Calcium, Iron Supplements Can Affect HIV Med Levels
the MPR take:
Dolutegravir, an integrase strand transfer inibitor, is indicated for the treatment of HIV-1 infection in adults and children aged ≥12 years and weighing at least 40kg, in combination with other antiretroviral agents. This agent inhibits HIV integrase by binding to the integrase active site and blocking the strand transfer step of retroviral deoxyribonucleic acid (DNA) integration, which is essential for the HIV replication cycle. Drugs of this class are susceptible to interactions with metal cation-containing drugs and in a study published in the journal Annals of Pharmacotherapy, both calcium and iron supplements reduced dolutegravir plasma levels under fasted conditions. Given that HIV-infected patients commonly take mineral supplements while on antiretroviral therapy, the researchers aimed to determine strategies to attenuate the effects that mineral supplements have on dolutegravir. In this study, researchers examined dolutegravir plasma levels under various conditions: dolutegravir without mineral supplements, fasting; dolutegravir with ferrous fumarate or calcium carbonate, fasting; dolutegravir with ferrous fumarate or calcium carbonate with a moderate-fat meal; and dolutegravir given two hours before ferrous fumarate or calcium carbonate, fasting. Under fasting conditions, both mineral supplements reduced plasma dolutegravir AUC, Cmax, and C24 (ferrous fumarate: 54%, 57%, 56%; calcium carbonate: 39%, 37%, 39%). However, when administered with a meal or when dolutegravir was given two hours before the supplements (fasted), the effect was counteracted. The authors conclude that dolutegravir and iron and calcium supplements can be adminsitered together if taken with a meal. Under fasted conditions, dolutegravir should be taken 2 hours before or 6 hours after the supplements; co-administration under fasted conditions is not recommended.
All commercially available integrase inhibitors are 2-metal binders and may be affected by co-administration with metal cations.