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.

  •   Table of Contents

Download Guidelines

Integrase Inhibitors

Dolutegravir

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

Dolutegravir (DTG, Tivicay)
Dolutegravir (DTG, Tivicay)
For additional information see Drugs@FDA: https://www.accessdata.fda.gov/scripts/cder/daf/
Formulations
Tablets: 10 mg, 25 mg, and 50 mg

Fixed-Dose Combination Tablets:
  • [Juluca] Dolutegravir 50 mg/rilpivirine 25 mg
  • [Triumeq] Abacavir 600 mg/dolutegravir 50 mg/lamivudine 300 mg
Dosing Recommendations Selected Adverse Events
Neonate and Infant Dose:
  • Dolutegravir is not approved for use in neonates/infants.
Child and Adolescent Dose:
  • No dosing recommendations can be made for children weighing <25 kg.
  • The Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV (the Panel) recommends an investigational dose of dolutegravir 50 mg once daily for children and adolescents weighing ≥25 kg who are antiretroviral (ARV)-naive or ARV-experienced (but integrase strand transfer inhibitor [INSTI]-naive) and who are not being treated with uridine diphosphate glucuronyl transferase (UGT) 1A1 or cytochrome P450 3A (CYP3A) inducers.
  • The Panel’s recommended dose is based on interim data from ongoing trials that indicate that using the FDA-approved dose of dolutegravir 35 mg in patients weighing ≥30 kg to 40 kg may result in suboptimal trough concentrations (see text). Using a 50-mg dose also avoids the need to administer two tablets with different strengths (i.e., a 10-mg tablet plus a 25-mg tablet). Dolutegravir is not approved by the Food and Drug Administration (FDA) for use in children weighing <30 kg.
Child and Adolescent (Weighing ≥40 kg) and Adult Dose
Population Recommended Dose
ARV-naive or ARV-experienced/INSTI-naive patients Dolutegravir 50 mg once daily
ARV-naive or ARV-experienced/INSTI-naive patients who are also receiving one of the following potent UGT1A/CYP3A inducers: efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, or rifampin Dolutegravir 50 mg twice daily
INSTI-experienced patients with any INSTI-associated resistance substitutions or clinically suspected INSTI resistancea Dolutegravir 50 mg twice daily
a These patients should receive drug combinations that do not include metabolic inducers when possible.

[Juluca] Dolutegravir/Rilpivirine
Adult Dose:
  • One tablet once daily with a meal as a complete regimen to replace the current ARV regimen in patients who have been virologically suppressed (HIV RNA <50 copies/mL) on a stable ARV regimen for at least 6 months with no history of treatment failure and no known substitutions associated with resistance to the individual components of Juluca.
  • Juluca is not approved for use in children or adolescents. See the Simplification of Treatment section below.
[Triumeq] Abacavir/Dolutegravir/Lamivudine
Child and Adolescent (Weighing ≥25 kg) and Adult Dose:
  • One tablet once daily
  • For use in patients who are ARV-naive or ARV-experienced (but INSTI-naive) and who are not being treated with UGT1A1 or CYP3A inducers
  • See the abacavir section for special instructions about testing for abacavir hypersensitivity.
  • The FDA-approved dose for pediatric patients weighing >40 kg is one tablet once daily.
  • Insomnia
  • Headache
  • Neuropsychiatric symptoms (i.e., depression and/or suicidal thoughts or actions), especially in patients with a history of psychiatric illness
  • Rare cases of hypersensitivity reactions, including rash and drug reaction (or rash) with eosinophilia and systemic symptoms, constitutional symptoms, and organ dysfunction (including liver injury) have been reported.
Special Instructions
  • Dolutegravir may be taken without regard to meals.
  • Dolutegravir should be taken 2 hours before or 6 hours after taking cation-containing antacids or laxatives, sucralfate, oral iron supplements, oral calcium supplements, or buffered medications.
  • In patients who have difficulty swallowing tablets whole, 10-mg, 25-mg, and 50-mg tablets may be either split into halves followed by immediate ingestion of both halves of the tablet, or crushed and added to a small amount of semisolid food or liquid, all of which should be consumed immediately.1
  • The efficacy of dolutegravir 50 mg twice daily is reduced in patients with certain combinations of INSTI-resistance mutations (see the Resistance section below).
  • When using fixed-dose combination (FDC) tablets that contain dolutegravir, see other sections of the Drug Appendix for special instructions and additional information about the individual components of the FDC.
Metabolism/Elimination
  • UGT1A1 and CYP3A substrate. Drugs that induce these enzymes and transporters may decrease plasma concentrations of dolutegravir.
Dolutegravir Dosing in Patients with Hepatic Impairment:
  • No dose adjustment is necessary in patients with mild or moderate hepatic impairment. Due to a lack of data, dolutegravir is not recommended for use in patients with severe hepatic impairment.
  • Dolutegravir decreases tubular secretion of creatinine and increases measured serum creatinine, without affecting glomerular filtration.
Dolutegravir Dosing in Patients with Renal Impairment:
  • No dose adjustment is required in INSTI-naive patients with mild, moderate, or severe renal impairment, or in INSTI-experienced patients with mild or moderate renal impairment.
  • Use dolutegravir with caution in INSTI-experienced patients with severe renal impairment (creatinine clearance <30 mL/min), because dolutegravir concentrations will be decreased. The cause of this decrease is unknown.

Download Guidelines