Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection
Protease Inhibitors (PIs)
Last Updated: May 22, 2018; Last Reviewed: May 22, 2018
|Fosamprenavir (FPV, Lexiva)
For additional information see Drugs@FDA: https://www.accessdata.fda.gov/scripts/cder/daf/
|Tablets: 700 mg
Oral Suspension: 50 mg/mL
|Dosing Recommendations||Selected Adverse Events|
|Pediatric Dose (Aged >6 Months to 18 Years):
Pediatric Dose (Aged ≥6 Months to 18 Years):
Note: When administered with ritonavir, the adult regimen of 700 mg fosamprenavir tablets plus 100 mg ritonavir, both given twice daily, can be used in patients weighing ≥39 kg. Ritonavir tablets can be used in patients weighing ≥33 kg.
Adolescent and Adult Dose:
- Fosamprenavir may interact with a number of other drugs, and using ritonavir as a boosting agent increases the potential for drug interactions. Before administration, a patient’s medication profile should be carefully reviewed for potential drug interactions with fosamprenavir.
- More common: Vomiting, nausea, diarrhea, perioral paresthesia, headache, rash, and lipid abnormalities.
- Less common (more severe): Life-threatening rash, including Stevens-Johnson syndrome, in <1% of patients. Fat maldistribution, neutropenia, and elevated serum creatinine kinase levels.
- Rare: New-onset diabetes mellitus, hyperglycemia, ketoacidosis, exacerbation of preexisting diabetes mellitus, spontaneous bleeding in hemophiliacs, hemolytic anemia, elevation in serum transaminases, angioedema, and nephrolithiasis.
- Pediatric-specific: Vomiting was more frequent in children than in adults during clinical trials of fosamprenavir with ritonavir (20% to 36% vs. 10%, respectively) and in trials of fosamprenavir without ritonavir (60% vs. 16%, respectively). Neutropenia was also more common in children across all the trials (15% vs. 3%, respectively).1
Fosamprenavir is Food and Drug Administration (FDA)-approved for use in children as young as age 4 weeks, but the Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV (the Panel) recommends use only in children aged ≥6 months. While unboosted fosamprenavir has been approved by the FDA for antiretroviral-naive children aged 2 to 5 years, the Panel does not recommend unboosted fosamprenavir for this—or any other—age group because of low exposures and also because unboosted fosamprenavir may select for mutations associated with resistance to darunavir.2
Efficacy and Pharmacokinetics
Dosing recommendations for fosamprenavir are based on three pediatric studies that enrolled more than 200 children aged 4 weeks to 18 years. In two, open-label trials in both treatment-experienced and treatment-naive children aged 2 to 18 years,3,4 fosamprenavir was well-tolerated and effective in suppressing viral load and increasing CD4 T lymphocyte count. However, data were insufficient to support a once-daily dosing regimen of fosamprenavir/ritonavir in children; therefore, once-daily dosing is not recommended for pediatric patients.
Pharmacokinetics in Infants
In a study of infants, higher doses of both fosamprenavir and ritonavir were used in treatment-naive infants as young as age 4 weeks and in treatment-experienced infants as young as age 6 months.1,5 Exposures in those aged <6 months were much lower than those achieved in older children and adults and comparable to those seen with unboosted fosamprenavir (see table below). Given these low exposures, limited data, large dosing volumes, unpleasant taste, and the availability of alternatives for infants and young children, the Panel does not recommend fosamprenavir use in infants aged <6 months.
Except Where Noted
|Infants Aged <6 Months||FPV 45 mg/kg plus RTV 10 mg/kg twice daily||26.6a||0.86|
|Children Aged 2 Years to <6 Years||FPV 30 mg/kg twice daily (no RTV)||22.3a||0.513|
|Children Weighing <11 kg||FPV 45 mg/kg plus RTV 7 mg/kg twice daily||57.3||1.65|
|Children Weighing 15 kg to <20 kg||FPV 23 mg/kg FPV plus RTV 3 mg/kg twice daily||121.0||3.56|
|Children Weighing ≥20 kg||FPV 18 mg/kg plus RTV 3 mg/kg twice daily (maximum 700/100 mg)||72.3–97.9||1.98–2.54|
|Adults||FPV 1400 mg twice daily (no RTV)||33||0.35|
|Adults||FPV 1400 mg plus RTV 100–200 mg RTV once daily||66.4–69.4||0.86–1.45|
|Adults||FPV 700 mg plus RTV 100 mg twice daily||79.2||2.12|
|a AUC0-12 (mcg*hr/mL)
Key to Acronyms: AUC0-24h = area under the curve for 24 hours post-dose; Cmin = minimum plasma concentration; FPV = fosamprenavir; RTV = ritonavir
Note: Dose for those weighing 11 kg to <15 kg is based on population pharmacokinetic studies; therefore, AUC and Cmin are not available.
- Fosamprenavir [package insert]. Food and Drug Administration. 2016. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022116s023_21548-s39lbl.pdf.
- Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. 2016. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. .
- Chadwick E, Borkowsky W, Fortuny C, et al. Safety and antiviral activity of fosamprenavir/ritonavir once daily regimens in HIV-infected pediatric subjects ages 2 to 18 years (48-week interim data, study apv20003). Presented at: 14th Conference on Retroviruses and Opportunistic Infections. 2007. Los Angeles, CA.
- Fortuny C, Duiculescu D, Cheng K, et al. Pharmacokinetics and 48-week safety and antiviral activity of fosamprenavir-containing regimens in HIV-infected 2- to 18-year-old children. Pediatr Infect Dis J. 2014;33(1):50-56. Available at http://www.ncbi.nlm.nih.gov/pubmed/23811744.
- Cotton M, Cassim H, Pavia-Ruz N, et al. Pharmacokinetics, safety and antiviral activity of fosamprenavir/ritonavir-containing regimens in HIV-infected children aged 4 weeks to 2 years-48-week study data. Pediatr Infect Dis J. 2014;33(1):57-62. Available at http://www.ncbi.nlm.nih.gov/pubmed/23811743.