efavirenz
HIV non-nucleoside reverse transcriptase inhibitor· Brands: Sustiva, StocrinPO
Mechanism of action
Efavirenz is a non-nucleoside reverse transcriptase inhibitor. It binds directly to a hydrophobic pocket near the catalytic site of HIV-1 reverse transcriptase, inducing a conformational change that inhibits the enzyme's activity. This prevents the transcription of viral RNA into DNA, thereby blocking viral replication. It is active against HIV-1 but not HIV-2, and requires no intracellular phosphorylation for activation.
Pharmacokinetics
Oral bioavailability is approximately 40 to 50% and is increased by a high-fat meal, which raises exposure and peak concentrations. Efavirenz is extensively bound to plasma proteins (99%) and has a long elimination half-life of 40 to 55 hours, permitting once-daily dosing. It is metabolised primarily by cytochrome P450 enzymes CYP2B6 and CYP3A4, and it induces both CYP3A4 and CYP2B6, causing clinically significant drug interactions. Approximately 14 to 34% of a dose is excreted in urine as metabolites, with the remainder in faeces. It penetrates well into cerebrospinal fluid.
Indications & dosing
Treatment of HIV-1 infection (in combination with other antiretrovirals) in adults
Take on an empty stomach. May be taken with food if gastrointestinal upset occurs. Use with caution in patients with psychiatric history.
- adult · PO: 600 mg once daily · Take on an empty stomach, preferably at bedtime; food increases absorption and CNS adverse effects, so avoid taking with food. Use with caution in patients with psychiatric history.
Treatment of HIV-1 infection (in combination with other antiretrovirals) in children
Weight-based dosing: 100-600 mg once daily depending on body weight. Not recommended for children <3.5 kg.
- pediatric · PO: 100–600 mg once daily · Weight-based dosing: 100-600 mg once daily depending on body weight. Not recommended for children <3 years of age or <10 kg.
Post-exposure prophylaxis of HIV-1 infection (in combination with other antiretrovirals)off-label
Not a preferred agent; consider alternatives. Duration is typically 28 days.
- adult · PO: 600 mg once daily · Not a preferred agent; consider alternatives. Duration is typically 28 days.
Interactions
- methadonemajorMonitor patients closely for signs of opioid withdrawal when starting efavirenz. An increase in the methadone dose may be necessary; dose should be titrated based on clinical response. Reassess after stopping efavirenz, as methadone levels may rise.
Renal & hepatic adjustment
- Hepatic impairment (mild): No dose adjustment required, use with caution.
- Hepatic impairment (moderate): No dose adjustment required, use with caution.
- Hepatic impairment (severe): Avoid use. (avoid)
Monitoring, pregnancy & toxicity
- HIV viral load · every 3-6 months
- CD4 count · every 3-6 months
- Liver function tests · baseline and periodically
- Lipid profile · baseline and periodically
- CNS symptoms (e.g., dizziness, abnormal dreams) · during first weeks of therapy
- Pregnancy: Efavirenz may be used in pregnancy; historical teratogenicity concerns are not supported by current evidence. Women of childbearing potential should be counselled and effective contraception considered. Local guidelines may prefer alternative agents in the first trimester.
- Toxicity: CNS effects (dizziness, insomnia, vivid dreams, confusion) · Usually transient; recommend taking dose at bedtime. Severe symptoms may require discontinuation.
- Toxicity: Skin rash (maculopapular, usually benign) · Monitor; usually self-limiting. If severe like Stevens-Johnson syndrome, discontinue and treat symptomatically.
- Toxicity: Hepatotoxicity (elevated liver enzymes) · Monitor LFTs; discontinue if significant elevation or signs of hepatic failure.
- Toxicity: Overdose (nausea, vomiting, CNS excitation) · Supportive care; no specific antidote. Consider activated charcoal if recent ingestion.
Clinical notes
Efavirenz was historically avoided in early pregnancy over neural tube defect concerns, but current evidence has not confirmed an increased risk and it is no longer contraindicated; effective contraception is still advised in women of childbearing potential.
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BNF; local formulary