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 14, 2020; Last Reviewed: April 14, 2020

Atazanavir (ATV, Reyataz)
Atazanavir (ATV, Reyataz)
Formulations
Powder Packet: 50 mg/packet
Capsules: 150 mg, 200 mg, 300 mg

Generic Formulations:
  • 150 mg, 200 mg, and 300 mg capsules
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 (ATV) is not approved for use in neonates and infants aged <3 months. ATV should not be administered to neonates due to risks associated with hyperbilirubinemia (e.g., bilirubin-induced neurologic dysfunction).
Infant and Child Dose
Powder Formulation of Atazanavir:a
  • The powder formulation of ATV must be administered with ritonavir (RTV).
  • 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 ATV 200 mg (four packets) plus RTV 80 mg (1 mL oral solution), with food
15 kg to <25 kgb ATV 250 mg (five packets) plus RTV 80 mg (1 mL oral solution), both with food

Capsule Formulation of Atazanavir:a
  • ATV capsules are not approved for use in children aged <6 years or weighing <15 kg.
Atazanavir/Ritonavir 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 ATV/rc 200 mg/100 mg, both with food
≥35 kg ATV/rc 300 mg/100 mg, both with food

ART-Naive Patients Who Are Unable to Tolerate Ritonavir
Child and Adolescent (Aged ≥13 Years and Weighing ≥40 kg) and Adult Dose:
  • ATV 400 mg (capsule formulation only) once daily with food
  • ATV powder is not an option, since it must be administered with RTV.
  • For the capsule formulation, while the Food and Drug Administration (FDA) does not recommend the use of unboosted ATV in children aged <13 years, adolescents aged ≥13 years and weighing ≥40 kg may be prescribed unboosted ATV if they are not concurrently taking tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF). 
  • In order to achieve target drug concentrations, adolescents may require doses of ATV that are higher than those recommended for use in adults (see Pediatric Use below).
  • The Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV does not recommend the use of unboosted ATV.
ART-Naive and ART-Experienced Patients
Child and Adolescent (Weighing ≥35 kg) and Adult Dose:
  • Atazanavir/ritonavir (ATV/r) 300 mg/100 mg once daily with foodd
  • Atazanavir/cobicistat (ATV/c) 300 mg/150 mg once daily with food, administered as single agents simultaneously or as the coformulated drug Evotaze
  • Both ATV/r and ATV/c must be used in combination with other antiretroviral drugs.
[Evotaz] Atazanavir/Cobicistat
Child and Adolescent (Weighing ≥35 kg) and 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 RTV boosting)
Special Instructions
  • Administer ATV with food to enhance absorption.
  • Capsules and powder packets are not interchangeable.
  • Do not open capsules.
  • Because ATV can prolong the PR interval of the electrocardiogram, use ATV 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).
  • ATV absorption is dependent on low gastric pH; therefore, when ATV is administered with medications that alter gastric pH, dosing adjustments may be indicated (see the Drug Interactions section in the ATV package insert).
  • The plasma concentration, and therefore the therapeutic effect, of ATV can be expected to decrease substantially when ATV is coadministered with proton-pump inhibitors (PPIs). Antiretroviral therapy (ART)-naive patients who are receiving any PPI should receive a dose of that PPI that is equivalent to no more than a 20-mg dose of omeprazole. PPIs should be taken approximately 12 hours before taking boosted ATV. Coadministration of ATV with PPIs is not recommended in ART-experienced patients.
  • Patients with hepatitis B virus or hepatitis C virus infections and patients who had marked elevations in transaminase levels before treatment may have an increased risk of further elevations in transaminase levels or hepatic decompensation.
  • ATV 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 ATV 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 RTV immediately following powder administration.
  • Administer the entire dose of oral powder within 1 hour of preparation.
Metabolism/Elimination
  • ATV 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:
  • ATV 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.
  • ATV 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.
  • ATV 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 ATV powder packets than for the capsules. In P1020A, children of similar age and size who were taking ATV powder had lower exposures than those who were taking ATV capsules.

b Children weighing ≥25 kg who cannot swallow ATV capsules may receive ATV 300 mg oral powder (six packets) plus RTV 100 mg oral solution, both administered once daily with food.

c Either RTV capsules or RTV oral solution can be used.

d Adult patients who cannot swallow capsules may take ATV oral powder once daily with food using the adult dose for the capsules. ATV oral powder should be administered with RTV.

e See the Cobicistat section for important information about toxicity, drug interactions, and monitoring of patients who receive cobicistat (COBI) and the combination of COBI and TDF.

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