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)

Lopinavir/Ritonavir

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

Lopinavir/Ritonavir (LPV/r, Kaletra)
Lopinavir/Ritonavir (LPV/r, Kaletra)
For additional information see Drugs@FDA: https://www.accessdata.fda.gov/scripts/cder/daf/
Formulations
Oral Solution:
  • [Kaletra] Lopinavir 80 mg/mL and ritonavir 20 mg/mL (contains 42.4% alcohol by volume and 15.3% propylene glycol by weight/volume)
Film-Coated Tablets:
  • [Kaletra] Lopinavir 100 mg/ritonavir 25 mg
  • [Kaletra] Lopinavir 200 mg/ritonavir 50 mg
Dosing Recommendations Selected Adverse Events
Neonatal (Aged <14 Days) Dose:
  • There are no data on the appropriate dose of lopinavir/ritonavir (LPV/r) for neonates and no data on the safety of using this drug combination in this age group. Do not administer LPV/r to neonates before a postmenstrual age of 42 weeks and a postnatal age of at least 14 days due to the risk of toxicities.
Dosing for Individuals Who Are Not Receiving Concomitant Nevirapine, Efavirenz, Fosamprenavir, or Nelfinavir
Infant (Aged 14 Days–12 Months) Dose:
  • Once-daily dosing is not recommended.
  • LPV/r 300 mg/75 mg per m2 of body surface area per dose twice daily. This approximates LPV/r 16 mg/4 mg (both per kg body weight) twice daily.
    Note: Use of this dose in infants aged <12 months is associated with lower lopinavir trough levels than those found in adults; lopinavir dosing should be adjusted for growth at frequent intervals (see text below). Also see text for transitioning infants to lower mg per m2 dose.
Child and Adolescent Dose (Aged >12 Months to 18 Years):
  • Once-daily dosing is not recommended.
  • LPV/r 300 mg/75 mg per m2 of body surface area per dose twice daily (maximum dose LPV/r 400 mg/100 mg twice daily, except as noted below). For patients weighing <15 kg, this approximates LPV/r 13 mg/3.25 mg (both per kg body weight) twice daily. For patients weighing ≥15 kg to 45 kg, this dose approximates LPV/r 11 mg/2.75 mg (both per kg body weight) twice daily. This dose is routinely used by many clinicians and is the preferred dose for treatment-experienced patients who could harbor virus with decreased lopinavir susceptibility (see text below).
  • LPV/r 230 mg/57.5 mg per m2 of body surface area per dose twice daily can be used in antiretroviral (ARV)-naive patients aged >1 year. For patients weighing <15 kg, this dose approximates LPV/r 12 mg/3 mg per kg body weight given twice daily. For patients weighing ≥15 kg to 40 kg, this dose approximates LPV/r 10 mg/2.5 mg per kg body weight given twice daily. This lower dose should not be used in treatment-experienced patients who could harbor virus with decreased lopinavir susceptibility.
Weight-Band Dosing for Lopinavir 100 mg/Ritonavir 25 mg Pediatric Tablets in Children and Adolescents
Recommended Number of LPV/r 100 mg/25 mg Tablets Given Twice Daily
Dosing Target 300 mg/m2/dose given twice daily 230 mg/m2/dose given twice daily
Body Weight
15 kg to 20 kg 2 2
>20 kg to 25 kg 3 2
>25 kg to 30 kg 3 3
>30 kg to 35 kg 4a 3
>35 kg to 45 kg 4a 4a
>45 kg 4a or 5b 4a
a Two tablets that each contain LPV/r 200 mg/50 mg can be substituted for the four LPV/r 100 mg/25 mg tablets in children who are capable of swallowing a larger tablet.
b In patients who weigh >45 kg and who are receiving concomitant nevirapine, efavirenz, fosamprenavir, or nelfinavir, the Food and Drug Administration (FDA)-approved adult dose is LPV/r 500 mg/125 mg twice daily, given as a combination of two tablets of LPV/r 200 mg/50 mg and one tablet of LPV/r 100 mg/25 mg. Alternatively, three tablets of LPV/r 200 mg/50 mg can be used for ease of dosing.

