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 14, 2020; Last Reviewed: April 14, 2020

Lopinavir/Ritonavir (LPV/r, Kaletra)
Lopinavir/Ritonavir (LPV/r, Kaletra)
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
For additional information, see Drugs@FDA or DailyMed.
Dosing Recommendations Selected Adverse Events
Neonate (Aged <14 Days) Dose:
  • Lopinavir/ritonavir (LPV/r) is not approved by the Food and Drug Administration (FDA) for use in neonates before a postmenstrual age of 42 weeks and a postnatal age of at least 14 days. However, when no alternatives are available for neonates who have not met these age thresholds, some members of the Panel would consider using LPV/r oral solution at a dose of 300 mg/75 mg per m2 of body surface area per dose twice daily in combination with careful monitoring of serum osmolality, serum creatinine, liver function enzymes, cardiac function, and electrolytes. This use of LPV/r is based on limited research and clinical experience. The potential benefit of using LPV/r in premature infants must be carefully balanced with the risk of metabolic and cardiac toxicity.
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. Use of this dose in infants aged <12 months is associated with lower LPV trough levels than those found in adults; LPV dosing should be adjusted for growth at frequent intervals (see text below). Also see text for information on transitioning infants to the lower mg per m2 dose.
Child and Adolescent (Aged >12 Months to 18 Years) Dose:
  • 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 antiretroviral therapy (ART)-experienced patients who could harbor virus with decreased LPV 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 LPV 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 per dose given twice daily 230 mg/m2 per 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 (NVP), efavirenz (EFV), fosamprenavir (FPV), or nelfinavir (NFV), the 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 NVP, EFV, FPV, or NFV; or in patients with three or more LPV-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 or Efavirenz:
  • These drugs induce LPV metabolism and reduce LPV 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.
Lopinavir/Ritonavir 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 Formulations).
  • 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.
  • Children aged <18 years who receive once-daily dosing of LPV/r have shown considerable variability in plasma concentrations and have a higher incidence of diarrhea. Therefore, once-daily dosing is not recommended for this age group.
  • Use of LPV/r once daily is contraindicated if three or more of the following LPV 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 LPV trough concentrations may be required to suppress resistant virus.
Metabolism/Elimination
  • Cytochrome P450 3A4 substrate and inhibitor.
Lopinavir/Ritonavir Dosing in Patients with Hepatic Impairment:
  • LPV/r is primarily metabolized by the liver. Use caution when administering LPV to patients with hepatic impairment. No dosing information is currently available for children or adults with hepatic insufficiency.
  • In the coformulation of LPV/r, ritonavir acts as a pharmacokinetic enhancer, not as an ARV agent. It does this by inhibiting the metabolism of LPV and increasing LPV plasma concentrations.

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