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.
Nucleoside and Nucleotide Analogue Reverse Transcriptase Inhibitors (NRTIs)
Last Updated: May 22, 2018; Last Reviewed: May 22, 2018
|Emtricitabine (FTC, Emtriva)
For additional information see Drugs@FDA: http://www.accessdata.fda.gov/scripts/cder/daf/
|Pediatric Oral Solution: 10 mg/mL
Capsules: 200 mg
Fixed-Dose Combination Tablets:
|Dosing Recommendations||Selected Adverse Events|
|Note: See Antiretroviral Management of Newborns with Perinatal HIV Exposure or Perinatal HIV for information about the prevention of perinatal transmission.
Neonatal and Infant (Aged 0 to <3 Months) Dose
Oral Solution for Those Unable to Swallow Capsules:
[Truvada] Emtricitabine plus TDF (FTC/TDF)
Truvada Pediatric Dosing Table
Adolescent (Weighing ≥35 kg) and Adult Dose:
[Descovy] Emtricitabine plus TAF
Pediatric and Adolescent (Weighing ≥25 kg) and Adult Dose:
[Atripla] Efavirenz plus Emtricitabine plus TDF
Adolescent (Weighing ≥40 kg) and Adult Dose:
[Complera] Emtricitabine plus Rilpivirine plus TDF
Adolescent (Weighing ≥35 kg) and Adult Dose:
[Odefsey] Emtricitabine plus Rilpivirine plus TAF
Adolescent (Weighing ≥35 kg) and Adult Dose:
[Stribild] Elvitegravir plus Cobicistat plus Emtricitabine plus TDF
Adolescent (Weighing ≥35 kg with a Sexual Maturity Rating of 4 or 5) and Adult Dose:
[Genvoya] Elvitegravir plus Cobicistat plus Emtricitabine plus TAF
Child and Adolescent (Weighing ≥25 kg) and Adult Dose:
[Biktarvy] Bictegravir plus Emtricitabine plus TAF
Pediatric and Adolescent Dose (Aged <18 Years):
- Other nucleoside reverse transcriptase inhibitors (NRTIs): Do not use emtricitabine in combination with lamivudine because these agents share similar resistance profiles and lack additive benefit. Do not use emtricitabine separately with Combivir, Epzicom, or Trizivir because lamivudine is a component of these fixed-dose combinations. Do not use emtricitabine separately when prescribing Truvada, Atripla, Complera, Biktarvy, Stribild, Genvoya, Descovy, or Odefsey because emtricitabine is a component of these fixed-dose combinations. Please see other sections of the drug appendix for drug interaction information about each individual component when using these fixed-dose combinations.
- Renal elimination: Emtricitabine competes with other compounds that undergo renal elimination (possible competition for renal tubular secretion). Drugs that decrease renal function could decrease clearance of emtricitabine.
- More common: Headache, insomnia, diarrhea, nausea, rash, and hyperpigmentation/skin discoloration (possibly more common in children)
- Less common (more severe): Neutropenia. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported. Exacerbations of hepatitis have occurred in patients with HIV and hepatitis B virus (HBV) who changed from emtricitabine-containing to non-emtricitabine-containing regimens.
Emtricitabine is Food and Drug Administration approved for once-daily administration in children, starting at birth. Owing to its once-daily dosing, minimal toxicity, and pediatric pharmacokinetic (PK) data, emtricitabine is used as part of a dual-NRTI backbone in antiretroviral therapy.
Efficacy and Pharmacokinetics
Comparative Clinical Trials
Studies assessing the efficacy and/or potency of nucleoside/nucleotide analogues have been more concerned with the dynamic components of the regimen, such as tenofovir or abacavir, than the more static components, such as emtricitabine or lamivudine. Emtricitabine and lamivudine have been considered interchangeable, but there are little data to support this perspective in antiretroviral (ARV)-naive patients. Investigators studying the ATHENA cohort compared the efficacy of tenofovir disoproxil fumarate (TDF) plus emtricitabine or TDF plus lamivudine in combination with a ritonavir-boosted protease inhibitor (darunavir, atazanavir, or lopinavir) in ARV-naive patients.1 The adjusted hazard ratio for virologic failure of lamivudine-containing regimens compared to emtricitabine-containing regimens within 240 weeks of starting therapy was 1.15 (95% CI; 0.58–2.27). There was also no difference in time to virologic suppression in the first 48 weeks of therapy or time to virologic failure after attaining suppression. Yang et al. in the Swiss cohort found a potential difference in efficacy that disappeared after adjusting for pill burden.2 Current evidence suggests that emtricitabine and lamivudine have equivalent efficacy and toxicity in ARV-naive patients.
