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

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
Pediatric Oral Solution:
  • [Kaletra] Lopinavir 80 mg plus 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 plus ritonavir 25 mg
  • [Kaletra] Lopinavir 200 mg plus ritonavir 50 mg
Dosing Recommendations Selected Adverse Events
Neonatal Dose (Aged <14 Days):
  • No data on appropriate dose or safety in this age group. Do not administer to neonates before a post-menstrual age of 42 weeks and a postnatal age of at least 14 days due to potential toxicities.
Dosing for Individuals Not Receiving Concomitant Nevirapine, Efavirenz, Fosamprenavir, or Nelfinavir
Infant Dose (Aged 14 Days–12 Months):
  • Once-daily dosing is not recommended.
  • Lopinavir/ritonavir (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: 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.
Pediatric 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/Ritonavir 100 mg/25 mg Pediatric Tablets for 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 Four of the LPV/r 100 mg/25 mg tablets can be substituted with two tablets each containing LPV/r 200 mg/50 mg in children capable of swallowing a larger tablet.
b In patients receiving concomitant nevirapine, efavirenz, fosamprenavir, or nelfinavir, weighing >45 kg, 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 Dose (Aged >18 Years):
  • 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 or adolescents, or 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 list).
In Patients 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.
Pediatric Dose (Aged >12 Months to 18 Years):
  • 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 Dose (Aged >18 Years):
  • 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 Saquinavir Hard-Gel Capsules or in Combination with Maraviroc:
  • Saquinavir and maraviroc doses may need modification (see the Saquinavir and Maraviroc sections for more information). The combination of saquinavir and LPV/r is not recommended.
  • Gastrointestinal (GI) intolerance, nausea, vomiting, diarrhea, taste alteration
  • 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 77º F (25º C) if used within 2 months. If kept refrigerated (2º C to 8º C or 36º F to 46º F), 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 specifically 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 P (CYP) 3A4 inhibitor and substrate.
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 co-formulation 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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