after the first few weeks. · This medication does not cure HIV or prevent transmission to others. Continue safe sex practices. · Avoid alcohol and recreational drugs as they may worsen side effects. · Tell your doctor if you are pregnant or plan to become pregnant; this medicine can harm an unborn baby. · Use effective birth control while taking this medication. · Report any signs of liver problems: yellowing of skin or eyes, dark urine, or persistent nausea. |