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Dolutegravir

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Dolutegravir, Tivicay, DTG, Dovato, Juluca

  • See Also
  1. Integrase Strand Transfer Inhibitor
  2. Anti-Retroviral Therapy
  • Indications
  1. HIV Infection (part of combination therapy)
  • Contraindications
  1. Severe hepatic Impairment (Child-Pugh Class C)
  • Mechanism
  1. See Integrase Strand Transfer Inhibitor
  • Medications
  1. Dolutegravir (Tivicay) tablets: 10, 25 and 50 mg
  2. Combinations
    1. Dolutegravir and Lamivudine (Dovato)
    2. Dolutegravir 50 mg AND Rilpivirine 25 mg (Juluca)
      1. Indicated in stable disease with HIV RNA <50 copies/ml for >=6 months (no resistance or treatment failures)
      2. Dose one tablet orally daily
      3. (2018) Presc Lett, New Drug: Juluca, Resource #340209
  • Dosing
  • Adult
  1. Used as part of combination therapy
  2. Once daily protocol (InSTI naive)
    1. Take 50 mg orally daily
  3. Twice daily protocol (InSTI experienced)
    1. Take 50 mg orally twice daily
    2. Other indications (in addition to InSTI experienced)
      1. CYP3A4 Inducer (see below)
      2. UGT1A Inducer
  • Dosing
  • Child
  1. Indicated as part of combination therapy in InSTI naive children, weight >=30 kg
  2. Dose
    1. Weight 30 to 40 kg: 35 mg orally daily
    2. Weight >40 kg: 50 mg orally daily (adult dose)
  3. Frequency
    1. Dose twice daily if concurrent use of CYP3A4 Inducer or UGT1A Inducer
    2. Otherwise daily dosing
  • Adverse Effects
  1. Serum Creatinine increase
    1. Mild increases of Serum Creatinine without affecting GFR
  2. Hepatotoxicity
    1. Increased serum transaminases
    2. Higher risk in comorbid Hepatitis B or Hepatitis CVirus Infection
  • Safety
  1. Avoid in Lactation
  2. Pregnancy
    1. Preferred Integrase Strand Transfer Inhibitor in pregnancy (as of 2022, includes first trimester, which had been category X)
    2. Pregnancy registry exists
    3. Initial data with risk of Neural Tube Defects (and had been avoided at conception and first trimester)
      1. However further study demonstrates no increased risk compared with other ART
      2. Patel (2022) N Engl J Med 387(9):799-809 +PMID: 36053505 [PubMed]
  • Drug Interactions
  1. CYP3A4 Inducer or UGT1A Inducer
    1. Carbamazepine
    2. Efavirenz
    3. Fosamprenavir/r
    4. Rifampin
    5. Tipranavir/r
  2. Metformin
    1. Limit Metformin dose to 1000 mg/day
    2. Dolutegravir increases Metformin levels
  3. Medications that interfere with absorption (take Dolutegravir 2 hours before or 6 hours after these agents)
    1. Aluminum Hydroxide and Magnesium Hydroxide Antacid
    2. Sucralfate
    3. Oral Calcium supplement (may be taken with Dolutegravir if during mealtime)
    4. Oral iron supplement (may be taken with Dolutegravir if during mealtime)
    5. Buffered medications
  4. Medications contraindicated with Dolutegravir
    1. Dofetilide
    2. Oxcarbazepine
    3. Phenytoin
    4. Phenobarbital
    5. St Johns Wort
  • Pharmacokinetics
  1. Excretion via Glucuronidation
  2. No dose adjustment in renal disease, but severe renal disease is associated with decreased serum levels of Dolutegravir
  • Resources
  1. Dolutegravir (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=807b0cd2-093c-4353-a4a5-2e1f264616ba