As with other HIV integrase inhibitors, bictegravir may be subject to chelation by high concentrations of divalent cations which may result in reduced bictegravir concentrations. Bictegravir and calcium supplements can be coadministered simultaneously. The European product label for Biktarvy recommends they can be taken together without regard to food, but the US product label recommends to administer simultaneously with food. (The decision to administer with or without food should be decided on a case-by-case basis.) The simultaneous administration of calcium carbonate (1200 mg) and bictegravir with food did not significantly modify bictegravir exposure whereas exposure was decreased by 33% when coadministered in fasted conditions. No interaction is expected with emtricitabine and tenofovir alafenamide.

Coadministration has not been studied. Zinc is poorly absorbed from the gastro-intestinal tract. It is widely distributed throughout the body and is excreted in the faeces with traces appearing in the urine. Coadministration may decrease bictegravir concentrations due to chelation with the polyvalent zinc cations. Bictegravir should be administered at least 2 hours before zinc, or taken together with food.