Adult (Aged >18 Years) Dose:
  • LPV/r 800 mg/200 mg once daily; or
  • LPV/r 400 mg/100 mg twice daily
  • Do not use once-daily dosing in children; adolescents; in patients receiving concomitant therapy with nevirapine, efavirenz, fosamprenavir, or nelfinavir; or in patients with three or more lopinavir-associated mutations (see Special Instructions for a list of mutations).
Dosing for Individuals with Three or More Lopinavir-Associated Mutations (See Special Instructions for List):
  • LPV/r 400 mg/100 mg twice daily
Dosing for Individuals Receiving Concomitant Nevirapine, Efavirenz, Fosamprenavir, or Nelfinavir:
  • Note: These drugs induce lopinavir metabolism and reduce lopinavir plasma levels. Increased LPV/r dosing is required with concomitant administration of these drugs. Once-daily dosing should not be used in these patients.
Child and Adolescent (Aged >12 Months to 18 Years) Dose:
  • LPV/r 300 mg/75 mg per m2 of body surface area per dose twice daily. See table for weight-band dosing when using tablets.
Adult (Aged >18 Years) Dose:
  • The FDA-approved dose is LPV/r 500 mg/125 mg twice daily, given as a combination of two tablets of LPV/r 200 mg/50 mg and one tablet of LPV/r 100 mg/25 mg. Alternatively, three tablets of LPV/r 200 mg/50 mg can be used for ease of dosing. Once-daily dosing should not be used.
LPV/r Used in Combination with Maraviroc:
  • Maraviroc doses may need modification (see the maraviroc section for more information).
  • Gastrointestinal (GI) intolerance, nausea, vomiting, diarrhea, alteration of taste
  • Hyperlipidemia, especially hypertriglyceridemia
  • Elevated transaminases
  • Hyperglycemia
  • PR interval prolongation
  • QT interval prolongation and Torsades de Pointes
  • Risk of toxicity—including life-threatening cardiotoxicity—is increased in premature infants (see Major Toxicities below).
Special Instructions
  • LPV/r tablets can be administered without regard to food; administration with or after meals may enhance GI tolerability.
  • LPV/r tablets must be swallowed whole. Do not crush or split tablets.
  • LPV/r oral solution should be administered with food, because a high-fat meal increases absorption.
  • The poor palatability of LPV/r oral solution is difficult to mask with flavorings or foods (see Pediatric Use).
  • LPV/r oral solution can be kept at room temperature (up to 77ºF or 25ºC) if used within 2 months. If kept refrigerated (36ºF to 46ºF or 2ºC to 8ºC), LPV/r oral solution remains stable until the expiration date printed on the label.
  • Once-daily dosing is not recommended because of considerable variability in plasma concentrations in children aged <18 years and a higher incidence of diarrhea.
  • Use of LPV/r once daily is contraindicated if three or more of the following lopinavir resistance-associated substitutions are present: L10F/I/R/V, K20M/N/R, L24I, L33F, M36I, I47V, G48V, I54L/T/V, V82A/C/F/S/T, and I84V. This is because higher lopinavir trough concentrations may be required to suppress resistant virus.
Metabolism/Elimination
  • Cytochrome P450 3A4 substrate and inhibitor.
LPV/r Dosing in Patients with Hepatic Impairment:
  • LPV/r is primarily metabolized by the liver. Use caution when administering lopinavir to patients with hepatic impairment. No dosing information is currently available for children or adults with hepatic insufficiency.
  • In the coformulation of LPV/r, the ritonavir acts as a pharmacokinetic enhancer, not as an ARV agent. It does this by inhibiting the metabolism of lopinavir and increasing lopinavir plasma concentrations.

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