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.

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Protease Inhibitors (PIs)

Atazanavir

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

Atazanavir (ATV, Reyataz)
Atazanavir (ATV, Reyataz)
For additional information see Drugs@FDA: https://www.accessdata.fda.gov/scripts/cder/daf/
Formulations
Powder Packet: 50 mg/packet
Capsules: 150 mg, 200 mg, and 300 mg

Generic Formulations
Capsules: 150 mg, 200 mg, 300 mg

Fixed-Dose Combination Tablets:
  • [Evotaz] Atazanavir 300 mg/cobicistat 150 mg
Capsules and powder packets are not interchangeable.
Dosing Recommendations Selected Adverse Events
Neonate Dose:
  • Atazanavir is not approved for use in neonates and infants aged <3 months. Atazanavir should not be administered to neonates due to risks associated with hyperbilirubinemia (kernicterus).
Infant and Child Dose
Powder Formulation:a
  • The powder formulation must be administered with ritonavir.
  • The powder formulation is not approved for use in infants aged <3 months or weighing <5 kg.
Atazanavir Powder Dosing Table for Infants and Children Aged ≥3 Months and Weighing ≥5 kga
Weight Once-Daily Dose
5 kg to <15 kg Atazanavir 200 mg (four packets) plus ritonavir 80 mg (1 mL oral solution), both once daily with food
15 kg to <25 kgb Atazanavir 250 mg (five packets) plus ritonavir 80 mg (1 mL oral solution), both once daily with food

Capsule Formulation:a
  • Capsules are not approved for use in children aged <6 years or weighing <15 kg.
Atazanavir Capsule Dosing Table for Children and Adolescents Aged ≥6 Years and Weighing ≥15 kg
Weight Once-Daily Dose
<15 kg Capsules not recommended
15 kg to <35 kg Atazanavir/ritonavirc 200 mg/100 mg, both once daily with food
≥35 kg Atazanavir/ritonavirc 300 mg/100 mg, both once daily with food

For Treatment-Naive Children and Adolescents Who Do Not Tolerate Ritonavir:
  • Atazanavir powder is not an option, since it must be administered with ritonavir. For the capsule formulation, while the Food and Drug Administration (FDA) does not recommend the use of unboosted atazanavir in children aged <13 years, adolescents aged ≥13 years weighing ≥40 kg may be prescribed unboosted atazanavir if they are not concurrently taking tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF). However, in order to achieve target drug concentrations, adolescents may require doses of atazanavir that are higher than those recommended for use in adults (see Pediatric Use).
  • The Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV does not recommend use of unboosted atazanavir.
Adolescent and Adult Dose
Treatment-Naive Patients:
  • Atazanavir/ritonavir (ATV/r) 300 mg/100 mg once daily with food.d
  • Atazanavir/cobicistat (ATV/c) is currently not approved by the FDA for use in children or adolescents aged <18 years.
  • Atazanavir 400 mg once daily with food. If unboosted atazanavir is used in adolescents, higher doses than those used in adults may be required to achieve target drug concentrations (see Pediatric Use).
  • Emtricitabine/TAF is approved for use with ATV/r in patients weighing ≥35 kg.
Treatment-Experienced Patients:
  • ATV/r 300 mg/100 mg once daily with food.d
  • ATV/ce 300 mg/150 mg once daily with food, or coformulated Evotaz once daily with food.
  • ATV/c is currently not approved by the FDA for use in children aged <18 years.
  • Emtricitabine/TAF is approved for use with ATV/r in patients who weigh ≥35 kg.
[Evotaz] Atazanavir/Cobicistat
Child and Adolescent Dose:
  • ATV/c is currently not approved by the FDA for use in children aged <18 years.
Adult Dose:
  • One tablet once daily with food
  • Indirect hyperbilirubinemia
  • Prolonged electrocardiogram PR interval, first-degree symptomatic atrioventricular block in some patients
  • Nephrolithiasis
  • Increased serum transaminases
  • Hyperlipidemia (occurs primarily with ritonavir boosting)
Special Instructions
  • Administer atazanavir with food to enhance absorption.
  • Capsules and powder packets are not interchangeable.
  • Do not open capsules.
  • Because atazanavir can prolong the PR interval, use atazanavir with caution in patients with pre-existing cardiac conduction system disease or with other drugs that are known to prolong the PR interval (e.g., calcium channel blockers, beta-blockers, digoxin, verapamil).
  • Atazanavir absorption is dependent on low gastric pH; therefore, when atazanavir is administered with medications that alter gastric pH, dosing adjustments may be indicated (see the Drug Interactions section in the atazanavir package insert).
  • The plasma concentration, and therefore the therapeutic effect, of atazanavir can be expected to decrease substantially when atazanavir is coadministered with proton-pump inhibitors. ART-naive patients who are receiving proton-pump inhibitors should receive no more than a 20-mg dose equivalent of omeprazole, which should be taken approximately 12 hours before taking boosted atazanavir. Coadministration of atazanavir with proton-pump inhibitors is not recommended in ART-experienced patients.
  • Patients with hepatitis B virus or hepatitis C virus infections and patients who had marked elevations in transaminases before treatment may have an increased risk of further elevations in transaminases or hepatic decompensation.
  • Atazanavir oral powder contains phenylalanine, which can be harmful to patients with phenylketonuria. Each packet of oral powder contains 35 mg of phenylalanine.
Powder Administration:
  • Mix atazanavir oral powder with at least 1 tablespoon of soft food (e.g., applesauce, yogurt). Oral powder mixed with a beverage (at least 30 mL of milk or water) may be used for older infants who can drink from a cup. For young infants (aged <6 months) who cannot eat solid food or drink from a cup, oral powder should be mixed with at least 10 mL of infant formula and given using an oral dosing syringe.
  • Administer ritonavir immediately following powder administration.
  • Administer the entire dose of oral powder within 1 hour of preparation.
Metabolism/Elimination
  • Atazanavir is a substrate and inhibitor of cytochrome P450 (CYP) 3A4 and an inhibitor of CYP1A2, CYP2C9, and uridine diphosphate glucuronyl transferase 1A1.
Atazanavir Dosing in Patients with Hepatic Impairment:
  • Atazanavir should be used with caution in patients with mild or moderate hepatic impairment. Consult the manufacturer’s prescribing information for the dose adjustment in patients with moderate impairment.
  • Atazanavir should not be used in patients with severe hepatic impairment.
Atazanavir Dosing in Patients with Renal Impairment:
  • No dose adjustment is required for patients with renal impairment.
  • Atazanavir should not be given to ART-experienced patients with end-stage renal disease who are on hemodialysis.
a mg/kg dosing is higher for the powder packets than for the capsules. In P1020A, children of similar age and size taking atazanavir powder had lower exposures compared with those taking atazanavir capsules.
b Children who weigh ≥25 kg and who cannot swallow atazanavir capsules may receive atazanavir 300 mg (six packets) oral powder plus ritonavir 100 mg oral solution, both administered once daily with food.
c Either ritonavir capsules or ritonavir oral solution can be used.
d Adult patients who cannot swallow capsules may take atazanavir oral powder once daily with food at the same adult dose as the capsules, along with ritonavir.
e See the cobicistat section for important information about toxicity, drug interactions, and monitoring of patients who receive cobicistat and the combination of cobicistat and TDF.

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