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

Raltegravir (RAL, Isentress)
Raltegravir (RAL, Isentress)
For additional information see Drugs@FDA: https://www.accessdata.fda.gov/scripts/cder/daf/
Formulations
Tablet: 400 mg (film-coated poloxamer tablet)
HD Tablet: 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 a final concentration of 10 mg/mL.

Note: Film-coated tablets, chewable tablets, and oral suspension are not interchangeable.
Dosing Recommendations Selected Adverse Events
Note: No dosing information is available for preterm infants or infants weighing <2 kg at birth. (See Antiretroviral Management of Newborns with Perinatal HIV Exposure or Perinatal HIV and Table 12 for information about using raltegravir for the prevention of perinatal HIV transmission).

Neonate (Weighing ≥2 kg) Dose
Raltegravir Oral Suspension Dosing Table for Full-Term Neonates from Birth to Age 4 Weeks:
Neonates Aged ≥37 Weeks and Weighing ≥2 kg
Body Weight Volume (Dose) of Suspension
Birth to 1 Week of Age:
Once-Daily Dosing
Approximately 1.5 mg/kg/dose
2 kg to <3 kg 0.4 mL (4 mg) once daily
3 kg to <4 kg 0.5 mL (5 mg) once daily
4 kg to <5 kg 0.7 mL (7 mg) once daily
1–4 Weeks of Age:
Twice-Daily Dosing
Approximately 3 mg/kg/dose
2 kg to <3 kg 0.8 mL (8 mg) twice daily
3 kg to <4 kg 1 mL (10 mg) twice daily
4 kg to <5 kg 1.5 mL (15 mg) twice daily

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

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

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

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

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

Child and Adolescent Dose for Chewable Tablets, Film-Coated Tablets, and HD Tablets
Children Weighing ≥11 kg:
  • Weighing <25 kg: Chewable tablets twice daily. See table below for chewable tablet dose.
  • Weighing ≥25 kg: Raltegravir 400-mg, film-coated tablet twice daily or chewable tablets twice daily. See table below for chewable tablet dose.
Children and Adolescents Weighing ≥50 kg:
  • Two raltegravir 600-mg HD tablets (1,200 mg) once daily
  • This dose is for treatment-naive or virologically suppressed patients who are on an initial dose of raltegravir 400 mg twice daily.
  • See the Approval section under the Pediatric Use heading below for more information.
Chewable Tablet Dosing Tablea
Body Weight Dose Number of Chewable Tablets
11 kg to <14 kg Raltegravir 75 mg twice daily  Three 25-mg tablets twice daily 
14 kg to <20 kg Raltegravir 100 mg twice daily  One 100-mg tablet twice daily 
20 kg to <28 kg Raltegravir 150 mg twice daily  One and a half 100-mg tabletsb twice daily 
28 kg to <40 kg Raltegravir 200 mg twice daily  Two 100-mg tablets twice daily 
≥40 kg Raltegravir 300 mg twice daily  Three 100-mg tablets twice daily 
a The weight-based dose recommendation for the chewable tablet is based on approximately raltegravir 6 mg/kg per dose twice daily.
b The raltegravir 100-mg chewable tablet can be divided into equal halves.

Note:
Maximum dose of chewable tablets is raltegravir 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
  • Raltegravir can be given without regard to food.
  • Coadministration or staggered administration of aluminum-containing 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 coadministered: 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.
  • The 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 formulations.
  • The chewable tablets should be stored in the original package with a desiccant to protect them from moisture.
  • The chewable tablets contain phenylalanine. Therefore, patients with phenylketonuria should make the necessary dietary adjustments.
  • The oral suspension comes in a kit that includes mixing cups, oral dosing syringes, and 60 foil packets. Detailed instructions for preparation 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 raltegravir 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 in patients who have mild-to-moderate hepatic insufficiency and are receiving twice daily dosing of raltegravir.
  • No dose adjustment is necessary for patients with mild-to-moderate hepatic insufficiency who are receiving either raltegravir 1,200 mg once daily or 400 mg twice daily.
  • No studies have been conducted on the use of raltegravir HD 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 is necessary in patients with any degree of renal impairment.

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