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: May 22, 2018; Last Reviewed: May 22, 2018

Darunavir (DRV, Prezista)
Darunavir (DRV, Prezista)
For additional information see Drugs@FDA: https://www.accessdata.fda.gov/scripts/cder/daf/
Formulations
Oral Suspension: 100 mg/mL
Tablets: 75 mg, 150 mg, 600 mg, and 800 mg

Fixed-Dose Combination Tablets:
  • [Prezcobix] Darunavir 800 mg plus cobicistat 150 mg
Dosing Recommendations Selected Adverse Events
Note: Darunavir should not be used without a pharmacokinetic (PK) enhancer (i.e., boosting agent): ritonavir (for children and adults) or cobicistat (for adults only).

Neonate/Infant Dose:
  • Not approved for use in neonates/infants.
Pediatric Dose Aged <3 Years:
  • Do not use darunavir in children aged <3 years or weighing ≤10 kg because of toxicity concerns based on seizures and death observed in infant rats and attributed to immaturity of the blood-brain barrier and liver metabolic pathways.
Aged ≥3 Years:
  • See table below for children aged ≥3 years who are antiretroviral treatment-naive and treatment-experienced with or without at least 1 darunavir resistance-associated mutation.
Aged 3 Years to <12 Years and Weighing ≥10 kg
Weight
(kg)
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 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; PK, efficacy, and safety of darunavir/cobicistat is currently under investigation in children aged 12 to 18 years.

Adolescent (Weighing ≥40 kg)e and Adult Dose (Treatment-Naive or Treatment-Experienced with No Darunavir Resistance-Associated Mutations)
  • Darunavir 800 mg (tablet or combination of tablets) plus ritonavir 100 mg once daily
Adult Dose (Treatment-Naive or Treatment-Experienced with No Darunavir Resistance-Associated Mutations)
  • Darunavir 800 mg (tablet) plus cobicistatf 150 mg (tablet) or coformulated as Prezcobix once daily with food
Adolescent (Weighing ≥30 to <40 kg; Treatment Naive or Treatment-Experienced with or without at Least 1 Darunavir Resistance-Associated Mutation)
  • Darunavir 450 mg (combination of tablets) plus ritonavir 100 mg both twice daily with food
Adolescent (Weighing ≥40 kg) and Adult Dose (Treatment-Experienced with at Least 1 Darunavir Resistance-Associated Mutation)
  • 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.
  • Skin rash, including Stevens-Johnson syndrome and erythema multiforme
  • Hepatotoxicity
  • Diarrhea, nausea
  • Headache
  • Hyperlipidemia, transaminase elevation, hyperglycemia
  • Fat maldistribution
Special Instructions
  • In patients with 1 or more darunavir-associated mutations, darunavir should only be used twice daily. Darunavir resistance-associated mutations are: V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, and L89V.
  • Darunavir must be administered with food, which increases plasma concentrations by 30%.
  • Darunavir contains a sulfonamide moiety. Use darunavir with caution in patients with known sulfonamide allergy.
  • Pediatric dosing requires co-administration of tablets with different strengths to achieve the recommended doses for each weight band. Careful instructions to caregivers when recommending a combination of different-strength tablets is very important.
  • Store darunavir tablets and oral suspension at room temperature (25ºC or 77ºF). Suspension must be shaken well before dosing.
Metabolism/Elimination
  • Cytochrome (CYP) P450 3A4 inhibitor and substrate.
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 [CrCl] 30–60 mL/min).
a Once-daily dosing is Food and Drug Administration (FDA)-approved, but the Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV (the Panel) does not recommend it for children (see Frequency of Administration section below).
b Note that the dose in children weighing 10 kg to 15 kg is 20 mg/kg darunavir and 3 mg/kg ritonavir per kg body weight per dose, which is higher than the weight-adjusted dose in children with higher weight.
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 (combination of tablets) plus ritonavir 100 mg once daily for adolescents weighing ≥30 kg to <40 kg (see Table B below).
f See cobicistat section for important information about toxicity, drug interactions, and monitoring patients who receive cobicistat.

Download Guidelines