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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Integrase Inhibitors

Raltegravir

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

Raltegravir (RAL, Isentress)
Raltegravir (RAL, Isentress)
For additional information see Drugs@FDA: https://www.accessdata.fda.gov/scripts/cder/daf/
Formulations
Tablets: 400 mg (film-coated poloxamer tablet)
HD Tablets: 600 mg (film-coated poloxamer tablet)
Chewable Tablets: 100 mg (scored) and 25 mg
Granules for Oral Suspension: Single-use packet of 100 mg of raltegravir, suspended in 10 mL of water for final concentration of 10 mg/mL.

Note: Film-coated tablets, chewable tablets, and oral suspension are not interchangeable.

Dosing Recommendations Selected Adverse Events
See Antiretroviral Management of Newborns with Perinatal HIV Exposure or Perinatal HIV and Table 12. Newborn Antiretroviral Dosing Recommendations for prevention of perinatal transmission.

Neonate Dose
Neonates ≥37 Weeks of Gestation (Weighing ≥2 kg):
  • No dosing information is available for preterm or low birthweight infants.
Oral Suspension Dosing Table
Full-Term Neonates (Birth to 4 Weeks [28 Days] of Age):
Body Weight (kg) Volume (Dose) of Suspension to be Administered
Birth to 1 Week: Once-Daily Dosing Approximately 1.5 mg/kg/dose
2 to <3 0.4 mL (4 mg) once daily
3 to <4 0.5 mL (5 mg) once daily
4 to <5 0.7 mL (7 mg) once daily
1–4 Weeks: Twice-Daily Dosing Approximately 3 mg/kg/dose
2 to <3 0.8 mL (8 mg) twice daily
3 to <4 1 mL (10 mg) twice daily
4 to <5 1.5 mL (15 mg) twice daily

Note: If the mother has taken raltegravir 2 to 24 hours prior to delivery, the neonate’s first dose should be delayed until 24 to 48 hours after birth.

Note: Metabolism by uridine diphosphate glucotransferase (UGT1A1) is low at birth and increases rapidly over the next 4 to 6 weeks of life.

Infant and Pediatric Dose
Oral Suspension Dosing Tablea
Children Aged ≥4 Weeks and Weighing ≥3 kg to <20 kg:
Body Weight (kg) Volume (Dose) of Suspension to be Administered
3 to <4 2.5 mL (25 mg) twice daily
4 to <6 3 mL (30 mg) twice daily
6 to <8 4 mL (40 mg) twice daily
8 to <11 6 mL (60 mg) twice daily
11 to <14 8 mL (80 mg) twice daily
14 to <20 10 mL (100 mg) twice daily
a The weight-based dosing recommendation for the oral suspension is based on approximately 6 mg/kg/dose twice daily.

Note: Maximum dose of oral suspension is 10 mL (100 mg) twice daily.

Note: For children weighing 11 kg to 20 kg, either oral suspension or chewable tablets can be used.

Pediatric Dose for Chewable Tablets, Film-Coated Tablets, and HD Tablets
Children Weighing ≥11 kg:
  • <25 kg: Chewable tablets twice daily. See table below for chewable tablet dose.
  • ≥25 kg: 400-mg film-coated tablet twice daily or chewable tablets twice daily. See table below for chewable tablet dose.
Child and Adolescent Weighing ≥50 kg (HD), see Pediatric Use, Approval:
  • 1200 mg (two 600 mg HD) once daily
  • For treatment-naive or virologically suppressed patients on an initial regimen of 400 mg twice daily.
Chewable Tablet Dosing Tablea
Body Weight (kg) Dose Number of Chewable Tablets
11 to <14 75 mg twice daily 3 X 25 mg twice daily
14 to <20 100 mg twice daily 1 X 100 mg twice daily
20 to <28 150 mg twice daily 1.5 X 100 mgb twice daily
28 to <40 200 mg twice daily 2 X 100 mg twice daily
≥40 300 mg twice daily 3 X 100 mg twice daily
a The weight-based dose recommendation for the chewable tablet is based on approximately 6 mg/kg/dose twice daily.
b The 100-mg chewable tablet can be divided into equal halves.

Note: Maximum dose of chewable tablets is 300 mg twice daily.
  • Rash, including Stevens-Johnson syndrome, hypersensitivity reaction, and toxic epidermal necrolysis
  • Nausea, diarrhea
  • Headache, dizziness, fatigue
  • Insomnia
  • Fever
  • Creatine phosphokinase elevation, muscle weakness, and rhabdomyolysis
Special Instructions
  • Can be given without regard to food.
  • Co-administration or staggered administration of aluminum- and magnesium-containing antacids is not recommended with any raltegravir formulations.
  • Significant drug interactions are more likely to occur when the raltegravir HD formulation is used once daily. The following drugs should not be co-administered: calcium carbonate, rifampin, tipranavir/ritonavir, and etravirine.
  • Chewable tablets can be chewed, crushed (before administration), or swallowed whole.
  • Film-coated tablets, including HD tablets, must be swallowed whole.
  • Chewable tablets and oral suspension have better bioavailability than the film-coated tablets. Because the formulations are not interchangeable, do not substitute chewable tablets or oral suspension for film-coated tablets. See specific recommendations for proper dosing of different preparations.
  • Chewable tablets should be stored in the original package with desiccant to protect them from moisture.
  • Chewable tablets contain phenylalanine. Therefore, patients with phenylketonuria should make the necessary dietary adjustments.
  • Oral suspension is provided in kits that include mixing cups, oral dosing syringes, and 60 foil packets. Detailed instructions are provided in the Instructions for Use document. Each foil packet is single-use and contains 100 mg of raltegravir, which will be suspended in 10 mL of water for a final concentration of 10 mg/mL. Gently swirl the mixing cup for 45 seconds in a circular motion to mix the powder into a uniform suspension.
  • Do not shake the oral suspension. Dose should be administered within 30 minutes of mixing; unused solution should be discarded as directed in the Instructions for Use document.
Metabolism/Elimination
  • UGT1A1-mediated glucuronidation.
Raltegravir Dosing in Patients with Hepatic Impairment:
  • No dose adjustment is necessary for standard-dose raltegravir in patients with mild-to-moderate hepatic insufficiency. No dosing studies of raltegravir HD have been done in patients with hepatic impairment. Therefore, administration of raltegravir HD is not recommended in patients with hepatic impairment. The effect of severe hepatic impairment on raltegravir pharmacokinetics has not been studied.
Raltegravir Dosing in Patients with Renal Impairment:
  • No dose adjustment necessary in patients with any degree of renal impairment.

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