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.

  •   Table of Contents

Download Guidelines

Protease Inhibitors (PIs)

Darunavir

Last Updated: April 16, 2019; Last Reviewed: April 16, 2019

Darunavir (DRV, Prezista)
Darunavir (DRV, Prezista)
For additional information see Drugs@FDA: http://www.accessdata.fda.gov/scripts/cder/daf/
Formulations
Oral Suspension: 100 mg/mL
Tablets: 75 mg, 150 mg, 600 mg, 800 mg
Fixed-Dose Combination Tablets:
  • [Prezcobix] Darunavir 800 mg/cobicistat 150 mg
  • [Symtuza] Darunavir 800 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide (TAF) 10 mg
Dosing Recommendations Selected Adverse Events
Note: Darunavir should not be used without a pharmacokinetic (PK) enhancer (boosting agent). Ritonavir may be used as the boosting agent in children and adults; cobicistat should only be used in adults.

Neonate/Infant Dose:
  • Darunavir is not approved for use in neonates/infants.
Child Dose
Aged <3 Years:
  • Do not use darunavir in children aged <3 years or weighing ≤10 kg. Seizures and death have been observed in infant rats who received darunavir, and these events have been attributed to immaturity of the blood-brain barrier and liver metabolic pathways.
Aged ≥3 Years to <12 Years:
  • Dosing recommendations in the table below are for children aged ≥3 years to <12 years and weighing ≥10 kg who are treatment-naive or treatment-experienced and with or without resistance testing results that demonstrate that they have at least one mutation that is associated with darunavir resistance.
Twice Daily Darunavir and Ritonavir Doses for Children Aged 3 Years to <12 Years and Weighing ≥10 kg
Weight Dose
(Twice Daily with Food)a
10 kg to <11 kgb Darunavir 200 mg (2.0 mL) plus ritonavir 32 mg (0.4 mL)
11 kg to <12 kgb Darunavir 220 mg (2.2 mL) plus ritonavir 32 mg (0.4 mLc)
12 kg to <13 kgb Darunavir 240 mg (2.4 mL) plus ritonavir 40 mg (0.5 mLc)
13 kg to <14 kgb Darunavir 260 mg (2.6 mL) plus ritonavir 40 mg (0.5 mLc)
14 kg to <15 kg Darunavir 280 mg (2.8 mL) plus ritonavir 48 mg (0.6 mLc)
15 kg to <30 kg Darunavir 375 mg (combination of tablets or 3.8 mLd) plus ritonavir 48 mg (0.6 mLd)
30 kg to <40 kg Darunavir 450 mg (combination of tablets or 4.6 mLd,e) plus ritonavir (100 mg tablet or powder or 1.25 mLb)
≥40 kg Darunavir 600 mg (tablet or 6 mL) plus ritonavir 100 mg (tablet or 1.25 mL)

Boosting darunavir with cobicistat is currently not recommended in children aged <18 years; PKs, efficacy, and safety of darunavir/cobicistat is currently under investigation in children aged 12 years to 18 years.

Child and Adolescent (Aged ≥12 Years and Weighing ≥30 to <40 kg) Dose for Treatment-Naive or Treatment-Experienced Patients With or Without at Least One Mutation Associated With Darunavir Resistance:
  • Darunavir 450 mg (using a combination of tablets) plus ritonavir 100 mg, both twice daily with food
Child and Adolescent (Aged ≥12 years and Weighing ≥40 kg)e and Adult Dose for Treatment-Naive or Treatment-Experienced Patients with No Mutations Associated With Darunavir Resistance:
  • Darunavir 800 mg (using a tablet or combination of tablets) plus ritonavir 100 mg once daily with food
Adult Dose for Treatment-Naive or Treatment-Experienced Patients with No Mutations Associated with Darunavir Resistance:
  • Darunavir 800 mg (tablet) plus cobicistatf 150 mg (tablet) or the coformulation Prezcobix once daily with food
Adolescent (Weighing ≥40 kg) and Adult Dose for Treatment-Experienced Patients with at Least One Mutation Associated with Darunavir Resistance:
  • Darunavir 600 mg plus ritonavir 100 mg, both twice daily with food
  • The use of cobicistat is not recommended with darunavir 600 mg twice daily.
[Prezcobix] Darunavir/Cobicistat
Child and Adolescent (Aged <18 Years) Dose:
  • Prezcobix has not been approved by the Food and Drug Administration (FDA) for use in patients aged <18 years.
Adult Dose for Treatment-Naive or Treatment-Experienced Patients with No Mutations Associated with Darunavir Resistance:
  • One tablet once daily with food.
[Symtuza] Darunavir/Cobicistat/Emtricitabine/TAF
Child and Adolescent (Aged <18 Years) Dose:
  • Symtuza has not been approved by the FDA for use in patients aged <18 years.
Adult Dose:
  • One tablet once daily with food in ARV-naive patients or in patients who have been virologically suppressed (HIV RNA <50 copies per mL) for at least 6 months with no known substitutions associated with resistance to darunavir or tenofovir.
  • Skin rash, including Stevens-Johnson syndrome and erythema multiforme
  • Hepatotoxicity
  • Diarrhea, nausea
  • Headache
  • Hyperlipidemia, transaminase elevation, hyperglycemia
  • Fat maldistribution
Special Instructions
  • Once-daily darunavir is not generally recommended for use in children aged <12 years or weighing <40 kg. Dosing estimates for these patients were based on limited data and there is limited clinical experience with this dosing schedule in this age group.
  • Once-daily darunavir should not be used if any one of the following resistance-associated substitutions is present: V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, or L89V.
  • Darunavir must be administered with food, which increases darunavir plasma concentrations by 30%.
  • Darunavir contains a sulfonamide moiety. Use darunavir with caution in patients with known sulfonamide allergies.
  • Pediatric dosing requires coadministration of tablets with different strengths to achieve the recommended doses for each weight band. It is important to provide careful instructions to caregivers when recommending a combination of different-strength tablets.
  • Store darunavir tablets and oral suspension at room temperature (25ºC or 77ºF). Suspension must be shaken well before dosing.
  • When using fixed-dose combination (FDC) tablets, see other sections of the Drug Appendix for special instructions and additional information about the individual components of the FDC.
Metabolism/Elimination
  • Cytochrome P450 3A4 substrate and inhibitor.
Darunavir Dosing in Patients with Hepatic Impairment:
  • Darunavir is primarily metabolized by the liver. Caution should be used when administering darunavir to patients with hepatic impairment. Darunavir is not recommended in patients with severe hepatic impairment.
Darunavir Dosing in Patients with Renal Impairment:
  • No dose adjustment is required in patients with moderate renal impairment (creatinine clearance 30–60 mL/min).
a Once-daily dosing of darunavir is approved by the FDA, but the Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV (the Panel) does not generally recommend using this dosing schedule in children (see Frequency of Administration below).
b Note that the dose in children weighing 10 kg to 15 kg is darunavir 20 mg/kg plus ritonavir 3 mg/kg of body weight per dose, which is higher than the weight-adjusted dose in children with higher weights.
c Ritonavir 80 g/mL oral solution.
d The volumes for the 375-mg and 450-mg darunavir doses are rounded for suspension-dose convenience.
e Some Panel members recommend the FDA-approved dose of once-daily darunavir 675 mg (administered using a combination of tablets) plus ritonavir 100 mg once daily for adolescents weighing ≥30 kg to <40 kg (see Table B below).
f See the cobicistat section for important information about toxicity, drug interactions, and monitoring patients who receive cobicistat.

Download Guidelines