Dolutegravir

Products

Dolutegravir was approved in the United States and EU in 2013 in film-coated tablet form (Tivicay). It was registered in many countries in 2014. A fixed-dose combination with dolutegravir, abacavir, and lamivudine is also available (Triumeq). In 2017, a combination product with rilpivirine was launched in the US (Juluca). It was approved in the EU in 2018 and in many countries in 2019. Dolutegravir is further also combined with lamivudine fixed (Dovato, approval 2019).

Structure and properties

Dolutegravir (C20H19F2N3O5, Mr = 419.4 g/mol) is present in the drug as dolutegravir sodium, a white to yellowish powder that is sparingly soluble in water. It is a tricyclic carbamoylpyridone.

Effects

Dolutegravir (ATC J05AX12) has antiviral properties against HIV. It is a specific inhibitor of HIV integrase, an enzyme responsible for the integration of the HIV genome into the host cell genome at the onset of infection. This prevents the virus from replicating. Dolutegravir has a half-life of approximately 14 hours and remains bound to integrase for days.

Indications

For treatment of HIV-1 infection (combination antiretroviral therapy).

Dosage

According to the SmPC. Tablets are taken once daily, regardless of meals.

Contraindications

  • Hypersensitivity
  • Dolutegravir should not be co-administered with dofetilide because it inhibits its renal elimination via OCT2

Full precautions can be found in the drug label.

Interactions

Dolutegravir is metabolized primarily by UGT1A1, with involvement of CYP3A. Metabolic inducers may decrease plasma concentrations. Antacids, laxatives, iron, calcium, and buffered drugs should be administered at least two hours apart because they may reduce absorption.

Adverse effects

The most common possible adverse effects include headache, nausea, and diarrhea.