Based on a dose-finding study by Wang et al. (described in the Pharmacokinetics: Liquid Versus Capsule subsection below),3 emtricitabine 6 mg/kg once daily in combination with other ARV drugs was studied in 116 patients aged 3 months to 16 years.4 The study used a maximum dosage of 240 mg of the emtricitabine liquid formulation. PK results showed that plasma exposures were similar to those in adults receiving emtricitabine 200 mg once daily. Follow-up data extending to Week 96 indicated that 89% of the ARV-naive children and 76% of the ARV-experienced children maintained plasma HIV RNA <400 copies/mL (75% of ARV-naive children and 67% of ARV-experienced children had HIV RNA <50 copies/mL). Minimal toxicity was observed in this trial. PACTG P10215 studied ARV-naive children aged 3 months to 21 years using emtricitabine 6 mg/kg (with a maximum of emtricitabine 200 mg/day of the liquid formulation) in combination with didanosine and efavirenz, all given once daily. Eighty-five percent of children achieved HIV RNA <400 copies/mL, and 72% of children maintained HIV RNA suppression at <50 copies/mL through 96 weeks of therapy. The median CD4 T lymphocyte count rose by 329 cells/mm3 at Week 96.
Pharmacokinetics: Liquid Versus Capsule
A single-dose PK study of emtricitabine liquid solution and capsules enrolled 25 children with HIV aged 2 to 17 years.3 Emtricitabine was found to be well absorbed following oral administration, with a mean elimination half-life of 11 hours (range 9.7–11.6 hours). Plasma concentrations in children receiving the emtricitabine 6 mg/kg once-daily dose were approximately equivalent to those seen in adults receiving the standard emtricitabine 200-mg dose. However, plasma concentrations of emtricitabine after administration of the capsule formulation were slightly higher (approximately 20%) that those observed with the liquid solution in this small cohort of children.
Pharmacokinetics in Infants
A study in South Africa evaluated the PKs of emtricitabine in 20 infants aged <3 months with perinatal HIV exposure. The participants received a dose of emtricitabine 3 mg/kg once daily for two 4-day courses, separated by an interval of ≥2 weeks.6 Emtricitabine exposure (area under the curve [AUC]) in neonates receiving emtricitabine 3 mg/kg once daily was in the range of pediatric patients aged >3 months receiving the recommended dose of emtricitabine 6 mg/kg once daily and adults receiving the once-daily recommended dose of emtricitabine 200 mg (AUC approximately 10 hr*µg/mL). Over the first 3 months of life, emtricitabine AUC decreased with increasing age, correlating with an increase in total body clearance of the drug. In a small group of neonates (N = 6) receiving a single dose of emtricitabine 3 mg/kg after a single maternal dose of 600 mg during delivery, the AUC exceeded that seen in adults and older children, but the half-life (9.2 hours) was similar.7 Extensive safety data are lacking for this age range.
Considerations for Use
Formulations favor liquid emtricitabine over liquid lamivudine, since liquid emtricitabine can be given once daily at ARV initiation but liquid lamivudine needs to be given twice daily at ARV initiation. When pill formulations can be administered, lamivudine and emtricitabine are equivalent.
Both emtricitabine and lamivudine have antiviral activity and efficacy against HBV. For a comprehensive review of this topic, please see the Hepatitis B Virus section of the Pediatric Opportunistic Infection Guidelines.
- Rokx C, Gras L, van de Vijver D, Verbon A, Rijnders B, Study ANOC. Virological responses to lamivudine or emtricitabine when combined with tenofovir and a protease inhibitor in treatment-naive HIV-1-infected patients in the Dutch AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort. HIV Med. 2016. Available at: http://www.ncbi.nlm.nih.gov/pubmed/26842457.
- Yang WL, Kouyos RD, Scherrer AU, et al. Assessing efficacy of different nucleos(t)ide backbones in NNRTI-containing regimens in the Swiss HIV Cohort Study. J Antimicrob Chemother. 2015;70(12):3323-3331. Available at: http://www.ncbi.nlm.nih.gov/pubmed/26362944.
- Wang LH, Wiznia AA, Rathore MH, et al. Pharmacokinetics and safety of single oral doses of emtricitabine in human immunodeficiency virus-infected children. Antimicrob Agents Chemother. 2004;48(1):183-191. Available at: http://www.ncbi.nlm.nih.gov/pubmed/14693538.
- Saez-Llorens X, Violari A, Ndiweni D, et al. Long-term safety and efficacy results of once-daily emtricitabine-based highly active antiretroviral therapy regimens in human immunodeficiency virus-infected pediatric subjects. Pediatrics. 2008;121(4):e827-835. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18332076.
- McKinney RE, Jr., Rodman J, Hu C, et al. Long-term safety and efficacy of a once-daily regimen of emtricitabine, didanosine, and efavirenz in HIV-infected, therapy-naive children and adolescents: Pediatric AIDS Clinical Trials Group Protocol P1021. Pediatrics. 2007;120(2):e416-423. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17646352.
- Blum M, Ndiweni D, Chittick G, al e. Steady state pharmacokinetic evaluation of emtricitabine in neonates exposed to HIV in utero. Presented at: Conference on Retroviruses and Opportunistic Infections; 2006; Denver, CO.
- Flynn PM, Mirochnick M, Shapiro DE, et al. Pharmacokinetics and safety of single-dose tenofovir disoproxil fumarate and emtricitabine in HIV-1-infected pregnant women and their infants. Antimicrob Agents Chemother. 2011;55(12):5914-5922. Available at: http://www.ncbi.nlm.nih.gov/pubmed/21896911.