EFAVIRENZ

Clinical safety rating: avoid

Contraindicated (not allowed)

How it works

Non-nucleoside reverse transcriptase inhibitor (NNRTI) that binds to and inhibits HIV-1 reverse transcriptase, blocking RNA-dependent and DNA-dependent DNA polymerase activities.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Induces CYP3A4 and inhibits CYP2C9/CYP2C19 affecting many drugs Can cause severe psychiatric symptoms and rash.

Breastfeeding	Excreted in human milk. M/P ratio not established. Due to risk of infant adverse effects and low milk transfer, breastfeeding is not recommended while on efavirenz.
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.

Warnings & precautions

■ FDA Black Box Warning

May cause severe, life-threatening hepatotoxicity; monitor hepatic function closely. Contraindicated in patients with moderate to severe hepatic impairment.

Side Effect Profile

Common Effects	Rash
Serious Effects

Absolute Contraindications

["Concurrent use with voriconazole or St. John's wort","Moderate to severe hepatic impairment (Child-Pugh Class B or C)","Known hypersensitivity to efavirenz"]

Clinical Precautions

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"]

Clinical Tips & Counseling

Drug interactions

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