Raltegravir

Body
Raltegravir (RAL, Isentress)
Formulations

Tablet: 400 mg (film-coated poloxamer tablet)
High-Dose (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.

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

For additional information, see Drugs@FDA or DailyMed.
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 HIV Infection and Table 12 for information about using raltegravir (RAL) for the prevention of perinatal HIV transmission.

Neonate (Weighing ≥2 kg) Dose:
  • RAL is metabolized by uridine diphosphate glucuronyl transferase (UGT1A1), and enzyme activity is low at birth; enzyme activity increases rapidly during the next 4 to 6 weeks of life.

Raltegravir Oral Suspension Dosing Table for Full-Term Neonates from Birth to Age 4 Weeks
Neonates Aged ≥37 Weeks and Weighing ≥2 kg:
Weight Volume (Dose) of Suspension
Birth to 1 Week of Age:
Once-Daily Dosing		 Approximately 1.5 mg/kg per 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 per 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 RAL 2 hours to 24 hours prior to delivery, the neonate’s first dose should be delayed until 24 hours to 48 hours after birth.            

Infant and Child (Weighing ≥3 kg to <20 kg) Dose:

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

Raltegravir Oral Suspension Dosing Table for Patients Aged >4 Weeksa
Note: The maximum dose of oral suspension is 10 mL (RAL 100 mg) twice daily.
Weight Twice-Daily Volume (Dose) of Suspension
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 a dose of approximately RAL 6 mg/kg per dose twice daily.

Child and Adolescent Dose for Chewable Tablets, Film-Coated Tablets, and High-Dose Tablets
Children Weighing ≥11 kg

Weighing <25 kg:

  • Chewable tablets twice daily. See table below for chewable tablet dose.

Weighing ≥25 kg:

  • RAL 400-mg, film-coated tablet twice daily or chewable tablets twice daily. See table below for chewable tablet dose.
Children and Adolescents Weighing ≥40 kg:
  • Two RAL 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 RAL 400 mg twice daily.

Chewable Tablet Dosing Tablea
Note: The maximum dose of chewable tablets is RAL 300 mg twice daily.

Weight Twice-Daily Dose Number of Chewable Tablets
11 kg to <14 kg RAL 75 mg 3 tablets (25 mg) twice daily 
14 kg to <20 kg RAL 100 mg  1 tablet (100 mg) twice daily 
20 kg to <28 kg RAL 150 mg  1 ½ tabletsb (100 mg) twice daily
28 kg to <40 kg RAL 200 mg  2 tablets (100 mg) twice daily 
≥40 kg RAL 300 mg 3 tablets (100 mg) twice daily 
a The weight-based dose recommendation for the chewable tablet is based on a dose of approximately RAL 6 mg/kg per dose twice daily.
b The RAL 100-mg chewable tablet can be divided into equal halves.
  • 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
  • RAL can be given without regard to food.
  • Coadministration or staggered administration of aluminum-containing and magnesium-containing antacids is not recommended with any RAL formulations.
  • Significant drug interactions are more likely to occur when the RAL HD formulation is used once daily. The following drugs should not be coadministered with once daily RAL HD dosing: 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, a component of aspartame. Phenylalanine can be harmful to patients with phenylketonuria, and the necessary dietary adjustments should be made in consultation with a metabolic specialist.
  • 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 single-use foil packet contains 100 mg of RAL, which will be suspended in 10 mL of water for a final concentration of RAL 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. For neonates, most of the prepared oral suspension will be discarded, as the volume for the required dose is much smaller than 10 mL.
Metabolism/Elimination
  • UGT1A1-mediated glucuronidation
Raltegravir Dosing in Patients with Hepatic Impairment:
  • No dose adjustment is necessary for patients with mild-to-moderate hepatic insufficiency who are receiving RAL twice daily.
  • No dose adjustment is necessary for patients with mild-to-moderate hepatic insufficiency who are receiving either RAL 1,200 mg once daily or RAL 400 mg twice daily.
  • No studies have been conducted on the use of RAL HD in patients with hepatic impairment. Therefore, administering RAL HD is not recommended in patients with hepatic impairment.
  • The effect of severe hepatic impairment on RAL 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.