SUSTIVA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SUSTIVA (SUSTIVA).
Non-nucleoside reverse transcriptase inhibitor (NNRTI) which binds to reverse transcriptase and blocks RNA-dependent and DNA-dependent DNA polymerase activities, causing a conformational change and inhibiting HIV-1 replication.
| Metabolism | Metabolized primarily by cytochrome P450 (CYP) isoenzymes CYP2B6 and CYP3A4/5; it is a moderate inducer of CYP3A4 and a weak inhibitor of CYP2C9 and CYP2C19. |
| Excretion | Fecal (primarily, ~51% as metabolites, ~14% as unchanged drug); renal (~34%, <1% unchanged). |
| Half-life | 42 hours (range 22–72), steady state achieved in ~7–10 days. |
| Protein binding | ~99% bound to albumin and α1-acid glycoprotein. |
| Volume of Distribution | 2.4 L/kg; extensive tissue distribution including CNS (CSF:plasma ratio ~0.01). |
| Bioavailability | Oral: ~42% (capsules) to ~50% (tablets); increased ~50% with high-fat meal. |
| Onset of Action | Oral: 2–4 weeks for maximal virologic response; rapid absorption with peak plasma at 4–5 hours. |
| Duration of Action | 24 hours; sustained suppression with once-daily dosing. |
| Molecular Weight | 315.68 |
600 mg orally once daily, preferably at bedtime to minimize central nervous system symptoms; take on an empty stomach (1 hour before or 2 hours after a meal).
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for renal impairment; hemodialysis does not significantly affect elimination. |
| Liver impairment | Mild hepatic impairment (Child-Pugh A): 600 mg once daily; Moderate hepatic impairment (Child-Pugh B): 400 mg once daily or 200 mg twice daily; Severe hepatic impairment (Child-Pugh C): contraindicated. |
| Pediatric use | For patients ≥3 months and weighing ≥3.5 kg: weight-based dosing capsules or oral solution; 600 mg (tablet) for ≥40 kg; dose formulations vary by weight bands; consult specific guidelines. |
| Geriatric use | No specific dose adjustment required; monitor for CNS symptoms and hepatic function due to age-related changes. |
| 1st trimester | Should be avoided during first trimester unless benefit outweighs risk; teratogenic effects (neural tube defects) reported in animal studies and some human data. |
| 2nd trimester | Use only if clearly needed; monitor for hepatotoxicity and lactic acidosis. |
| 3rd trimester | Use only if clearly needed; monitor for hepatotoxicity and lactic acidosis. |
Clinical note
Comprehensive clinical and safety monograph for SUSTIVA (SUSTIVA).
| Placental transfer | Efavirenz crosses the placenta; cord blood/maternal plasma concentration ratio approximately 0.5-0.9. |
| Breastfeeding | Efavirenz is excreted in human breast milk; potential for adverse effects in nursing infant (CNS toxicity, hepatotoxicity) and risk of viral resistance if mother is viremic. Breastfeeding not recommended in HIV-infected mothers in settings where formula is available. |
■ FDA Black Box Warning
Efavirenz can cause hepatotoxicity, including severe hepatic necrosis and hepatic failure. Discontinue if liver toxicity is suspected. Contraindicated in patients with moderate to severe hepatic impairment (Child-Pugh Class B or C).
| Serious Effects |
Hypersensitivity to efavirenz or any excipientConcomitant use with terfenadine, astemizole, cisapride, midazolam, triazolam, ergot derivatives, pimozide, or St. John's wortSevere hepatic impairment (Child-Pugh class C)
| Precautions | Hepatotoxicity (monitor liver enzymes), psychiatric symptoms (including depression, suicidal ideation, psychosis), severe skin reactions (e.g., Stevens-Johnson syndrome), immune reconstitution syndrome, fat redistribution, hyperlipidemia, decreased bone mineral density, convulsions (use with caution in patients with history of seizures), and potential for drug interactions. |
| Food/Dietary | High-fat meals increase absorption and risk of side effects; take on empty stomach. Avoid grapefruit juice? Not significant; no known interaction. St. John's Wort reduces efavirenz levels and is contraindicated. |
Loading safety data…
| Lactation Rating | L4 |
| Teratogenic Risk | FDA Pregnancy Category D. There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use in pregnant women despite potential risks. Efavirenz is associated with an increased risk of neural tube defects when administered during the first trimester. Animal studies have shown increased fetal resorptions and malformations. Use only if benefit outweighs risk, and avoid during first trimester if possible. |
| Fetal Monitoring | Monitor maternal liver function tests, lipid profile, and CD4 count. Perform pregnancy testing before initiation. In pregnant women, perform fetal ultrasound during first trimester to detect neural tube defects. Monitor for signs of teratogenicity and neonatal toxicity (e.g., CNS effects, hyperbilirubinemia). Monitor infant for HIV status and adverse effects postnatally. |
| Fertility Effects | Efavirenz does not appear to significantly impair fertility in animal studies. In humans, limited data suggest no major impact on male or female fertility. However, hormonal contraceptives may be less effective due to enzyme induction; use additional barrier methods. |
| Clinical Pearls | Administer on empty stomach, preferably at bedtime to minimize CNS side effects. High-fat meals increase absorption and toxicity. Avoid in patients with history of psychiatric disorders. Monitor for rash, particularly during first 2 weeks. Contraindicated with certain benzodiazepines, ergots, and St. John's Wort. |
| Patient Advice | Take exactly as prescribed; do not miss doses to prevent drug resistance. · Take on an empty stomach (1 hour before or 2 hours after a meal). · Taking at bedtime may reduce dizziness or vivid dreams. · Report any rash immediately; could be serious. · This drug does not cure HIV or prevent transmission. · Avoid alcohol and illegal drugs. · Tell your doctor about all medications, including herbal supplements. · Women of childbearing potential: use effective contraception; efavirenz may reduce effectiveness of hormonal contraceptives. |