Coadministration of calcium supplements decreased dolutegravir AUC, Cmax and C24 by 39%, 37% and 39%, respectively due to complex binding to polyvalent ions. Calcium supplements should be taken well separated in time from the administration of dolutegravir (minimum 2 hours after or 6 hours before). Factors that decrease dolutegravir exposure should be avoided in the presence of integrase class resistance. This includes co-administration with medicinal products that reduce dolutegravir exposure (e.g. calcium supplements).

Coadministration may decrease dolutegravir concentrations. Coadministration of calcium carbonate (1200 mg) and dolutegravir (50 mg single dose) was studied under fasted, fed and temporally separated conditions. Simultaneous coadministration to fasting subjects (n=12) decreased dolutegravir Cmax, AUC and Cmin by 37%, 39% and 39%, respectively. Simultaneous coadministration to fed subjects (n=11) increased dolutegravir Cmax, AUC and Cmin by 7%, 9% and 8%, respectively. Coadministration of calcium carbonate 2 h after dolutegravir (n=11) had no effect on dolutegravir Cmax and decreased dolutegravir AUC and Cmin by 6% and 10%, respectively. Administer dolutegravir 2 hours before or 6 hours after taking supplements containing calcium. Alternatively, dolutegravir and supplements containing calcium can be taken together with food.

Coadministration of calcium carbonate (1200 mg) and dolutegravir (50 mg single dose) was studied under fasted, fed and temporally separated conditions. Simultaneous coadministration to fasting subjects (n=12) decreased dolutegravir Cmax, AUC and Cmin by 37%, 39% and 39%, respectively. Simultaneous coadministration to fed subjects (n=11) increased dolutegravir Cmax, AUC and Cmin by 7%, 9% and 8%, respectively. Coadministration of calcium carbonate 2 h after dolutegravir (n=11) had no effect on dolutegravir Cmax and decreased dolutegravir AUC and Cmin by 6% and 10%, respectively. Dolutegravir and calcium supplements can be co-administered if taken with a meal. Under fasted conditions, dolutegravir should be administered 2 hours before or 6 hours after calcium supplements.