Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection
Protease Inhibitors (PIs)
Last Updated: April 27, 2017; Last Reviewed: April 27, 2017
|Fosamprenavir (FPV, Lexiva)
For additional information see Drugs@FDA: http://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):
Once-daily dosing is not recommended for any pediatric patient.
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 (Aged >18 Years) Dose:
Boosted with Ritonavir, Twice-Daily Regimen:
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/)
- Fosamprenavir has the potential for multiple 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 in 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
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/).
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 or older. 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 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 over 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 ritonavir-boosted fosamprenavir 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 4 weeks and in treatment-experienced infants as young as 6 months.1,5 Exposures in those younger than 6 months were much lower than those achieved in older children and adults and comparable to those seen with unboosted fosamprenavir. 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 younger than 6 months.
Except Where Noted
|Infants <6 Months||45 mg fosamprenavir/10 mg ritonavir per kg twice daily||26.6a||0.86|
|Children Aged 2 to <6 Years||30 mg fosamprenavir per kg twice daily (no ritonavir)||22.3a||0.513|
|Children Weighing <11 kg||45 mg fosamprenavir/7 mg ritonavir per kg twice daily||57.3||1.65|
|Children Weighing 15 to <20 kg||23 mg fosamprenavir/3 mg ritonavir per kg twice daily||121.0||3.56|
|Children Weighing ≥20 kg||18 mg fosamprenavir/3 mg ritonavir per kg twice daily (maximum 700/100 mg)||72.3–97.9||1.98–2.54|
|Adults||1400 mg fosamprenavir twice daily (no ritonavir)||33||0.35|
|Adults||1400 mg fosamprenavir/100–200 mg ritonavir once daily||66.4–69.4||0.86–1.45|
|Adults||700 mg fosamprenavir/100 mg ritonavir twice daily||79.2||2.12|
a AUC0-12 (mcg*hr/mL)
Note: Dose for those weighing 11 to <15 kg is based on population pharmacokinetic studies, therefore, area under the curve and Cmin are not available.
- Food and Drug Administration. LEXIVA (fosamprenavir calcium) package insert. Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021548s035,022116s019lbl.pdf.
- Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Accessed on November 25, 2014.
- Chadwick E, Borkowsky W, Fortuny C, al e. 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). 14th Conference on Retroviruses and Opportunistic Infections; February 25-28, 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.