Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

The information in the brief version is excerpted directly from the full-text guidelines. The brief version is a compilation of the tables and boxed recommendations.

  •   Table of Contents

Download Guidelines

Non-Nucleoside Analogue Reverse Transcriptase Inhibitors (NNRTIs)

Efavirenz

Last Updated: May 22, 2018; Last Reviewed: May 22, 2018

Efavirenz (EFV, Sustiva)
Efavirenz (EFV, Sustiva)
For additional information see Drugs@FDA: http://www.accessdata.fda.gov/scripts/cder/daf/
Formulations
Capsules: 50 mg, 200 mg
Tablets: 600 mg
Fixed-Dose Combination Tablets:
  • [Atripla] Efavirenz 600 mg plus emtricitabine 200 mg plus tenofovir disoproxil fumarate (TDF) 300 mg
  • [Symfi Lo] Efavirenz 400 mg plus lamivudine 300 mg plus TDF 300 mg
Dosing Recommendations Selected Adverse Events
Neonatal Dose:
  • Efavirenz is not approved for use in neonates.
Pediatric Dose:
  • Efavirenz capsules can be opened and the contents used as a sprinkle preparation for infants and children who are unable to swallow capsules.
Infants and Children Aged 3 Months to <3 Years and Weighing ≥3.5 kg:
  • The Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV (the Panel) does not recommend the use of efavirenz in children aged 3 months to <3 years due to highly variable pharmacokinetics in this age group.
  • Note: If the use of efavirenz is unavoidable due to a clinical situation, the Panel suggests using investigational doses of efavirenz in this age group (see investigational dosing tables A1 and A2 in the Pharmacokinetics and Dosing: Infants and Children Aged <3 Years section below). Evaluation of CYP2B6 genotype is required prior to use in this age group. Therapeutic drug monitoring should be used with an efavirenz plasma concentration measured 2 weeks after initiation; some experts would also measure plasma concentration at age 3 years after making the transition to the new dose (see Therapeutic Drug Monitoring in the text below). For dose adjustment based on efavirenz concentrations, consultation with an expert is recommended.
Children Aged 3 Years and Weighing 10 kg:

Once-Daily Doses of Efavirenz by Weight
Weight Efavirenz Dosea,b
10 kg to <15 kg 200 mg
15 kg to <20 kg 250 mg
20 kg to <25 kg 300 mg
25 kg to <32.5 kg 350 mg
32.5 kg to <40 kg 400 mg
≥40 kg 600 mg
a The dose in mg can be dispensed in any combination of capsule strengths. Capsules may be administered by sprinkling the contents into an age-appropriate food (see Special Instructions).

Some experts recommend a dose of efavirenz 367 mg/m2 body surface area (maximum dose 600 mg) because of concern for underdosing at the upper end of each weight band (see Pediatric Use in text below for details). Weight bands approximate a dose of efavirenz 367 mg/m2, with a maximum dose of 600 mg.

Adolescent (Weighing ≥40 kg) and Adult Dose:
  • Efavirenz 600 mg once daily
[Atripla] Efavirenz plus Emtricitabine plus TDF:
  • Atripla should not be used in pediatric patients <40 kg, as the dose of efavirenz 600 mg would be excessive.
Adult Dose:
  • One tablet once daily
[Symfi Lo] Efavirenz plus Lamivudine plus TDF:
Pediatric (Weighing ≥35 kg) and Adult Dose:
  • One tablet once daily
Note: The new fixed-dose combination (Symfi Lo), which has a lower dose of efavirenz, has not yet been discussed by the Panel. The Panel will address its use in children in a later update.
  • Rash, which is generally mild and transient and appears to be more common in children than in adults
  • Central nervous system symptoms such as fatigue, poor sleeping patterns, insomnia, vivid dreams, impaired concentration, agitation, seizures, depression, suicidal ideation
  • False-positive with some cannabinoid and benzodiazepine tests
  • Gynecomastia
  • Hepatotoxicity
  • QTc prolongation has been observed with the use of efavirenz. Clinicians should consider using an alternative to efavirenz in patients taking a drug that has a known risk of Torsades de Pointes or in patients who are at higher risk of Torsades de Pointes.
Special Instructions
  • Efavirenz can be swallowed as a whole capsule/tablet or administered by sprinkling the contents of an opened capsule on food as described below.
  • Bedtime dosing is recommended, particularly during the first 2 to 4 weeks of therapy, to improve tolerability of central nervous system side effects.
  • Administer efavirenz, Atripla, or Symfi Lo on an empty stomach. Avoid administration with a high-fat meal because this has the potential to increase absorption.
  • When using fixed-dose combination tablets, see other drug sections in Appendix A: Pediatric Antiretroviral Drug Information for special instructions and additional information about the individual drug components.
  • The Food and Drug Administration cautions that efavirenz should not be used during the first trimester of pregnancy because of potential teratogenicity. However, after a review of updated evidence regarding teratogenicity risks, the Perinatal Guidelines do not restrict use of efavirenz in female adolescents and adults who are pregnant or may become pregnant.
Instructions for Use of Efavirenz Capsule as a Sprinkle Preparation with Food or Formula:
  • Hold capsule horizontally over a small container and carefully twist to open to avoid spillage.
  • Gently mix capsule contents with 1–2 teaspoons of an age-appropriate soft food (e.g., applesauce, grape jelly, yogurt) or reconstituted infant formula at room temperature.
  • Administer infant formula mixture using a 10-mL syringe.
  • After administration, an additional 2 teaspoons of food or infant formula must be added to the container, stirred, and dispensed to the patient.
  • Administer within 30 minutes of mixing and do not consume additional food or formula for 2 hours after administration.
Metabolism/Elimination
  • Cytochrome P450 3A (CYP3A) and CYP2B6 inducer in vivo and CYP2C9, 2C19, and 3A4 isozyme inhibitor in vitro.
  • Efavirenz is not recommended for patients with moderate or severe hepatic impairment.
  • Interpatient variability in efavirenz exposure can be explained in part by polymorphisms in CYP450, with slower metabolizers at higher risk of toxicity (see Therapeutic Drug Monitoring in the text below for information about the management of mild or moderate toxicity).
Atripla and Symfi Lo Dosing in Adults with Renal Impairment:
  • Because these are fixed-dose combination products and TDF and emtricitabine require dose adjustment based on renal function, Atripla and Symfi Lo should not be used in patients with creatinine clearance <50 mL/minute or in patients on dialysis.

Download Guidelines