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Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection
Nucleoside and Nucleotide Analogue Reverse Transcriptase Inhibitors (NRTIs)
(Last updated: April 27, 2015; last reviewed: April 27, 2015)
Fixed-Dose Combination Tablets Truvada Adolescent (Aged ≥12 Years and Weighing ≥35 kg) and Adult Dose:
1 tablet once daily.
Atripla Adolescent (Aged ≥12 Years and Weighing ≥40 kg) and Adult Dose:
1 tablet once daily.
Administer without food.
See efavirenz section for pregnancy warning.
Complera Adult Dose (Aged ≥18 Years):
1 tablet once daily in treatment-naive adults with baseline plasma RNA <100,000 copies/mL or virologically suppressed adults with no history of virologic failure, resistance to rilpivirine and other ARVs, and who currently on their first or second regimen.
Administer with a meal of at least 400 calories.
Stribild Adult Dose (Aged ≥18 Years):
1 tablet once daily in treatment-naive adults or virologically suppressed adults.
Administer with a meal.
Selected Adverse Events
Severe acute exacerbation of hepatitis can occur in hepatitis B virus (HBV)-coinfected patients who discontinue emtricitabine.
Hyperpigmentation/skin discoloration on palms and/or soles
Although emtricitabine can be administered without regard to food, food requirements vary depending on the other ARVs contained in a combination tablet. For Atripla (administer without food) and Complera (administer with a meal of at least 400 calories), refer to efavirenz or rilpivirine special instructions.
Emtricitabine oral solution can be kept at room temperature up to 77º F (25º C) if used within 3 months; refrigerate for longer-term storage.
If using Stribild, please see the elvitegravir section of the drug appendix for additional information.
Before using emtricitabine, screen patients for HBV.
Limited metabolism: No cytochrome P (CYP) 450 interactions.
Renal excretion 86%: Competition with other compounds that undergo renal elimination.
Dosing of emtricitabine in patients with renal impairment: Decrease dosage in patients with impaired renal function. Consult manufacturer’s prescribing information.
Do not use Atripla (fixed-dose combination) in patients with creatinine clearance (CrCl) <50 mL/min or in patients requiring dialysis.
Do not use Truvada (fixed-dose combination) in patients with CrCl <30 mL/min or in patients requiring dialysis.
Use Complera with caution in patients with severe renal impairment or end-stage renal disease. Increase monitoring for adverse effects because rilpivirine concentrations may be increased in patients with severe renal impairment or end-stage renal disease.
Stribild should not be initiated in patients with estimated CrCl <70 mL/min and should be discontinued in patients with estimated CrCl <50 mL/min.
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, or Stribild because emtricitabine is a component of these formulations.
Renal elimination: Competition with other compounds that undergo renal elimination (possible competition for renal tubular secretion). Drugs that decrease renal function could decrease clearance.
Use with Stribild: If using Stribild, please see the elvitegravir section of the drug appendix for additional information.
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 HIV/hepatitis B virus (HBV)-coinfected patients who changed from emtricitabine-containing to non-emtricitabine-containing regimens.
Emtricitabine is Food and Drug Administration (FDA)-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 commonly used as part of a dual-NRTI backbone in combination antiretroviral therapy.
Efficacy and Pharmacokinetics
A single-dose PK study of emtricitabine liquid solution and capsules was performed in 25 HIV-infected children ages 2 to 17 years.1 Emtricitabine was found to be well absorbed following oral administration, with a mean elimination half-life of 11 hours (range 9.7 to 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.
A study in South Africa evaluated the PKs of emtricitabine in 20 HIV-exposed infants aged <3 months, given emtricitabine as 3 mg/kg once daily for two, 4-day courses, separated by an interval of ≥2 weeks.2 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*ug/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.3 Extensive safety data are lacking in this age range.
Based on the aforementioned dose-finding study,1 emtricitabine was studied at a dose of 6 mg/kg once daily in combination with other antiretroviral (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. In PACTG P1021,4 emtricitabine at a dose of 6 mg/kg (maximum 240 mg/day as liquid or 200 mg/day as capsules) in combination with didanosine and efavirenz, all given once daily, was studied in 37 ARV-naive HIV-infected children ages 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.
Both emtricitabine and lamivudine have antiviral activity and efficacy against HBV. For a comprehensive review of this topic, hepatitis C, and tuberculosis during HIV coinfection, please see the Pediatric Opportunistic Infections Guidelines.
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.
Blum M, Ndiweni D, Chittick G, al e. Steady state pharmacokinetic evaluation of emtricitabine in neonates exposed to HIV in utero. Presented at: 13th Conference on Retroviruses and Opportunistic Infections (CROI). 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.
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.