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Dolutegravir FDA Product Information - ART Drug Interactions
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TIVICAY tablets may be taken with or without food.
Effects of Food on Oral Absorption
TIVICAY may be taken with or without food. Food increased the extent of absorption and slowed the rate of absorption of dolutegravir. Low-, moderate-, and high-fat meals increased dolutegravir AUC(0-∞) by 33%, 41%, and 66%; increased Cmax by 46%, 52%, and 67%; and prolonged Tmax to 3, 4, and 5 hours from 2 hours under fasted conditions, respectively.
The UGT1A1 inhibitor atazanavir, and atazanavir/ritonavir, raised dolutegravir area under the concentration-time curve (AUC) 69% to 91% and raised maximum concentrations 33% to 49%. UGT and CYP3A inducers, such as darunavir, tipranavir, fosamprenavir, efavirenz, and rifabutin, lowered dolutegravir exposure from 30% to 76%. The investigators believe these changes in dolutegravir levels are not clinically relevant because dolutegravir exposures remained above those that proved effective in phase 2 dose-ranging trials. Study results indicated that dolutegravir should be dosed at 50 mg twice daily instead of once daily when given with rifampin, a CYP3A4 inducer, in integrase inhibitor-naive people.
Etravirine, a strong CYP3A inducer, lowered dolutegravir trough concentrations by 88%, though that drop was eased by coadministration of CYP3A inhibitors lopinavir/ritonavir or darunavir/ritonavir. The ViiV team believes dolutegravir may be prescribed with etravirine without dose adjustment in people also taking boosted lopinavir or darunavir, but it should not be administered with 200 mg of etravirine twice daily in people not taking a boosted PI.
The antacid Maalox cut dolutegravir exposure more than 70% when the drugs were taken together, not because of a pH effect but because of metal cation chelation. Separating administration of Maalox and dolutegravir by 2 hours attenuated this interaction. ViiV is proposing administering dolutegravir 2 hours before or 6 hours after an antacid.
Darunavir/ritonavir, lopinavir/ritonavir, rilpivirine, tenofovir, boceprevir, prednisone, rifabutin, and omeprazole had no clinically significant effect on the pharmacokinetics of dolutegravir.





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