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

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

Fixed-Dose Combination Tablets:
  • [Evotaz] Atazanavir 300 mg plus cobicistat 150 mg

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

Capsules and powder packets are not interchangeable.
Dosing Recommendations Selected Adverse Events
Neonate Dose:
  • 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).
Pediatric Dose Powder Formulation:a
  • Powder formulation must be administered with ritonavir.
  • Not approved for use in infants aged <3 months or weighing <5 kg.
Infants and Children (Aged ≥3 Months; Weighing ≥5 kg) Atazanavir Powdera
Weight (kg) Once-Daily Dose
5 kg to <15 kg Atazanavir 200 mg (4 packets) plus ritonavir 80 mg (1 mL oral solution), both once daily with food
15 kg to <25 kgb Atazanavir 250 mg (5 packets) plus ritonavir 80 mg (1 mL oral solution), both once daily with food


Capsule Formulation:a
  • Not approved for use in children aged <6 years or weighing <15 kg.
Children (Aged ≥6 Years; Weighing ≥15 kg) Atazanavir Capsulesa
Weight (kg) Once-Daily Dose
<15 kg Capsules not recommended
15 kg to <35 kg Atazanavir 200 mg plus ritonavirc 100 mg, both once daily with food
≥35 kg Atazanavir 300 mg plus ritonavirc 100 mg, both once daily with food


For Treatment-Naive Pediatric Patients Who Do Not Tolerate Ritonavir:
  • Atazanavir powder must be administered with ritonavir.
  • For capsule formulation, atazanavir/ritonavir (ATV/r) is preferred for children and adolescents. Current Food and Drug Administration (FDA)-approved prescribing information does not recommend unboosted atazanavir in children aged <13 years. 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).
  • Only ATV/r should be used in combination with tenofovir disoproxil fumarate (TDF), because TDF decreases atazanavir exposure.
Adolescent and Adult Dose
Treatment-Naive Patients:
  • Atazanavir 300 mg plus ritonavir 100 mg, both once daily with food.d
  • Atazanavir 300 mg plus cobicistate 150 mg, both once daily with food or as co-formulated Evotaz once daily with food. Atazanavir/cobicistat is currently not FDA-approved for use in children 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).
Treatment-Experienced Patients:
  • Atazanavir 300 mg plus ritonavir 100 mg, both once daily with food.d
  • Atazanavir 300 mg plus cobicistate 150 mg, both once daily with food or as co-formulated Evotaz once daily with food. Atazanavir/cobicistat is currently not FDA-approved for use in children aged <18 years.
Atazanavir in Combination with Efavirenz (Adults) in Treatment-Naive Patients Only:
  • Atazanavir 400 mg plus ritonavir 100 mg plus efavirenz 600 mg, all once daily at separate times.d
  • Although ATV/r should be taken with food, efavirenz should be taken on an empty stomach, preferably at bedtime. Efavirenz should not be co-administered with atazanavir (with or without ritonavir) in treatment-experienced patients, because efavirenz decreases atazanavir exposure.
Atazanavir in Combination with TDF (Adults):
  • Atazanavir 300 mg plus ritonavir 100 mg plus TDF 300 mg, all once daily with food.d
  • Atazanavir 300 mg plus cobicistate 150 mg plus TDF 300 mg, all once daily with food. Atazanavir/cobicistat is currently not FDA-approved for use in children aged <18 years.
  • Only boosted atazanavir should be used in combination with TDF, because TDF decreases atazanavir exposure.
  • Indirect hyperbilirubinemia
  • Prolonged electrocardiogram PR interval, first-degree symptomatic atrioventricular block in some patients
  • Nephrolithiasis
  • Increased serum transaminases
  • Hyperlipidemia (primarily with ritonavir boosting)
Special Instructions
  • Administer atazanavir with food to enhance absorption.
  • Capsules and powder packets are not interchangeable.
  • Do not open capsules.

Powder Administration:
  • Mix atazanavir oral powder with at least 1 tablespoon of 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.

  • Because atazanavir can prolong the electrocardiogram PR interval, use atazanavir with caution in patients with pre-existing cardiac conduction system disease or with other drugs 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, special dosing information is indicated (see the Drug Interactions section on the atazanavir package insert). When administered with buffered didanosine formulations or antacids, give atazanavir at least 2 hours before or 1 hour after antacid or didanosine administration.
  • The plasma concentration, and therefore the therapeutic effect, of atazanavir can be expected to decrease substantially when atazanavir is co-administered with proton-pump inhibitors. Antiretroviral therapy-naive patients receiving proton-pump inhibitors should receive no more than a 20-mg dose equivalent of omeprazole, which should be taken approximately 12 hours before boosted atazanavir. Co-administration of atazanavir with proton-pump inhibitors is not recommended in treatment-experienced patients.
  • Patients with hepatitis B virus or hepatitis C virus infections and patients with marked elevations in transaminases before treatment may be at 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 contains 35 mg of phenylalanine.
Metabolism/Elimination
  • Atazanavir is a substrate and inhibitor of cytochrome P (CYP) 3A4 and an inhibitor of CYP1A2, CYP2C9, and uridine diphosphate glucuronosyltransferase (UGT1A1).
Atazanavir Dosing in Patients with Hepatic Impairment:
  • Atazanavir should be used with caution in patients with mild or moderate hepatic impairment; consult manufacturer’s prescribing information for 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 treatment-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. Bioavailability was higher for the capsules than for the powder when studied in adults.
b For a child weighing ≥25 kg who cannot swallow atazanavir capsules, atazanavir 300 mg (6 packets) oral powder plus ritonavir 100 mg oral solution, both once daily with food, may be used.
c Either ritonavir capsules or ritonavir oral solution can be used.
d For adult patients who cannot swallow capsules, atazanavir oral powder is taken once daily with food at the same adult dose as the capsules, along with ritonavir.
e See 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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