Dolutegravir is neither an inducer nor an inhibitor of metabolising enzymes, and it therefore has a low propensity to act as a perpetrator of drug-drug interactions. Clinically significant decreases in dolutegravir exposure occur when it is co-administered with strong inducers (e.g. rifampicin, efavirenz) of drug metabolising enzymes and drug efflux transporters for which dolutegravir is a substrate – this can be overcome by increasing the dose of dolutegravir from 50 mg once daily to 50 mg twice daily. Dolutegravir significantly increases metformin plasma exposure: one must not exceed metformin 500 mg twice daily with concomitant dolutegravir. Divalent or trivalent cations chelate dolutegravir. Therefore, concomitant administration of dolutegravir with aluminium- and calcium-containing antacids should be avoided. Dolutegravir can be administered with calcium and iron supplements, provided these are taken together with food.