Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection
Nucleoside and Nucleotide Analogue Reverse Transcriptase Inhibitors (NRTIs)
Last Updated: April 27, 2017; Last Reviewed: April 27, 2017
|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
Generic Formulations: None available
Fixed-Dose Combination Tablets
|Dosing Recommendations||Selected Adverse Events|
|Neonatal/Infant Dose (Aged 0 to <3 Months)
Pediatric Dose (Aged ≥3 Months to 17 Years)
Oral Solution for Those Unable to Swallow Capsules:
[Truvada tablet] Emtricitabine plus TDF
[Descovy] Emtricitabine plus TAF
Adolescent (Weighing >35 kg) and Adult Dose:
Adolescent (Weighing ≥40 kg) and Adult Dose:
Adolescent (Weighing ≥35 kg) and Adult Dose:
Adolescent (Weighing ≥35 kg) and Adult Dose:
Adult Dose (Aged ≥18 Years):
Adolescent (Aged ≥12 Years and Weighing ≥35 kg) and Adult Dose:
Drug Interactions (see also the Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents and http://www.hiv-druginteractions.org/)
- Other nucleoside reverse transcriptase inhibitors (NRTIs): Do not use emtricitabine in combination with lamivudine because the agents share similar resistance profiles and lack additive benefit. Do not use separately with Combivir, Epzicom, or Trizivir because lamivudine is a component of these combinations. Do not use separately when prescribing Truvada, Atripla, Complera, Stribild, Genvoya, Descovy, and Odefsey because emtricitabine is a component of these formulations. Please see the appropriate section of the drug appendix when using these fixed-dose combinations.
- Renal elimination: Competition with other compounds that undergo renal elimination (possible competition for renal tubular secretion). Drugs that decrease renal function could decrease clearance.
- 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/hepatitis B (HBV) coinfection who changed from emtricitabine-containing to non-emtricitabine-containing regimens.
The International Antiviral Society-USA (IAS-USA) maintains a list of updated resistance mutations (see http://iasusa.org/sites/default/files/tam/october_november_2015.pdf#page=10) and the Stanford University HIV Drug Resistance Database offers a discussion of each mutation (see http://hivdb.stanford.edu/DR/).
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 combination 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 (e.g., tenofovir or abacavir versus the more static components like emtricitibine or lamivudine). Emtricitabine and lamivudine have been considered interchangeable, but little data exist to make this recommendation in antiretroviral (ARV)-naive patients. Investigators in the ATHENA cohort compared naive patients who started tenofovir plus emtricitabine or tenofovir plus lamivudine in combination with a ritonavir-boosted protease inhibitor (darunavir, atazanavir, or lopinavir).1 The adjusted hazard ratio for virologic failure of lamivudine compared to emtricitabine 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 the time to virologic failure after attaining suppression. Yang et al. in the Swiss cohort found a potential difference in efficacy which 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 described below,3 emtricitabine was studied at a dose of 6 mg/kg once daily in combination with other ARV drugs in 116 patients aged 3 months to 16 years.4,5 PK results were similar, and follow-up data extending to Week 96 indicated that 89% of the ARV-naive and 76% of the ARV-experienced children maintained suppression of plasma HIV RNA <400 copies/mL (75% of ARV-naive children and 67% of ARV-experienced children at <50 copies/mL). Minimal toxicity was observed in this trial. The Saez-Lorens study used a maximum of 240 mg of the liquid formulation. In PACTG P1021,4 emtricitabine at a dose of 6 mg/kg (maximum 200 mg/day as liquid) in combination with didanosine and efavirenz, all given once daily, was studied in 37 ARV-naive children with HIV aged 3 months to 21 years. Eighty-five percent of children achieved HIV RNA <400 copies/mL and 72% maintained HIV RNA suppression to <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 was performed in 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 6 mg/kg emtricitabine once-daily dose were approximately equivalent to those in adults receiving the standard 200-mg dose. However, plasma concentrations of emtricitabine after administration of the capsule formulation were slightly higher (approx. 20%) in this small cohort.
Pharmacokinetics in Infants
A study in South Africa evaluated the PKs of emtricitabine in 20 infants with perinatal HIV exposure aged <3 months, given emtricitabine as 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 3 mg/kg emtricitabine once daily was in the range of pediatric patients aged >3 months receiving the recommended emtricitabine dose of 6 mg/kg once daily and adults receiving the once-daily recommended 200-mg emtricitabine dose (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 in this age range.
Considerations for Use
Formulations favor liquid emtricitabine over liquid lamivudine, since the 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, again lamivudine and emtricitabine are equivalent.
Both emtricitabine and lamivudine have antiviral activity and efficacy against hepatitis B virus. For a comprehensive review of this topic, please see the Hepatitis B Virus section of the Pediatric Opportunistic Infections 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.
- 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.
- 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.
- Blum M, Ndiweni D, Chittick G, et al. Steady state pharmacokinetic evaluation of emtricitabine in neonates exposed to HIV in utero. Presented at: 13th 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.