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

Dolutegravir

Last Updated: September 12, 2019; Last Reviewed: September 12, 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:
  • [Dovato] Dolutegravir 50 mg/lamivudine 300 mg
  • [Juluca] Dolutegravir 50 mg/rilpivirine 25 mg
  • [Triumeq] Abacavir 600 mg/dolutegravir 50 mg/lamivudine 300 mg
When using fixed-dose combination (FDC) tablets, refer to other sections of the Drug Appendix for special instructions, drug interaction information, and additional information about the individual components of the FDC. See also Appendix A, Table 2. Antiretroviral Fixed-Dose Combination Tablets: Minimum Body Weights and Considerations for Use in Children and Adolescents.

Dosing Recommendations Selected Adverse Events
Neonate and Infant Dose:
  • Dolutegravir is not approved for use in neonates/infants.
Child (Weighing <20 kg) Dose:
  • No dosing recommendations can be made for children weighing <20 kg.
Child and Adolescent (Weighing ≥20 kg to <40 kg) Dose:
  • 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 ≥20 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 or inhibitors.
  • Dolutegravir is not approved by the Food and Drug Administration (FDA) for use in children weighing <30 kg. However, 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, and additional data supports the 50-mg dose recommended by the Panel (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).


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 dailya
INSTI-experienced patients with any INSTI-associated resistance substitutions or clinically suspected INSTI resistance8 Dolutegravir 50 mg twice dailya,b
a The 50-mg, twice-daily dose should not be used in patients weighing <40 kg.

b These patients should receive drug combinations that do not include metabolic inducers when possible.

[Dovato] Dolutegravir/Lamivudine
Adult Dose:
  • One tablet once daily with or without food as a complete regimen in ARV-naive adults with no known substitutions associated with resistance to the individual components of Dovato.
  • Dovato is not approved for use in children or adolescents. See the Simplification of Treatment section below.
[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 with or without food.
  • 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).
  • Patients should be tested for hepatitis B virus (HBV) infection prior to use of Triumeq or Dovato. Lamivudine-resistant HBV variants have been reported in patients who recieved lamivudine-containing ARV regimens. Patients with HBV/HIV coinfection who receive Dovato will require additional treatment for chronic HBV infection. Severe exacerbation of hepatitis can occur in patients with HBV/HIV coinfection who discontinue lamivudine.
Metabolism/Elimination
  • UGT1A1 and CYP3A substrate: Drugs that induce these enzymes and transporters may decrease plasma concentrations of dolutegravir. Drugs that inhibit these enzymes may increase dolutegravir plasma concentrations.
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.

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