What are drug interactions of integrase strand transfer inhibitors (INSTIs)?

Answer

The main concern regarding interactions with integrase strand transfer inhibitors (INSTIs) is the potential for decreased absorption from the gut by polyvalent cations. If coadministration is necessary, give INSTI at least 2 hours before or at least 6 hours after supplements containing polyvalent cations, including but not limited to the following: cation-containing laxatives or antacids; Fe, Ca, or Mg supplements; and sucralfate. Monitor for virologic efficacy.^[7]

INSTIs are substrates of UGT1A1. Strong UGT1A1 inducers (eg, rifampin) may result in reduced INSTI plasma concentrations, resulting in treatment failure. Elvitegravir (EVG) is also a substrate of CYP3A4. Coadministration with CYP3A4 inducers may result in loss of virologic efficacy.^[9]

The INSTIs bictegravir and dolutegravir have mixed metabolic pathways, including both CYP3A4 and UGT1A1. Drugs that induce or inhibit these enzymes may have variable effect on the PKs of these INSTIs.

For more information, see NIH Guidelines for Drug Interactions between Integrase Inhibitors and Other Drugs.

Table 4. INSTIs and Their Metabolic Pathways^[7] (Open Table in a new window)

Generic (Brand)	Metabolized by (ie, Substrate of)	Induces	Inhibits
Dolutegravir (Tivicay) DTG	P-gp CYP3A4 (small contribution) UGT1A1	-	Renal transporters OCTS and MATE
Elvitegravir (Vitekta) EVG	CYP3A4 UGT1A1	-	-
Raltegravir (Isentress) RAL	UGT1A1	-	-
Bictegravir (Biktarvy) BIC	CYP3A UGT1A1	-	OCT2 and MATE1

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