Drug Detail

Dolutegravir

Last Updated June 10, 2016

Trade Names

  • Dolutegravir: Tivicay
  • Dolutegravir/abacavir/lamivudine: Triumeq

Drug Classification

Integrase strand transfer inhibitor antiretroviral

Formulations

  • Dolutegravir: 10 mg, 25 mg, 50 mg tablets*
  • Dolutegravir/abacavir/lamivudine: 50/600/300 mg tablets*

Indications and Pharmacology

Indication*: treatment of HIV infection in combination with other antiretrovirals.

Mechanism of action: inhibits the catalytic activity of HIV-1 integrase, the enzyme responsible for inserting the viral DNA into the human genome, thereby preventing integration of the proviral gene into the human DNA.

Pharmacokinetics*: metabolized via UGT1A1 with some contribution from CYP3A. 53% excreted in feces and 31% in the urine. Terminal half-life: approximately 14 hours.

Dosage

Adult Dose (can be taken with or without food)

  • Treatment-naive or treatment-experienced INSTI-naive: 50 mg once daily
  • INSTI resistance: 50 mg twice daily

Use in Renal or Hepatic Insufficiency:

  • No dosage adjustment necessary for renal impairment
  • No dose adjustments necessary for mild liver impairment; contraindicated in moderate/severe liver impairment

Use in Pregnancy and Breastfeeding: There are insufficient human data on dolutegravir use during pregnancy to determine if there are drug-associated risks of birth defects or miscarriage. Use during pregnancy only if potential benefit outweighs potential risk.*

Use in Children:

Pediatric patients (INSTI-naive and weighing at least 30 kg) (off-label in South Africa)*

  • Weight ≥ 40 kg: 50 mg once daily
  • Weight 30 kg to < 40 kg: 35 mg once daily
  • If coadministered with certain UGT1A or CYP3A inducers, adjust weight-based dose to twice daily.

Warnings

Contraindicated in patients with previous hypersensitivity reaction to dolutegravir, in patients with moderate or severe hepatic impairment, and in patients receiving metformin, dofetilide, or pilsicainide.

Hypersensitivity reactions characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury, have been reported. Immediately discontinue dolutegravir and other suspected drugs if signs or symptoms of hypersensitivity reaction occur; delay in discontinuation may result in life-threatening reaction.

Patients with hepatitis B or C virus infection may be at higher risk for development or worsening of transaminase elevations when taking dolutegravir. Appropriate laboratory testing before beginning dolutegravir therapy and on-treatment monitoring for hepatotoxicity is recommended in patients with underlying hepatic disease.*

Redistribution/accumulation of body fat, immune reconstitution syndrome, and osteonecrosis have been reported in patients treated with combination antiretroviral therapy.

Drug–Drug Interactions

Metabolic inducers may decrease dolutegravir plasma concentrations. Dolutegravir should be taken 2 hours before or 6 hours after taking sucralfate, cation-containing antacids or laxatives, calcium- or iron-containing oral supplements, or buffered medications. Alternatively, calcium- or iron-containing supplements and dolutegravir may be taken together with food.*

Considerations for Special Populations

See above for pregnancy and lactation

Adverse Effects

Insomnia, fatigue, dizziness, headache, abnormal dreams, nausea, diarrhea, vomiting, flatulence, abdominal pain, hepatitis, rash, pruritus.

*Information from US prescribing information.