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 14, 2020; Last Reviewed: April 14, 2020

Darunavir (DRV, Prezista)
Darunavir (DRV, Prezista)
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 10 mg
When using fixed-dose combination (FDC) tablets, refer to other sections of the Drug Appendix for information about the individual components of the FDC. See also Appendix A, Table 2. Antiretroviral Fixed-Dose Combination Tablets: Minimum Body Weights and Considerations for Use in Children and Adolescents

For additional information, see Drugs@FDA or DailyMed.
Dosing Recommendations Selected Adverse Events
Note: Darunavir (DRV) should not be used without a pharmacokinetic (PK) enhancer (boosting agent). Ritonavir (RTV) may be used as the boosting agent in children and adults. Cobicistat (COBI) may be used as a boosting agent with DRV in children weighing ≥40 kg and in adults.

Neonate/Infant Dose:
  • DRV is not approved for use in neonates/infants.
Child Dose
Aged <3 Years:
  • Do not use DRV in children aged <3 years or weighing ≤10 kg. In juvenile rats, DRV caused convulsions and death, 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 antiretroviral therapy (ART)-naive or treatment-experienced and with or without resistance testing results that demonstrate that they have at least one mutation that is associated with DRV 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 DRV 200 mg (2.0 mL) plus RTV 32 mg (0.4 mL)
11 kg to <12 kgb DRV 220 mg (2.2 mL) plus RTV 32 mg (0.4 mL)c
12 kg to <13 kgb DRV 240 mg (2.4 mL) plus RTV 40 mg (0.5 mL)c
13 kg to <14 kgb DRV 260 mg (2.6 mL) plus RTV 40 mg (0.5 mL)c
14 kg to <15 kg DRV 280 mg (2.8 mL) plus RTV 48 mg (0.6 mL)c
15 kg to <30 kg DRV 375 mg (combination of tablets or 3.8 mL)d plus RTV 48 mg (0.6 mL)d
30 kg to <40 kg DRV 450 mg (combination of tablets or 4.6 mL)d,e plus RTV (100 mg tablet or powder or 1.25 mL)b
≥40 kg DRV 600 mg (tablet or 6 mL) plus RTV 100 mg (tablet or 1.25 mL)


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:
  • DRV 450 mg (using a combination of tablets) plus RTV 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:
  • DRV 800 mg (using a tablet or combination of tablets) plus RTV 100 mg once daily with food
Child and Adolescent (Weighing ≥40 kg) and Adult Dose for Treatment-Naive or Treatment-Experienced Patients with No Mutations Associated with Darunavir Resistance:
  • DRV 800 mg (tablet) plus COBIf 150 mg (tablet) or the coformulation Prezcobix once daily with food
Child and Adolescent (Weighing ≥40 kg) and Adult Dose for Treatment-Experienced Patients with at Least One Mutation Associated with Darunavir Resistance:
  • DRV 600 mg plus RTV 100 mg, both twice daily with food
  • The use of COBI is not recommended with DRV 600 mg twice daily.
[Prezcobix] Darunavir/Cobicistat
Child and Adolescent (Weighing ≥40 kg) and 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/ Tenofovir Alafenamide (TAF)
Child and Adolescent (Weighing ≥40 kg) and Adult Dose:
  • One tablet once daily with food in ARV-naive patients or in patients who have been virologically suppressed (HIV RNA <50 copies/mL) for at least 6 months with no known mutations associated with resistance to DRV 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 DRV 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 DRV should not be used if any one of the following resistance-associated mutations are present: V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, or L89V.
  • DRV must be administered with food, which increases DRV plasma concentrations by 30%.
  • DRV contains a sulfonamide moiety. Use DRV 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 DRV tablets and oral suspension at room temperature (25ºC or 77ºF). Suspension must be shaken well before dosing.
  • Screen patients for hepatitis B virus (HBV) infection before using emtricitabine (FTC) or TAF. Severe acute exacerbation of HBV infection can occur when FTC or TAF are discontinued; therefore, liver function should be monitored for several months after patients with HBV infection stop taking FTC or TAF.
Metabolism/Elimination
  • Cytochrome P450 3A4 substrate and inhibitor.
Darunavir Dosing in Patients with Hepatic Impairment:
  • DRV is primarily metabolized by the liver. Caution should be used when administering DRV to patients with hepatic impairment. DRV 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 DRV is approved by the Food and Drug Administration (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 DRV 20 mg/kg plus RTV 3 mg/kg of body weight per dose, which is higher than the weight-adjusted dose in children with higher weights.

c RTV 80 g/mL oral solution.

d The volumes for the 375-mg and 450-mg DRV doses are rounded for suspension-dose convenience.

e Some Panel members recommend using the FDA-approved dose of once-daily DRV 675 mg (administered using a combination of tablets) plus RTV 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 in patients who receive COBI.

Download Guidelines